<PAGE>
AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON APRIL 3, 2000.
REGISTRATION NO. 333-96351
- --------------------------------------------------------------------------------
- --------------------------------------------------------------------------------
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
------------------------
AMENDMENT NO. 4
TO
FORM S-1
REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933
------------------------
PRAECIS PHARMACEUTICALS INCORPORATED
(Exact name of registrant as specified in its charter)
<TABLE>
<S> <C> <C>
DELAWARE 2834 04-3200305
(State or other jurisdiction (Primary Standard Industrial (I.R.S. Employer
of incorporation or organization) Classification Code Number) Identification No.)
</TABLE>
PRAECIS PHARMACEUTICALS INCORPORATED
ONE HAMPSHIRE STREET
CAMBRIDGE, MASSACHUSETTS 02139-1572
(617) 494-8400
(Address, including zip code, and telephone number,
including area code, of registrant's principal executive offices)
------------------------------
MALCOLM L. GEFTER, PH.D.
CHAIRMAN OF THE BOARD,
CHIEF EXECUTIVE OFFICER AND PRESIDENT
ONE HAMPSHIRE STREET
CAMBRIDGE, MASSACHUSETTS 02139-1572
(617) 494-8400
(Name, address, including zip code, and telephone number, including area code,
of agent for service)
------------------------------
COPIES TO:
<TABLE>
<S> <C>
STUART M. CABLE, P.C.
KENT A. COIT, ESQ. KATHRYN I. MURTAGH, ESQ.
SKADDEN, ARPS, SLATE, MEAGHER & FLOM LLP GOODWIN, PROCTER & HOAR LLP
ONE BEACON STREET EXCHANGE PLACE
BOSTON, MASSACHUSETTS 02108 BOSTON, MASSACHUSETTS 02109
(617) 573-4800 (617) 570-1000
</TABLE>
--------------------------
APPROXIMATE DATE OF COMMENCEMENT OF PROPOSED SALE TO THE PUBLIC: As soon as
practicable after the effective date of this registration statement.
If any of the securities being registered on this Form are to be offered on
a delayed or continuous basis pursuant to Rule 415 under the Securities Act of
1933, as amended, check the following box. / /
If this Form is filed to register additional securities for an offering
pursuant to Rule 462(b) under the Securities Act, please check the following box
and list the Securities Act registration statement number of the earlier
effective registration statement for the same offering. / / ____________
If this Form is a post-effective amendment filed pursuant to Rule 462(c)
under the Securities Act, check the following box and list the Securities Act
registration statement number of the earlier effective registration statement
for the same offering. / / ____________
If this Form is a post-effective amendment filed pursuant to Rule 462(d)
under the Securities Act, check the following box and list the Securities Act
registration statement number of the earlier effective registration statement
for the same offering. / / ____________
If delivery of the prospectus is expected to be made pursuant to Rule 434,
please check the following box. / /
--------------------------
THE REGISTRANT HEREBY AMENDS THIS REGISTRATION STATEMENT ON SUCH DATE OR
DATES AS MAY BE NECESSARY TO DELAY ITS EFFECTIVE DATE UNTIL THE REGISTRANT SHALL
FILE A FURTHER AMENDMENT WHICH SPECIFICALLY STATES THAT THIS REGISTRATION
STATEMENT SHALL THEREAFTER BECOME EFFECTIVE IN ACCORDANCE WITH SECTION 8(a) OF
THE SECURITIES ACT OF 1933 OR UNTIL THIS REGISTRATION STATEMENT SHALL BECOME
EFFECTIVE ON SUCH DATE AS THE SECURITIES AND EXCHANGE COMMISSION, ACTING
PURSUANT TO SAID SECTION 8(a), MAY DETERMINE.
- --------------------------------------------------------------------------------
- --------------------------------------------------------------------------------
<PAGE>
PART II
INFORMATION NOT REQUIRED IN PROSPECTUS
ITEM 13. OTHER EXPENSES OF ISSUANCE AND DISTRIBUTION.
We estimate that the expenses, other than underwriting discounts and
commissions, that we will incur in connection with the issuance and distribution
of the securities we are registering under this registration statement will be
as follows:
<TABLE>
<S> <C>
SEC registration fee........................................ $ 41,290
NASD filing fees............................................ 16,140
The Nasdaq National Market listing fee...................... 95,000
Printing and engraving expenses............................. 200,000
Legal fees and expenses..................................... 475,000
Accounting fees and expenses................................ 250,000
Blue Sky fees and expenses (including legal fees)........... 10,000
Transfer agent fees......................................... 25,000
Miscellaneous............................................... 137,570
----------
Total................................................. $1,250,000
==========
</TABLE>
ITEM 14. INDEMNIFICATION OF DIRECTORS AND OFFICERS.
Section 145 of the Delaware General Corporate Law permits indemnification of
officers, directors and other corporate agents under certain circumstances and
subject to certain limitations. Our amended and restated certificate of
incorporation and our amended and restated by-laws, effective upon the closing
of this offering, provide that we will indemnify our directors and officers to
the fullest extent authorized or permitted by law.
Our amended and restated certificate of incorporation further provides that
our directors will not be personally liable to us or any stockholder for
monetary damages for breach of fiduciary duty, except to the extent such
exemption is not permitted by law. Section 102 of the Delaware General Corporate
Law provides that officers and directors will not be personally liable for
monetary damages for breach of their fiduciary duties as directors, except
liability for:
- any breach of their duty of loyalty to the corporation or its
stockholders;
- acts or omissions not in good faith or which involve intentional
misconduct or a knowing violation of law;
- unlawful payments of dividends or unlawful stock repurchases or
redemptions; or
- any transaction from which the director derived an improper personal
benefit.
This provision has no effect on any non-monetary remedies that may be
available to us or our stockholders, nor does it relieve us or our officers or
directors from compliance with federal or state securities laws.
Insofar as indemnification for liabilities arising under the Securities Act
may be permitted to directors, officers or persons controlling us pursuant to
the foregoing provisions or otherwise, we have been informed that in the opinion
of the Securities and Exchange Commission, such indemnification is against
public policy as expressed in the Securities Act and is therefore unenforceable.
Our by-laws also permit us to purchase and maintain insurance on behalf of
any officer or director for any liability arising out of his or her actions in
such capacity, regardless of whether our by-laws
II-1
<PAGE>
would otherwise permit indemnification for that liability. We are in the process
of obtaining directors' and officers' liability insurance which would indemnify
our directors and officers against damages arising out of claims which might be
made against them based on their negligent acts or omissions while acting in
their capacity as officers and directors.
The underwriting agreement provides that the underwriters must, under
various circumstances, indemnify our directors, officers and controlling persons
against some liabilities, including liabilities under the Securities Act.
Reference is made to the form of underwriting agreement filed as Exhibit 1.1 to
this registration statement.
Under agreements with J.H. Whitney & Co. and affiliated entities, William
Laverack, Jr., a director, is indemnified for certain liabilities which he may
incur in his capacity as a director.
ITEM 15. RECENT SALES OF UNREGISTERED SECURITIES.
In the three years preceding the filing of this registration statement, we
have issued the securities set forth below that we did not register under the
Securities Act. We adjusted the common stock share amounts and the option and
warrant exercise prices set forth below to give effect to the 2-for-1 stock
split of the common stock effected March 8, 2000.
(a) ISSUANCE OF CAPITAL STOCK.
In May 1997, we issued to one accredited investor 1,617,772 shares of common
stock and a warrant to purchase 404,445 shares of common stock, at an exercise
price of $12.88 per share, for an aggregate purchase price of $10,000,000.
In June 1997, we issued to one accredited investor 359,324 shares of our
Series D convertible preferred stock, par value $.01 per share, for an aggregate
purchase price of $10,000,000. Upon the closing of this offering, the shares of
Series D convertible preferred stock will automatically convert into
2,695,414 shares of common stock.
In April 1998, we issued to 23 accredited investors 900,478 shares of our
Series E convertible preferred stock, par value $.01 per share, for an aggregate
purchase price of $37,820,076. Upon the closing at this offering, the shares of
Series E convertible preferred stock will automatically convert into
6,753,582 shares of common stock.
No underwriters were involved in the foregoing sales of securities. We made
the sales of capital stock in reliance upon an exemption from registration under
the Securities Act provided by Section 4(2) of the Securities Act, and its
related rules and regulations, regarding sales by an issuer not involving a
public offering. All of the foregoing securities are deemed restricted
securities for purposes of the Securities Act.
(b) GRANTS AND EXERCISES OF STOCK OPTIONS AND STOCK AWARDS.
From January 1, 1997 through December 31, 1999, we had granted options to
employees, directors and consultants under our Amended and Restated 1995 Stock
Plan, as amended, to purchase a total of 5,804,338 shares of common stock at a
weighted average exercise price of $4.79 per share. Of these options, options to
purchase 1,417,018 shares of common stock have been exercised for aggregate
consideration of $272,067 as of December 31, 1999. Subsequent to December 31,
1999 through March 30, 2000: (i) we granted options to purchase an additional
542,430 shares of common stock at an exercise price of $14.50 per share; and
(ii) options to purchase an additional 615,874 shares of common stock have been
exercised for aggregate consideration of $656,871.
In March 2000, we issued a stock award for 1,500 shares of common stock,
with an estimated fair market value of $21,750 to one of our consultants for
services rendered.
II-2
<PAGE>
The issuance of options and common stock awards, and the issuance of common
stock upon the exercise of options, were exempt from registration under the
Securities Act either pursuant to Rule 701 under the Securities Act, as a
transaction pursuant to a compensatory benefit plan, or pursuant to Section 4(2)
of the Securities Act, as a transaction by an issuer not involving a public
offering. All of the foregoing securities are deemed restricted securities for
purposes of the Securities Act.
ITEM 16. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES.
(a) EXHIBITS
<TABLE>
<CAPTION>
EXHIBIT NO. EXHIBIT
- ----------- -------
<C> <S>
**1.1 Form of Underwriting Agreement
**3.1 Amended and Restated Certificate of Incorporation, as
amended
**3.2 Amendment to Amended and Restated Certificate of
Incorporation, as amended
**3.3 Form of Amended and Restated Certificate of Incorporation
(to be filed upon the closing of this offering)
**3.4 Amended and Restated By-Laws
**3.5 Form of Amended and Restated By-Laws (to become effective
upon the closing of this offering)
**4.1 Specimen certificate representing shares of common stock
**4.2 Warrant to purchase Series A Convertible Preferred Stock
dated as of August 12, 1998 held by Comdisco, Inc.
**4.3 Warrant to purchase Series A Convertible Preferred Stock
dated as of August 12, 1998 held by Gregory Stento
**4.4 Warrant to purchase Common Stock dated May 13, 1997
**5.1 Opinion of Skadden, Arps, Slate, Meagher & Flom LLP
**10.1 Form of Second Amended and Restated 1995 Stock Plan
**10.2 Executive Management Bonus Plan
**10.3 Form of Employee Stock Purchase Plan
**10.4 Amended and Restated Stockholders Agreement dated as of
April 30, 1998 by and among PRAECIS and certain stockholders
referred to therein, as amended by Amendment No. 1 dated as
of May 14, 1998, Amendment No. 2 dated as of July 21, 1998
and Amendment No. 3 dated January 31, 2000
**10.5 Stock and Warrant Purchase Agreement dated as of May 13,
1997 by and between Sylamerica, Inc. and PRAECIS
+10.6 License Agreement dated as of May 13, 1997 by and between
PRAECIS and Synthelabo, as amended by letters dated July 31,
1997, October 1, 1998 and June 17, 1999
+10.7 Amended and Restated Binding Agreement in Principle
effective as of March 8, 1999 by and between PRAECIS and
Amgen Inc.
**+10.8 Collaboration Agreement dated as of January 31, 2000 by and
between Human Genome Sciences, Inc. and PRAECIS
+10.9 Collaboration and License Agreement dated as of August 1,
1996 by and between PRAECIS and Boehringer Ingelheim
International GmbH
**+10.10 License Agreement effective as of October 17, 1996 by and
between PRAECIS and Indiana University Foundation, as
amended as of June 3, 1998
**+10.11 License Agreement dated as of April 15, 1999 between
Pharmaceutical Applications Associates LLC, C. Donald
Williams, M.D.C.G.P., Robert Murdock, R.Ph. and PRAECIS
</TABLE>
II-3
<PAGE>
<TABLE>
<CAPTION>
EXHIBIT NO. EXHIBIT
- ----------- -------
<C> <S>
**+10.12 Development and Supply Agreement effective as of March 12,
1998 between UCB-Bioproducts S.A. and PRAECIS
**+10.13 Supply Agreement dated as of July 23, 1998 by and between
PRAECIS and Salsbury Chemicals, Inc.
10.14 Intentionally omitted
**10.15 License Agreement dated December 23, 1993 between
Massachusetts Institute of Technology and PRAECIS
**10.16 Lease dated as of April 28, 1994 by and between PRAECIS and
The Charles Stark Draper Laboratory, Inc.
**10.17 Lease dated as of August 19, 1998 by and between PRAECIS and
BDG Piscataway, LLC
**10.18 Contract of Sale dated as of January 14, 2000 by and between
Best Property Fund, L.P. and PRAECIS, as amended as of
February 7, 2000
**23.1 Consent of Skadden, Arps, Slate, Meagher & Flom LLP
(included in Exhibit 5.1)
**23.2 Consent of Ernst & Young LLP
**23.3 Consent of Lahive & Cockfield, LLP
**24.1 Power of Attorney (included on the signature page of this
registration statement)
**27 Financial Data Schedule
</TABLE>
- ------------------------
** Previously filed
+ Confidential treatment requested as to certain portions of this exhibit.
Omitted portions have been filed separately with the Securities and Exchange
Commission.
(b) FINANCIAL STATEMENT SCHEDULES:
All other schedules for which provision is made in the applicable accounting
regulations of the Securities and Exchange Commission are not required under the
related instructions or are inapplicable, and therefore have been omitted.
ITEM 17. UNDERTAKINGS.
The undersigned registrant hereby undertakes to provide to the underwriters
at the closing specified in the underwriting agreement, certificates in the
denominations and registered in the names as required by the underwriters to
permit prompt delivery to each purchaser.
Insofar as indemnification for liabilities arising under the Securities Act
of 1933 may be permitted to directors, officers and controlling persons of the
registrant pursuant to the foregoing provisions, or otherwise, the registrant
has been advised that in the opinion of the Securities and Exchange Commission
such indemnification is against public policy as expressed in the Securities Act
and is, therefore, unenforceable. In the event that a claim for indemnification
against such liabilities (other than the payment by the registrant of expenses
incurred or paid by a director, officer or controlling person of the registrant
in the successful defense of any action, suit or proceeding) is asserted by such
director, officer or controlling person in connection with the securities being
registered, the registrant will, unless in the opinion of its counsel the matter
has been settled by controlling precedent, submit to a court of appropriate
jurisdiction the question whether such indemnification by it is against public
policy as expressed in the Securities Act and will be governed by the final
adjudication of such issue.
The registrant hereby undertakes:
(1) That for purposes of determining any liability under the Securities
Act of 1933, the information omitted from the form of prospectus filed as
part of this registration statement in
II-4
<PAGE>
reliance upon Rule 430A and contained in a form of prospectus filed by the
registrant pursuant to Rule 424(b)(1) or (4) or 497(h) under the Securities
Act is deemed to be part of this registration statement as of the time it
was declared effective.
(2) That for the purpose of determining any liability under the
Securities Act of 1933, each post-effective amendment that contains a form
of prospectus is deemed to be a new registration statement relating to the
securities offered therein, and the offering of such securities at that time
will be deemed to be the initial BONA FIDE offering thereof.
II-5
<PAGE>
SIGNATURES
Pursuant to the requirements of the Securities Act of 1933, as amended, the
registrant certifies that it has reasonable grounds to believe that it meets all
of the requirements for filing on Form S-1 and has duly caused this Amendment
No. 4 to the registration statement to be signed on its behalf by the
undersigned, there unto duly authorized, in Cambridge, Massachusetts on
April 3, 2000.
<TABLE>
<S> <C> <C>
PRAECIS PHARMACEUTICALS INCORPORATED
By /s/ KEVIN F. MCLAUGHLIN
-----------------------------------------
Kevin F. McLaughlin
CHIEF FINANCIAL OFFICER, SENIOR VICE
PRESIDENT, SECRETARY AND TREASURER
</TABLE>
Pursuant to the requirements of the Securities Act of 1933, this Amendment
No. 4 to the registration statement has been signed by the following persons in
the capacities indicated on April 3, 2000.
<TABLE>
<CAPTION>
SIGNATURE TITLE
--------- -----
<C> <S>
*
------------------------------------------- Chairman of the Board, Chief Executive Officer
Malcolm L. Gefter, Ph.D. and President (PRINCIPAL EXECUTIVE OFFICER)
/s/ KEVIN F. MCLAUGHLIN Chief Financial Officer, Senior Vice
------------------------------------------- President, Secretary and Treasurer
Kevin F. McLaughlin (PRINCIPAL FINANCIAL AND ACCOUNTING OFFICER)
*
------------------------------------------- Director
G. Leonard Baker, Jr.
*
------------------------------------------- Director
William Laverack, Jr.
*
------------------------------------------- Director
Henry F. McCance
*
------------------------------------------- Director
David B. Sharrock
*
------------------------------------------- Director
Damion E. Wicker, M.D.
*
------------------------------------------- Director
Albert L. Zesiger
</TABLE>
<TABLE>
<S> <C> <C> <C>
*By: /s/ KEVIN F. MCLAUGHLIN
--------------------------------------
Kevin F. McLaughlin
Attorney-in-Fact
</TABLE>
II-6
<PAGE>
EXHIBIT INDEX
<TABLE>
<CAPTION>
EXHIBIT NO. EXHIBIT
- ----------- -------
<C> <S>
**1.1 Form of Underwriting Agreement
**3.1 Amended and Restated Certificate of Incorporation, as
amended
**3.2 Amendment to Amended and Restated Certificate of
Incorporation, as amended
**3.3 Form of Amended and Restated Certificate of Incorporation
(to be filed upon the closing of this offering)
**3.4 Amended and Restated By-Laws
**3.5 Form of Amended and Restated By-Laws (to become effective
upon the closing of this offering)
**4.1 Specimen certificate representing shares of common stock
**4.2 Warrant to purchase Series A Convertible Preferred Stock
dated as of August 12, 1998 held by Comdisco, Inc.
**4.3 Warrant to purchase Series A Convertible Preferred Stock
dated as of August 12, 1998 held by Gregory Stento
**4.4 Warrant to purchase Common Stock dated May 13, 1997
**5.1 Opinion of Skadden, Arps, Slate, Meagher & Flom LLP
**10.1 Form of Second Amended and Restated 1995 Stock Plan
**10.2 Executive Management Bonus Plan
**10.3 Form of Employee Stock Purchase Plan
**10.4 Amended and Restated Stockholders Agreement dated as of
April 30, 1998 by and among PRAECIS and certain stockholders
referred to therein, as amended by Amendment No. 1 dated as
of May 14, 1998, Amendment No. 2 dated as of July 21, 1998
and Amendment No. 3 dated January 31, 2000
**10.5 Stock and Warrant Purchase Agreement dated as of May 13,
1997 by and between Sylamerica, Inc. and PRAECIS
+10.6 License Agreement dated as of May 13, 1997 by and between
PRAECIS and Synthelabo, as amended by letters dated July 31,
1997, October 1, 1998 and June 17, 1999
+10.7 Amended and Restated Binding Agreement in Principle
effective as of March 8, 1999 by and between PRAECIS and
Amgen Inc.
**+10.8 Collaboration Agreement dated as of January 31, 2000 by and
between Human Genome Sciences, Inc. and PRAECIS
+10.9 Collaboration and License Agreement dated as of August 1,
1996 by and between PRAECIS and Boehringer Ingelheim
International GmbH
**+10.10 License Agreement effective as of October 17, 1996 by and
between PRAECIS and Indiana University Foundation, as
amended as of June 3, 1998
**+10.11 License Agreement dated as of April 15, 1999 between
Pharmaceutical Applications Associates LLC, C. Donald
Williams, M.D.C.G.P., Robert Murdock, R.Ph. and PRAECIS
**+10.12 Development and Supply Agreement effective as of March 12,
1998 between UCB-Bioproducts S.A. and PRAECIS
</TABLE>
<PAGE>
<TABLE>
<CAPTION>
EXHIBIT NO. EXHIBIT
- ----------- -------
<C> <S>
**+10.13 Supply Agreement dated as of July 23, 1998 by and between
PRAECIS and Salsbury Chemicals, Inc.
10.14 Intentionally omitted
**10.15 License Agreement dated December 23, 1993 between
Massachusetts Institute of Technology and PRAECIS
**10.16 Lease dated as of April 28, 1994 by and between PRAECIS and
The Charles Stark Draper Laboratory, Inc.
**10.17 Lease dated as of August 19, 1998 by and between PRAECIS and
BDG Piscataway, LLC
**10.18 Contract of Sale dated as of January 14, 2000 by and between
Best Property Fund, L.P. and PRAECIS, as amended as of
February 7, 2000
**23.1 Consent of Skadden, Arps, Slate, Meagher & Flom LLP
(included in Exhibit 5.1)
**23.2 Consent of Ernst & Young LLP
**23.3 Consent of Lahive & Cockfield, LLP
**24.1 Power of Attorney (included on the signature page of this
registration statement)
**27 Financial Data Schedule
</TABLE>
- ------------------------
** Previously filed
+ Confidential treatment requested as to certain portions of this exhibit.
Omitted portions have been filed separately with the Securities and Exchange
Commission.
<PAGE>
EXHIBIT 10.6
CONFIDENTIAL TREATMENT HAS BEEN REQUESTED FOR CERTAIN
PORTIONS OF THIS DOCUMENT. SUCH PORTIONS HAVE BEEN
REDACTED AND MARKED WITH ASTERISKS (**). THE NON-
REDACTED VERSION OF THIS DOCUMENT HAS BEEN SENT TO
THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO
AN APPLICATION FOR CONFIDENTIAL TREATMENT.
LICENSE AGREEMENT
BY AND BETWEEN
SYNTHELABO
AND
PRAECIS PHARMACEUTICALS, INC.
May 13, 1997
<PAGE>
TABLE OF CONTENTS
ARTICLE 1 DEFINITIONS................................................2
ARTICLE 2 GRANT OF EXCLUSIVE LICENSE TO
SYNTHELABO................................................14
2.1 Exclusive License and Sublicense
For Licensed Products.....................................14
2.2 PRAECIS Covenant to Honor
Synthelabo's Exclusive Rights.............................15
2.3 Acknowledgement of PRAECIS'
Retained Rights...........................................16
2.4 Sublicenses...............................................18
2.5 Agreement Regarding Sales in
Section B Territory Countries.............................19
2.6 Use of Improvements by IUF and IU.........................21
ARTICLE 3 MANUFACTURING.............................................21
3.1 PRAECIS' Supply Commitment................................21
3.2 Preliminary Three-Year Forecasts..........................21
3.3 Long-Term Forecasts.......................................22
3.4 Long-Term Forecasts Nonbinding............................22
3.5 Short-Term Forecasts......................................23
3.6 Purchase Orders...........................................24
3.7 PRAECIS' Supply Obligations and
Rights....................................................25
3.8 [Intentionally Omitted]
3.9 Manufacturing Rights of Synthelabo Upon
PRAECIS Material Breach...................................26
3.10 Payment for Licensed Products
Manufacture By Synthelabo;
Synthelabo Duty to Mitigate...............................27
3.11 Suspension of Manufacture By
Synthelabo; Termination of
Manufacturing License.....................................29
3.12 Agreement Regarding Third Party
Manufacturers.............................................30
3.13 Direct Billing............................................32
3.14 Force Majeure.............................................33
3.15 Form and Terms of License Product
Shipments.................................................33
3.16 Supply of Licensed Product For
Certain Supplemental Development
Plan Clinical Studies.....................................35
ARTICLE 4 DEVELOPMENT AND APPROVAL OF
LICENSED PRODUCTS.........................................35
4.1 Diligence.................................................35
4.2 Development Program and Plans.............................36
i
<PAGE>
4.3 Additional Applications...................................38
4.4 Regulatory Meetings.......................................39
4.5 Development Costs.........................................39
4.6 Registration and Reimbursement
Approvals.................................................41
4.7 Development Costs Records.................................42
4.8 Technical Information.....................................43
4.9 Clinical Trials...........................................44
4.10 Material Adverse Development;
Material Adverse Patent
Development; Competition..................................45
4.11 Synthelabo Formulation....................................47
4.12 Reporting on Adverse Reaction.............................47
ARTICLE 5 MARKETING AND SALES OBLIGATIONS OF
SYNTHELABO................................................47
5.1 Diligence Generally.......................................47
5.2 Advertising...............................................47
ARTICLE 6 GOVERNANCE................................................48
6.1 Joint Steering Committee..................................48
6.2 Operations of the Parties Under the
Collaboration.............................................48
6.3 Timing of Regular Meetings; Agendas
.........................................................49
6.4 Special Meetings..........................................49
6.5 Decisions and Disputes....................................49
6.6 Development Subcommittee..................................51
6.7 Cooperation...............................................51
6.8 Visitation................................................52
6.9 Committee and Certain Other Costs.........................52
ARTICLE 7 CONFIDENTIALITY...........................................53
7.1 General...................................................53
7.2 Certain Exceptions........................................54
7.3 Publications..............................................55
ARTICLE 8 TRADEMARKS................................................56
8.1 Exclusive License for Rel-Ease(TM)
Trademark.................................................56
8.2 PRAECIS Approval Right....................................57
8.3 Trademark Designations....................................58
8.4 Labelling, etc............................................58
8.5 Indemnification By PRAECIS................................59
8.6 Licensed Products Names and
Trademarks................................................59
ii
<PAGE>
8.7 PRAECIS Registration of Licensed
Product Territory Trademark Outside
the Territory.............................................61
ARTICLE 9 PAYMENTS..................................................62
9.1 Signing and Milestone Payments............................62
9.2 Benchmark Transfer Price..................................64
9.3 Determination of Selling Price of
Licensed Products.........................................65
9.4 Transfer Price............................................66
9.5 Payment of Benchmark Transfer Price
.........................................................66
9.6 Adjustments; Reports......................................67
9.7 Miscellaneous Sales Costs.................................68
9.8 Royalties.................................................68
9.9 Samples...................................................69
9.10 Currency..................................................70
9.11 PRAECIS Audit Rights......................................70
ARTICLE 10 REMEDIES FOR NON-PAYMENT..................................72
10.1 Interest..................................................72
10.2 Other.....................................................72
10.3 Collateral................................................73
10.4 Insurance on Unsold Goods.................................74
ARTICLE 11 COOPERATION AND ASSISTANCE................................74
11.1 General...................................................74
11.2 Specific Cooperation of Synthelabo........................75
11.3 Specific Cooperation of PRAECIS...........................75
11.4 Patent Prosecution and Maintenance........................76
ARTICLE 12 REPRESENTATIONS AND WARRANTIES............................77
12.1 Conformity to Specifications..............................77
12.2 Representations as to Intellectual
Property..................................................79
12.3 Authority; Binding Agreement; Other
Matters...................................................80
12.4 IUF License Agreement.....................................81
12.5 Warranty Disclaimer.......................................81
ARTICLE 13 INDEMNIFICATION...........................................82
13.1 Synthelabo Indemnification of
PRAECIS...................................................82
13.2 PRAECIS' Indemnification of
Synthelabo................................................83
13.3 Mutual Indemnification for Breach.........................83
13.4 Procedure For Third Party Claims..........................84
iii
<PAGE>
ARTICLE 14 INSURANCE.................................................85
ARTICLE 15 NON-COMPETITION...........................................85
15.1 Mutual Non-Competition Covenant...........................85
15.2 Competitive Acquisition...................................86
ARTICLE 16 IMPROVEMENTS..............................................86
ARTICLE 17 TERM & TERMINATION........................................90
17.1 Term; Expiration..........................................90
17.2 Bankruptcy, Etc...........................................91
17.3 Breach....................................................92
17.4 Effect of Termination.....................................93
17.5 Surviving Provisions......................................94
17.6 Continuation of Sublicense Rights.........................94
17.7 Termination for Material Adverse
Events....................................................95
17.8 Right to Sell Inventory...................................95
ARTICLE 18 ARBITRATION...............................................96
18.1 Procedure; Decision Final and
Binding...................................................96
18.2 Assumption Regarding Intellectual
Property Rights...........................................97
18.3 Exception to Exclusive Dispute
Resolution Procedure......................................97
ARTICLE 19 INFRINGEMENT AND MAINTENANCE..............................98
19.1 Infringement by Third Parties.............................98
19.2 Infringement Suit By Third Parties........................99
19.3 Cooperation...............................................99
19.4 Differing Interests......................................100
ARTICLE 20 ASSIGNMENT...............................................100
ARTICLE 21 COMMUNICATIONS...........................................101
ARTICLE 22 MISCELLANEOUS PROVISIONS.................................102
22.1 Relationship of the Parties..............................102
22.2 Advertising; Trademarks, Etc.............................103
22.3 Public Disclosures.......................................103
22.4 Governing Law............................................104
22.5 Entire Agreement.........................................104
22.6 Severability.............................................104
22.7 No Waiver................................................105
22.8 Captions and References..................................105
22.9 Counterparts.............................................105
iv
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APPENDICES
Appendix I PRAECIS Proposed Core Development Studies
Appendix II Patent Applications
Appendix III IUF License Agreement
Appendix IV PPI-149 Definition
Appendix V Territory
Appendix VI Additional Supply Provisions
Appendix VII Example Form of Quality Charter
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LICENSE AGREEMENT
This Agreement is made as of the 13th day of May, 1997 (the "Effective
Date"), by and between Synthelabo, a societe anonyme organized in France, having
principal offices at 22 Avenue Galilee 92350 Le-Plessis-Robinson, France
("Synthelabo"), and PRAECIS PHARMACEUTICALS, INC., a Delaware corporation having
principal offices at One Hampshire Street, Cambridge, MA 02139 ("PRAECIS").
R E C I T A L S:
PRAECIS(TM) is the owner of patent applications and know-how related to
its depot formulation Rel-Ease(TM) system (the "Rel-Ease System") and certain
uses of LHRH Antagonist Compounds, and is the exclusive licensee of PPI-149 and
the other PPI Licensed Rights.
Synthelabo wishes to enter into a license agreement with PRAECIS for the
development and commercialization of therapeutic LHRH antagonist products which
contain PPI-149 or potentially other LHRH Antagonist Compounds and which are
formulated by or on behalf of PRAECIS.
PRAECIS is willing to enter into a license agreement with Synthelabo for
the development and commercialization of therapeutic LHRH antagonist products
which contain PPI-149 or potentially other LHRH Antagonist Compounds and which
are formulated by or on behalf of PRAECIS.
<PAGE>
NOW, THEREFORE, in consideration of the foregoing, and the
representations, warranties, covenants and agreements contained herein, the
parties hereby agree as follows:
ARTICLE 1 - DEFINITIONS
For the purposes of this Agreement, the following words and phrases shall
have the following meanings:
1.1 "Advertise" shall mean to create, distribute and display
information and artistic material for the purpose of promoting sales of the
Licensed Products to Third Parties, including but not limited to articles, print
ads, brochures, symposia, commercial exhibits, video and audio recordings, and
television, radio, and internet advertisements or commercials (hereinafter
"Forms").
1.2 "Adjustment Amount" is defined in Section 9.6.
1.3 An "Affiliate" of a party shall mean a company or other entity
which controls, is controlled by, or is under common control with such party. A
corporation or other entity shall be regarded as in control of another
corporation or entity if it owns or directly or indirectly controls more than
fifty percent (50%) of the voting stock or other ownership interest of the other
corporation or entity, or if it possesses, directly or indirectly, the power to
direct or cause the direction of the management and policies of the corporation
or other entity or the power to elect or appoint fifty percent (50%) or more of
the members of the governing body of the corporation or other entity; provided
that for all purposes of this Agreement, the following
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entities shall be deemed to be Affiliates of Synthelabo: Synthemedic (Morocco),
Synthelabo - Byk Pharma GmbH (Austria), Astra Synthelabo AB (Sweden) and Leiras
Synthelabo Oy (Finland).
1.4 [INTENTIONALLY OMITTED]
1.5 "Applications" shall mean all existing and future therapeutic
uses for Licensed Products, including without limitation the treatment of
prostate cancer, breast cancer, endometriosis, uterine fibroids, benign
prostatic hypertrophy (BPH), infertility, and precocious puberty.
1.6 "Benchmark Transfer Price" is defined in Section 9.2.
1.7 "Binding Estimate" is defined in Section 3.5(b).
1.8 "Clinical Trials" shall mean research in which Licensed Products
are used to treat human patients for the purpose of evaluating the safety,
efficacy and performance of the Licensed Products in such use, and for the
purpose of preparing reports as may be required in order to obtain Registration
Approval or Reimbursement Approval or for the purpose of preparing marketing
studies.
1.9 "Confidential Information" shall mean private information
transmitted by one party to the other pursuant to this Agreement or the
collaboration contemplated hereby, including but not limited to plans, results,
data, ideas, concepts, Improvements, conclusions, suggestions, know-how,
show-how, inventions, discoveries, products, processes, trade secrets, and all
information relating to the Licensed Products (including
3
<PAGE>
without limitation, the information set forth in Appendix IV); any financial or
business information relating to the Licensed Products, this Agreement or the
collaboration contemplated hereby; strategies with respect to Clinical Trials;
and any other information marked "Confidential" prior to transmittal. With
regard to oral communications, information conveyed thereby shall be considered
"Confidential Information" if made in the context of discussions specifically
relating to the Licensed Products, this Agreement or the collaboration
contemplated hereby, or if reduced to a writing marked "CONFIDENTIAL" and
transmitted to the other party within forty-five (45) days after said oral
communication. Confidential Information shall not include information which the
recipient can show: (i) is generally known or readily available to the public at
the time of disclosure other than as a result of a breach of any obligation of
confidentiality (including hereunder); (ii) was already known to the recipient
without a breach of any obligation of confidentiality (including hereunder);
(iii) became available to the public independent of the recipient; (iv) was
disclosed to the recipient by a Third Party having legal rights to same, which
disclosure did not violate a confidentiality obligation of such Third Party; or
(v) is subsequently and independently developed by an employee of the recipient
who did not have knowledge of the information disclosed by the disclosing party.
1.10 "Core Development Plan" shall mean the development plan to be
prepared and revised as necessary by
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Synthelabo and PRAECIS, in accordance with Section 4.2, which will include on an
annual basis a detailed set of milestones, timeframes and operating plans with
respect to the Core Development Studies.
1.11 "Core Development Studies" shall mean preclinical studies and
Clinical Trials to be undertaken by PRAECIS in the United States and/or other
countries in order to seek and obtain FDA Registration Approval for (i) the
Application of prostate cancer and (ii) the Applications of endometriosis or
uterine fibroids as the Joint Steering Committee shall determine, and (iii) any
other Application approved for development by the Joint Steering Committee and
the Development Subcommittee as provided in Section 4.3. The Core Development
Studies proposed by PRAECIS as of the Effective Date are summarized in Appendix
I.
1.12 "Cost of Goods" or its abbreviation "COGS" shall mean the unit
cost of manufacture of a given Licensed Product, as determined in accordance
with generally accepted accounting principles in the place of manufacture of
such Licensed Product, which cost in any event includes, without limitation,
costs of direct labor, contracts with Third Parties, manufacturing overhead
(including fixed costs), materials and supplies, all freight, duties, taxes
assessed on sales and transportation costs, but excludes any amount payable as
royalties in respect of the PPI Licensed Rights.
1.13 "Development Costs" shall mean all external costs (e.g., costs
of contracts with clinical research organizations)
5
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and direct internal costs (including direct labor, materials, supplies, and
specially procured essential equipment, but excluding rent, utilities,
administrative, secretarial, clerical, accounting and management allocations),
plus a fixed amount for overhead equal to ten percent (10%) of the direct
internal costs, which in each case are incurred after the Effective Date and
during the term hereof by PRAECIS or Synthelabo, as applicable, in connection
with a Development Phase (but excluding such costs incurred before or after the
Effective Date in connection with the prostate cancer Clinical Trials (IND
#51,170, Protocol #149-96-01) which are underway as of the Effective Date).
1.14 "Development Phase" in any country with respect to any
Application for any Licensed Product shall mean the period commencing on the
Effective Date and continuing until Registration Approval and Reimbursement
Approval of such Licensed Product for such Application in such country has been
obtained.
1.15 "Development Program" shall mean the collaboration by PRAECIS
and Synthelabo hereunder during the Development Phase.
1.16 "Diligence" or "diligent efforts" shall mean commercially
reasonable efforts consistent with efforts made by businesses of similar size
and resources for similar products in a similar context.
1.17 "Dispute Notice" is defined in Section 6.4.
1.18 "Disputed Matter" is defined in Section 6.4.
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1.19 "Effective Date" is defined in the first paragraph of this
Agreement.
1.20 "FDA" shall mean the United States Food and Drug Administration
or any successor agency.
1.21 "Field" shall mean the field as defined by the Applications
taken collectively.
1.22 "First Commercial Sale" of a Licensed Product shall mean the
first commercial sale by Synthelabo or its Affiliates for use or consumption by
the general public of such Licensed Product based on Registration Approval of
such Licensed Product in any Territory Country.
1.23 "Improvements" shall mean changes in composition, design or
manufacture of the Licensed Products which result in enhancements or alterations
of any component of the Licensed Products with respect to, without limitation,
efficacy, safety, drug delivery profiles, stability, shelf-life, dosage, cost,
ease of use, or styling, except that for purposes of Section 2.6 only,
"Improvements" shall have the meaning set forth in the IUF License Agreement.
1.24 "Incoterms" shall mean that body of trade rules as published in
1990 by the International Chamber of Commerce, Paris, France.
1.25 "Intellectual Property Rights" shall mean all rights, including
unpatented inventions and know-how, of PRAECIS in and to or with respect to the
Licensed Products, including the rights in the Territory in and to the patent
applications listed
7
<PAGE>
in Appendix II (which is incorporated herein by reference), and all patents
issuing therefrom and all continuations, continuations-in-part, reissues,
divisionals, extensions, supplementary certificates of protection and
equivalents of any of the foregoing throughout the Territory; and further
including all other rights, including unpatented inventions and know-how, in and
to or with respect to the Licensed Products as may subsist or may be secured by
PRAECIS under and in accordance with the patent, copyright, and trade secret
statutes, rules, regulations, orders and decrees of any governments of the
Territory, or which otherwise exist or can be obtained under constitutions,
treaties, common law, or civil law of any and all Territory Countries, together
with all rights of PRAECIS under contracts, licenses and other agreements
relating to the Licensed Products or any Intellectual Property Rights; but
excluding trademark rights and the PPI Licensed Rights which are provided for
separately hereunder.
1.26 "Inventions" and "Invention Rights" shall have the respective
meanings set forth in the IUF License Agreement.
1.27 "IU" shall mean Indiana University.
1.28 "IUF" shall mean Indiana University Foundation.
1.29 "IUF License Agreement" shall mean the License Agreement dated
as of October 17, 1996 between IUF and PRAECIS as in effect from time to time, a
copy of which Agreement as currently in effect is attached hereto as Appendix
III.
8
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1.30 "Joint Steering Committee" is defined in Section 6.1
1.31 "LHRH Antagonist Compounds" shall mean compounds which exhibit
Lutenizing Hormone Releasing Hormone (LHRH) antagonist activity.
1.32 "Licensed Products" shall mean therapeutic products which
contain PPI-149, or any other LHRH Antagonist Compound as to which PRAECIS has
all the rights necessary to make the grants to Synthelabo hereunder, in either
case in a depot or other formulation owned by or licensed to PRAECIS. Unless
otherwise specified herein, references to Licensed Products include
Improvements.
1.33 "Licensed Product Territory Trademark" is defined in Section
8.5.
1.34 "Long-Term Forecast" is defined in Section 3.3.
1.35 "Material Adverse Development" means, with respect to a
Licensed Product for a particular Application, an event or development (other
than a Material Adverse Patent Development) which occurs after the date of this
Agreement (other than an event or development which constitutes or arises from a
breach hereof by Synthelabo) which results in a material adverse change in the
commercial prospects of such Licensed Product for such Application.
1.36 "Material Adverse Patent Development" means the occurrence of
any of the events described in clauses (A), (B) or (C): (A) the reasonable
determination of Synthelabo, at any stage
9
<PAGE>
in the patent procedure after receipt of the European search report and the
first official letter from the European Patent Office referred to in Section
11.4, that it is not reasonably likely that a European patent will be granted on
PPI-149 or the formulation, respectively, substantially as described in the
respective European equivalents of patent applications PCT/US96/09852 or US
08/762,747, respectively (the "Material Patent Applications"); (B) the lack of
any valid or enforceable patent issued substantially as described in the
Material Patent Applications as the individual or combined result of (i) no such
patents having issued and the unrevivable abandonment of any of the Material
Patent Applications, (ii) all such patents having been finally and unappealably
declared invalid or unenforceable, or (iii) all such patents having prematurely
expired for failure to pay maintenance fees or annuities; or (C) a timely filed
action by a Third Party to annul, cancel or revoke a patent issued substantially
as described in the Material Patent Applications, other than any such action
which has no reasonable likelihood of success on the merits.
1.37 "Net Sales" shall mean the sales price per unit of a Licensed
Product invoiced by Synthelabo or an Affiliate thereof to a Third Party with
respect to the sale of Licensed Products to a Third Party, less, to the extent
such amounts are included in the invoiced sales price, the direct cost of trade
discounts, credits for returns and rebates, discounts for prompt payments to the
extent such discounts are customary in the
10
<PAGE>
applicable Territory Country, insurance and transportation charges (unless
reimbursed by a Third Party), and duties and taxes assessed on sales; provided
that neither Synthelabo nor its Affiliates shall (i) sell Licensed Products in
combination with other products unless the price of the Licensed Products is
separately identified in the invoice with such other products, nor (ii) discount
Licensed Products by a greater percentage than other products with which such
Licensed Products are sold. Units of Licensed Products which are provided to
Synthelabo or its Affiliates at Cost of Goods in accordance with Section 9.9 for
use as salesman's exhibits or as Promotional free samples, shall not be
considered sales for purposes of this definition, but units of Licensed Products
which are provided to Synthelabo or its Affiliates in connection with any Phase
IV Clinical Trials shall be considered sales for purposes of this definition.
For purposes of this definition as used throughout this Agreement, any
co-marketing partner of Synthelabo or its Affiliates shall be deemed an
"Affiliate" and not a Third Party.
1.38 "Notice" is defined in Article 21.
1.39 "Notice Address" means the addresses listed as such in Article
21.
1.40 "Patent Rights" shall have the meaning set forth in the IUF
License Agreement.
1.41 "Plateau Amount" is defined in Section 3.9.
1.42 "PPI-149" shall have the meaning set forth in Appendix IV.
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1.43 "PPI Licensed Rights" shall mean all rights licensed to PRAECIS
pursuant to Section 3.01(a) of the IUF License Agreement, together with, if
applicable, any rights to LHRH Antagonist Compounds licensed to PRAECIS in
accordance with Section 3.01(b) of the IUF License Agreement.
1.44 "Promote" shall mean to encourage Third Parties to consider
purchasing the Licensed Products, through in-person calls by qualified and
trained salespeople, and through such other promotional means as are reasonable
and customary in the pharmaceutical industry in each Territory Country for
products which are similar to Licensed Products.
1.45 "Quarterly Shortfall" is defined in Section 3.7(b).
1.46 "Registration Application" shall mean a registration dossier
filed with the appropriate regulatory authorities of a country or with an agency
representing a group of countries to obtain Registration Approval and
Reimbursement Approval for a Licensed Product in such country or group of
countries.
1.47 "Registration Approval" shall mean governmental approval for
marketing and sale of a Licensed Product in a country prior to the commencement
of sales of Licensed Product in such country.
1.48 "Reimbursement Approval" shall mean approval by the
governmental health care cost reimbursement agency or agencies in a country,
including any required pricing approval,
12
<PAGE>
required in order for patients in such country to receive reimbursement for
purchases of a Licensed Product.
1.49 "Requesting Party" is defined in Section 4.7.
1.50 "Revenue" or its abbreviation "REV" shall mean the arithmetic
average of Net Sales for a given Licensed Product during a given calendar
quarter.
1.51 "Reviewed Party" is defined in Section 4.7.
1.52 "Short-Term Forecast" is defined in Section 3.5(a).
1.53 "Startup Date" is defined in Section 3.3.
1.54 "Supplemental Development Plan" shall mean the supplemental
development plan to be prepared and revised, as necessary, by Synthelabo in
accordance with Section 4.2, which will include on an annual basis a detailed
set of milestones, timeframes and operating plans with respect to the
Supplemental Development Studies.
1.55 "Supplemental Development Studies" shall mean preclinical
studies and Clinical Trials to be undertaken by Synthelabo in order to fulfill
the requirements for Registration Approval and Reimbursement Approval in any
Territory Country which have not fully been satisfied by the Core Development
Studies.
1.56 "Synthelabo Formulation" shall mean any formulation for PPI-149
or for any other LHRH Antagonist Compound licensed to Synthelabo hereunder,
which formulation is
13
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discovered, conceived or developed solely by or on behalf of Synthelabo, its
employees or agents.
1.57 "Territory" shall mean the geographic areas which, as of the
Effective Date, are denominated as set forth in Appendix V, including their
respective territories and possessions, irrespective of any changes in
government or name after the Effective Date.
1.58 "Territory Countries" shall mean the countries which make up
the Territory as defined hereinabove and in Appendix V, both individually and
collectively.
1.59 "Third Party" shall mean any person or entity other than
PRAECIS, Synthelabo and their respective Affiliates.
1.60 "Transfer Price" is defined in Section 9.4.
ARTICLE 2 - GRANT OF EXCLUSIVE LICENSE TO SYNTHELABO
2.1 Exclusive License and Sublicense For Licensed Products. Subject
to the other terms and conditions herein, PRAECIS hereby grants Synthelabo and
its Affiliates (i) an exclusive license under the Intellectual Property Rights
and an exclusive sublicense under the PPI Licensed Rights to develop Licensed
Products, to use Licensed Products, to import Licensed Products from PRAECIS, to
offer to sell Licensed Products to Third Parties, to Advertise and Promote
Licensed Products, and to distribute and sell Licensed Products to Third
Parties, with each such licensed and sublicensed right being limited to the
Field and to the Territory and (ii) an exclusive sublicense under the PPI
Licensed Rights and with respect to any LHRH Antagonist
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Compound not included in the PPI Licensed Rights as to which PRAECIS has all the
rights necessary to make the grant set forth in this clause (ii), to develop
Synthelabo Formulations. The right to manufacture Licensed Products or have
Licensed Products manufactured and the right to import Licensed Products from
other than PRAECIS are included in this grant in accordance with and only to the
extent permitted by Article 3. Notwithstanding the foregoing or any other
provision of this Agreement, (i) in no event shall the scope of the grant of a
sublicense with respect to the PPI Licensed Rights as set forth herein be deemed
to exceed the scope of the grant of rights to PRAECIS pursuant to the IUF
License Agreement and (ii) the grant of a sublicense with respect to the PPI
Licensed Rights as set forth herein shall be subject to any reservations or
restrictions with respect to PPI Licensed Rights contained in the IUF License
Agreement.
2.2 PRAECIS Covenant to Honor Synthelabo's Exclusive Rights. PRAECIS
and its Affiliates shall honor the exclusive license rights of Synthelabo
hereunder and shall neither take, nor permit to be taken, any action which is
inconsistent with such exclusive rights, including, by way of example and not
limitation, by (i) offering to sell or selling Licensed Products inside the
Territory, (ii) knowingly offering to sell or knowingly selling Licensed
Products to Third Parties who intend to transport or use same inside the
Territory, (iii) knowingly offering to sell or knowingly selling any Licensed
Products to Third Parties who intend to sell same in the Territory or (iv)
15
<PAGE>
maintaining any branch or distribution depot for the purpose of selling Licensed
Products in the Territory; however, subject to the foregoing restrictions on
PRAECIS, nothing herein shall obligate PRAECIS to impose any restriction upon
the use or resale of any Licensed Product by a purchaser (except for a licensee
of PRAECIS outside the Territory) thereof from PRAECIS, and the use or resale of
any Licensed Product in the Territory by such a purchaser (except for a licensee
of PRAECIS outside the Territory) shall not constitute a breach of any provision
of this Agreement by PRAECIS. Neither PRAECIS nor Synthelabo shall be under any
obligation to procure the termination of such use or resale, but either may, at
their discretion, seek to do so.
2.3 Acknowledgement of PRAECIS' Retained Rights. Synthelabo and its
Affiliates hereby agree and acknowledge that PRAECIS and its Affiliates may
develop Licensed Products and Improvements, distribute, offer for sale,
Advertise, Promote, and sell the Licensed Products, and otherwise develop and
exploit the market for Licensed Products outside of the Territory, either on
their own behalf or through marketing partnerships, strategic alliances, or
other relationships with Third Parties, as PRAECIS may determine in its sole
discretion, and without any obligation to Synthelabo therefor. In addition,
Synthelabo and its Affiliates hereby agree that PRAECIS and its Affiliates,
either on their own behalf or through marketing partnerships, strategic
alliances, or other relationships with Third Parties, shall have the right
within the Territory to (i) develop the Licensed
16
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Products and Improvements, conduct Clinical Trials and engage in academic
research and publication (so long as in accordance with the confidentiality and
publication provisions herein) and (ii) with the prior approval of Synthelabo
which will not be unreasonably withheld or delayed, hold, sponsor and
participate in conferences and symposia related to the Licensed Products or LHRH
Antagonist Compounds generally. Synthelabo and its Affiliates shall honor the
exclusive rights of PRAECIS outside of the Territory and shall neither take, nor
permit to be taken, any action which is inconsistent with such exclusive rights,
including, by way of example and not limitation, by (i) offering to sell or
selling Licensed Products outside the Territory, (ii) knowingly offering to sell
or knowingly selling Licensed Products to Third Parties who intend to transport
or use same outside the Territory, (iii) knowingly offering to sell or knowingly
selling any Licensed Products to Third Parties who intend to sell same outside
of the Territory or (iv) maintaining any branch or distribution depot for the
purpose of selling Licensed Products outside the Territory; however, subject to
the foregoing restrictions on Synthelabo, nothing herein shall obligate
Synthelabo to impose any restriction upon the use or resale of any Licensed
Product by a purchaser thereof (except for a licensee of Synthelabo inside the
Territory) from Synthelabo or its Affiliates, and the use or resale of any
Licensed Product outside of the Territory by such a purchaser (except for a
licensee of Synthelabo inside the Territory) shall not constitute
17
<PAGE>
a breach of any provision of this Agreement by Synthelabo. Neither PRAECIS nor
Synthelabo shall be under any obligation to procure the termination of such use
or resale, but either may, at their discretion, seek to do so.
2.4 Sublicenses. Pursuant to sublicense or similar agreements,
Synthelabo and its Affiliates may, with the written consent of PRAECIS which
shall not be unreasonably withheld or delayed, extend the grant of Section 2.1,
along with its other rights hereunder, to one or more Third Parties; provided
such agreement is consistent with the terms hereof and the IUF License Agreement
and contains all of the terms required by the IUF License Agreement to be
included in any sublicense granted by PRAECIS. By granting any such sublicense,
Synthelabo shall be deemed to have consented to the amendment of this Agreement
to render the license and sublicense provided for herein co-exclusive as between
Synthelabo and its Affiliates on the one hand, and their respective
sublicensee(s) on the other, but not as between any such parties, on the one
hand, and any other Third Party on the other. Synthelabo will deliver to PRAECIS
a true and correct copy of each agreement entered into by Synthelabo and a Third
Party pursuant to this Section 2.4 and shall promptly advise PRAECIS in writing
of any modification (and shall supply a copy of the same) or termination of each
such agreement. If IUF should object that the IUF License Agreement does not
entitle PRAECIS to grant any such sublicense, Synthelabo may request PRAECIS to
grant such sublicense directly to such Third Party.
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Any such agreement shall automatically terminate upon termination (but not
expiration) of this Agreement, unless such termination is pursuant to Section
17.2 due to an event described therein with respect to PRAECIS or such
termination is by Synthelabo for breach pursuant to Section 17.3 and the special
provisions of Section 17.4 are applicable.
2.5 Agreement Regarding Sales in Section B Territory Countries. It
is the intention of the parties that Synthelabo, either alone or acting through
its Affiliates or its or their permitted assigns or permitted sublicensees, will
itself take full responsibility for the marketing and distribution activities
contemplated herein. As such, Synthelabo hereby agrees that it and its
Affiliates shall not, in those Territory Countries listed in Section A of
Appendix V ("Section A Territory Countries"), knowingly sell or otherwise
transfer Licensed Products to a Third Party which has substantially assumed or
will substantially assume the marketing responsibilities of Synthelabo hereunder
with respect to Licensed Products purchased by such Third Party, provided that
the foregoing shall not prohibit Synthelabo and its Affiliates from entering
into co-marketing arrangements with Third Parties on customary terms, it being
understood and agreed that any such arrangement shall not affect Synthelabo's
responsibility for the performance of its obligations hereunder and Synthelabo's
indemnification obligations hereunder shall apply to the acts or omissions of
any such co-marketing partner as if such acts or omissions were those of
Synthelabo. However,
19
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the parties agree that in certain of the Territory Countries listed in Section B
of Appendix V (the "Section B Territory Countries"), direct marketing by
Synthelabo or its Affiliates or by a co-marketing partner thereof may not be
possible, practicable or feasible. Therefore, in the Section B Territory
Countries, Synthelabo may have its marketing activities in such countries
performed by other Third Parties to the extent such performance of such
activities is customarily performed by such Third Parties in such countries, and
Synthelabo may sell Licensed Products through any distribution channels in each
such country as are considered normal and customary for such country; provided
that Synthelabo shall remain responsible for the performance of its obligations
hereunder and Synthelabo's indemnification obligations hereunder shall apply to
the acts or omissions of any such Third Party as if such acts or omissions were
those of Synthelabo. If more than 20% of cumulative Net Sales in the Territory
during any calendar year is from sales of Licensed Products in the Section B
Territory Countries, then PRAECIS and Synthelabo shall promptly negotiate in
good faith a special Transfer Price for Licensed Products sold in the Section B
Territory Countries, with a view to preserving for both PRAECIS and Synthelabo
the economic benefits intended to be provided hereunder. If agreement with
respect to such a special Transfer Price cannot be reached within 30 days after
the commencement of such negotiations, the parties hereby agree that the dispute
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resolution procedures set forth in Sections 6.5 and 18.1 may be invoked by
either party and the resolution achieved through such procedures shall be
binding on the parties.
2.6 Use of Improvements by IUF and IU. Synthelabo hereby grants to
PRAECIS, for further grant to IUF and IU, a royalty-free, nonexclusive license,
to use for research and educational purposes only, and without the right to
sublicense, any and all Improvements made by or on behalf of Synthelabo or any
Affiliate thereof.
ARTICLE 3 - MANUFACTURING
3.1 PRAECIS' Supply Commitment. PRAECIS shall provide Synthelabo
with all of its requirements for the Licensed Products, upon the terms and
subject to the conditions and limitations specified herein. PRAECIS shall be
entitled to subcontract the manufacture of all or part of such requirements to
one or more Third Party manufacturers, but any such subcontract shall not
diminish or alter PRAECIS' obligations hereunder. All manufacture of Licensed
Products shall be in accordance with current Good Manufacturing Practices (cGMP)
applicable to the pharmaceutical industry.
3.2 Preliminary Three-Year Forecasts. As promptly as practicable
after the Effective Date, but in any event at least eighteen (18) months prior
to the date which Synthelabo reasonably expects will be the date of First
Commercial Sale of a Licensed Product in the Territory, Synthelabo shall prepare
and deliver to PRAECIS a preliminary, good-faith, non-binding
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forecast of its total estimated requirements for Licensed Products during the
first three years following the projected date of First Commercial Sale of
Licensed Products in the Territory. Such non-binding three-year forecast shall
be updated by Synthelabo from time to time during the Development Phase to
reflect changes in Synthelabo's projected requirements for the first three years
following the anticipated date of such First Commercial Sale, provided that such
updates shall be prepared by Synthelabo no less frequently than annually during
the Development Phase.
3.3 Long-Term Forecasts. Not less than six months prior to the
actual date of First Commercial Sale of Licensed Products in the Territory (the
"Startup Date"), Synthelabo shall provide PRAECIS with a non-binding forecast (a
"Long-Term Forecast") of its total good-faith estimate of its requirements for
Licensed Products during the first three annual periods following the Startup
Date, with such projected requirements to be broken down on a quarter-by-quarter
basis for each such annual period. Not later than the first December 1 following
the Startup Date and, thereafter, on each anniversary of such date, Synthelabo
shall provide PRAECIS with a revised Long-Term Forecast covering the three
calendar years following the year in which such revised Long-Term Forecast is
provided, with such projected requirements to be broken down on a
quarter-by-quarter basis for each such calendar year.
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3.4 Long-Term Forecasts Nonbinding. It is acknowledged and agreed
that the Long-Term Forecasts are intended solely to assist the parties in their
long-range planning and shall not be binding on the parties in any respect, and
neither party shall have any liability to the other with respect to any
Long-Term Forecast.
3.5 Short-Term Forecasts.
(a) Periods Covered By and Delivery Dates for Short-Term Forecasts.
Synthelabo shall also provide PRAECIS with short-term forecasts of its
good-faith estimate of its requirements for Licensed Products on a rolling five
calendar quarter basis (i.e., covering five successive calendar quarters from
January-March, April-June, July-September and October-December, as applicable)
(each a "Short-Term Forecast"). The initial Short-Term Forecast shall be
delivered to PRAECIS simultaneously with the initial Long-Term Forecast to be
delivered six months prior to the Startup Date pursuant to the first sentence of
Section 3.3 above, and shall cover the calendar quarter in which the Startup
Date occurs and the next four succeeding calendar quarters. Each subsequent
Short-Term Forecast shall be delivered to PRAECIS not later than the first day
of each succeeding calendar quarter.
(b) Binding Estimates. Each Short-Term Forecast shall be provided at
least six months in advance of the commencement of the five-quarter period
covered by such Short-Term Forecast. The forecast for the first calendar quarter
covered by each Short-
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Term Forecast shall be treated as a binding forecast with respect to such
quarter (each a "Binding Estimate"), subject to the remaining provisions of this
Article 3. Each Short-Term Forecast shall revise and update the projections set
forth in the applicable Long-Term Forecast.
(c) Synthelabo's Purchase Commitment Based on Binding Estimates.
Subject to the provisions of Section 3.7 below, Synthelabo's delivery to PRAECIS
of each Short-Term Forecast shall constitute Synthelabo's binding commitment to
purchase during the first calendar quarter covered thereby at least 80% of the
Binding Estimate contained in such Short-Term Forecast.
3.6 Purchase Orders. Synthelabo shall submit written purchase orders
for Licensed Products to PRAECIS at least ninety days prior to the requested
delivery date. Subject only to the volume limitations set forth in Section 3.7,
each purchase order shall be accepted and confirmed by PRAECIS within ten days
of its receipt. The parties agree that no term or provision contained in any
Synthelabo purchase order, or in any PRAECIS sales confirmation form, shall
modify or supersede any of the terms or provisions of this Agreement, and that
this Agreement shall dominate any such purchase order or sales confirmation form
in all respects, unless otherwise agreed in a separate written instrument
executed by duly authorized representatives of both Synthelabo and PRAECIS.
Toward this end, the parties agree that all purchase orders and confirmations
shall state on their face:
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"ALL TERMS AND CONDITIONS OF THE AGREEMENT OF MAY 13, 1997 SHALL APPLY TO THIS
TRANSACTION."
3.7 PRAECIS' Supply Obligations and Rights.
(a) Maximum and Minimum Quantities. Notwithstanding anything to the
contrary herein, unless otherwise agreed in writing by PRAECIS, in no event
shall PRAECIS be obligated to deliver quantities of Licensed Products during any
calendar quarter which exceed in the aggregate 120% of the Binding Estimate
previously provided by Synthelabo with respect to such calendar quarter. Subject
to the immediately preceding sentence, PRAECIS shall be obligated to supply
Licensed Products in an amount not less than 90% of the amount of Licensed
Products set forth in purchase orders submitted by Synthelabo pursuant to and in
accordance with the terms of Section 3.6.
(b) Quarterly Shortfalls. If the aggregate quantity of Licensed
Products actually ordered by Synthelabo for delivery during any calendar quarter
is less than 80% of the Binding Estimate for such calendar quarter (a "Quarterly
Shortfall"), then at the election of Synthelabo set forth in a notice which
Synthelabo shall give to PRAECIS within 15 days after the end of such calendar
quarter (i) PRAECIS shall have the right, exercisable within 45 days after the
end of such calendar quarter, to deliver to Synthelabo a quantity of Licensed
Products equal to such Quarterly Shortfall, and Synthelabo shall make timely
payment for such additional goods in accordance with Article 9, in the same
manner as if Synthelabo had ordered such goods or
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(ii) Synthelabo shall pay for such goods without requiring delivery thereof. The
purchase price payable by Synthelabo for the goods comprising any Quarterly
Shortfall shall be the average Transfer Price paid by Synthelabo to PRAECIS for
all deliveries made during the calendar quarter in which such Quarterly
Shortfall occurs, or if no such deliveries were made during such calendar
quarter, shall be equal to the average Transfer Price for the most recent
calendar quarter in which orders were placed and deliveries were made hereunder.
3.8 [INTENTIONALLY OMITTED]
3.9 Manufacturing Rights of Synthelabo Upon PRAECIS Material Breach.
If PRAECIS shall fail to materially comply with its supply obligations
hereunder, then PRAECIS shall provide Synthelabo with manufacturing protocols
and other manufacturing know-how and information, all of which shall be
Confidential Information hereunder, in order that Synthelabo may prepare to make
or have made such Licensed Products. If any other such material non-compliance
occurs within eight calendar quarters of the first such material noncompliance,
then PRAECIS shall grant to Synthelabo a sole, non-exclusive license under the
Intellectual Property Rights and PPI Licensed Rights to make and have made such
Licensed Products in such quantities as Synthelabo may thereafter require which
exceed the quantity which PRAECIS is able to supply in accordance with the terms
hereof (hereinafter, the "Plateau Amount"). In the event that Synthelabo has
such Licensed Products made by a Third Party, the agreement with such
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Third Party shall contain the same confidentiality provisions as this Agreement,
and a copy of such agreement shall promptly be provided to PRAECIS. No such
agreement shall have a term of more than one year, unless PRAECIS otherwise
agrees. Synthelabo shall continue to obtain from PRAECIS the Plateau Amount. If
Synthelabo makes or has made Licensed Products pursuant to this Section 3.9,
then Synthelabo shall, or shall have the Third Party manufacturer, apply for and
obtain a supplementary manufacturing approval with the appropriate regulatory
agencies, such that the PRAECIS manufacturing regulatory approval status remains
active with the appropriate regulatory agency, and the cost and expenses thereof
shall be included in Synthelabo's "Cost of Goods" for purposes of Section 3.10.
3.10 Payment for Licensed Products Manufacture By Synthelabo;
Synthelabo Duty to Mitigate. Synthelabo shall pay to PRAECIS the Transfer Price
for all Licensed Products made or had made by Synthelabo within forty-five (45)
days following the sale of same to Third Parties, less Synthelabo's Cost of
Goods; and Synthelabo shall timely pay to PRAECIS the Adjustment Amounts due and
payable for same, in accordance with Article 9. Subject to Section 3.14, if
Synthelabo's Cost of Goods for Licensed Products made or had made by Synthelabo
in accordance with Section 3.9 shall be greater than the Transfer Price, then
PRAECIS shall credit the difference to the account of Synthelabo, which credit
shall be reduced by any Adjustment Amounts due and payable for same, of which
PRAECIS shall be timely notified. Any remaining
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credits to Synthelabo will be applied to future payments due hereunder until
such credits are used in full. For purposes of this Section 3.10, Synthelabo's
"Cost of Goods" shall include the items set forth in Section 1.12 as well as
Synthelabo's reasonable costs of cover and other reasonable expenses incident to
any material breach by PRAECIS of its supply obligations hereunder, including,
without limitation, the cost of making Licensed Products itself or having such
products made by a Third Party and the costs and expenses referred to in the
last sentence of Section 3.9. At any time during which Synthelabo is making or
having made Licensed Products pursuant to Section 3.9, (i) Synthelabo shall be
required to minimize its Cost of Goods to the extent commercially reasonable,
and (ii) if PRAECIS can arrange to have a reputable Third Party manufacturer
provide Licensed Products to Synthelabo that are of the same quality and in the
same quantity as are being made or had made by Synthelabo, but at a cost that is
less than Synthelabo's (or its Affiliate's) Cost of Goods by ten percent (10%)
or more, and if such Third Party manufacturer is willing to enter into a supply
contract for same with a term of at least one (1) year, on supply terms at least
as favorable as those of this Agreement, then PRAECIS may contract for such
manufacture with such Third Party manufacturer and Synthelabo shall, as soon
thereafter as is commercially practicable (without requiring it to breach its
supply agreement with any Third Party unless PRAECIS obtains a release of
Synthelabo from such agreement), discontinue making or having
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made such Licensed Products, and shall instead order and obtain same from
PRAECIS and PRAECIS shall have such Licensed Products made by such Third Party
manufacturer for delivery to Synthelabo upon instruction by PRAECIS. In such
instance, all other terms and conditions hereof shall apply, as if PRAECIS were
manufacturing such Licensed Products itself; and PRAECIS shall continue to be
responsible for performance of its supply obligations hereunder notwithstanding
the manufacture of Licensed Products by such Third Party manufacturer.
Consistent with the foregoing and with Synthelabo's obligation to minimize its
Cost of Goods to the extent commercially reasonable, Synthelabo will not itself
construct a manufacturing facility to manufacture Licensed Products unless it
demonstrates with commercially reasonable evidence that (i) PRAECIS will
permanently be unable to comply in all material respects with its supply
obligations hereunder or (ii) no commercially feasible alternative source of
supply is available or will be available in the reasonably foreseeable future.
The provisions of Section 3.9 and this Section 3.10 set forth the sole remedy of
Synthelabo for any breach by PRAECIS of its supply obligations hereunder unless
Synthelabo has validly terminated this Agreement in accordance with Section
17.3, in which event, as contemplated by the first sentence of Section 17.4,
Synthelabo shall have available all remedies with respect to any liability or
obligation that matured prior to the effective date of termination.
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3.11 Suspension of Manufacture By Synthelabo; Termination of
Manufacturing License. Should PRAECIS provide Synthelabo with commercially
reasonable evidence that it is ready, willing and able, directly or through
subcontractors, to resume material compliance with its supply obligations
hereunder, Synthelabo shall suspend its manufacture of Licensed Products or
having the Licensed Products manufactured, provided that in no event shall
Synthelabo be required to (i) suspend such manufacture until it has continued
for at least nine (9) months from its inception or (ii) prematurely terminate
any Third Party manufacturing agreement the terms of which are in compliance
with Section 3.9. If PRAECIS shall thereafter materially comply with its supply
obligations hereunder for four (4) consecutive calendar quarters, then the
Synthelabo license to make or have Licensed Products made which was granted in
accordance with Section 3.9 shall thereupon terminate, subject to being
re-granted if the conditions precedent stated in Section 3.9 are again met.
3.12 Agreement Regarding Third Party Manufacturers. Without
limitation of Sections 3.10 and 3.11, PRAECIS acknowledges its obligation to
undertake commercially reasonable measures to keep the average Cost of Goods at
an amount such that, on average, the share of Net Sales retained by Synthelabo
(prior to making the royalty payments pursuant to Section 9.8)
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pursuant to Article 9 is at least *** percent (***%). If (i) PRAECIS is making
or having made Licensed Products hereunder, (ii) the Transfer Price for a given
Licensed Product exceeds *** percent (***%) of REV for any two consecutive
calendar quarters and (iii) Synthelabo presents PRAECIS with commercially
reasonable evidence that a one (1) year supply agreement can be concluded with a
reputable Third Party manufacturer whereby such Third Party manufacturer will
agree to make such Licensed Product in the same quality, quantity and on
delivery terms at least as favorable as those of PRAECIS, but at a Cost of Goods
that is at least *** percent (***%) less than PRAECIS's average Cost of Goods
for such two quarters, then PRAECIS shall either (A) match that Cost of Goods
for all quantities of such Licensed Product ordered by Synthelabo for one (1)
year, irrespective of whether it must suffer a loss in order to do so, or (B)
enter into such one (1) year supply contract with such Third Party manufacturer
and provide the Licensed Products manufactured by such Third Party manufacturer
to Synthelabo in accordance with the remaining provisions of this Agreement. Any
such Third Party manufacturer shall be subject to approval by PRAECIS, which
shall not be unreasonably withheld; and PRAECIS shall provide a manufacturing
license under the Intellectual Property Rights and the PPI Licensed Rights as
may be required for such Third Party manufacturer to make such Licensed Product.
In the event that a Third Party manufacturer shall assume manufacturing
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responsibilities in accordance with this Section, PRAECIS shall, as soon as
reasonably commercially practicable, discontinue making or having made Licensed
Products hereunder. Synthelabo shall pay PRAECIS for all Licensed Products
obtained from such Third Party manufacturer in accordance with Article 9. Should
PRAECIS, prior to renewal or extension of any one-year contract between PRAECIS
and such Third Party manufacturer, notify Synthelabo (and provide it with
commercially reasonable evidence) that it is ready, willing and able to make or
have made such Licensed Products and deliver such Licensed Products to
Synthelabo at a Transfer Price which is less than ***% of then-current Net
Sales, then PRAECIS may allow the above-described Third Party manufacturer
contract to expire, terminate the license of Intellectual Property Rights and
PPI Licensed Rights granted in accordance with this Section 3.12, and resume
manufacturing of Licensed Products itself in accordance with the terms hereof or
make supply arrangements with another Third Party manufacturer of its own
choosing, but without prejudice to Synthelabo's right to invoke the provisions
of this Section 3.12 at a later date if the conditions described in the second
sentence of this Section again become applicable.
3.13 Direct Billing. Synthelabo shall obtain PRAECIS's agreement
before issuing orders for direct billing, showing payment due to Synthelabo, and
shipping of Licensed Products from PRAECIS to a Third Party. If PRAECIS agrees
and accepts such orders, Synthelabo shall include such sales in all
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reports required hereunder and shall make payment to PRAECIS therefor as if such
products had been shipped to Synthelabo and then shipped by Synthelabo to such
Third Party as provided herein, less any remittances therefor received by
PRAECIS from such Third Party.
3.14 Force Majeure. Each party shall take all actions that are
commercially reasonable in order to assure that it can perform its obligations
hereunder. Notwithstanding the foregoing, however, a party shall not be liable
for loss or damage resulting from any cause beyond its reasonable control,
including, but not limited to, acts of God, acts or omissions of the other
party, acts of civil or military authorities, fires, strikes, facilities
shutdowns or alterations, embargoes, war, riot, epidemic, delays in
transportation, or inability to obtain necessary labor, manufacturing facilities
or materials from usual sources, and any delays resulting from any such cause
shall extend the time for performance correspondingly. Should any such force
majeure result in a shortfall or delay and the consequent grant to Synthelabo of
a manufacturing license pursuant to Section 3.9 hereinabove, then Sections 3.10
and 3.11 shall also apply, except that PRAECIS shall not be required to make any
credits to the account of Synthelabo and any excess of Synthelabo's Cost of
Goods over the Transfer Price shall be borne by Synthelabo. In no event shall
either party be liable for consequential or special damages arising out of force
majeure.
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3.15 Form and Terms of License Product Shipments. Licensed Products
manufactured and delivered hereunder shall meet the specifications set forth in
the Registration Approval for such Licensed Product and shall be adequately
labelled to fulfill all customs, legal, regulatory and patent requirements
required for delivery as provided hereunder. If Licensed Products are delivered
in bulk, they will subsequently be packaged and labelled by Synthelabo in
compliance with all local market and regulatory requirements for the respective
Territory Countries, and shall clearly identify PRAECIS as the
manufacturer/developer of the formulation and Rel-Ease(TM) (if the Rel-Ease(TM)
system is utilized), together with appropriate trademarks. Licensed Products
shall be delivered to Synthelabo CIP (as such term is defined by the Incoterms)
Paris, France. Each shipment shall be accompanied by a certificate of analysis,
and a batch report containing information reasonably required by Synthelabo,
with respect to the batch or batches of Licensed Product contained therein.
Synthelabo shall inspect all shipments for obvious defects within thirty (30)
days of receipt thereof. Claims for shortages, breakage, damage or non-obvious
defects must be made by Synthelabo to PRAECIS within thirty (30) days of when
such shortage, breakage, damage or non-obvious defect is or reasonably should
have been discovered. Without limitation of any other provision of this
Agreement and subject thereto, (i) the parties agree to the additional supply
provisions set forth in Appendix VI and (ii) PRAECIS and Synthelabo agree that
prior to commence-
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ment of the manufacture of Licensed Products for commercial sale they will
execute and deliver a Quality Charter that shall reflect the general spirit of
the example form of Quality Charter set forth as Appendix VII hereto and which
shall be adapted in a manner intended to be consistent with this Agreement and
which is reasonable under the circumstances in light of the specific facts
pertaining to the particular Licensed Product, the particular situation of the
parties and other relevant considerations, it being understood and agreed (with
respect to both clauses (i) and (ii)) that in the event of any conflict or
inconsistency between such additional supply provisions or such executed Quality
Charter and any other provision(s) of this Agreement, such other provision(s) of
this Agreement shall control.
3.16 Supply of Licensed Product For Certain Supplemental Development
Plan Clinical Studies. PRAECIS shall supply Synthelabo with all Licensed
Products required for Synthelabo to conduct the Supplemental Development Studies
pursuant to the Supplemental Development Plan. Such supply of Licensed Products
shall be (i) at a price equal to PRAECIS' COGS if Synthelabo is not entitled,
pursuant to Section 4.5, to receive reimbursement from PRAECIS for a portion of
its Development Costs incurred in connection with such Supplemental Development
Studies and (ii) otherwise charged to Synthelabo as a Development Cost pursuant
to Sections 1.13 and 4.5.
ARTICLE 4 - DEVELOPMENT AND APPROVAL OF LICENSED PRODUCTS
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4.1 Diligence. During the Development Phase, Synthelabo and PRAECIS
shall diligently seek to develop the Licensed Products for (i) the Application
of prostate cancer and (ii) the Applications of endometriosis or uterine
fibroids as the Joint Steering Committee shall determine and (iii) any other
Application approved for development by the Joint Steering Committee and the
Development Subcommittee as provided in Section 4.3 in accordance with the Core
Development Plan, and the Supplemental Development Plan, in each case subject to
the further provisions of this Article 4. The Development Program shall be
directly supervised by the Development Subcommittee to be established pursuant
to Article 6 hereof, working with designated individuals at PRAECIS and
Synthelabo and subject to the oversight and direction of the Joint Steering
Committee. The Development Subcommittee will have oversight responsibilities
with respect to pre-clinical testing and Clinical Trials for Licensed Products
and will coordinate the preparation of regulatory filings for Licensed Products
in accordance with the Core Development Plan and the Supplemental Development
Plan, provided that Synthelabo shall have responsibility for filing and
obtaining Registration Approval and Reimbursement Approval for the Licensed
Products for each Application to be developed by the parties as contemplated by
the first sentence of this Section 4.1 in all of the Territory Countries in
which such Licensed Product will be commercialized pursuant to the terms hereof.
PRAECIS
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shall cooperate with Synthelabo in connection with such filing(s) and any
amendments or supplements thereto.
4.2 Development Program and Plans. The Development Program shall be
conducted in accordance with the Core Development Plan and Supplemental
Development Plan, as defined in this Section 4.2, which shall describe the work
to be supervised by the Development Subcommittee with respect to the development
of the Licensed Products, each of which shall include annual budgets. These
plans shall include detailed milestones, timeframes, operating plans and
objectives, including with respect to pre-clinical studies, toxicology and
Clinical Trials and obtaining Registration Approvals and Reimbursement
Approvals, and shall be updated annually. Without limitation of the foregoing,
these plans shall also set forth in detail the studies to be performed by each
party for purposes of obtaining Registration Approvals and Reimbursement
Approvals. The initial Core Development Plan shall be prepared by PRAECIS and
Synthelabo as promptly as practicable after the Effective Date (and shall
provide that initially the parties will seek to develop and commercialize as
soon as practicable Licensed Products (i) for the Application of prostate
cancer, and (ii) the Applications of endometriosis or uterine fibroids as the
Joint Steering Committee shall determine) and the initial Supplemental
Development Plan shall be prepared by Synthelabo as promptly as practicable
after the Effective Date, and each shall be subject to approval by the
Development Subcommittee and the Joint Steering Committee.
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Thereafter, these plans will be updated by these same parties, respectively, and
submitted to the Development Subcommittee and the Joint Steering Committee no
later than thirty (30) days prior to the beginning of each calendar year. The
Joint Steering Committee shall, with guidance from the Development Subcommittee,
approve such plans within thirty (30) days of the commencement of each calendar
year, or alternatively, shall return same to their source for revision and
resubmission.
4.3 Additional Applications. If the development and marketing of a
given Licensed Product for a given Application other than (i) prostate cancer or
(ii) endometriosis or uterine fibroids is proposed by PRAECIS to the Development
Subcommittee (on the cost-sharing basis set forth in Section 4.5) but not
approved, then PRAECIS may, but shall not be required to, carry out Development
Phase activities with respect to such Licensed Product for such Application, at
its own expense. If the Joint Steering Committee determines that Phase II or
Phase III Clinical Trials funded by PRAECIS demonstrate safety and efficacy of
such Licensed Product for such Application and that such Application is
commercially viable, and Synthelabo determines that the commercialization of
such Application should be pursued in the Territory, then Synthelabo shall
promptly reimburse PRAECIS for *** (***%) of all Development Costs theretofore
incurred by PRAECIS with respect to such Licensed Product for such Application
and shall share on an equal basis all future Development Costs required for FDA
Registration Approval of such
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Licensed Product for such Application, Section 4.5 notwithstanding. Within sixty
(60) days after such determination, the Development Subcommittee shall add the
continued development and marketing of such Licensed Product for such
Application to the Core Development Plan and/or the Supplemental Development
Plan by amendment, which amendment shall be approved by the Joint Steering
Committee within thirty (30) days thereafter; and Synthelabo and PRAECIS, as
applicable, shall promptly and diligently pursue such continued development and
marketing, in accordance with Article 4 and Article 5 hereof.
4.4 Regulatory Meetings. PRAECIS or Synthelabo, as the case may be,
will provide the other party with reasonable prior notice of all meetings
between its representatives and regulatory authorities regarding any
Registration Approval of the Licensed Products in any jurisdiction. The
recipient of such notice shall have the right to have a representative present
at all important meetings. Each of PRAECIS and Synthelabo will furnish, at the
other's request, a representative to attend regulatory meetings of the other
regarding Registration Approval of the Licensed Products.
4.5 Development Costs. Except as provided in Section
4.3, PRAECIS shall pay seventy-five percent (75%), and Synthelabo
shall pay twenty-five percent (25%), of all Development Costs incurred in
carrying out the Core Development Plan. The foregoing cost sharing provisions
shall also apply if PRAECIS enters into an agreement with a Third Party under
which such
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Third Party shall undertake PRAECIS' development activities pursuant to the Core
Development Plan, unless PRAECIS and Synthelabo shall agree otherwise.
Synthelabo shall pay all Development Costs which are incurred in carrying out
the Supplemental Development Plan, provided that PRAECIS shall reimburse
Synthelabo for seventy-five percent (75%) of such Development Costs to the
extent the results of the Development Phase activities in respect of which such
Development Costs were incurred are used to seek or obtain Registration
Approvals or Reimbursement Approvals in the United States. If (i) PRAECIS or its
licensee or sublicensee wishes to use both outside of the Territory and outside
of the United States the results of the Supplemental Development Studies
obtained by Synthelabo in carrying out the Supplemental Development Plan and
(ii) PRAECIS is not required hereunder to reimburse Synthelabo 75% of the
Development Costs incurred in connection with such Supplemental Development
Studies, then PRAECIS and Synthelabo shall meet to negotiate in good faith an
equitable sharing of such Development Costs. Anything herein to the contrary
notwithstanding, (i) each of Synthelabo and PRAECIS shall have full and complete
access to and use of the safety data of the other regarding each Licensed
Product, and each may use the safety data of the other for Advertising and
Promotion, in each case without any cost or reimbursement therefor and (ii)
regulatory submission, registration fees and maintenance fees in the Territory
shall be paid by Synthelabo, and registration fees and maintenance fees
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outside the Territory shall be paid by PRAECIS. If a party is claiming
reimbursement pursuant to this Section 4.5, then within forty-five (45) days
after the end of a calendar quarter during which the Development Costs for which
reimbursement is being claimed were incurred, a party will submit to the other a
statement (each a "Development Cost Statement") itemizing in reasonable detail
such Development Costs and setting forth the total amount, if any, of such
Development Costs to be reimbursed by the other party pursuant to this Section
4.5. Such reimbursement amounts shall be paid within twenty (20) days after
receipt of a Development Cost Statement, except to the extent such Development
Cost Statement is being disputed in good faith. Except as otherwise provided
herein, each party shall assume full responsibility for its own Development
Costs.
4.6 Registration and Reimbursement Approvals. All Registration
Approvals and Reimbursement Approvals within the Territory shall be applied for,
obtained and maintained in the name of Synthelabo; provided that Synthelabo
hereby agrees to promptly take any and all action necessary to transfer or
assign such Registration Approvals and Reimbursement Approvals to PRAECIS or its
designee upon the termination of this Agreement pursuant to Section 17.2 upon
the occurrence of an event described therein with respect to Synthelabo or
pursuant to Section 17.3 as a result of Synthelabo's breach. Without limitation
of the immediately preceding sentence, upon termination of this Agreement in its
entirety by Synthelabo
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pursuant to Section 17.7, Synthelabo shall provide PRAECIS with such
documentation, authorization, or permission as may be available to Synthelabo to
enable PRAECIS to obtain access to, and to officially make reference to, the
Synthelabo Registration Approval and Reimbursement Approval files, data,
correspondence and records throughout the entire period of their existence. All
Registration Approvals and Reimbursement Approvals outside the Territory shall
be applied for and obtained by PRAECIS in its own name and/or in the name of its
one or more marketing partners, and PRAECIS shall provide Synthelabo with such
documentation, authorization, or permission as may be available to PRAECIS to
enable Synthelabo to obtain access to, and to officially make reference to, such
Registration Approval and Reimbursement Approval files, data, correspondence and
records throughout the entire period of their existence.
4.7 Development Costs Records. Each party shall keep complete and
accurate records of its Development Costs, which records each party shall retain
for five (5) years after the end of the calendar year in which such expenses
were incurred. The records shall conform to generally accepted accounting
principles consistently applied in the country where such Development Costs were
incurred. Each party shall have the right at its own expense during each year of
a Development Phase and during the subsequent five (5) year period to appoint an
independent public accountant reasonably acceptable to the other party to
inspect said records or to have its own representatives inspect such
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records. Upon reasonable notice from the other party (the "Requesting Party"), a
party (the "Reviewed Party") shall make its records available during regular
business hours for inspection by the requesting party's representatives and the
independent public accountant at the place or places where the Reviewed Party
customarily keeps such records, to the extent reasonably necessary to verify the
accuracy of the expenditures. The right of inspection shall not be exercised by
a party more than once in any calendar year. A Requesting Party shall hold in
strict confidence all information concerning such expenditures and all
confidential information learned in the course of any audit or inspection,
except to the extent necessary for the Requesting Party to enforce any rights it
may have pursuant to this Agreement or if disclosure is required by law. Absent
fraud or manifest material error, the failure of either party to request
verification of any expenditures during the period the other party is required
to retain the records for any calendar year shall be considered acceptance of
the accuracy of the reports concerning such expenditures.
4.8 Technical Information. To the best knowledge and belief of
PRAECIS, as of the Effective Date PRAECIS has provided Synthelabo with all
material information concerning the Licensed Products that PRAECIS believes in
its reasonable business judgment would be relevant to Synthelabo's decision to
enter into this Agreement. PRAECIS will provide Synthelabo with access to all
confidential technical information in PRAECIS' possession
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from the Effective Date and during the term of this Agreement relating to the
Licensed Products, including all documentation in the possession of PRAECIS
based on work performed by PRAECIS with the Licensed Products. Upon request,
PRAECIS shall provide copies of such materials to Synthelabo. In addition, as
further provided in Section 11.4, PRAECIS shall keep Synthelabo informed
regarding progress in prosecution of the patent applications licensed hereunder,
shall timely provide Synthelabo with copies of all applications, office actions,
amendments, and other documents pertaining thereto, and shall provide Synthelabo
with reasonable opportunities to discuss same with PRAECIS's patent counsel.
Furthermore, PRAECIS and Synthelabo shall extend to one another the same
information and access with regard to patent applications covering Improvements.
4.9 Clinical Trials. Synthelabo shall from time to time notify
PRAECIS of any Clinical Trial or technical activity which it intends to
undertake with respect to any Licensed Product; and PRAECIS shall communicate
any reasonable technical or scientific concerns in relation thereto within
fifteen (15) days of notification in which event the parties shall promptly
discuss the same. In the event that PRAECIS has any such technical or scientific
concerns which cannot be satisfied, then PRAECIS may notify Synthelabo to that
effect and Synthelabo shall not undertake the Clinical Trial or other technical
activity contemplated, provided that no such determination shall (i) be made
unreasonably by PRAECIS or (ii) prevent Synthelabo from
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applying for, obtaining or maintaining a Registration Approval or Reimbursement
Approval in the Territory. Synthelabo and PRAECIS will provide one another with
a copy of each master dossier and all correspondence and submissions regarding
each Registration Approval or Reimbursement Approval which they (or their
respective sublicensees or co-marketing partners) seek, on or prior to the date
of submitting the same; and shall also promptly provide one another with the
results of all toxicology and pharmacology studies and Clinical Trials conducted
by or under their supervision with respect to the Licensed Products. Synthelabo
will specify the data and processes required from PRAECIS in order to obtain
Registration Approval and Reimbursement Approval in the Territory Countries at
least eighteen (18) months in advance of such data and processes being needed.
All relevant documents in support of each such Registration Approval and
Reimbursement Approval will be archived by each party in compliance with
applicable regulatory and legal requirements.
4.10 Material Adverse Development; Material Adverse Patent
Development; Competition. If (i) the results of Clinical Trials of a Licensed
Product with respect to an Application in a Territory Country constitute a
Material Adverse Development, or (ii) a Material Adverse Patent Development
shall occur, or (iii) a competitor makes a product containing the same LHRH
Antagonist Compound as a Licensed Product in a functionally equivalent delivery
system and has Registration Approval to sell such
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product for the same Application, and the number of units of such product sold
by such competitor in a Territory Country over any calendar year equals more
than *** percent (***%) of the number of units of Licensed Product, if any, sold
in such Territory Country for such Application by Synthelabo or its Affiliates
over such calendar year, then, in the case of clauses (i) and (iii) Synthelabo
shall be entitled to terminate this Agreement with respect to such Licensed
Product for such Application in such Territory Country only, and, in the case of
clause (ii), Synthelabo shall be entitled to terminate this Agreement in its
entirety only, subject, however, in the case of each of clauses (i), (ii) or
(iii), to compliance with Section 17.7. If the parties reasonably and in good
faith disagree as to whether an event described in clause (i), (ii) or (iii)
above has occurred, such matter may be resolved by the dispute resolution
procedures described in Section 6.5 and Article 18.
4.11 Synthelabo Formulation. In the event that (i) four years have
elapsed from the Effective Date, (ii) safety and efficacy in humans of a depot
or other formulation owned by or licensed to PRAECIS for PPI-149 or any other
LHRH Antagonist Compound licensed by PRAECIS to Synthelabo hereunder for at
least one of the Applications then included in the Core Development Plan has not
been demonstrated in Phase II Clinical Trials and (iii) Synthelabo has, pursuant
to license rights granted hereunder, developed a Synthelabo Formulation for at
least one of the Applications then included in the Core Development Plan,
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which formulation has demonstrated safety and efficacy in humans in Phase II
clinical trials, then, without prejudice to Synthelabo's rights under Section
17.7, Synthelabo shall have the right to propose that such Synthelabo
Formulation be used in connection with PPI-149 or any other LHRH Antagonist
Compound licensed hereunder for such Application. In such event, the parties
shall negotiate in good faith appropriate adjustments to the terms and
conditions of this Agreement to permit the incorporation of such Synthelabo
Formulation as aforesaid. Such good faith negotiations shall give due regard to
the costs incurred by the parties in the development of their respective
formulations and the relative benefits, if any, derived therefrom.
4.12 Reporting on Adverse Reaction. Each party shall promptly inform
the other about any suspected serious and/or unexpected adverse drug reaction
associated with the use of a Licensed Product. The parties shall, quarterly,
exchange reports of suspected, deemed "non-serious" adverse drug reactions
associated with the use of the Licensed Products.
ARTICLE 5 - MARKETING AND SALES OBLIGATIONS OF SYNTHELABO
5.1 Diligence Generally. Throughout the term of this Agreement,
promptly after Registration Approval of a Licensed Product for a particular
Application has been obtained in or with respect to a Territory Country,
Synthelabo shall use diligent efforts to Advertise, Promote and sell such
Licensed Product for
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such Application throughout such Territory Country, provided such
commercialization is reasonably economically viable.
5.2 Advertising. Subject to Section 5.1, Synthelabo shall at its own
expense develop, procure, and supervise distribution of appropriate and
effective Advertising for each of the Licensed Products throughout the Territory
where permitted by applicable law, and assess and revise same as needed; and
shall actively Promote and, where permitted, actively Advertise same in a manner
that is commercially reasonable and is reasonably designed to be effective in
each Territory Country.
ARTICLE 6 - GOVERNANCE
6.1 Joint Steering Committee. Within thirty (30) days after the
Effective Date, Synthelabo and PRAECIS shall notify one another of the names,
addresses, and telephone numbers of three (3) senior representatives that they
have appointed to a committee which shall be charged with coordinating and
overseeing the collaboration in the manner and to the extent provided hereunder
(the "Joint Steering Committee") including, without limitation, approval of the
Core Development Plan and Supplemental Development Plan, and the attempted
resolution of any disputes which arise in connection with the collaboration
hereunder. The Joint Steering Committee shall be chaired by one of the three
appointees of PRAECIS, which Chairperson shall initially be designated in the
above-required notice from PRAECIS to Synthelabo. Synthelabo and PRAECIS shall
be permitted at their own discretion at any time to remove and/or replace those
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members of the Joint Steering Committee which they have appointed.
6.2 Operations of the Parties Under the Collaboration. It is
intended that the strategy for the clinical development, Regulatory Approval and
Reimbursement Approval of Licensed Products in the Territory shall be jointly
conceived, and that the parties shall communicate regularly. Decisions of the
Joint Steering Committee shall be binding on the parties; provided however, that
the operations of the parties in connection with the collaboration hereunder
shall be conducted by the operating management and employees of PRAECIS and
Synthelabo, respectively, as their obligations and responsibilities under this
Agreement require.
6.3 Timing of Regular Meetings; Agendas. The Joint Steering
Committee shall hold quarterly or more frequent regular meetings on mutually
agreeable dates, with the location of the meetings to alternate between PRAECIS
and Synthelabo facilities. For any such meeting, the Chairman of the Joint
Steering Committee shall prepare an agenda which shall be provided to the other
members at least five business days prior to the meeting.
6.4 Special Meetings. Any member of the Joint Steering Committee may
call a special meeting of the Joint Steering Committee upon notice duly given in
person or by telephone to each other member (which notice shall include an
agenda for the meeting) at least forty-eight (48) hours in advance of the
meeting (unless such member waives receipt of
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notice either before or after the meeting or by attending the meeting without
protestation); provided that such special meeting (and any other meeting) may
take place by means of a telephone or video conference.
6.5 Decisions and Disputes. The objective of the Joint Steering
Committee and of any Subcommittee (as defined in Section 6.6) shall be to seek
to reach agreement on all matters by consensus. Each of PRAECIS and Synthelabo
shall have one (1) vote on the Joint Steering Committee and on any Subcommittee.
Concurring votes of both parties shall be required for any decision by the Joint
Steering Committee or any Subcommittee. A quorum of the Joint Steering Committee
or any Subcommittee, respectively, shall consist of the representatives from
each party with authority to cast the vote of the party on issues before the
Joint Steering Committee or any Subcommittee, respectively, and each party shall
use reasonable efforts to assure that its representatives so authorized are
present at all meetings. If the Joint Steering Committee is unable to reach a
decision on any matter, including any matter referred to the Joint Steering
Committee by any Subcommittee pursuant to Section 6.6 (a "Disputed Matter"),
PRAECIS and Synthelabo shall engage in good faith discussions in an effort to
resolve the Disputed Matter in a mutually satisfactory manner. If the Disputed
Matter is not resolved within thirty (30) days of the date such matter was
initially considered by the Joint Steering Committee, the Chairperson of the
Joint Steering Committee shall notify the
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respective Chief Executive Officers of PRAECIS and Synthelabo, in writing, of
the nature and basis of the Disputed Matter (the "Dispute Notice") within five
(5) days after the end of such thirty (30) day period. The Chief Executive
Officers of PRAECIS and Synthelabo shall use their best efforts to resolve the
Disputed Matter. If the Disputed Matter is not resolved by the Chief Executive
Officers within thirty (30) days after the date of the Dispute Notice, either
Party may request, in writing, that the matter be resolved by binding
arbitration in accordance with the provisions of Article 18 of this Agreement.
6.6 Development Subcommittee. The Joint Steering Committee shall be
authorized to establish subcommittees consisting of an equal number of
representatives from each of PRAECIS and Synthelabo (each, a "Subcommittee"). At
the first meeting of the Joint Steering Committee, it shall establish a
Development Subcommittee comprised of at least three (3) Synthelabo
representatives and three (3) PRAECIS representatives, which shall be charged
with overseeing and coordinating the preparation and implementation of the Core
Development Plan and Supplemental Development Plan by PRAECIS and Synthelabo,
respectively, and strategies generally with respect to the clinical development
of, and obtaining Registration Approvals and Reimbursement Approvals for,
Licensed Products (the "Development Subcommittee"). If any Subcommittee
(including without limitation the Development Subcommittee) is unable to reach a
decision on any matter, such matter shall be referred to the
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Joint Steering Committee for resolution as contemplated by Section 6.5.
6.7 Cooperation. Each party agrees to make its employees and
non-employee consultants reasonably available at their respective places of
employment to consult with the other party on issues arising during the
Development Phase and thereafter and in connection with any request from any
regulatory agency, including regulatory, scientific, technical and clinical
testing issues, or otherwise, throughout the term of this Agreement.
6.8 Visitation. Representatives of PRAECIS and Synthelabo may, with
the other party's prior approval, which approval shall not be unreasonably
withheld, visit the sites of any Clinical Trials or other experiments being
conducted by such other party in connection with the Development Phase and,
subject to any necessary approvals of the relevant Third Party, which either
PRAECIS or Synthelabo shall obtain for the other, manufacturing sites used for
making or having made any Licensed Products. Each party hereto shall have the
right to audit the quality control records of the other or any Third Party
manufacturers regarding Licensed Products, and shall sign customary "quality
charters" as required by the other party. If requested by the other party,
PRAECIS and Synthelabo shall cause appropriate individuals to be available for
meetings at the location of the facilities where such individuals are employed
at
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times reasonably convenient to the party responding to such request.
6.9 Committee and Certain Other Costs. Each of Synthelabo and
PRAECIS shall bear their own costs and expenses arising from the appointment,
operation, and maintenance of the Joint Steering Committee, the Development
Subcommittee and any other subcommittee established by the Joint Steering
Committee or arising from any other visitation, consultation or inspection
provided for in this Article 6.
ARTICLE 7 - CONFIDENTIALITY
7.1 General. Synthelabo and PRAECIS hereby agree to, and to use
their best efforts to cause their respective officers, directors, employees and
agents to, maintain one another's Confidential Information in strict secrecy,
through at a minimum the use of the same security measures as each uses to
protect its own confidential records and information of the same nature, but in
no case less than a reasonable degree of care for such information. Synthelabo
and PRAECIS each hereby agree that they shall cause each of their respective
officers, directors, employees, Affiliates and agents who receive Confidential
Information to maintain such Confidential Information in secrecy. Synthelabo and
PRAECIS further agree that each of their respective directors, employees,
officers, and agents who receive Confidential Information have been and will be
so bound in writing upon their employment. Synthelabo and PRAECIS also agree
that Confidential Information will be provided only to directors,
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officers, employees and agents who will utilize such information in their work
as permitted under this Agreement, and that all directors, officers, employees
and agents receiving such Confidential Information will be informed of the
obligations of confidentiality hereunder. Synthelabo and PRAECIS agree that they
will not, and will use their best efforts to cause their respective Affiliates,
directors, officers, employees and agents not to, communicate Confidential
Information of the other party to directors, officers, employees or agents of
any Third Party unless (i) such Third Party has a need to know in order for the
disclosing party or for such Third Party to meet its obligations hereunder or
those undertaken by either party in conformity with this Agreement (e.g.,
clinical research organizations, Affiliates and sublicensees); (ii) such persons
are bound by confidentiality obligations no less stringent than those of this
Article 7, and (iii) such persons are first made aware of the confidential
nature of the information being provided.
7.2 Certain Exceptions. Notwithstanding Section 7.1, Synthelabo and
PRAECIS acknowledge that there may be key trade secrets, Licensed Product
formulas, patient identification information, and other extremely confidential
information which is entitled to special treatment; and neither party shall be
required to disclose such Confidential Information to the other unless the other
party agrees to undertake special security precautions and agrees not to further
distribute same without specific written permission from the disclosing party,
which
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shall not be unreasonably withheld. Notwithstanding anything contained herein to
the contrary, the disclosure restrictions set forth in this Article 7 shall not
preclude disclosure of Confidential Information by either party hereto (or any
of their respective Affiliates, officers, directors, employees or agents) (i)
with the prior written consent of the other party hereto, (ii) to the extent
necessary to comply with law or the valid order of a court or other governmental
or regulatory body of competent jurisdiction, in which event the party making
such disclosure shall so notify the other party hereto as promptly as
practicable (and, if possible, prior to making such disclosure) and shall seek
confidential treatment of such Confidential Information, (iii) to any
not-for-profit, governmental or quasi-governmental organization which may
require such disclosure, in which event the party making such disclosure shall
take all available measures to have such organization maintain such Confidential
Information in confidence, provided the party making such disclosure shall
notify the other party hereto as promptly as practicable (and, if possible,
prior to making such disclosure), in order to allow the other party to consider
and to undertake the filing of patent applications or other protective measures,
(iv) to the extent required to file this Agreement or file and prosecute a
patent with respect thereto and (v) to the extent required to commercialize a
Licensed Product. This Article shall remain in effect during the term of the
Agreement and shall survive for a period of ten (10) years following
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termination or expiration of this Agreement, notwithstanding any provision to
the contrary in this Agreement.
7.3 Publications. The following restrictions shall apply with
respect to the disclosure in scientific journals, publications or scientific
presentations by any party relating to any scientific work performed as part of
the collaboration hereunder:
(a) a party (the "Publishing Party") shall provide the other party
with an advance copy of any proposed publication containing Confidential
Information prior to submission for publication, and such other party shall have
a reasonable opportunity to recommend any changes it reasonably believes are
necessary to preserve the Confidential Information belonging in whole or in part
to PRAECIS or Synthelabo, and the incorporation of such recommended changes
shall not be unreasonably refused;
(b) if such other party informs the Publishing Party, within thirty
(30) days of receipt of an advance copy of a proposed publication, that such
publication in its reasonable judgment could be expected to have a material
adverse effect on the commercial value of any Confidential Information belonging
in whole or in part to PRAECIS or Synthelabo, the Publishing Party shall delay
or prevent such publication as proposed. In the case of inventions, the delay
shall be sufficiently long to permit the timely preparation and filing of a
patent application(s) or application(s) with respect to such invention(s); and
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(c) the parties shall use their best efforts to gain the right to
review proposed publications relating to the collaboration hereunder by
consultants or contractors of a party, and shall use their best efforts to
protect any Confidential Information of either party that may be contained in
any such publication.
ARTICLE 8 - TRADEMARKS
8.1 Exclusive License for Rel-Ease(TM) Trademark. Subject to the
review and approval of each of Synthelabo's uses of same, as set forth in
Section 8.2, PRAECIS hereby grants to Synthelabo an exclusive royalty-free
license to use the Rel-Ease(TM) trademark in the Field throughout the Territory,
such license to cover the existing and all future forms of such trademark and
all associated logos, but shall be limited to use only on Licensed Products that
conform to the specifications for such Licensed Products on which Registration
Approval of such Licensed Products was based. Such license shall be perpetual
fully paid up and royalty free, except that it may be revoked by PRAECIS for
breach of Sections 8.2 or 8.3 or upon the termination of this Agreement in any
Territory Country pursuant to Section 17.3 by reason of breach by Synthelabo,
and shall survive any other termination or expiration of this Agreement. PRAECIS
agrees that it will promptly file for registration of the Rel-Ease(TM) trademark
in each Territory Country designated by Synthelabo where such registration is
possible and affords potential protection for such trademark in such Territory
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Country, and will take all such actions as are necessary or appropriate and
commercially reasonable to secure such registration and, thereafter, to
maintain such registration for the benefit of Synthelabo. PRAECIS shall further
take all such actions as are necessary or appropriate and commercially
reasonable to protect the Rel-Ease(TM) trademark against impairment or
infringement in such Territory Countries.
8.2 PRAECIS Approval Right. Prior to the first use of the
Rel-Ease(TM) trademark on any materials in any form, Synthelabo shall first
provide PRAECIS with at least one sample of same in each such form; or if not
yet made, shall provide an artist's rendering of same. If PRAECIS does not
reasonably object to same within ten (10) business days of receipt, PRAECIS
shall be deemed to have approved such use. Synthelabo may thereafter use the
Rel-Ease(TM) trademark in the manner and form so approved, provided that such
use is on materials which have substantially the same content and are of
substantially the same quality as the samples that were the basis for approval.
8.3 Trademark Designations. Synthelabo hereby agrees that each use
of the Rel-Ease(TM) trademark shall be accompanied by the designation "(R)" or
"TM", as is appropriate depending upon whether such mark has been registered in
the Territory Country of use; or by such other designation as may be appropriate
under the trademark laws of the Territory Country of use.
8.4 Labelling, etc. Synthelabo shall be responsible for labelling
Licensed Products and repackaging Licensed Products
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in such form as is suitable and in compliance with all applicable laws for
resale in each Territory Country. To the extent permitted by law, Licensed
Products shall be represented in all labelling and other documentation as
jointly developed by PRAECIS and Synthelabo, and all packaging shall, among
other things, clearly bear the following language: "Licensed from PRAECIS
PHARMACEUTICALS INCORPORATED", or its translation in the language of the country
of commercialization, and shall clearly bear the Rel-Ease(TM) trademark (if the
Rel-Ease(TM) system is utilized).
8.5 Indemnification By PRAECIS. PRAECIS hereby agrees to indemnify
and hold Synthelabo harmless against any liability, damages, loss or expense
(including reasonable attorneys fees and expenses of litigation) arising out of
the proper use by Synthelabo in accordance with the provisions of this Article 8
of the Rel-Ease(TM) trademark and the name PRAECIS PHARMACEUTICALS INCORPORATED.
8.6 Licensed Products Names and Trademarks. Prior to First
Commercial Sale of a Licensed Product in each Territory Country, the parties
shall consult and agree on an appropriate name and trademark for such Licensed
Product to be used in such Territory Country (any such name and trademark so
agreed upon being referred to as a "Licensed Product Territory Trademark").
PRAECIS shall not unreasonably withhold its agreement to the Licensed Product
Territory Trademark selected by Synthelabo. The parties agree that, subject to
the further provisions of this Article 8, Synthelabo shall be the owner in the
Territory of each
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Licensed Product Territory Trademark, together with all associated logos and
related goodwill, and may sublicense same to its Affiliates and Third Parties to
whom it sublicenses its other rights hereunder. Synthelabo (i) acknowledges and
agrees that (A) PRAECIS shall be the owner of each Licensed Product Territory
Trademark outside the Territory and (B) neither Synthelabo nor any Affiliate
thereof will, directly or indirectly, so long as this Agreement is in force and
thereafter if this Agreement is terminated pursuant to Section 17.2 by reason of
the occurrence of one or more of the events described therein with respect to
Synthelabo or pursuant to Section 17.3 due to breach by Synthelabo, (1)
challenge or in any way oppose such ownership rights of PRAECIS or (2) file for
the registration outside the Territory of any Licensed Product Territory
Trademark, (ii) agrees that it will promptly file for the registration in each
Territory Country of each Licensed Product Territory Trademark to be used by
Synthelabo in such Territory Country, provided such registration is possible and
affords potential protection for such Licensed Product Territory Trademark in
such Territory Country, and will take all such other actions as are necessary or
appropriate and commercially reasonable to protect such Licensed Product
Territory Trademark against impairment or infringement anywhere in the Territory
where such Licensed Product Territory Trademark is so used and (iii)
acknowledges and agrees that (A) automatically upon termination of this
Agreement pursuant to Section 17.2 by reason of the occurrence of one or
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more of the events described therein with respect to Synthelabo or pursuant to
Section 17.3 due to breach by Synthelabo, and without any further action by
PRAECIS or Synthelabo, ownership in the Territory of each Licensed Product
Territory Trademark, together with its good will, shall be deemed assigned to,
and vested solely in, PRAECIS, and Synthelabo shall have no further right or
interest therein, (B) following any such termination for breach, Synthelabo
shall promptly, at PRAECIS' request, and without further consideration, execute
and deliver and file or cause to be filed in all jurisdictions in the Territory
where such a filing is necessary or appropriate to protect the rights of PRAECIS
as assignee appropriate instruments of assignment reflecting and confirming the
foregoing assignment(s) and (C) PRAECIS shall be, and hereby is, constituted
Synthelabo's true and lawful attorney-in-fact with full power and authority to
execute and deliver in the name and on behalf of Synthelabo the instrument(s)
referred to in clause (iii)(B) above, which shall be binding upon Synthelabo
with the same effect as if executed and delivered by it. If clause (iii)
immediately above applies, the value of the Licensed Product Territory Trademark
and associated goodwill assigned to PRAECIS shall be available as an offset
against any damages for the breach by Synthelabo referred to in such clause
(iii). Without limitation of and subject to the foregoing terms and conditions
of this Section 8.6 and Synthelabo's compliance therewith, during the term of
this Agreement and thereafter (i) Synthelabo shall retain all
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ownership rights in the Territory in and to each Licensed Product Territory
Trademark (and no compensation or indemnity shall be payable in respect of such
ownership rights) and (ii) neither PRAECIS nor any of its Affiliates shall,
directly or indirectly, challenge or in any way oppose the ownership rights of
Synthelabo in any Licensed Product Territory Trademark in any of the Territory
Countries.
8.7 PRAECIS Registration of Licensed Product Territory Trademark
Outside the Territory. If PRAECIS intends to use a Licensed Product Territory
Trademark in one or more countries outside the Territory, it will promptly file
for the registration in each such country of each Licensed Product Territory
Trademark to be so used in such country, provided such registration is possible
and affords potential protection for such Licensed Product Territory Trademark
in such country, and will take all such other actions as are necessary or
appropriate and commercially reasonable to protect such Licensed Product
Territory Trademark against impairment or infringement in each such country
where such Licensed Product Territory Trademark is so used.
ARTICLE 9 - PAYMENTS
9.1 Signing and Milestone Payments. Synthelabo shall make the
following payments to PRAECIS (without withholding deductions of any kind other
than required withholding taxes as to which Synthelabo shall secure and send to
PRAECIS proof of any such taxes withheld and paid by Synthelabo), all of which
shall be non-refundable:
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(i) Upon signature of this Agreement, (A) *** dollars ($***)
in partial consideration of the sublicense granted hereunder with respect
to the PPI Licensed Rights, (B) *** dollars ($***) in partial
consideration of the license granted hereunder with respect to the
Intellectual Property Rights, and (C) *** dollars ($***) in consideration
of the license granted hereunder with respect to the Rel-Ease(TM)
trademark; and
(ii) Within thirty (30) days after the date of each occurrence
shown below, the occurrence of which shall be demonstrated by providing
reasonable documentary evidence of same, the amounts shown opposite such
occurrence below, *** of each of such amounts being in consideration of
the sublicense granted hereunder with respect to the PPI Licensed Rights
and *** of each of such amounts being in consideration of the license
granted hereunder with respect to the Intellectual Property Rights. Should
one or more occurrence set forth below occur substantially (but not
exactly) as described, and Synthelabo proceeds in commercialization
despite such inexact occurrence without a written waiver by PRAECIS, such
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occurrence shall be deemed to have occurred for the purposes of this
Section 9.1:
Occurrence Payment
- ---------- -------
*** $***
*** $***
*** $***
*** $***
*** $***
*** $***
*** $***
*** $***
TOTAL $63,000,000.00
Notwithstanding the foregoing, Synthelabo shall be required to make
any of the payments otherwise payable with respect to any of the second through
the eighth occurrences set forth above only if (i) forty-five (45) days have
elapsed after Synthelabo's receipt of the European search report and the first
official letter from the European Patent Office referred to in Section 11.4 and
(ii) on or before the end of such forty-five (45) day period Synthelabo has not
validly elected to terminate this Agreement pursuant to Section 17.7 due to a
Material Adverse Patent Development by delivering to PRAECIS on or before the
end of such forty-five (45) day period a Section 17.7 Notice setting forth a
Section 17.7 Termination Date which is not later than thirty (30) days after the
end of such forty-five (45) day period.
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Only one payment in the amount set forth opposite each occurrence
set forth above shall be payable in respect of such occurrence, and the maximum
aggregate amount payable by Synthelabo in respect of all such occurrences
(excluding amounts paid pursuant to subparagraph (i) above) shall be sixty-three
million dollars ($63,000,000) regardless of the number of Licensed Products or
Applications developed hereunder.
9.2 Benchmark Transfer Price. As of the Effective Date, Synthelabo
and PRAECIS hereby agree to a Benchmark Transfer Price for the first Licensed
Product of *** United States dollars ($U.S.***) per unit (the "Benchmark
Transfer Price"), which Benchmark Transfer Price shall not change for the first
two (2) quarters after the date of First Commercial Sale of such Licensed
Product. At the end of the second calendar quarter of sales of such Licensed
Product, the first Adjustment Amount is to be paid or credited in accordance
with Section 9.6 with respect to the preceding quarter; and the report showing
the Adjustment Amount due or creditable shall state the Transfer Price for each
Licensed Product during such first calendar quarter of sales, as determined in
accordance with Section 9.4. Thereafter, the Benchmark Transfer Price for a
given calendar quarter of sales of such Licensed Product shall be equal to the
actual Transfer Price for Licensed Products which were shipped by PRAECIS to
Synthelabo two calendar quarters earlier. At least thirty (30) days prior to the
First Commercial Sale in the Territory of any other Licensed Product, Synthelabo
and PRAECIS shall meet to determine
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an initial Benchmark Transfer Price for such Licensed Product; and such
Benchmark Transfer Price shall apply for the first two quarters of sales, and
shall thereafter be adjusted in accordance with this paragraph.
9.3 Determination of Selling Price of Licensed Products. Synthelabo
shall determine the price at which it shall sell the Licensed Products it
obtains from PRAECIS. The Benchmark Transfer Prices of this Agreement are solely
for the purposes of determining the initial amount that Synthelabo shall pay to
PRAECIS for Licensed Products, and shall not be considered by Synthelabo,
PRAECIS or any Third Party to dictate prices at which Synthelabo should offer to
sell or sell Licensed Products to Third Parties.
9.4 Transfer Price. The Transfer Price is hereby defined as:
***Approximately 22 lines omitted***
.33 multiplied by REV for cumulative Net Sales for all Licensed Products
in a given calendar year that exceed $***; Notwithstanding the foregoing, (i) in
no instance shall the Transfer Price be less than COGS + .06 times REV, except
to the extent otherwise expressly provided in Section 3.10 and (ii) the Transfer
Price with respect to Licensed Products sold in Latin America shall in all cases
be .33 for such Net Sales.
9.5 Payment of Benchmark Transfer Price. When received by PRAECIS,
and as a condition to approval by PRAECIS,
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each Synthelabo purchase order shall show on its face a stated transfer amount
equal to the Benchmark Transfer Price times the number of units ordered; and
such stated amount shall be followed by the phrase, "plus or minus Adjustment
Amounts", which refers to the adjustment payments or credits to be made pursuant
to Section 9.6. Within forty five (45) days of the issuance by PRAECIS to
Synthelabo of an invoice for Licensed Products pursuant to a Synthelabo purchase
order (the date of such invoice to be no earlier than the date of delivery),
Synthelabo shall pay PRAECIS the amount stated on the invoice. Any other
provision of this Agreement notwithstanding, under no circumstances shall
PRAECIS be required to ship Licensed Products to Synthelabo pursuant to a given
Synthelabo purchase order if a payment due and payable under this Section 9.5
with regard to a prior Synthelabo purchase order has not been paid to PRAECIS,
unless and to the extent that such payment is being disputed in good faith by
Synthelabo.
9.6 Adjustments; Reports. Within seventy (70) days after the end of
each calendar quarter of Licensed Product sales, Synthelabo shall submit to
PRAECIS a sales, adjustment and royalty report, which shall specify (i) the
Transfer Price for Licensed Products ordered by Synthelabo during such calendar
quarter, as determined pursuant to Section 9.4; (ii) the number of units of
Licensed Products delivered by PRAECIS during such quarter; (iii) the cumulative
Transfer Price owed to PRAECIS for such Licensed Products, calculated as the
Transfer Price for such
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quarter times the number of units delivered during such quarter; (iv) the
Benchmark Transfer Price applicable to such quarter; (v) the cumulative payments
already made to PRAECIS for such quarter, calculated as the Benchmark Transfer
Price for such quarter times the number of units delivered during such quarter;
(vi) the "Adjustment Amount", which is defined as the cumulative Transfer Price
owed to PRAECIS (as described in (iii) above) less the cumulative payments
already made to PRAECIS (as described in (v) above), (vii) the total Net Sales,
and Net Sales on a country-by-country basis, during such calendar quarter and
(viii) the total amount of royalties, and the amount of royalties on a
country-by-country basis, payable to PRAECIS pursuant to Section 9.8. If the
Adjustment Amount is a positive number, Synthelabo shall make payment to PRAECIS
of same along with such report. If the Adjustment Amount is negative, then
Synthelabo shall so report; and PRAECIS shall credit such amount to the account
of Synthelabo, which credit shall be applied against future amounts due from
Synthelabo to PRAECIS.
9.7 Miscellaneous Sales Costs. PRAECIS shall be responsible for
shipping and handling costs arising from the return and replacement of defective
goods. Synthelabo shall itself directly pay all license fees, sales, use,
service use, occupation, service occupation, personal property, and excise taxes
and any other fees, assessments or taxes which may be assessed or levied by any
foreign, national, state or local
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government and any departments or subdivisions thereof, against any of the
Licensed Products ordered by Synthelabo and under Synthelabo's direct or
indirect control. Each party shall be directly responsible for the payment of
all other taxes properly levied or assessed against it with respect to its
obligations hereunder.
9.8 Royalties.
(a) Royalty Rate; Payments to IUF. Synthelabo shall pay to
PRAECIS a running royalty equal to either (i) ***, or (ii) ***. PRAECIS
shall remit to IUF all royalty payments made by Synthelabo hereunder at
the times required under the IUF License Agreement.
(b) Accrual of Royalties. Royalties pursuant to this Section
9.8 shall accrue when Licensed Products are sold or otherwise transferred
by Synthelabo or an Affiliate thereof to a Third Party, and Licensed
Products shall be considered sold when each invoice of Synthelabo or an
Affiliate thereof is issued to the Third Party. Synthelabo shall make
payments to PRAECIS in accordance with the requirements of subsection
9.8(d) below.
(c) Royalty Reduction. In the event that IUF and PRAECIS agree
to a lower royalty rate pursuant to Section 14.01 of the IUF License
Agreement, or otherwise, the royalty rate payable by Synthelabo to PRAECIS
hereunder shall be adjusted downward to match such lower royalty rate.
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(d) Semi-Annual Royalty Payments. Payments of royalties from
Synthelabo to PRAECIS pursuant to this Section 9.8 shall be made by
Synthelabo to PRAECIS on a semi-annual basis, not later than sixty (60)
days after the last day of June and the last day of December for as long
as such obligations continue under this Agreement.
(e) Single Royalty Liability. Synthelabo and its Affiliates
shall be liable for only one royalty hereunder with respect to the sale of
Licensed Products.
(f) Deduction for Taxes. Any tax required to be withheld by
Synthelabo or its Affiliates on any royalty payments payable to PRAECIS
hereunder shall be deducted from the total amount of the payment otherwise
due. Synthelabo shall secure and send to PRAECIS proof of any such taxes
withheld and paid by Synthelabo or its Affiliates.
9.9 Samples. PRAECIS hereby agrees that it shall upon written
request provide Synthelabo with "free samples" of Licensed Product in a quantity
no greater than one tenth of one percent (0.1%) of the amount of Licensed
Product that Synthelabo has ordered during the calendar quarter immediately
prior to such request. Synthelabo shall pay PRAECIS only the Cost of Goods for
such samples. PRAECIS shall mark such samples "not for sale;" and Synthelabo
agrees that such samples will be used only as salesman's exhibits and as
promotional free samples, and will not in any instance be sold.
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9.10 Currency. All payments hereunder shall be made by wire transfer
of U.S. Dollars in immediately available funds to PRAECIS as follows:
c/o Chase Manhattan Bank, NY
ABA #021-0000-21
A/C Goldman, Sachs & Co.
A/C #930-1-011483
FFC A/C Name: PRAECIS PHARMACEUTICALS INCORPORATED
Account #: 010-08933-2
In the event that any currency conversions are required in the calculating of or
making of payments hereunder, such conversions shall be made using the
conversion rates set forth in The Wall Street Journal on the day that such
payments become due and payable to PRAECIS.
9.11 PRAECIS Audit Rights. Synthelabo hereby agrees that Synthelabo
shall, and shall cause its Affiliates to, keep and maintain full and accurate
books of account and records showing for each calendar quarter, without
limitation, the number of units of each Licensed Product sold for each
Application in each Territory Country, and showing cumulative Net Sales for each
Licensed Product sold for each Application in each Territory Country, as well as
copies of invoices and other normal and customary sales records. All such books
and records shall be maintained for at least four (4) years after the latest
calendar quarter to which they pertain. Synthelabo further agrees that PRAECIS
shall have the right to engage (at its own cost and expense, except as otherwise
provided below in this Section 9.11) an independent accounting firm to examine
Synthelabo's books and records pertaining to the sale of Licensed Products, and
that
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Synthelabo shall cause its Affiliates' to allow such firm to examine its
Affiliates' books and records pertaining to the sale of Licensed Products, in
order to confirm the accuracy and timeliness of reports and payments hereunder.
Such examination shall be made at the location of Synthelabo or the relevant
Affiliate, during normal business hours, and with reasonable advance notice.
Prior to any such examination, Synthelabo may require the accounting firm to
maintain all information of Synthelabo and its Affiliate confidential, through
the execution of a confidentiality agreement having reasonable terms and
conditions; however, such firm shall be permitted to disclose to PRAECIS
sufficient information to allow PRAECIS to confirm the accuracy and timeliness
of reports and payments hereunder, and to fully understand any discrepancy or
underpayment. Such examination shall not be performed more than once per year
for each of Synthelabo and each Affiliate, and the right to examine records for
a given calendar quarter shall expire four (4) years following that quarter. If
such an examination discloses an underpayment, Synthelabo shall immediately
remit such amount to PRAECIS unless and to the extent that the amount in
question is being disputed in good faith by Synthelabo; and any such unpaid
amount shall be subject to interest as provided in Section 10.1. If such
examination reveals an underpayment of seven and one-half percent (7.5%) or more
for the period examined, Synthelabo shall also reimburse PRAECIS for the
reasonable cost of the examination, in-
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cluding without limitation all reasonable travel costs, meals, and other
reasonable costs incidental thereto.
ARTICLE 10 - REMEDIES FOR NON-PAYMENT
10.1 Interest. Amounts due and payable hereunder but not paid by the
date due hereunder will be subject to an interest charge from the date such
payment was due until payment equal to the highest U.S. Prime Interest Rate per
annum published in The Wall Street Journal on the first business day after the
payment first became due, plus 3.0 percentage points.
10.2 Other. Failure on the part of Synthelabo to timely pay for
Licensed Products when such payment is due as provided herein shall give PRAECIS
the right (without prejudice to any other remedies):
10.2.1 to enforce its security interest granted pursuant to
Section 10.3; or
10.2.2 to give written notice to Synthelabo that Synthelabo
shall not sell or part with possession of the Licensed Products until the
transfer payments set forth in Article 9 shall have been paid in full, with
which Synthelabo shall comply.
10.3 Collateral. As collateral security for the due and punctual
payment by Synthelabo of all amounts payable by it either under this Agreement
or on account of any sale of one or more Licensed Products from PRAECIS to
Synthelabo, Synthelabo hereby grants to PRAECIS a purchase money security
interest in all Licensed Products hereafter acquired by Synthelabo from PRAECIS,
together with the proceeds (including, without limita-
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tion, proceeds under insurance policies) therefrom, and in all right, title and
interest of Synthelabo in and to all instruments and other documents, whenever
arising, covering or relating to such Licensed Products and proceeds and all
rights, remedies and claims of Synthelabo under or with respect to such
documents, whether now existing or hereafter arising, in each case until the
purchase price for such Licensed Products has been paid in full in accordance
with the terms hereof; provided, however, that PRAECIS hereby releases such
security interest effective upon such payment in full, and provided further,
that the security arrangements hereunder shall in no way impair Synthelabo's
right to sell any Licensed Products to any Third Party. PRAECIS shall have all
the rights, powers, privileges and remedies with respect to such collateral as
shall be permitted for a secured party under the Uniform Commercial Code of the
State of New York as is in effect at such time. Synthelabo agrees that it will
join with PRAECIS in executing, filing and refiling such documents as PRAECIS
may reasonably deem necessary or appropriate to perfect, preserve and deliver
such additional documents as PRAECIS may reasonably deem necessary or
appropriate to carry into effect the purpose of this Section 10.3 or to better
assure and confirm to PRAECIS its rights, powers and remedies under this Section
10.3. Synthelabo hereby authorizes PRAECIS, in its discretion, to file financing
statements and similar documents relative to all or any part of the
above-described collateral without the signature of Synthelabo wherever
permitted by law.
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10.4 Insurance on Unsold Goods. Synthelabo at its own cost and
expense shall keep all of the Licensed Products in which PRAECIS has an
interest, and which are under Synthelabo's direct or indirect control, insured
under a standard policy with coverage and in an amount which shall be sufficient
to prevent PRAECIS from sustaining any financial loss caused by the loss, damage
or destruction of such Licensed Products unless and until such Licensed Products
undergo manufacturing transformation by Synthelabo or a Third Party
manufacturer.
ARTICLE 11 - COOPERATION AND ASSISTANCE
11.1 General. Subject to the other provisions of this Agreement,
Synthelabo and PRAECIS shall each take such steps as are reasonably necessary to
assist one another in securing their trademark rights, intellectual property
rights and any other rights in connection with the Licensed Products, and to
assist one another in taking any steps necessary to defend such rights. Except
as otherwise provided in Article 19, any reasonable expenses incurred in this
regard by an assisting party shall be refunded by the party receiving such
assistance, provided that such party has agreed to such expenses in advance.
11.2 Specific Cooperation of Synthelabo. Synthelabo shall cooperate
with PRAECIS in the following ways with respect to Licensed Products:
11.2.1 Synthelabo shall inform PRAECIS of any suggested
Improvements;
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11.2.2 Synthelabo shall give representatives from PRAECIS
reasonable opportunity to participate in sales meetings and exhibitions in order
to enable PRAECIS to understand marketing problems and opportunities within the
Territory, and to give adequate assistance when and where required; and
11.2.3 Synthelabo shall submit to PRAECIS from time to time
and at the end of each December reports detailing all relevant information as to
the prevailing market situation, the attitude of customers, and the activities
of competitors, in each Territory Country.
11.3 Specific Cooperation of PRAECIS. PRAECIS shall cooperate with
Synthelabo in the following ways with respect to Licensed Products:
11.3.1 PRAECIS shall inform Synthelabo of any suggested
Improvements;
11.3.2 PRAECIS shall give representatives from Synthelabo
reasonable opportunity to participate in sales meetings and exhibitions in order
to enable Synthelabo to understand marketing problems and opportunities outside
of the Territory, and to give adequate assistance when and where required; and
11.3.3 PRAECIS shall submit to Synthelabo from time to time
and at the end of each December reports detailing all relevant information as to
the prevailing market situation, the attitude of customers, and the activities
of competitors, in each country outside of the Territory.
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11.4 Patent Prosecution and Maintenance. The parties agree that they
will coordinate with each other in all reasonable respects the worldwide
prosecution of all patents and patent applications relating to this Agreement,
subject to the provisions of this Section 11.4. PRAECIS shall, at its expense,
diligently pursue the filing, prosecution and maintenance of all patents and
patent applications included in the Intellectual Property Rights and the PPI
Licensed Rights (except for Improvements owned exclusively by Synthelabo) in all
Territory Countries where protection of intellectual property rights in general
is available, Synthelabo reasonably requires such protection and such protection
is available, and PRAECIS shall bear all costs associated therewith. PRAECIS
shall furnish Synthelabo with copies of any patent application concerning the
Intellectual Property Rights sufficiently in advance of the anticipated filing
date therefor (but in no event less than 20 business days before filing) so as
to give Synthelabo a reasonable opportunity to review and comment thereon.
PRAECIS shall also furnish copies to Synthelabo of all communications to and
from United States and foreign patent offices regarding patents or patent
applications relating to this Agreement within a reasonable time prior to filing
such communication or promptly following the receipt thereof. PRAECIS shall
reasonably consider any comments Synthelabo may have related to such patent
applications or communications. Each of Synthelabo and PRAECIS shall have the
right, at its expense, to file, prosecute and
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maintain patents in all countries on Improvements owned solely by it. Each party
shall have the reasonable right to review and comment on such filings by the
other party and all patent office communications related thereto to the same
extent as Synthelabo is permitted by this Section 11.4 with respect to filings
made by PRAECIS. PRAECIS shall designate Synthelabo its European patent agent,
and shall deliver any power of attorney required to give effect to such
designation, in order that Synthelabo may, and Synthelabo agrees to, implement
and diligently carry out an accelerated procedure to obtain a European search
report and the first official letter from the European Patent Office with
respect to the patentability of PPI-149 and the formulation, respectively,
described in the European patent applications to be filed based on the
respective Material Patent Applications (as defined in Section 1.36).
ARTICLE 12 - REPRESENTATIONS AND WARRANTIES
12.1 Conformity to Specifications. PRAECIS warrants that each
Licensed Product delivered to Synthelabo for sale to Third Parties shall conform
to the specifications for such Licensed Product as shall be developed by PRAECIS
and provided to Synthelabo from time to time, which shall be consistent with
those upon which Registration Approval of such Licensed Product was based, and
shall have a minimum remaining shelf life at delivery of at least 83% of the
total shelf life of such Licensed Product. PRAECIS further warrants that (i)
neither it nor any Third Party manufacturer engaged by it shall make any change
to
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its Licensed Product manufacturing process or place of manufacture which would
adversely affect Registration Approvals in the Territory, unless consent to such
change is first obtained from Synthelabo and (ii) PRAECIS will make any change
to the manufacturing process or place of manufacture required by regulatory
authorities to maintain Registration Approval in a Territory Country. Synthelabo
warrants that any Licensed Products manufactured by, or pursuant to agreements
with, it or any of its Affiliates, pursuant to Article 3, for sale to Third
Parties shall conform to the specifications for such Licensed Product as shall
be developed by PRAECIS and provided to Synthelabo from time to time, which
shall be consistent with those upon which Registration Approval of such Licensed
Product was based. Synthelabo further warrants that neither it nor any of its
Affiliates nor any Third Party manufacturer which it engages, shall make any
change to any Licensed Product manufacturing process which it employs which
would adversely affect Registration Approvals in the Territory, unless consent
to such change is first obtained from PRAECIS.
12.2 Representations as to Intellectual Property. PRAECIS represents
and warrants that PRAECIS owns or possesses adequate licenses or other rights to
use all patents, patent rights, inventions and know-how included in the
Intellectual Property Rights and the PPI Licensed Rights being licensed to
Synthelabo hereunder and to grant the licenses granted herein. To the best
knowledge of PRAECIS, the manufacture, use or sale of
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the Licensed Products pursuant to this Agreement will not infringe or conflict
with any Third Party right or patent and PRAECIS is not aware of any pending
patent application that if issued would be infringed by the manufacture, use or
sale of the Licensed Products pursuant to this Agreement. Appendix II hereto
correctly identifies all patent applications included within the Intellectual
Property Rights and the PPI Licensed Rights as of the date hereof. With respect
to all such patent applications, except as disclosed in writing by PRAECIS to
Synthelabo prior to the Effective Date, PRAECIS has no knowledge of any prior
patent or publication, public use, offer for sale or actual sale that would
invalidate the claims of such patent applications, and PRAECIS has no knowledge
of any actions heretofore taken by a patent office that would render such patent
unenforceable. As of the Effective Date, neither Synthelabo nor PRAECIS has
knowledge that any infringement referred to above in this Section 12.2 has
occurred, and neither party has been notified or is aware of any actual or
potential claims of infringement.
12.3 Authority; Binding Agreement; Other Matters. Each of Synthelabo
and PRAECIS hereby represent and warrant to one another that:
12.3.1 They are duly incorporated and are validly existing
corporations in good standing under the laws of their respective jurisdictions
of incorporation.
12.3.2 Each has the corporate power and authority to execute,
deliver and perform this Agreement.
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12.3.3 This Agreement constitutes a valid and binding
obligation of such party, enforceable against such party in accordance with its
terms, except as enforceability may be limited by applicable bankruptcy,
insolvency, reorganization, moratorium or similar laws affecting creditors'
rights generally or by the principles governing the availability of equitable
remedies.
12.3.4 Neither it nor any of its Affiliates is a party to,
subject to, or bound by any agreement, understanding or judgment, award, order,
writ, injunction or decree of any court, governmental body or arbitrator which
would (i) prevent it from carrying out of this Agreement or (ii) conflict with
or be breached by the execution, delivery or performance by it of this
Agreement. There is no action, suit, dispute or governmental, administrative,
arbitration or regulatory proceeding pending or, to the best of such party's
knowledge, threatened against or relating to such party which, in each case,
could prevent such party from carrying out its obligations under this Agreement.
12.4 IUF License Agreement. PRAECIS represents and warrants that, as
of the date of this Agreement, (i) the IUF License Agreement is in full force
and effect, (ii) PRAECIS is in compliance in all material respects with its
obligations thereunder and has heretofore delivered to Synthelabo a true and
complete copy thereof, (iii) there have been no amendments or modifications
thereof and (iv) IUF has not breached the IUF License Agreement. So as not to
adversely affect Synthelabo's
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rights under this Agreement, PRAECIS will not, during the term of this
Agreement, take any actions to terminate or restrict its rights under the IUF
License Agreement as the same relate to the Licensed Products, and will
discharge all of its obligations and responsibilities thereunder, including,
without limitation, making any required payments. If PRAECIS receives any notice
of default under the IUF License Agreement, PRAECIS will promptly notify
Synthelabo thereof.
12.5 Warranty Disclaimer. PRAECIS MAKES NO WARRANTIES, EXPRESSED OR
IMPLIED, AS TO THE MERCHANTABILITY OR FITNESS FOR ANY PURPOSE OF ANY LICENSED
PRODUCTS. PRAECIS SHALL NOT BE LIABLE FOR ANY DIRECT, CONSEQUENTIAL OR OTHER
DAMAGES SUFFERED BY SYNTHELABO OR ANY THIRD PARTY RESULTING FROM THE USE OF THE
LICENSED PRODUCTS, EXCEPT TO THE EXTENT OF (I) ANY BREACH OF A REPRESENTATION OR
WARRANTY OF PRAECIS SET FORTH HEREIN, OR (II) ANY EXPRESS INDEMNIFICATION BY
PRAECIS HEREUNDER.
ARTICLE 13 - INDEMNIFICATION
13.1 Synthelabo Indemnification of PRAECIS. Synthelabo hereby agrees
to indemnify and hold harmless PRAECIS, its directors, officers, employees,
agents, subsidiaries and Affiliates against any and all liability, damages, loss
or expenses (including those arising out of personal injury claims), including
reasonable attorney fees and expenses of litigation, arising out of the actions
of Synthelabo, its directors, officers, employees, agents, subsidiaries or
Affiliates, or any Third Party acting on behalf of or under authorization by
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Synthelabo, in connection with Synthelabo's development, Improvement, testing,
importation, Advertising, Promotion, marketing, distribution, manufacture
(whether complete manufacture or "fill and finish"), use, transport, offering
for sale, sale, labeling, handling, storage or support of the Licensed Products,
or otherwise arising out of or resulting from such actions by Synthelabo or its
customers, or arising out of Synthelabo's failure to procure insurance as
required hereunder. These provisions shall survive for six (6) years beyond the
termination or expiration of this Agreement. Without limiting the foregoing, in
the event that any of the duties and obligations of Synthelabo hereunder are
performed by any Affiliate or permitted third party sublicensee of Synthelabo,
PRAECIS shall be indemnified by Synthelabo for the acts or omissions of such
other party to the same extent as PRAECIS is indemnified for the acts and
omissions of Synthelabo under this Section 13.1.
13.2 PRAECIS' Indemnification of Synthelabo. PRAECIS hereby agrees
to indemnify and hold harmless Synthelabo, its directors, officers, employees,
agents, subsidiaries and Affiliates against any and all liability, damages, loss
or expenses (including those arising out of personal injury claims), including
reasonable attorney fees and expenses of litigation, arising out of the actions
of PRAECIS, its directors, officers, employees, agents, subsidiaries or
Affiliates, or any Third Party acting on behalf of or under authorization by
PRAECIS, in connection with PRAECIS's design, development, Improvement,
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testing, manufacture, labeling, handling or support of Licensed Products, or
otherwise arising out of or resulting from such actions by PRAECIS or its
customers, or arising out of PRAECIS' failure to procure insurance as required
hereunder. These provisions shall survive for six (6) years beyond the
termination or expiration of this Agreement. Without limiting the foregoing, in
the event that any of the duties and obligations of PRAECIS hereunder are
performed by any Affiliate or permitted third party licensee of PRAECIS,
Synthelabo shall be indemnified by PRAECIS for the acts or omissions of such
other party to the same extent as Synthelabo is indemnified for the acts and
omissions of PRAECIS under this Section 13.2.
13.3 Mutual Indemnification for Breach. PRAECIS hereby agrees to
indemnify and hold Synthelabo harmless against any liability, damages, loss or
expense (including reasonable attorneys fees and expenses of litigation) arising
out of the breach of any representation, warranty, covenant or agreement of
PRAECIS contained herein. Synthelabo hereby agrees to indemnify and hold PRAECIS
harmless against any liability, damages, loss or expense (including reasonable
attorneys fees and expenses of litigation) arising out of the breach of any
representation, warranty, covenant or agreement of Synthelabo contained herein.
13.4 Procedure For Third Party Claims. Any person that intends to
claim indemnification under this Article 13 (an "Indemnitee") arising out of a
Third Party claim shall promptly notify the indemnifying party (the
"Indemnitor") of such claim in respect of which the Indemnitee intends to claim
such indemnifi-
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cation, and the Indemnitor shall, to the extent applicable, assume the defense
thereof with counsel mutually satisfactory to the parties; provided, however,
that an Indemnitee shall have the right to retain its own counsel, with the
reasonable fees and expenses thereof to be paid by the Indemnitor, if
representation of such Indemnitee by the counsel retained by the Indemnitor
would be inappropriate due to actual or potential differing interests between
such Indemnitee and any other party represented by such counsel in such
proceedings. The parties' indemnity obligations under this Article 13 shall not
apply to amounts paid in settlement of any loss, claim, liability or action if
such settlement is effected without the consent of the Indemnitor, which consent
shall not be withheld unreasonably. Any Indemnitee's failure to deliver notice
to the Indemnitor within a reasonable time after the commencement of any such
action, if materially prejudicial to the Indemnitor's ability to defend such
action, shall relieve the Indemnitor of any liability to the Indemnitee under
this Article 13, but not any liability that it may have to the Indemnitee
otherwise than under this Article 13. The Indemnitee and its employees and
agents shall cooperate fully with the Indemnitor and its legal representatives
in the investigation and defense of any action, claim or liability covered by
this indemnification.
ARTICLE 14 - INSURANCE
The parties shall maintain insurance coverage with respect to their
activities and potential liabilities in
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connection with the collaboration hereunder as is commercially reasonable in the
circumstances.
ARTICLE 15 - NON-COMPETITION
15.1 Mutual Non-Competition Covenant. Except as provided in Section
15.2, neither PRAECIS nor Synthelabo shall, during the term of this Agreement or
any extension thereof and for one (1) year thereafter, without the consent of
the other party, be concerned or interested, directly or indirectly (including
through a licensing arrangement), in the advertising, promotion, manufacture,
use, importation, offering for sale, sale or marketing in any Territory Country
of any products containing an LHRH Antagonist, other than, in the case of
Synthelabo, Licensed Products. For the avoidance of doubt, activities undertaken
by Synthelabo to discover, conceive or invent Improvements or Synthelabo
Formulations shall not be prohibited by this Section 15.1. The above restriction
on competition shall not apply after termination of this Agreement (i) to a
party if this Agreement has terminated pursuant to Section 17.2 by reason of the
occurrence of one or more of the events described therein with respect to the
other party or if this Agreement has been validly terminated by such party for
breach by the other party pursuant to Section 17.3 or (ii) to Synthelabo or
PRAECIS if this Agreement has been terminated in its entirety pursuant to
Section 17.7 (including without limitation as contemplated by Section 9.1).
15.2 Competitive Acquisition. Synthelabo shall promptly notify
PRAECIS if Synthelabo shall acquire, or
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Synthelabo or substantially all its business or assets shall be acquired by,
directly or indirectly, an entity which, directly or indirectly, is developing,
or which Advertises, Promotes, manufactures, imports, offers for sale, sells or
markets, any product which contains an LHRH Antagonist and which is competitive
with any Licensed Product in the Territory. The occurrence of any of the events
described in the preceding sentence shall not relieve either party of its
obligations hereunder or otherwise modify or vary the rights and obligations of
the parties hereunder, including without limitation Synthelabo's general
obligation as provided herein to diligently develop, market and sell Licensed
Products in the Territory.
ARTICLE 16 - IMPROVEMENTS
It is contemplated that PRAECIS and Synthelabo, separately or
jointly, may discover, conceive or develop Improvements as defined herein, and
that Synthelabo may discover, conceive or develop Synthelabo Formulations. All
intellectual property rights in and to Improvements discovered, conceived or
developed by PRAECIS, its employees or agents shall be owned by PRAECIS, and
shall be included in the Intellectual Property Rights licensed hereunder. All
intellectual property rights in and to Improvements discovered, conceived or
developed by Synthelabo, its employees or agents shall be owned by Synthelabo,
and an exclusive fully paid-up, royalty-free license, with the right to grant
sublicenses in connection with licenses granted by PRAECIS related to Licensed
Products, under such rights for use only with Licensed Products outside the
Territory is hereby
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granted to PRAECIS, it being understood and agreed that, subject to Section
15.1, Synthelabo may use or license such Improvement (i) in the Territory in
connection with Licensed Products to the extent provided in this Agreement and
(ii) in or outside the Territory for uses other than in connection with Licensed
Products. Such license to PRAECIS shall be perpetual, except that such license
shall automatically terminate if this Agreement is terminated by Synthelabo
pursuant to Section 17.2 by reason of the occurrence of one or more of the
events described therein with respect to PRAECIS or is validly terminated by
Synthelabo pursuant to and in accordance with Section 17.3 by reason of any
material breach of this Agreement by PRAECIS. All intellectual property rights
in and to Synthelabo Formulations shall be owned by Synthelabo. All intellectual
property rights in and to Improvements jointly discovered, conceived or
developed by PRAECIS and Synthelabo employees or agents shall be jointly owned
by PRAECIS and Synthelabo, as dictated by U.S. law regarding ownership of
jointly discovered, conceived or developed intellectual property rights; and the
rights of each of PRAECIS and Synthelabo in and to same shall be licensed to the
other as provided for Improvements made by each alone, as set forth hereinabove.
Each party shall promptly disclose to the other any Improvements developed by
its employees or agents acting on its behalf and Synthelabo shall promptly
disclose to PRAECIS any Synthelabo Formulations. The parties shall discuss in
good faith the manner in which such Improvements or such Synthelabo
Formulations, as applicable, may be incorporated into the
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Licensed Products which have been commercialized (or are in the course of
development for commercialization) hereunder. If and to the extent that any
Synthelabo Formulation is incorporated into any Licensed Product as aforesaid,
the term "Licensed Product" hereunder shall be amended in the manner mutually
agreed upon by the parties as provided below. The Joint Steering Committee shall
determine in good faith whether any Improvement or Synthelabo Formulation should
be incorporated into any Licensed Product intended for sale in the Territory.
Notwithstanding the foregoing, if incorporation of such Improvement or
Synthelabo Formulation would have a material impact on the economic terms and
conditions of this Agreement applicable to either party, then the parties shall
negotiate in good faith appropriate adjustments to the economic terms and
conditions of this Agreement with a view to preserving the relative economic
benefits of the parties under this Agreement (except as otherwise mutually
agreed) to permit the incorporation of such Improvement. If mutual agreement of
the parties is reached as to the incorporation of any Synthelabo Formulation as
aforesaid, then Synthelabo shall be deemed to have granted to PRAECIS a
fully-paid up, royalty-free exclusive license, with the right to grant
sublicenses in connection with licenses granted by PRAECIS related to the
Licensed Products or other products containing PPI-149 or another LHRH
Antagonist Compound licensed to Synthelabo hereunder and formulated in such
Synthelabo Formulation, of its rights in such Synthelabo Formulation solely for
use outside the Territory with Licensed Products or other
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products containing PPI-149 or another LHRH Antagonist Compound licensed to
Synthelabo hereunder and formulated in such Synthelabo Formulation. Such license
shall be perpetual, except that such license shall automatically terminate if
this Agreement is terminated by Synthelabo pursuant to Section 17.2 by reason of
the occurrence of one or more of the events described therein with respect to
PRAECIS or is validly terminated by Synthelabo pursuant to and in accordance
with Section 17.3 by reason of any material breach of this Agreement by PRAECIS.
It is understood and agreed that, subject to Section 15.1, Synthelabo may use or
license a Synthelabo Formulation (i) in the Territory to the extent provided in
this Agreement and (ii) in or outside the Territory for uses other than in
connection with (A) Licensed Products or (B) other products containing PPI-149
or other LHRH Antagonist Compounds licensed to Synthelabo hereunder and
formulated in such Synthelabo Formulation. Each of PRAECIS and Synthelabo hereby
represent and warrant that their relevant employees are bound by a written
agreement which requires them to assign to their employer all intellectual
property rights arising within the scope of their employment.
ARTICLE 17 - TERM & TERMINATION
17.1 Term; Expiration. Unless terminated earlier, as provided
herein, the term of this Agreement shall expire, and the licenses granted by
PRAECIS to Synthelabo hereunder shall become fully paid-up, perpetual and
royalty-free and shall continue without any further obligation, with respect to
a Territory Country, upon the expiration in such Territory Country of the
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last to expire of the patents and any extensions thereof or supplementary
certificates of protection included in the Intellectual Property Rights or the
PPI Licensed Rights, respectively, which are licensed or sublicensed
respectively, hereunder and which cover a Licensed Product in such Territory
Country. In the event that no Intellectual Property Rights, Patent Rights or
Invention Rights licensed or sublicensed hereunder cover a Licensed Product in a
Territory Country, the term of this Agreement in such Territory Country for such
Licensed Product shall expire ten (10) years after the date of Registration
Approval of such Licensed Product in such Territory Country, whereupon the
licenses granted herein shall become fully paid-up, perpetual, royalty-free and
shall continue without any further obligation in such Territory Country. Upon
the expiration of this Agreement in a Territory Country pursuant to this Section
17.1, PRAECIS shall cease to have any further obligations to Synthelabo
hereunder with respect to such Territory Country, including to manufacture and
supply Licensed Products with respect to such Territory Country, and Synthelabo
shall cease to have any further obligations to PRAECIS hereunder with respect to
such Territory Country, except that such expiration shall not release either
party from any liability or obligation that matured prior to such expiration,
including for this purpose the obligation of Synthelabo to timely make all
payments required by Article 9 for Licensed Products ordered by Synthelabo or
its Affiliates pursuant hereto prior to such expiration.
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17.2 Bankruptcy, Etc.
(a) Automatic Termination. If either party (i) shall make a
general assignment for the benefit of creditors, (ii) shall file a
voluntary petition of bankruptcy, (iii) shall be adjudged a bankrupt or
insolvent, or have had entered against it an order for relief in any
bankruptcy or insolvency proceeding, (iv) shall file a petition or answer
seeking reorganization, arrangement, composition, readjustment,
liquidation, dissolution or similar relief under any statute, law or
regulation, (v) shall file an answer or other pleading admitting or
failing to contest the material allegations of a petition filed against it
in any proceeding specified in (vii) below, (vi) shall seek, consent to or
acquiesce in the appointment of a trustee, receiver or liquidator of said
party or of all or any substantial part of the assets of said party or
(vii) shall fail to obtain dismissal within 60 days of the commencement of
any proceeding against said party seeking reorganization, arrangement,
composition, readjustment, liquidation, dissolution or similar relief
under any statute, law or regulation, or the entry of any order appointing
a trustee, liquidator or receiver of said party or of said party's assets
or any substantial portion thereof, this Agreement shall automatically
terminate, inasmuch as permitted under applicable and prevailing law.
(b) Bypass of Payments. If PRAECIS enters into an arrangement
of creditors and/or bankruptcy, one week
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prior to such arrangement of creditors and/or bankruptcy Synthelabo shall
have the right to be notified by PRAECIS of such arrangement and/or
bankruptcy, and any and all license fees owed directly to PRAECIS by
Synthelabo pursuant to this Agreement shall thereafter be paid by
Synthelabo directly to IUF at the same royalty rate as set forth in this
Agreement.
17.3 Breach. Subject to the further provisions of this Section 17.3,
upon any material breach or default of this Agreement by either party, the
non-breaching party shall have the right to serve notice upon the breaching
party of its intention to terminate this Agreement upon the expiration of ninety
(90) days after the date said notice is given, unless the breaching party shall
cure any such breach or default within said ninety (90) day period. Upon the
expiration of said ninety (90) day period, if the breaching party shall not have
so cured, and if the non-breaching party gives a notice of final termination,
final termination of this Agreement shall be effective on the date such notice
is given. Notwithstanding the foregoing, in the case of a breach of a payment
obligation hereunder, the ninety day (90) period referred to above shall instead
be thirty (30) days.
17.4 Effect of Termination. Upon expiration or termination of this
Agreement as provided herein, this Agreement shall, except as otherwise provided
herein, be void and of no further force or effect and neither party shall have
any further liability hereunder, and except that no such expiration or
termination shall release either party from any liability or
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obligation that arose or is based upon events which occurred prior to the
effective date of such expiration or termination. The following special
provisions shall be applicable if this Agreement (i) terminates pursuant to
Section 17.2 by reason of the occurrence of one or more of the events described
therein with respect to PRAECIS or (ii) is validly terminated by Synthelabo
pursuant to and in accordance with Section 17.3 by reason of any material breach
of this Agreement by PRAECIS other than breach by PRAECIS of its supply
obligations hereunder:
(a) all of the license and sublicense rights granted to
Synthelabo and its Affiliates hereunder shall remain in full force and
effect on a fully paid-up, perpetual and royalty-free basis; and
(b) Synthelabo shall have a fully paid-up, perpetual,
royalty-free license of all manufacturing protocols, know-how and related
information and data necessary to enable Synthelabo to develop, have
developed, make and have made Licensed Products in the Territory from and
after the effective date of such termination.
17.5 Surviving Provisions. The parties agree that, subject to the
first sentence of Section 17.4, upon termination of this Agreement, the
following shall survive (subject to the limitations set forth in this Section
17.5): Section 4.6 (only upon termination as provided in such Section) and
Section 4.7, the confidentiality obligations of Article 7 hereof (to the extent
provided therein), the obligations of Synthelabo set forth in Section 8.6 (only
in the case of termination pursuant to
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Section 17.2 due to the occurrence of one or more of the events described
therein with respect to Synthelabo or termination by PRAECIS pursuant to Section
17.3 for breach by Synthelabo), the non-competition obligations set forth in
Section 15.1 (to the extent provided therein), Section 17.4 (with respect to the
special provisions set forth therein, only upon termination as provided in such
Section), this Section 17.5 and Section 17.8 (only upon termination as provided
in such Section).
17.6 Continuation of Sublicense Rights. The sublicense granted
hereunder with respect to the PPI Licensed Rights shall survive the termination
of the IUF License Agreement. Upon termination of the IUF License Agreement for
any reason during the term of this Agreement, PRAECIS shall assign to IUF all of
PRAECIS' rights in the PPI Licensed Rights in accordance with Section 12.05 of
the IUF License Agreement, and upon IUF's complete assumption of all of PRAECIS'
future obligations hereunder with respect to such sublicense, PRAECIS shall have
no further obligation whatsoever with respect thereto, except for any liability
or obligation of PRAECIS that matured prior to the effective date of such
assumption.
17.7 Termination for Material Adverse Events. Synthelabo may
terminate this Agreement to the extent provided in Section 4.10. However, such
termination right shall be exercisable only if, with respect to any event
referred to in Section 4.10 giving rise to such termination right, within nine
months after first becoming aware of the occurrence of such event (such date on
which Synthelabo first becomes aware of the
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occurrence of such event being referred to as a "Termination Right Trigger
Date"), Synthelabo notifies PRAECIS in writing of such event (a "Section 17.7
Notice"), which notice shall set forth a date (the "Section 17.7 Termination
Date") not less than sixty (60) days (except as provided in Section 9.1) and not
more than twelve months after the Termination Right Trigger Date on which this
Agreement shall terminate to the extent provided in Section 4.10, it being
understood and agreed that until the Section 17.7 Termination Date, the
obligations of the parties hereunder shall remain in effect, including without
limitation Synthelabo's general obligation as provided herein to diligently
develop, market and sell Licensed Products in the Territory.
17.8 Right to Sell Inventory. Upon termination of this Agreement
pursuant to Section 17.2 due to the occurrence of one or more of the events set
forth therein with respect to Synthelabo or pursuant to Section 17.3 due to a
breach by Synthelabo, Synthelabo may, for a period of six (6) months after the
termination date, sell all Licensed Products on hand as of the termination date,
provided that all payments therefor are timely paid in compliance with Article 9
hereof.
ARTICLE 18 - ARBITRATION
18.1 Procedure; Decision Final and Binding. Except as to issues
relating to the validity, construction or effect of any patent right licensed
hereunder, any and all claims, disputes or controversies arising under, out of,
or in connection with this Agreement, which have not been resolved by good faith
negotiations between the parties may be referred by either party
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to arbitration and finally settled in accordance with the UNCITRAL Arbitration
Rules (as supplemented or modified by this Section 18.1) in effect on the date
hereof (hereinafter, the "Rules"), by three arbitrators appointed in accordance
with said Rules. The appointing authority shall be the Court of Arbitration of
the International Chamber of Commerce ("ICC") located in Paris, France. The
place of arbitration shall be London, England. All arbitrators shall be fully
conversant with the English language and the opinion shall be rendered in
English. The English language shall be used in all documents, briefs, evidence
and any other writings submitted. All proceedings shall be in the English
language. Except as provided in Section 18.3 the procedures set forth in this
Section 18.1 shall be the sole and exclusive means of settling or resolving any
dispute hereunder. Accordingly, each party covenants and agrees with the other
party that except as expressly provided in Section 18.3, it will not seek to
have any such dispute adjudicated (except to enforce the provisions of this
Section 18.1 as provided below and except for the limited right to seek
injunctive relief where appropriate) in any court or other official forum of any
government, or otherwise seek to invalidate or circumvent the procedures set
forth in this Section 18.1 as the sole and exclusive means of settling or
resolving any such dispute.
The decision of the arbitrators contemplated by this Section 18.1
shall be final and binding on the parties and may be
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presented by either party for enforcement in any court of competent
jurisdiction; provided, however, that if such enforcement is sought in the
United States, it may only be sought in the state courts of the Commonwealth of
Massachusetts, or a United States federal court in the Commonwealth of
Massachusetts. The parties understand and agree that the provisions of this
Article 18 may be specifically enforced by injunction or otherwise in any court
of competent jurisdiction.
18.2 Assumption Regarding Intellectual Property Rights. In any
arbitration proceedings hereunder, the arbitrators shall assume the validity and
enforceability of any patent rights licensed hereunder.
18.3 Exception to Exclusive Dispute Resolution Procedure. Claims,
disputes or controversies concerning the validity, construction or effect of any
patent rights licensed hereunder shall be resolved in a court having subject
matter jurisdiction thereof.
ARTICLE 19 - INFRINGEMENT AND MAINTENANCE
19.1 Infringement by Third Parties. Synthelabo and PRAECIS shall
promptly inform one another in writing of any alleged infringement, unauthorized
use or misappropriation, of which either shall have notice of any trademarks or
Intellectual Property Rights or the PPI Licensed Rights licensed hereunder and
provide each other with any reasonably available evidence of infringement. Upon
such notice, the PRAECIS and Synthelabo
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representatives to the Joint Steering Committee shall promptly confer with their
respective patent counsel regarding such apparent infringement; and the Joint
Steering Committee shall promptly thereafter meet in person or by telephone to
discuss possible courses of action. Unless the Joint Steering Committee
recommends otherwise, PRAECIS shall, with respect to any such alleged
infringement, take action to compel such alleged infringers to cease and desist;
and that failing, shall bring legal action against such alleged infringers. All
costs of such legal action, including reasonable attorneys' fees and
disbursements, shall be borne by PRAECIS, and all judgments, settlements,
damages, license fee payments and future royalties shall first be applied to pay
or reimburse PRAECIS for all costs of such action, including reasonable
attorneys' fees and disbursements, and shall thereafter be split 60% for
Synthelabo and 40% for PRAECIS.
19.2 Infringement Suit By Third Parties. In the event that
Synthelabo (i) issued in an action which alleges infringement, unauthorized use
or misappropriation by Synthelabo in any Territory Country of any Intellectual
Property Rights or PPI Licensed Rights or which is based on the development,
importation, use, sale or distribution by Synthelabo in the Territory of any
Licensed Product as provided hereunder, or (ii) is sued in a declaratory
judgment or similar action alleging invalidity or unenforceability in any
Territory Country of any Intellectual Property Rights or PPI Licensed Rights,
Synthelabo shall promptly notify PRAECIS; and the PRAECIS and Synthelabo
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representatives to the Joint Steering Committee shall promptly confer with their
respective patent counsel regarding such alleged infringement. The Joint
Steering Committee shall promptly thereafter meet in person or by telephone to
discuss possible courses of action. Unless the Joint Steering Committee
recommends otherwise, PRAECIS shall take action to defend against such suit, and
Synthelabo shall cooperate fully with PRAECIS in such action. All costs of such
legal action, including reasonable attorneys' fees, and the cost of all
judgments, damages, settlements, license fee payments and future royalties shall
be borne by PRAECIS.
19.3 Cooperation. In any legal action contemplated under Article 8
or this Article 19, the parties shall provide reasonable cooperation and support
to each other, subject to applicable legal privileges, which each party shall
have the right to assert and maintain, and confidentiality requirements imposed
by a court or other competent tribunal. PRAECIS shall keep Synthelabo reasonably
informed of the status of any such legal action. Without limiting the foregoing,
the parties shall, to the extent possible, make their directors, officers,
employees and agents available to testify when reasonably requested and make
available relevant records, papers, information, samples, specimens, and the
like. The costs to Synthelabo of such cooperation shall be borne by PRAECIS.
19.4 Differing Interests. Synthelabo recognizes that PRAECIS may
have interests in the trademarks, the Intellectual Property Rights and the PPI
Licensed Rights licensed hereunder
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which are outside of the scope of the rights licensed to Synthelabo. Synthelabo
therefore hereby agrees that in any legal action under Article 8 or this Article
19, without limitation of PRAECIS' obligations under such Articles, PRAECIS
shall have the right to seek to protect the entirety of those separate interests
in any litigation regarding such trademarks, the Intellectual Property Rights or
the PPI Licensed Rights.
ARTICLE 20 - ASSIGNMENT
Subject to Section 2.4, Synthelabo may not assign or otherwise
transfer this Agreement or any rights acquired by it hereunder without the prior
written consent of PRAECIS, except for any such assignment to an entity which
acquires or acquires control of its entire business or that part of its business
to which this Agreement relates, whether pursuant to a merger, consolidation,
stock purchase, recapitalization, asset sale or otherwise. Notwithstanding the
foregoing, Synthelabo may have certain of its duties and obligations hereunder
performed by its Affiliates without an assignment or sublicense thereof. In such
cases, Synthelabo shall continue to be obligated to PRAECIS to perform
Synthelabo's obligations hereunder and Synthelabo's indemnification obligations
shall apply to the acts or omissions of any such Affiliate as if such acts or
omissions were those of Synthelabo. PRAECIS may assign this Agreement or its
rights hereunder to an entity which acquires, by license or otherwise, rights to
Licensed Products outside the Territory (provided that in such event PRAECIS
shall continue to be obligated to Synthelabo to perform PRAECIS' obligations
hereunder), or which
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acquires or acquires control of its entire business or that part of its business
to which this Agreement relates, whether pursuant to a merger, consolidation,
stock purchase, recapitalization, asset sale or otherwise (provided that in any
such event, PRAECIS or the successor entity in such transaction shall continue
to be liable to perform PRAECIS' obligations hereunder). This Agreement shall
inure to the benefit of and be binding upon the parties and their respective
heirs, executors, administrators, successors and permitted assigns.
ARTICLE 21 - COMMUNICATIONS
Any notice, request, report, recommendation, consent or other
communication (collectively, a "Notice") under this Agreement shall be effective
if it is in writing and (i) personally delivered, (ii) sent by certified or
registered mail, postage prepaid, return receipt requested, (iii) sent by an
internationally recognized overnight delivery service, with delivery confirmed,
or (iv) telexed or telecopied, with receipt confirmed, addressed as set forth in
this Article 21 or to such address as shall be furnished by either party hereto
to the other party hereto in accordance with the method of Notice set forth
herein. A Notice shall be deemed to have been given as of (i) the date when
personally delivered, (ii) seven (7) days after being deposited with the U.S or
French Postal Service, certified or registered mail, properly addressed, return
receipt requested, postage prepaid, (iii) three days after being sent by said
overnight delivery service properly addressed, or (iv) confirmation of receipt
of the telex or telecopy, as the case may
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be, unless the sending party has actual knowledge that a Notice was not received
by the intended recipient. All Notices shall specifically state: (i) the
Sections (or Sections) of this Agreement with respect to which such Notice is
given, and (ii) the relevant time period, if any, in which the party receiving
the Notice must respond.
Notice Addresses:
Synthelabo: Synthelabo
22 Avenue Galilee
92350 Le-Plessis-Robinson-France
Attention: General Counsel
Facsimile No. 011-33-1-45-37-58-04
PRAECIS: PRAECIS Pharmaceuticals, Inc.
One Hampshire Street
Cambridge, MA 02139
Attention: Director of Business Development
Facsimile No.: 617-494-8414
ARTICLE 22 - MISCELLANEOUS PROVISIONS
22.1 Relationship of the Parties. Each party shall conduct its
business hereunder as a principal for its own account and at its own expense and
risk, except as otherwise provided herein. This Agreement does not in any way
create the relationship of principal and agent, or any similar relationship,
between PRAECIS and Synthelabo. Each party covenants and warrants that it will
not act or represent itself directly or by implication as agent for the other
party, and will not attempt to create any obligation, or make any
representation, on behalf of or in the name of the other party.
22.2 Advertising; Trademarks, Etc. Neither party shall use the other
party's name in its advertising or elsewhere, or any trademark or trade name (or
any mark or name closely
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resembling the same) now or hereafter owned or licensed by the other party or
any of its Subsidiaries or Affiliates other than to the extent specifically
provided herein, without the prior written approval of the other party, except
as required by law.
22.3 Public Disclosures. The parties agree that public disclosures
regarding this Agreement, Regulatory Approvals, Reimbursement Approvals and
Licensed Products may be made at the time and in such manner as both parties
shall both approve; provided that such approval will not be unreasonably
withheld and shall not be required for any such disclosure which a party's
counsel advises is required by law or for public disclosure by such party in any
disclosure document in connection with any financing, strategic transaction,
acquisition or disposition involving PRAECIS or Synthelabo. The restriction on
disclosure contained herein shall not apply to any information disseminated to
the public which is information essentially identical to that contained in a
previous disclosure authorized hereunder.
22.4 Governing Law. This Agreement shall be construed, governed,
interpreted and applied in accordance with the laws of the State of New York,
U.S.A. without regard to the conflict of law principles thereof, and the United
Nations Convention on Contracts for the International Sale of Goods is expressly
disclaimed.
22.5 Entire Agreement. The parties hereto acknowledge that this
Agreement and the other agreements between the parties hereto referred to herein
set forth the entire agreement and
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understanding of the parties hereto as to the subject matter hereof and thereof.
This Agreement shall not be subject to any change or modification except by the
execution of a written instrument subscribed to by the parties hereto; provided
that all obligations of the parties under this Agreement and the Sublicense
Option Agreement shall be considered cumulative rather than contradictory, and
the more stringent or burdensome obligations of a party under one agreement
shall control over any less stringent or less burdensome obligation under the
other.
22.6 Severability. The provisions of this Agreement are severable,
and in the event that any provision of this Agreement shall be determined to be
invalid or unenforceable under any controlling body of law, such invalidity or
unenforceability shall not in any way affect the validity or enforceability of
the remaining provisions hereof.
22.7 No Waiver. The failure of either party to assert a right
hereunder or to insist upon compliance with any term or condition of this
Agreement shall not constitute a waiver of that right or excuse a similar
subsequent failure to perform any such term or condition by the other party.
22.8 Captions and References. Unless otherwise indicated, references
to Sections and Articles are references to Sections and Articles of this
Agreement. Headings, titles and captions of this Agreement are for convenience
only and shall not be used for the construction or interpretation of this
Agreement.
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22.9 Counterparts. This Agreement may be executed in counterparts,
each of which shall be deemed an original, but which together shall constitute
one and the same instrument.
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IN WITNESS WHEREOF, the parties hereto have duly executed this
Agreement through their duly authorized representatives, with the intention to
become bound thereby.
SYNTHELABO
By: /s/ Herve Guerin
--------------------------------
Name: Herve Guerin
Title: President
PRAECIS PHARMACEUTICALS, INC.
By: /s/ Malcolm L. Gefter
--------------------------------
Name: Malcolm L. Gefter
Title: Chairman & CEO
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APPENDIX I
PRAECIS PROPOSED CORE DEVELOPMENT STUDIES
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PRAECIS/SYNTHELABO COLLABORATION APPENDIX I
PPI-149 DEVELOPMENT PLAN
- --------------------------------------------------------------------------------
"CORE" DEVELOPMENT PLAN:
The Core Development Plan includes all preclinical and clinical studies
undertaken by PRAECIS in the U.S. and/or other countries to seek and
obtain Registration approval.
- Will form basis for U.S. Registration dossier with FDA as
well as the core of Registration dossiers in other countries
<PAGE>
PRAECIS/SYNTHELABO COLLABORATION
PPI-149 DEVELOPMENT PLAN
- --------------------------------------------------------------------------------
"SUPPLEMENTAL" DEVELOPMENT PLAN:
Includes pre-clinical and clinical studies undertaken by Synthelabo to
fulfill registration, pricing, reimbursement, and/or marketing
requirements for PPI- 149 in any country in the territory, not fully
satisfied via the Core Development Plan.
<PAGE>
PRAECIS/SYNTHELABO COLLABORATION
PPI-149 DEVELOPMENT PLAN
- --------------------------------------------------------------------------------
CLINICAL DEVELOPMENT PLAN:
PROSTATE CANCER:
- Phase I/II Safety & Efficacy Liquifill
- Phase II Brachytherapy Liquifill
- Phase I/II Safety & Efficacy Rel-Ease-TM- - Depot
- Phase III Metastatic Rel-Ease-TM- - Depot
REPRODUCTIVE ENDOCRINOLOGY/FEMALE INDICATIONS:
- Endometriosis Rel-Ease-TM- - Depot
- Uterine Fibroids Rel-Ease-TM- - Depot
<PAGE>
PHASE II OPEN LABELED STUDY OF PPI-149 ADMINISTERED AS A CONTINUOUS SUBCUTANEOUS
INFUSION FOR 60 TO 90 DAYS IN PATIENTS RECEIVING INITIAL HORMONAL THERAPY FOR
PROSTATE CANCER
- --------------------------------------------------------------------------------
PHASE II: Formulation--Liquid
LOCATION: 12-15 sites in the US
NUMBER OF PATIENTS: Approximately 35-50 patients
MAIN OBJECTIVE:
- To determine the safety of PPI-149 administered as a subcutaneous
infusion utilizing an ambulatory external pump for durations of
60-90 days.
- To determine the biochemical efficacy by determining
endocrinological response in patients receiving PPI-149.
- To determine the anti-cancer activity using NPCP criteria in
patients with metastatic prostate cancer.
- To determine the kinetics of PSA decline.
KEY INCLUSION CRITERIA: Any patient receiving initial hormonal
therapy for prostate cancer.
<PAGE>
START DATE: June 1997 END DATE: February 1998
CRITICAL PATH: Yes
<PAGE>
PHASE II STUDY UTILIZING PPI-149 AS A CONTINUOUS SUBCUTANEOUS INFUSION FOR 0-60
DAYS IN PATIENTS UNDERGOING RADIATION THERAPY WITH INTERSTITIAL SEED
IMPLANTATION
- --------------------------------------------------------------------------------
PHASE II: Formulation--Liquid
LOCATION: 5 sites; U. of Washington, U. of Colorado, St.
Elizabeth's Hospital, Boston University, Mt. Sinai
Hospital, NYC
NUMBER OF PATIENTS: 30
MAIN OBJECTIVE:
- To determine the safety of PPI-149 administered for 30-60 days
prior to brachytherapy.
- To determine the rate of prostate volume gland size reduction.
- To determine the kinetics of PSA decline.
KEY INCLUSION CRITERIA: Patients with clinical localized
prostate cancer who are being contemplated for brachytherapy
with or without external beam who required neodajuvant
hormonal therapy for prostate gland shrinkage.
START DATE: July 1997 END DATE: February 1998
CRITICAL PATH: No
<PAGE>
PHASE I/II EVALUATION OF PPI-149--DEPOT IN THE MANAGEMENT OF PATIENTS RECEIVING
HORMONAL THERAPY FOR THE FIRST TIME FOR PROSTATE CANCER
- --------------------------------------------------------------------------------
PHASE I/II: Formulation--PPI-149--Depot (release)
LOCATION: 25-35 centers
NUMBER OF PATIENTS: Phase I portion will include approximately 20
patients; the Phase II portion will include approximately 70 patients
MAIN OBJECTIVE:
- To determine the safety of PPI-149--Depot.
- To determine the biochemical efficacy of PPI-149--Depot.
- To determine the minimum dose of PPI-149 given as either a single
IM or subcutaneous injection which maintains castrate levels of
testosterone for 14-28 days.
- To determine the anti-cancer efficacy in selected patients who
receive PPI-149--Depot for greater than 84 days.
<PAGE>
PHASE I/II EVALUATION OF PPI-149--DEPOT IN THE MANAGEMENT OF PATIENTS RECEIVING
HORMONAL THERAPY FOR THE FIRST TIME FOR PROSTATE CANCER (CONTINUED)
- --------------------------------------------------------------------------------
KEY INCLUSION CRITERIA:
- Any patient receiving hormonal therapy for prostate cancer for the
first time. These include patients with Stage D1, Stage D2,
prostate cancer.
- Patients undergoing neoadjuvant hormonal therapies following
either radical prostatectomy, radiation therapy, or radiation plus
brachtyerapy or cryosurgery.
- Patients with an elevated PSA following either radical
prostatctomy, radiation therapy, or other definitive localized
therapy.
- Patients receiving "intermittent" hormonal therapy.
START DATE: August-September 1997 END DATE: September 1998
CRITICAL PATH: Yes
<PAGE>
PHASE III RANDOMIZED PROSPECT OF PPI-149--DEPOT VS. LEUPROLIDE ACETATE--DEPOT
IN PATIENTS WITH NEWLY-DIAGNOSED STAGE D2 METASTATIC PROSTATE CANCER
- --------------------------------------------------------------------------------
PHASE III: Formulation--PPI-149--Depot (Rel-Ease-TM-)
LOCATION: 40 centers in US and 20 centers in Europe
NUMBER OF PATIENTS: 200
MAIN OBJECTIVE:
- To determine the safety of PPI-149--Depot for patients with
metastatic prostate cancer.
- To determine the biochemical efficacy and endocrinological
efficacy of PPI-149--Depot vs. Leuprolide in terms of time of
developing castrate levels of testosterone, rate of fall of PSA,
clinical symptomatology includ ing worsening of bone pain,
incidence of hot flashes, and other adverse events.
- To determine the comparative efficacy of PPI-149--Depot compared
to Leuprolide acetate--Depot in patients with metastatic prostate
cancer being treated for at least 84 days.
KEY INCLUSION CRITERIA:
- Patients with newly-diagnosed Stage D2 metastatic prostate cancer.
<PAGE>
- Patients with a rising PSA following definitive localized therapy
or candi dates for hormonal therapy.
START DATE: January 1998 END DATE: January 1999
CRITICAL PATH: Yes, registration driven
<PAGE>
PHASE III RANDOMIZED PROSPECT OF PPI-149--DEPOT VS. LEUPROLIDE ACETATE--DEPOT
PLUS FLUTAMIDE (OR OTHER ANTI-ANDROGEN E.G. BICALUTAMIDE) WITH NEWLY-DIAGNOSED
STAGE D2 METASTATIC PROSTATE CANCER
- --------------------------------------------------------------------------------
PHASE III: Formulation--PPI-149--Depot (Rel-Ease-TM-)
LOCATION: 40 centers in US and 20 centers in Europe
NUMBER OF PATIENTS: 200
MAIN OBJECTIVE:
- To determine the safety of PPI-149--Depot for patients with
metatstatic prostate cancer.
- To determine the biochemical efficacy and endocrinological
efficacy of PPI-149--Depot vs. Leuprolide in terms of time of
developing castrate levels of testosterone, rate of fall of PSA,
clinical symptomatology includ ing worsening of bone pain,
incidence of hot flashes, and other adverse events.
- To determine the comparative efficacy of PPI-149--Depot compared
to Leuprolide acetate--Depot in patients with metatstatic prostate
cancer being treated for at least 84 days.
KEY INCLUSION CRITERIA:
- Patients with newly-diagnosed Stage D2 metastatic prostate cancer.
- Patients with a rising PSA following definitive localized therapy
or candi dates for hormonal therapy.
<PAGE>
START DATE: January 1998 END DATE: January 1999
CRITICAL PATH: Yes, registration driven
<PAGE>
***APPROXIMATELY 4 PAGES OMITTED***
<PAGE>
COMPLETED TOXICOLOGY STUDIES
STUDIES EMPLOYED LIQUID FORMULATION OF PPI-149
- Pharmacokinetics/Biodistribution/Mass Balance in Rats
- 28-day continuous SC infusion of PPI-149 rats
- up to 10,000 ug/kg/day PPI-149
- no clinically relevant toxicity
- 28-day twice-daily bolus SC of PPI-149 in monkeys
- up to 5,000 ug/kg/day PPI-149
- nodules at site of administration at high dose
- no other clinically relevant toxicity
<PAGE>
PLANNED GLP TOXICOLOGY STUDIES
- Intramuscular/Subcutaneous Local Tolerance in Rabbits
- Pharmacokinetics in Rats
- Chronic Six Month Repeat-Dose Toxicology in Rats
- Genotoxicology
- Reproductive Toxicology
- Carcinogenicity
<PAGE>
GLP IM/SC LOCAL TOLERANCE IN RABBITS
PLANNED TO START MAY 97
- 3 male/female rabbits/group
- 2 mg/kg (60 ug/kg/day) given IM and SC
- Biopsy the site of administration at 3, 7, 14, 28 and 56 days
after administration
- Histopathology of administration site for local irritancy
<PAGE>
GLP PHARMACOKINETICS/BIODISTRIBUTION IN RATS
PLANNED TO START MAY, 1997 (INCLUDED IN IND AMENDMENT)
(14)
C-PPI-149 Rel-Ease-TM- single bolus IM 1.5mg/kg
- the plasma profile of free PPI-149 following a single IM injection
of liquid formulation compared with Rel-Ease-TM-
- pharmacokinetic parameters
(t AUC, etc.)
(1/2)
of the depot formulation
- biodistribution determined at 3,7 and 14 days
<PAGE>
REPEAT DOSE TOXICOLOGY STUDY IN RATS
PLANNED TO START MAY 1997 (ONE MONTH INCLUDED IN IND AMENDMENT)
Drug Substance: PPI-149 Depot
Doses: 10X, 30X, 100X the anticipated clinical dose
Schedule: Monthly for six months
Sacrifice Groups: 1 month (for IND amendment)
3 months (dose-range for the
carcinogenicity studies)*
6 months (chronic toxicology endpoint)
9 months (recovery of pharm response +
any toxicity)
Endpoints: Full anatomical, clinical path, hematology, clinical
chem, histopath; also, toxicokinetics
- - In order to initiate carcinogenicity studies within the timeline for
CAA submission, we have included a three-month sacrifice group as a
dose-ranging fror the rat carcinogenicity studies
<PAGE>
CARCINOGENICITY STUDY IN RATS
PLANNED TO START NOV 1997
DRUG SUBSTANCE: PPI-149 Depot
DOSES: to be determined from 3 month repeat dose sacrifice
SCHEDULE: Monthly for lifetime of animals
ENDPOINTS: Full anatomical clinical path, hematology, clinical
chem, histopath
<PAGE>
GENOTOXICITY STUDIES
PLANNED TO START 6/97
Bacterial Mutagenicity Ames Test, several point/frame shift mutations
Mammalian Mutagenicity Mouse lymphoma
Mouse micronucleus
<PAGE>
REPRODUCTIVE TOXICOLOGY STUDIES
PLANNED TO START MAR 1998
Segment 1 and 2: Fertility and Teratogenicity
Drug Substance: PPI-149 Depot
Doses: less than the efficaceous doses*
Schedule: Single bolus IM dose
Endpoints: Seg 1: Sperm count, testicular and ovarian morphology,
number of offspring
Seg 2: Demonstration of interruption of pregnancy and
determination of dose to induce "teratogenicity"
- - PPI-149 and Rel-Ease-TM- will be contraindicated in pregnancy; PRAECIS
anticipates that a clear demonstration of reduction of sperm count,
ovarian morphological alterations and "teratogenic" effects (due to
pharmacological response) be sufficient for NDA filing purposes for all
indications (see Lupron SBA).
<PAGE>
STUDIES TO SUPPORT SPECIFIC INDICATIONS
STUDY Metastatic PC Breast C Brachy IVF
PK/BIODIST. US/EU US/EU US/EU US/EU
CHRONIC (6 mo) TOX US/EU US/EU US/EU US/EU
GENETOX US/EU US/EU US/EU US/EU
REPROTOX EU EU US/EU US/EU
CARCINOGEN EU EU US/EU
<PAGE>
APPENDIX II
PATENT APPLICATIONS
LHRH Related Patents
<TABLE>
<CAPTION>
- -----------------------------------------------------------------------------------------------------------------
Type Serial Number Title and Inventors Status
US, CIP, (PPI Number)
PCT
- -----------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
US 08/480,94 LHRH Antagonist Peptides by Filed 6/7/95;
(PPI-007) Roger W. Roeske Pending
- -----------------------------------------------------------------------------------------------------------------
PCT PCT/US96/09852 LHRH Antagonist Peptides by Filed 6/7/96;
(PPI-007CPPC) Roger W. Roeske Pending
- -----------------------------------------------------------------------------------------------------------------
- -----------------------------------------------------------------------------------------------------------------
US 08/573,109 Methods for Treating Prostate Cancer Filed 12/15/95;
with LHRH Antagonists by Marc B. Pending
Garnick, Christopher J. Molineaux and
Malcolm L. Gefter
- -----------------------------------------------------------------------------------------------------------------
US, CIP of 08/755,593 Methods for Treating Prostate Cancer Filed 11/25/96;
08/573,109 (PPI-013CP) with LHRH Antagonists by Marc B. Pending
Garnick, Christopher J. Molineaux and
Malcolm L. Gefter
- -----------------------------------------------------------------------------------------------------------------
PCT PCT/US96/18911 Methods for Treating Prostate Cancer Filed 11/25/96;
(PPI-013CPPC) with LHRH Antagonists by Marc B. Pending
Garnick, Christopher J. Molineaux and
Malcolm L. Gefter
- -----------------------------------------------------------------------------------------------------------------
</TABLE>
<PAGE>
<TABLE>
- -----------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
US 08/762,747 Pharmaceutical Formulations for Sus- Filed **;
tained Drug Delivery by Malcom, L. Pending
Gefter, Nicholas Barker, Gary Musso and
Christopher J. Molineaux
- -----------------------------------------------------------------------------------------------------------------
</TABLE>
110
<PAGE>
APPENDIX III
IUF LICENSE AGREEMENT
See Exhibit 10.10 to
the Registration Statement
111
<PAGE>
APPENDIX IV
PPI-149 DEFINITION
PPI-149 shall mean a peptide compound having the following structure:
***
112
<PAGE>
APPENDIX V
TERRITORY
SECTION A
Europe, consisting of:
Austria Belgium Denmark Greece
Finland *France *Germany Luxembourg
Ireland *Italy Liechtenstein *Spain
Monaco Netherlands Norway Portugal
San Marino Sweden Switzerland *United Kingdom
Vatican Iceland
Andora
*Major European Territory Countries
SECTION B
Latin America, consisting of:
Belize Costa Rica Guatemala Honduras
Mexico Nicaragua Panama San Salvador
Argentina Bolivia Brazil Chile
Columbia Ecuador French Guyana Guyana
Paraguay Peru Uruguay Venezuela
Eastern Europe, consisting of:
Albania Armenia Azerbaijan Belarusse
Bosnia-Herzegovina Bulgaria Croatia Czech Republic
Estonia Georgia Hungary Kazakhstan
Kyrgyz Latvia Lithuania Macedonia
Moldova Poland Roumania Russia
Slovakia Slovenia Tadzhikistan Turkmenistan
Ukrainia Uzbekistan Yugoslavia
The following countries of Africa, consisting of:
Algeria Benin Burkina-Fasso Cameroun
Central African Republic Chad Congo Djibouti
Gabon Guinea Guinea Bissau Ivory Coast
Madagascar Mali Mauritania Morocco
Niger Rwanda Senegal Seychelles
Tunisia Zaire South Africa
Middle East, consisting of:
Iran Iraq Israel Jordan
Kuwait Lebanon Oman Saudi Arabia
South Yemen Syria Turkey Yemen
Cyprus United Arab Bahrain
Malta Emirates Qatar
113
<PAGE>
APPENDIX VI
ADDITIONAL SUPPLY PROVISIONS
114
<PAGE>
APPENDIX VI
Additional Supply Terms
MANUFACTURING AND PRODUCT QUALITY
1. Licensed Products shall be delivered as finished products according to the
specifications in the Registration Approval and any further specifications
agreed to by the parties. Finished products shall be deemed to mean powder
and diluent in separate closed sterile and unlabeled vials packed in an
appropriately labeled bulk shipment container as per section 3.15 PRAECIS
shall not be responsible for final commercial packaging and labeling.
PRAECIS shall ensure that unlabeled vials shall at all times, until final
packaging by Synthelabo, be traceable.
2. Synthelabo and PRAECIS shall collaborate in the definition of
specifications in the registration processes within the Territory.
3. Synthelabo agrees, where in the best interest of the Parties to diligently
seek to obtain approval by the appropriate regulatory authorities in the
respective Territory Countries, of the specifications of the Licensed
Product proposed by PRAECIS.
4. The following is a general description of the manufacturing operations for
Licensed Products:
o purchasing, reception, storage of raw materials and bulk packing
material of Licensed Products,
o manufacturing and bulk packaging of Licensed Products,
o control of raw material, bulk packaging material, in process control
and control of Licensed Products as defined in the Quality Charter,
o Packing and storage of bulk Licensed Product,
o Releasing of bulk Licensed Products
<PAGE>
o file maintenance and storage of batch records and samples for
analysis.
5. The place of manufacture of the Licensed Products shall be communicated to
Synthelabo at least 6 months in advance of anticipated commencement of
manufacture of Licensed Product for commercial sale.
6. The raw materials and bulk packaging materials shall be stored by PRAECIS
or its subcontractor under its sole responsibility.
7. PRAECIS is solely responsible for the safe storage of the bulk Licensed
Products until delivery.
8. PRAECIS covenants to store in appropriate conditions the raw materials,
packaging materials and finished Licensed Products, according to cGMP.
9. PRAECIS undertakes to manufacture and package the Licensed Products
according to good manufacturing practices reasonably acceptable in Europe
as well as in accordance with the process set out in the Quality Charter.
In the absence of specific guidelines in the Quality Charter PRAECIS shall
follow the current European Guide and in particular chapter 7 of such
Guide.
10. PRAECIS undertakes to control raw materials, packaging materials and
Licensed Products according to the techniques and instructions for
analysis set out in the Quality Charter.
11. Any dispute as to whether or not the procedure is being correctly followed
shall be resolved in accordance with the provisions of the Quality
Charter.
12. PRAECIS must ensure that its representative signing the Quality Charter
has the appropriate experience and holds the appropriate position in
PRAECIS's manufacturing unit.
13. Synthelabo or its representative has the right to verify at any time that
the manufacture of the Licensed Products is being carried out in the
proper manner. To this end PRAECIS agrees, upon reasonable advance notice
by Synthelabo, to allow Synthelabo or such designee to have access to the
manufacturing and control areas, to take samples and in general to inspect
the manufacturing operations during
<PAGE>
reasonable business hours provided any such inspection does not interrupt
or impair in any significant manner the manufacturing operations. Access
to certain areas, information and samples may be restricted to the extent
PRAECIS reasonably determines that such verification, access, sampling or
inspection would constitute a transfer of technology prior to the events
which would mandate such transfer as contemplated in 3.9.
14. Critical and major deficiencies raised during such audit or inspection
shall be promptly notified to PRAECIS.
15. PRAECIS will send to Synthelabo a timetable of the corrective actions
within a prompt and reasonable period following the receipt of the written
audit report.
16. The timetable for correction of deficiencies will be commensurate with
their criticality.
17. PRAECIS may only ship the Licensed Products to Synthelabo after such
products have been released by PRAECIS according to the procedure defined
in the Quality Charter.
18. PRAECIS shall provide Synthelabo with the necessary documents and samples
specified in the Quality Charter, and shall do so in accordance with the
conditions (time limit, nature of documents etc.) set out in such Quality
Charter.
19. PRAECIS undertakes to prepare records of all stages of manufacture and
quality control on the basis of the Quality Charter and to keep them for
at least 5 years unless otherwise stipulated.
20. Synthelabo reserves the right to reject any batch which does not conform
to the specifications in the Quality Charter. In this event, PRAECIS may
then recover at PRAECIS's expense the rejected products according to the
rework process as described in the Quality Charter.
21. In the event the parties agree in writing that a batch does not conform to
the specifications, PRAECIS shall at its own expense, within forty-five
(45) days of Synthelabo's rejection thereof, replace the defective batch.
22. In the event of a dispute as to the acceptance of a batch, the parties
agree to discuss the problem with a view to finding an amicable solution
to the extent that the dispute
<PAGE>
cannot be resolved amicably, the issue shall be referred to an independent
expert nominated by PRAECIS and to whom Synthelabo does not reasonably
object.
23. If the parties are not able to agree on an expert within two (2) months of
a party's objection thereto, an expert will be appointed by the President
of the Court of Arbitration of the ICC upon request by either one of the
parties.
24. The expert so appointed will determine whether the batch in question
conforms with the general standards and with the procedure for analytical
control set out in the Quality Charter, and whether the manufacturing
conditions have been properly followed, having particular regard to the
file provided by PRAECIS for each Licensed Product.
25. The parties agree to accept the findings and conclusion reached by the
expert. If the expert considers the Licensed Products to be clearly
defective, all his fees, expenses and the cost of destruction of Licensed
Products will be paid for by PRAECIS, which party shall also be bound to
reimburse whatever sums Synthelabo has already paid for the defective
batch.
26. If the expert considers the Licensed Products to be not defective, all
fees and expenses of the expert will be paid for by Synthelabo.
27. The Parties agree to develop and register rework processes and procedures.
In the event a defective batch can not be reworked and necessitates
destruction, all destruction shall be performed by PRAECIS. Following
destruction, PRAECIS will send to Synthelabo a certificate of destruction
indicating the following:
o name of the Licensed Products
o batch number
o quantity
o name of the company who has destroyed the Licensed Products
28. Each party agrees to make the relevant Authorities such declarations as
are necessary to comply with pharmaceutical law applicable to such party.
<PAGE>
29. Any term of this Agreement that does not comply with the law regulating
the pharmaceutical profession must be modified accordingly within the
shortest possible time.
Capitalized terms used but not defined in this Appendix VI shall have the
respective meaning ascribed thereto in the License Agreement dated as of May 13,
1997 (the "License Agreement") between PRAECIS and Synthelabo to which this
Appendix VI is attached
<PAGE>
[LOGO Synthelabo]
Mr. Marc SILVER
Vice President
Business Development
PRAECIS PHARMACEUTICALS, Inc.
One Hampshire Street
Cambridge
MA 02139
Etats-Unis
Le Plessis-Robinson, 31 July, 1997
Ref.: BJJ/fm - 231
Sent via telefax: 00.1.617.494.8414
Dear Marc,
I refer to the discussions and deliberations we have had over the past few weeks
relating to the contribution that SYNTHELABO is to make to the costs of the core
development studies for PPI-149 for the treatment of prostate cancer (which
includes all pre-clinical costs for all indications).
At the Steering Committee of 24 July, it was agreed that, notwithstanding any
other term of our license agreement, SYNTHELABO's total contribution to these
core development costs shall be limited to 30 million French francs paid as
follows: 5 million every six months commencing 1 September 1997 (to be paid
within 30 days of this date and within 30 days of every subsequent six months
period). This will be the maximum paid for this programme and includes the cost
of all pre-clinical (for all indications) and clinical studies for the treatment
of prostate cancer whether performed by PRAECIS, SYNTHELABO or contact research
organisations, total formulated drug costs, any CMC studies and internal costs
incurred by PRAECIS.
As I discussed with Malcolm Gefter, the above core development costs are the
costs of all the studies necessary to obtain a full NDA including the mandatory
phase IV studies if the first approval is conditional.
If you agree with the above, would you please arrange for PRAECIS to sign both
copies of this letter returning one copy for our files.
<PAGE>
Best regards, Agreed and accepted by
PRAECIS PHARMACEUTICALS, INC.
Name: Marc A. Silver
/s/ Bernard Jordan Signature: /s/ Marc A. Silver
B.J. JORDAN Date: September 5, 1997
Director of Licensing Department
<PAGE>
CONFIDENTIAL TREATMENT HAS BEEN REQUESTED FOR CERTAIN
PORTIONS OF THIS DOCUMENT. SUCH PORTIONS HAVE BEEN
REDACTED AND MARKED WITH ASTERISKS (**). THE NON-
REDACTED VERSION OF THIS DOCUMENT HAS BEEN SENT TO
THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO
AN APPLICATION FOR CONFIDENTIAL TREATMENT.
[PRAECIS LOGO]
MEMORANDUM
To: Bernard Jordan
From: Marc A. Silver
Vice President of Corporate Development
Re: Summary of Endometriosis Development Costs
Date: June 17th, 1999
Dear Bernard;
Due to the increase in the endometriosis budget beyond the original expectation
of both parties, and as an indication of its continued good faith, PRAECIS will
implement the following contract adjustment to provide Sanofi-Synthelabo (SS)
some financial relief.
1. To the degree endometriosis validation lots are eligible for
commercial sale, SS will receive a proportional credit towards
their future transfer price obligation. (thus, if SS pays $2MM
of the $8MM for validation lots and 20% of the material is
used for various development work, including manufacturing
site registration, then a total of $1.6MM would be creditable
towards future transfer prices with regards to endometriosis
products.)
2. In the case that endometriosis validation lots are paid for
but the product is not approved, then SS will receive a credit
or cash payment of 50% of its incurred expenses on validation
lots.
Since we need to draft a letter addressing the modification in the transfer
price per our earlier discussions, perhaps it would be most efficient to include
language on this matter as well. Call me with any questions.
Sincerely,
/s/ Marc A. Silver
- -------------------------------------
Marc A. Silver
Vice President, Corporate Development
cc: M. Gefter, T. English, K. McLaughlin, K. Coit
<PAGE>
[PPI LOGO]
MEMORANDUM
To: Bernard Jordan cc: K. McLaughlin, J. Swirski,
N. Barker, H. Tan, T. English
From: Marc A. Silver
Vice President of Corporate Development
Re: PPI-149 Agenda Items
Date: October 1st, 1998
Dear Bernard;
This letter summarizes our understanding of the three agenda items discussed by
phone Wednesday morning.
1. Cost of Goods
- Current invoice for clinical supplies: We understand that you
have no objection to these amounts but rather that the cost
per vial heightened your concerns with regards to future
commercial costs of goods. As we discussed these invoices
represent the costs associated with pre-commercial supplies
only and are significantly higher than those projected for
commercial supplies due to volume considerations and
unrealized yield improvement. If you require any additional
backup information for the invoice please let us know.
- More importantly, as you have correctly pointed out, with the
recent dosage adjustment to 100mg/vial, and under an
assumption of ***. Malcolm's proposal enables an overall
superior gross margin potential for Synthelabo (over *** %)
over a typical product life and reduces the risk of COGS
inflation/unpredictability to Synthelabo.
<PAGE>
- In scenarios where ASP is below $***/unit, PRAECIS will reduce
its transfer price per the table below.
<TABLE>
<CAPTION>
YEAR *** AND YEAR *** OF YEARS *** AND AFTER OF SYNTHELABO
SYNTHELABO COMMERCIALIZATION COMMERCIALIZATION
---------------------------- ---------------------------------
<S> <C> <C>
For ASP below $***/unit Transfer Price equals $*** Transfer Price equals $***
For ASP $*** - $*** Transfer Price equals the higher (to Transfer Price equals the higher (to
PRAECIS) of *** % of ASP or PRAECIS) of *** % of ASP or $
$*** ***
For ASP greater than $***/unit Current contract formula for transfer Current contract formula for transfer
price is in effect price is in effect
</TABLE>
2. Milestone Discussions
All three parties have agreed to move forward with the phase III
pivotal studies using the 100mg dosage form. As you and Patrick pointed
out, the milestone however would only fully attained upon receipt of "a
green light" from the FDA to proceed with the aforementioned Phase III
study.
3. Endometriosis
Our understanding is that Synthelabo will meet internally on this topic
in mid-October and render a decision shortly thereafter. I'm sure that
you're aware that PRAECIS is spending funds on this clinical
development program. Since the intent of our original discussions was
to have a side by side risk sharing approach we would appreciate your
attention to a timely response.
Bernard, I hope that both the intention and the mechanics of the proposed
arrangements are clear. Please call me if there are any questions.
Sincerely,
/s/ Marc A. Silver
- -------------------------------------
Marc A. Silver
Vice President, Corporate Development
<PAGE>
EXHIBIT 10.7
CONFIDENTIAL TREATMENT HAS BEEN REQUESTED FOR CERTAIN
PORTIONS OF THIS DOCUMENT. SUCH PORTIONS HAVE BEEN
REDACTED AND MARKED WITH ASTERISKS (***). THE NON-
REDACTED VERSION OF THIS DOCUMENT HAS BEEN SENT TO THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN
APPLICATION FOR CONFIDENTIAL TREATMENT
AMENDED AND RESTATED BINDING AGREEMENT IN PRINCIPLE
AMENDED AND RESTATED BINDING AGREEMENT IN PRINCIPLE, effective
as of March 8, 1999 (the "Signing Date"), by and between PRAECIS PHARMACEUTICALS
INCORPORATED, a Delaware corporation with its principal place of business at 1
Hampshire Street, Cambridge, Massachusetts 02139-1572 ("Praecis"), and Amgen
Inc., a Delaware corporation with its principal place of business at One Amgen
Center Drive, Thousand Oaks, California 91320-1789 ("Amgen").
WHEREAS, the parties desire to enter into a collaboration
respecting the research, development and commercialization of certain LHRH
antagonist compounds;
WHEREAS, the parties desire to enter into a legal and binding
agreement with respect to the terms and conditions under which Praecis and Amgen
are prepared to conduct such collaboration;
NOW, THEREFORE, in consideration of the representations,
warranties and covenants contained herein, and for other good and valuable
consideration, and intending to enter into a legal and binding agreement, the
parties hereby agree to the terms and conditions of this Binding Agreement in
Principle and the accompanying exhibits and schedules, all of which are
incorporated herein by reference.
IN WITNESS WHEREOF, duly authorized representatives of the
parties hereto have duly executed this Binding Agreement in Principle as of the
Signing Date.
PRAECIS PHARMACEUTICALS INCORPORATED
By /s/ Malcolm L. Gefter
-----------------------------------
Name: Malcolm L. Gefter, Ph.D.
Title: Chief Executive Officer and President
1
<PAGE>
AMGEN INC.
By /s/ Gordon M. Binder
--------------------------------
Name: Gordon M. Binder
Title: Chief Executive Officer
2
<PAGE>
1. PARTIES. Amgen Inc. ("Amgen") and PRAECIS PHARMACEUTICALS INCORPORATED
("Praecis").
2. COLLABORATION TECHNOLOGY. As used in this Binding Agreement in Principle,
"Collaboration Technology" means any and all proprietary data, information,
materials, know-how or intellectual property (including Patent Rights) to which
Praecis or its Affiliates now or hereafter has any right, title or interest
which Praecis is entitled to license or sublicense, relating to LHRH Antagonist
Compounds (in the case of any depot or other formulation, for use with LHRH
Antagonist Compounds only), including but not limited to the Praecis Patent
Rights set forth on Exhibit A attached hereto and incorporated herein. "LHRH
Antagonist Compounds" means compounds (including salts and prodrugs) which
exhibit Lutenizing Hormone Releasing Hormone (LHRH) antagonist activity,
including but not limited to the decapeptide known as Abarelix or PPI-149 and
further described in Exhibit B (hereinafter referred to as "Abarelix"), all
compounds included in the IUF License Agreement (including those identified in
Section 3.01(b) thereof) and any other technology owned or controlled by Praecis
which Praecis is entitled to license or sublicense and which is necessary or
useful to make, have made, use, sell, or offer to sell any compounds that
exhibit LHRH antagonist activity. For purposes hereof, "Collaboration
Technology" shall include all prodrugs and salts used in connection with
compounds that exhibit LHRH antagonist activity, regardless of whether or not
such prodrugs or salts exhibit such activity.
3. LICENSED PRODUCTS. As used in this Binding Agreement in Principle, "Licensed
Products" means all products described in, claimed in, incorporating or
containing Collaboration Technology. Licensed Products shall also include
Praecis Improvements.
4. FIELD OF USE. As used in this Binding Agreement in Principle, "Field of Use"
means all human therapeutic, prophylactic and diagnostic uses of Licensed
Products. The Field of Use shall not include Licensed Products for ***, provided
that Praecis shall not, without Amgen's prior written consent (not to be
unreasonably withheld), directly or indirectly transfer (other than by operation
of law), assign or sublicense any rights to make, have made, use, sell, offer to
sell, export and import Licensed Products for *** and may use such rights only
to commercialize Licensed Products that, in Amgen's reasonable determination,
would not adversely effect the commercialization of Licensed Products sold for
human therapeutic, prophylactic or diagnostic use.
5. LICENSE GRANT. Praecis grants to Amgen and its Affiliates an exclusive
license, with a right to sublicense, under the Collaboration Technology, to
make, have made, use, sell, offer to sell, export and import Licensed Products
in the Field of Use in the Licensed Territory. This license grant shall include,
but not be limited to, the grant of an exclusive sublicense in the Field of Use
in the Licensed Territory under any and all rights granted to Praecis under the
IUF License Agreement. Notwithstanding the foregoing, Amgen shall not sublicense
or otherwise assign or transfer (other than by operation of law) substantially
all of its rights to market and sell the Licensed Products in the United States
without the prior written consent of Praecis (not to be
3
<PAGE>
unreasonably withheld). Praecis will be considered by Amgen as a possible
sublicensee. Any sublicense by Amgen shall be consistent with the terms hereof
and the IUF License Agreement and shall contain all of the terms required by the
IUF License Agreement to be included in any sublicense. If IUF should object
that the IUF License Agreement does not entitle Amgen or its Affiliates to grant
any such sublicense to a third party, upon request by Amgen, Praecis will grant
such sublicense directly to such third party.
6. LICENSED TERRITORY. As used in this Binding Agreement in Principle, "Licensed
Territory" means each and every country of the world (except those set forth on
Exhibit C), including their respective territories and possessions, regardless
of any changes relating to such countries, territories and possessions after the
Signing Date. Amgen recognizes that it shall not be entitled to rights to any of
the countries, including their territories and possessions, listed on Exhibit C
regardless of any changes relating to such countries, territories or possessions
after the Signing Date.
7. MILESTONE PAYMENT. A single non-refundable milestone payment in the amount of
$15 MM will be payable by Amgen to Praecis one time and for one indication only,
regardless of the number of Licensed Products developed or the number of
indications approved. This milestone payment shall be due within 30 days
following NDA approval by the FDA of Abarelix in either the prostate cancer or
endometriosis indication, whichever is approved first.
8. INITIAL PAYMENT. Amgen shall pay to Praecis a non-refundable payment of $10
MM in respect of R&D expenses incurred by Praecis prior to January 1, 1999. This
payment shall be exclusive of, and in addition to, the payments set forth in
Section 14e).
9. TRANSFER PRICE AND ROYALTY IN THE UNITED STATES.
a) AMGEN FUNDING. Amgen will be responsible for funding in the amount
of $200 MM, to be paid in the form of : (1) the Initial Payment of $10 MM as set
forth in Section 8, (2) one Milestone Payment of $15 MM as set forth in Section
7, and (3) $175 MM total combined actual operating expenses (including R&D,
Sales and Marketing, G&A and other expenses and purchases of Licensed Product,
whether inventoried or expensed), to be spent in accordance with: (a) the Long
Range Plan attached hereto as Exhibit D (except to the extent modified by the
Annual Budgets), (b) the Development Plan attached hereto as Exhibit E (to the
extent expenses in the Development Plan are included in the R&D component of the
Annual Budgets) and (c) the sales and marketing plan, the costs of which are
reflected in the Long Range Plan (except to the extent modified by the Annual
Budgets). If the Amgen $175 million has not been expended by the time of the
launch of the first Licensed Product, then the balance of such $175 million
shall be expended by Amgen to pay operating expenses for the Licensed Product as
incurred.
b) LONG RANGE PLAN. The Long Range Plan shall serve as guidance for
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preparing annual budgets for the Licensed Products ("Annual Budgets"). The Long
Range Plan may be amended at any time with the mutual agreement of the parties.
*** The parties will agree on a new long range plan one year prior to expiration
of the Long Range Plan, provided that such new long range plan shall include the
following assumptions: annual Sales and Marketing expenses shall be *** , annual
G&A expenses shall be ***.
c) ANNUAL BUDGET. An Annual Budget will be established and determined
by mutual agreement prior to each year based upon the Long Range Plan. If the
parties are unable to agree on the Annual Budget, then the Annual Budget for
that year shall be determined as follows: Amgen shall reasonably and in good
faith determine the sales forecast; expenses shall be as set forth for that year
in the Long Range Plan, provided that with respect to each expense item, the
party with final decision making authority with respect to an expense item shall
have the authority ***. Except as otherwise provided herein, expenses may be
incurred outside the Annual Budget by either party but such expenses shall be
borne solely by the party incurring such expenses without compensation from the
other party. Once the Annual Budget has been determined, each expense category
in the Annual Budget may be ***. In addition, once the Annual Budget has been
determined, each expense category in the Annual Budget may be ***.
Notwithstanding any of the foregoing, annual G&A expenses shall ***, annual
Distribution costs shall ***. Within 20 days following the end of each quarter
the parties agree to report and perform a reconciliation of Actual Expenses
incurred during the prior quarter to the Annual Budget.
d) TRANSFER PRICE AND ROYALTY. Following Amgen's funding of $175 MM in
total combined Actual Expenses as set forth above, and until the beginning of
the calendar year following the first calendar year in which there are Actual
Profits, Amgen and Praecis will each be responsible for 50% of all Research and
Development costs, including the costs of any additional qualifying and
commercial lots of Licensed Products which may be required, if any, to be
reconciled and paid on a quarterly basis. In addition, following Amgen's funding
of $175 MM in total combined Actual Expenses as set forth above and until the
beginning of the calendar year following the first calendar year in which there
are Actual Profits, in recognition of the costs of establishing a sales and
marketing infrastructure for the Licensed Products, Praecis will be responsible
and agrees to reimburse Amgen, on a quarterly basis, for 50% of Amgen's Sales
and Marketing costs, with such amounts so owing by Praecis to be reflected in a
quarterly reconciliation. In addition and not in lieu of any amount to which
Praecis is entitled pursuant to the foregoing provisions of this Section 9(d),
Amgen shall pay Praecis a transfer price per unit of Licensed Product (the
"Transfer Price") based upon a) *** . After the Transfer Price Margin has been
established for a given calendar year it may be adjusted (but in no event to
less than zero) in respect of such calendar year as mutually agreed by the
parties or by Amgen to reflect the occurrence of a material external medical,
scientific, legal or commercial event or events beyond the control of either
party. A payment equal to the Transfer Price multiplied by the number of units
of Licensed Product supplied by Praecis (or its Affiliates or sublicensees) and
received by Amgen (or its Affiliates or sublicensees)
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shall be paid by Amgen (or its Affiliates) to Praecis (or its Affiliates) within
30 days following the date invoiced by Praecis. Not later than 30 days after the
end of each calendar quarter, Amgen shall provide Praecis with a statement of
the Cumulative Adjusted Profits through such quarter and pay a royalty to
Praecis, if any is due. The royalty, if any, shall be equal to: *** Beginning
the calendar year following the first calendar year in which there are Actual
Profits, in the event the *** . Development cost payments by Synthelabo to
Praecis pursuant to the Synthelabo Agreement for indications other than prostate
cancer and endometriosis shall be shared equally by Praecis and Amgen.
e) LINE OF CREDIT. In the years 2000-2002, Amgen shall extend to
Praecis a line of credit not to exceed $150 MM. The line of credit will bear
interest at the prime rate as quoted in The Wall Street Journal plus *** per
annum, shall be secured by a security interest in all amounts receivable by
Praecis arising from the Collaboration Technology, including without limitation
pursuant to the Synthelabo Agreement (as well as a right of offset against
amounts payable to Praecis hereunder in the event of Praecis' default in
repayment when due) and the principal and interest of which shall be repaid
according to the schedule set forth in Exhibit F. Amounts outstanding under the
line of credit may be prepaid at any time without premium or penalty.
The line of credit shall be made available by Amgen only upon the satisfaction
of all of the following conditions (which conditions shall also apply with
respect to each drawdown):
a) The NDA for Abarelix for the treatment of prostate cancer is approved
and Abarelix is being commercially sold and such approval remains in
effect;
b) The loan can reasonably be expected to be repaid from the Transfer
Price Margin and royalties resulting from Licensed Product sales;
c) ***
d) Documentation reasonably satisfactory to Amgen (it being understood
that such documentation shall not include any operating or financial
covenants).
Notwithstanding the foregoing, conditions a) and b) shall not apply with respect
to the availability of the line of credit, or to drawdowns thereunder, for the
years 2000 and 2001 and the first $10 million of drawdowns in 2002. Praecis must
demonstrate a cash flow need reasonably acceptable to Amgen for each drawdown in
2002. Drawdowns on the line of credit may be made on a quarterly basis. The
maximum aggregate drawdown under the line of credit in each specified year shall
be up to the following amounts:
<TABLE>
<CAPTION>
Maximum Aggregate
Year Drawdown
<S> <C>
2000 $ 25 million
2001 $ 75 million
2002 the balance of the $150 million line of credit
remaining after all previous drawdowns
</TABLE>
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<PAGE>
The parties agree to discuss in good faith adjustments to the years of
availability and limitations on annual drawdowns based on changes in facts
and circumstances.
10. ROYALTY IN OTHER COUNTRIES IN THE LICENSED TERRITORY. In countries in
the Licensed Territory other than the United States, royalties will be
payable quarterly as follows:
a) ***
- *** of Net Sales of a Licensed Product
b) ***
- *** of Net Sales of a Licensed Product
c) ***
- *** of Net Sales of a Licensed Product
All the above royalties may be reduced on a country by country basis as follows,
provided that in no event will royalties in any country be reduced by more than
***%:
***
11. AUDIT RIGHTS. Each party agrees that the other party shall have reasonable
audit rights during reasonable times to confirm Net Sales in countries in the
Licensed Territory outside the United States, and in the United States to
confirm Net Sales, external expenses, and FTEs for internal expenses with
respect to Section 9. Such audit shall be performed not more than once per year.
Such audit shall be performed by the inquiring party's auditors and at the cost
of the inquiring party. If such audit discloses an underpayment, the party being
audited shall promptly pay the inquiring party unless the party being audited
disputes such amount in good faith. If such audit reveals an underpayment for
the year of *** or more, then the party being audited shall reimburse the
inquiring party for the reasonable costs of the audit.
12. IUF LICENSE AGREEMENT AND ROYALTY. Praecis shall be solely responsible for
the payment of all royalties or other payments due under the IUF License
Agreement. If:
(1) Praecis shall fail to make any such payments to IUF within 60
days after due; or
(2) the IUF License Agreement shall be terminated and the
sublicense thereunder to Amgen (as contained in this Binding
Agreement in Principle) shall survive; or
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(3) Praecis enters into an arrangement of creditors and/or
bankruptcy (in which case Praecis shall be obligated to give
Amgen one week prior written notice thereof),
then Amgen may (in the event of (1)) and shall (in the event of (2) and (3)),
make all payments due to IUF under the IUF License Agreement with respect to
sales of Licensed Product by Amgen in the Licensed Territory and Amgen shall
deduct the full amount of any such payments actually made by Amgen from any
amounts payable to Praecis hereunder.
The sublicense under the IUF License Agreement contained in this Binding
Agree-ment in Principle shall survive termination of the IUF License Agreement.
Praecis will not during the Term take any actions to terminate or restrict its
rights under the IUF License Agreement and will discharge all of its obligations
thereunder. Praecis will promptly notify Amgen in writing if (1) IUF notifies
Praecis that a breach of the IUF Agreement has occurred, and, to the extent
known by Praecis, Praecis shall further notify Amgen as to when such breach has
been or is intended to be cured; (2) Praecis notifies IUF that a breach of the
IUF Agreement has occurred, and Praecis will notify Amgen as to when such breach
has been or is intended to be cured; or (3) the rights to Praecis under the IUF
Agreement are converted, or IUF intends to convert such rights, from exclusive
to non-exclusive.
Amgen hereby grants to Praecis, for further grant to IUF, a royalty-free,
nonexclusive, non-transferable license, to use for research and educational
purposes only, and without the right to sublicense, any and all Improvements
owned or controlled by Amgen.
Not later than 90 days following the Signing Date, Praecis agrees to use all
reasonable efforts to obtain agreement with IUF that: (a) sections 5.01 (Market
Development) and 5.02 (Performance Standards) of the IUF License Agreement are
satisfied by Commercially Reasonable Efforts hereunder; (b) Amgen shall have the
first right, followed by Praecis, and then by IUF to carry out the patent
prosecution activities set forth in sections 10.01 and 10.02 of the IUF License
Agreement, with respect to Collaboration Patents, (c) section 12.05 of the IUF
License Agreement shall be amended so that in the event the license from IUF to
Praecis terminates, the sublicense to Amgen granted hereunder shall survive and
Amgen shall assume all rights and obligations of Praecis with respect to the IUF
License Agreement and (d) the sublicense to the IUF License granted to Amgen
hereunder is a valid sublicense under the IUF License Agreement.
13. TERM OF AMGEN PAYMENT OBLIGATIONS. Amgen's payment obligations hereunder
will be payable on a country by country basis: *** on a Patented Product until
the last to expire of the patents covering such Patented Product and ***.
Thereafter, Amgen shall have a paid up, consideration free, perpetual license to
make, have made, use, sell, offer to sell, export and import Licensed Products
in such country.
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<PAGE>
14. RESEARCH, DEVELOPMENT AND REGULATORY.
a) DEVELOPMENT PLAN FOR U.S. The parties have agreed to the Development
Plan attached hereto as Exhibit E, which shall determine development activities
to be undertaken in the United States States (to the extent expenses in the
Development Plan are included in the R&D component of the Annual Budget). It is
anticipated that the Development Plan will need to be modified based upon the
results of clinical trials and other unanticipated events and any such
modifications may affect, among other things, the R&D and Sales & Marketing
budgets, actual R&D, Sales and Marketing and other expenditures. Either party
may perform clinical studies outside the Development Plan at its own expense,
provided that if any such study is to be undertaken by the party that does not
have final decision making authority as provided in subsection c) below, then
such study shall take place only after obtaining the prior consent of the party
with final decision making authority. Notwithstanding anything to the contrary
contained in this Binding Agreement in Principle, Praecis shall obtain Amgen's
prior approval of any studies Praecis approves for the Licensed Territory at the
Praecis/Synthelabo Joint Steering Committee.
b) COMMITTEE. A product development and commercialization committee
shall be established to discuss and coordinate the information and data
necessary to obtain and maintain approval of the Licensed Products in the Field
of Use in the Licensed Territory, formulate the strategies and plans to most
effectively and efficiently obtain such approvals and to prepare plans to
commercialize the Licensed Products (including sales and marketing) in the Field
of Use in the United States. The committee shall be comprised of an equal number
of representatives from each company, consisting of a project team leader from
each company and other representatives appointed by each company. The committee
shall meet quarterly (either in person, by telephone or videoconference) to
review the progress and status of development and commercialization of Licensed
Products in the Field of Use in the Licensed Territory. In the event that the
committee is unable to reach a consensus decision on any issue, then the
committee representatives of either party may bring such matter to the attention
of senior management of the respective parties, following which either party's
senior management may contact the other party's senior management. The party
with the final decision making authority with respect to the subject matter of
such issue shall be entitled to make the final determination. The Annual Budget
will be prepared by the committee and submitted to senior management of both
companies for decision pursuant to Section 9.
c) GOVERNANCE: RESEARCH, DEVELOPMENT AND REGULATORY.
- UNITED STATES
(i) PROSTATE CANCER. Praecis will have final decision making
authority (subject to the R&D component of the Annual Budget (the "R&D Budget"))
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<PAGE>
over all research, development and regulatory matters for all Licensed Products
for the prostate cancer indication prior to the earlier of: a) NDA approval of
the first indication for the first Licensed Product or b) Amgen's completion of
its $175 MM funding obligation, or c) January 1, 2002. Following the earlier of
the occurrence of either a), b) or c) in the preceding sentence, Amgen will have
final decision making authority (within the R&D Budget) for all research,
development and regulatory matters for all Licensed Products in the prostate
cancer indication.
(ii) ENDOMETRIOSIS. Praecis will have final decision making
authority (subject to the R&D Budget) over all research, development and
regulatory matters for all Licensed Products for the endometriosis indication
prior to the earlier of: a) the decision of both parties in writing to start the
first Pivotal Trial for such indication (or the second Pivotal Trial for such
indication if the study 149-98-05, part B is modified and becomes the first
Pivotal Trial) or b) three months after the completion of the treatment period
of the last patient on the study 149-98-05 part B or its modification into a
Phase 3 study or c) upon NDA approval of the first indication for the first
Licensed Product (provided that Praecis shall, if applicable, retain
responsibility for completion of a first Pivotal Trial resulting from the
modification of study 149-98-05, part B) or d) September 1, 2000. Following the
occurrence of the earlier of: a), b), c) or d) in the preceding sentence, Amgen
will have final decision making authority (within the R&D Budget) over all
research, development and regulatory matters for all Licensed Products in the
endometriosis indication. Amgen shall submit a transition plan to Praecis for
possible transition earlier than contemplated in a), b), c) or d), which shall
be considered by Praecis in good faith.
(iii) ALL OTHER INDICATIONS. Amgen will have final decision
making authority (subject to the R&D Budget) over all research, development and
regulatory matters for all Licensed Products for all other indications.
- OTHER COUNTRIES IN THE LICENSED TERRITORY.
(i) Amgen will have final decision making authority over all
research, development and regulatory matters for Licensed Products in the Field
of Use in the Licensed Territory for all indications; provided that with respect
to any clinical trial that will be submitted as part of a United States IND for
prostate or endometriosis, then Praecis shall have the final decision making
authority during the time period during which it has final decision making
authority under subsections c)i) or c)ii) above.
d) OWNERSHIP OF REGULATORY FILINGS AND LICENSES. Initially Praecis
shall file and be the owner and party of record sponsoring all regulatory
filings (INDs, PLAs, BLAs, ELAs and NDAs or other equivalent filings) and
product licenses with respect to Licensed Products for all indications in the
Field of Use in the United States. Such ownership and control shall be
immediately transferred and assigned to Amgen upon the earlier of (1) NDA
approval of the first indication for any Licensed Product in the
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<PAGE>
United States, (2) Amgen's completion of its $175 MM funding obligation or (3)
September 1, 2000. Amgen will file INDs for all indications other than prostate
and endometriosis and Praecis shall permit Amgen to cross reference Praecis'
INDs as necessary consistent with final decision making authority in subsection
c) above. Each party shall inform, cooperate with and assist the other with
respect to all material communications to or from regulatory authorities and
both parties shall have the right to attend all FDA meetings and participate in
all telephone calls with the FDA. Amgen and Praecis will have equal and complete
access to the ongoing clinical trial databases for prostate cancer and
endometriosis. For each clinical trial the parties will establish a
corresponding master database for the data. When Amgen obtains final decision
making authority, master databases shall be transferred by Praecis to Amgen.
Outside the United States, Amgen shall have ownership and control of all
regulatory filings and licenses in the Licensed Territory.
e) RESEARCH, DEVELOPMENT AND OTHER OPERATING COSTS. Amgen will conduct
and pay for all research and development activities in countries in the Licensed
Territory outside the U.S. In the U.S., research and development costs shall be
within the R&D Budget. As part of the $175 million total combined expenses to be
paid by Amgen as described in Section 9, Amgen will pay to Praecis up to a total
of approximately $100 million, which shall include research and development to
be performed or contracted for by Praecis in accordance with the Development
Plan, payable to Praecis as follows:
$12.5 million on March 30, 1999
$6.25 million on June 30, 1999, 2000
$6.25 million on July 30, 1999, 2000
$6.25 million on September 30, 1999, 2000
$6.25 million on October 30, 1999, 2000
$6.25 million on December 31, 1999, 2000
$6.25 million on January 30, 2000, 2001
$6.25 million on March 30, 2000
$6.25 million on April 30, 2000
These payments are intended to cover estimated research and development expenses
to be expended pursuant to the Development Plan within the R&D Budget and other
operating expenses within the Annual Budget for such 8 quarters. These payments
shall be reconciled on a quarterly basis not later than 30 days after the end of
each quarter against actual external and internal expenses. Amounts paid but not
expended in such quarter or expended but not previously paid by Amgen in
accordance with this Section 14(e), as reflected in such reconciliation, shall
reduce or increase the next payment due.
f) SYNTHELABO. Praecis will use reasonable efforts to have both it and
Amgen meet with Synthelabo to coordinate worldwide clinical trial activities and
the provision of safety data.
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<PAGE>
g) DILIGENCE. The parties will use Commercially Reasonable Efforts to
develop Licensed Products in the Licensed Territory.
15. MANUFACTURING.
a) SUPPLY OF COMMERCIAL PRODUCT BY PRAECIS. Praecis shall use
Commercially Reasonable Efforts to supply Amgen with all of its requirements for
the Licensed Products for all countries in the Licensed Territory and all
indications. Praecis will provide such supply within, and have final decision
making authority with respect to, the COGS budget included in the Annual Budget
as provided in Section 9. Praecis shall supply the Licensed Products in "nude"
form (formulated and filled but unlabeled and unpackaged) and Amgen shall label
and package and release all lots. Amgen's costs for these activities shall
include QA/QC (Quality Assurance/Quality Control) and will be included in COGS
following launch of the first Licensed Product. To the extent permitted by
regulatory authorities, Praecis may subcontract the manufacture of all or any
part of the manufacturing process to any third party approved by Amgen (such
consent not to be unreasonably withheld and not to be required for any Praecis
contracts in effect as of the Signing Date). Praecis shall not extend existing
supply contracts or enter into new supply contracts without Amgen's prior
consent (not to be unreasonably withheld). If Amgen grants its consent, Praecis
may, to the extent permitted by law, regulation and regulatory authorities,
enter into new contractual arrangements with any such third party, provided that
(1) each such third party and Praecis shall be bound by the obligations of
Praecis to Amgen hereunder relating to manufacturing, (2) each such third party
passes Amgen's quality audits and (3) each such third party agrees to adhere to
the Amgen quality policy relating to third party contract manufacturers. During
the 120-day period following the Signing Date, Praecis shall use commercially
reasonable efforts (which shall not include payment by Praecis of any
significant additional consideration) to cause its existing third party contract
manufacturers to amend existing contracts with Praecis to provide for the
foregoing. The Licensed Products shall be manufactured in accordance with
mutually agreed specifications and in accordance with current Good Manufacturing
Practices in a manufacturing facility registered with and approved for such
purpose with the FDA. Amgen shall have the right to inspect and audit any
parties involved in the manufacturing process and have its representatives be
present at manufacturing facilities. Amgen shall have the right to ensure that
raw material suppliers maintain compliance with current Good Manufacturing
Practices, including having one or more Amgen employee in each supplier facility
during all hours of operation. Praecis shall provide a certificate of analysis
for all nude Licensed Products supplied to Amgen. Shelf life of Licensed Product
supplied shall be mutually agreed. Amgen will accept risk of loss for Licensed
Products following receipt of delivery from Praecis. Praecis shall supply
Licensed Products for clinical trials in the Licensed Territory at its cost, as
provided in the Annual Budget.
b) GOVERNANCE. Amgen shall have final decision making authority to
fulfill its regulatory responsibilities over all steps of the manufacturing
process (including bulk, finish and fill, labeling and packaging, lot release
and management of subcontractors).
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Notwithstanding the foregoing, if a Licensed Product incorporates Praecis'
proprietary depot formulation as currently anticipated, Praecis shall have final
decision making authority (within the COGS category of the Annual Budget) over
matters relating solely to such depot formulation, to the extent permitted by
regulatory authorities and subject to Amgen having sufficient knowledge of the
formulation process to satisfy itself that such formulation process is in
compliance with current Good Manufacturing Practices and that there is an
ability to perform suitable lot release assays. In order to help preserve the
proprietary nature of such formulation, to the extent permitted by regulatory
authorities, Praecis will file a drug master file with the FDA (or other
regulatory authorities) to make the information regarding such formulation
available directly to the FDA (or other regulatory authorities) and Praecis will
deal directly with the FDA (or other regulatory authorities) on all matters
relating solely to such depot formulation.
c) SUPPLY PROBLEM. If Praecis (or any subcontractor) shall fail to
materially comply with its supply obligations hereunder, then Praecis shall
provide to Amgen manufacturing protocols and other manufacturing know-how and
information (all of which shall be considered Confidential Information) in order
that Amgen may supply the Licensed Products itself or though third parties and
the Transfer Price shall be adjusted to reflect the COGS no longer borne by
Praecis provided Amgen assumes Praecis' rights and obligations under then
existing supply agreements to the extent such rights and obligations are
assignable.
d) AMGEN OPTIONS. Amgen shall have options to supply bulk Licensed
Product and/or perform finish and fill services on substantially equivalent
terms as Praecis or any third party contract manufacturer, considering economic
(maximizing profits), timing and quality considerations. These options may be
exercised by Amgen at any time by providing Praecis with not less than 90 days
prior written notice. The exercise of these options by Amgen shall not cause
Praecis to breach its then existing supply contracts and if such exercise would
cause a breach, Amgen and Praecis shall work together in good faith to, if
possible, enable Amgen to perform the function for which it has exercised its
option.
e) NEW FORMULATIONS. Either party may develop a new formulation for a
Licensed Product outside the R&D Budget and if either party develops such new
formulation, then it may offer it to the other party for inclusion in Licensed
Products. If so offered and the offer is accepted, the payment obligations
hereunder will be adjusted accordingly to reflect the terms agreed by the
parties with respect to such new formulation.
f) SUPPLY TRANSITION. Upon Amgen's written notice to Praecis, not later
than June 30, 2000 (or such later date specified by Amgen, but in any event no
later than January 1, 2002, whether or not such notice has been given) all
supply rights and responsibilities (including all of Praecis' rights and
obligations under then existing supply agreements to the extent assignable under
such agreements) shall transition to Amgen except with respect to the depot
formulation; provided that Amgen shall provide such written notice no less than
45 days prior to the specified date of transition. Therefore, following such
transition, to the extent that any of the provisions
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<PAGE>
in this Section 15 are no longer applicable to Praecis because of such
transition, such provisions shall no longer have any force and effect (it being
understood that in any event the provision in the second sentence of the last
paragraph of Section 10 shall continue in effect).
16. COMMERCIALIZATION. Amgen will make all decisions regarding the
commercialization and sales and marketing of Licensed Products for all countries
in the Licensed Territory and indications, including but not limited to
determination of prices, sales and distribution, packaging, labeling, language
to be included in the package insert with the FDA, detailing and selection and
registration of generic names (i.e. provided by USAN) and trademarks.
Notwithstanding the foregoing, Praecis has submitted to USAN an application to
use abarelix as the generic name and Amgen will diligently pursue the complete
registration of abarelix as the generic name for Abarelix. Amgen will use
Commercially Reasonable Efforts to market and sell Licensed Products in the
Licensed Territory. To the extent permitted by law, regulation or regulatory
authorities, Praecis' logo shall be included on promotional materials and
displayed with reasonable prominence. In order to satisfy Praecis' desire for
access to patients and physicians, Praecis may, to the extent permitted by
applicable laws and regulations and under the guidance and management of Amgen,
co-sponsor with Amgen conferences or seminars in the United States chosen by
Amgen to target urologists. Praecis may co-promote in the United States a
Licensed Product in mutually agreed indication(s) any time after *** full years
following launch of a Licensed Product, and upon satisfaction of the following
conditions: a) annual Net Sales of Licensed Products in the United States of
greater than *** and b) the parties mutually agree that such co-promotion
efforts will increase the profitability of Licensed Products. Co-promotion by
Praecis will be limited to Praecis field sales force representatives double
calling with Amgen's field sales force representatives on urologists' offices.
Praecis sales representatives will not call on national accounts. Co-promotion
by Praecis will be in accordance with Amgen's sales and marketing plan, under
Amgen's training and management and using Amgen's field sales materials. Praecis
will be entitled to have a maximum of *** field sales force representatives. The
fully loaded cost of the Praecis sales force representatives (calculated at the
same rate as the Amgen sales force representatives) shall be included as
expenses in the Annual Budget.
17. INTELLECTUAL PROPERTY.
a) EX PARTE PATENT PROSECUTION. At Amgen's direction, outside counsel
which is mutually acceptable to Amgen and Praecis will conduct ex parte patent
prosecution of Patent Rights having at least one Praecis or IUF inventor (as
determined under U.S. Patent law) included within Collaboration Technology
("Collaboration Patents") in the Licensed Territory, with consideration given to
Praecis' input. In the event Amgen elects not to pursue any Collaboration
Patents having at least one Amgen inventor (as determined under U.S. Patent
Law), Amgen shall give Praecis the opportunity to do so at Praecis' cost (which
shall not be included as an expense of Praecis in determining profits/losses),
in which event, Praecis will own any patents issuing thereon.
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b) INTER PARTES PATENT PROSECUTION. Amgen shall have the right but not
the obligation to conduct inter partes proceedings relating to all Patent Rights
included within Collaboration Technology (including interferences and
oppositions), in the Licensed Territory, with consideration given to Praecis'
input.
c) ENFORCEMENT OF PATENT RIGHTS. Amgen shall have the right but not the
obligation to enforce all Patent Rights included within the Collaboration
Technology against any third party suspected of infringing a claim of a Patent
Right included in Collaboration Technology, in the Licensed Territory, with
consideration given to Praecis' input.
d) INFRINGEMENT DEFENSE. Amgen shall have the right, but not the
obligation, to defend and control any suit alleging infringement of any patent
or other intellectual property right of a third party arising out of the
manufacture, use, sale, offer to sell, export or import of a Licensed Product by
Amgen or its sublicensees, in the Licensed Territory, with consideration given
to Praecis' input.
e) EXPENSES. Unless otherwise provided above, the expenses incurred by
a party in pursuing any of the above activities relating to Patent Rights or any
trademark filings, prosecution, enforcement or infringement defense ***.
f) COOPERATION BETWEEN THE PARTIES. Amgen and Praecis agree to
cooperate with each other and to use all reasonable efforts to ensure the
cooperation of any of their respective personnel and licensee(s) or licensor(s)
as might reasonably be requested in any of the above matters.
18. TERM; TERMINATION.
a) TERM. This Binding Agreement in Principle shall become effective as
of the Signing Date. Unless terminated earlier pursuant to the terms of this
Section 18, this Binding Agreement in Principle will continue in full force and
effect until the last to expire of the Patent Rights included in Collaboration
Technology. Following such expiration, Amgen shall have a fully paid up,
compensation free, perpetual, exclusive license, with a right to sublicense,
under the Collaboration Technology, to make, have made, use, sell, offer to
sell, export and import Licensed Products in the Field of Use in the Licensed
Territory.
b) TERMINATION BY AMGEN.
(i) TERMINATION FOR MATERIAL ADVERSE CLINICAL DEVELOPMENT. If
the results of any clinical trials of the Licensed Products constitute a
material adverse change in the commercial prospects of the Licensed Products,
then Amgen may terminate this Binding Agreement in Principle anytime within 30
days following its receipt of such clinical trial data.
15
<PAGE>
(ii) TERMINATION FOR CONVENIENCE. Amgen may terminate this
Binding Agreement in Principle by giving Praecis 90 days prior written notice,
and in such event this Binding Agreement in Principle shall be terminated at the
end of such 90 day period, provided that in the event of such termination, the
parties shall wind up clinical trials, sales and marketing activities and other
affairs hereunder in a timely, reasonable and businesslike manner, not to exceed
a period of *** months after the end of such ninety-day period. During such ***
month period, each party shall be responsible for winding up its own such
trials, activities and other affairs at its own expense and Amgen shall provide
for an orderly and businesslike transfer of the business to Praecis, including
assigning (to the extent permitted by law) all regulatory filings, regulatory
approvals and clinical data relating to Licensed Products.
(iii) Loan. If Amgen terminates this Binding Agreement in
Principle pursuant to b)(i) or b)(ii) above prior to NDA approval of Abarelix
for the treatment of prostate cancer and such NDA is subsequently approved prior
to January 1, 2002, Amgen shall make available to Praecis a loan in the amount
of $60 million (to be used exclusively to finance the launch of Abarelix in the
U.S.) bearing interest at 15% per annum, secured by a security interest in all
amounts received by Praecis arising from the Collaboration Technology (as well
as a right of offset against amounts payable to Praecis hereunder in the event
of Praecis' default in repayment when due), including without limitation
pursuant to the Synthelabo Agreement, with principal and interest to be repaid
within three years and upon commercial terms to be agreed, if all of the
following conditions exist:
a. The loan can reasonably be expected to be repaid from Abarelix
sales within three years;
b. Praecis is a public company as the result of an initial public
offering;
c. Praecis launches and sells the product on its own in the
United States (no co-promotion, licensing or other arrangement
with any third party);
d. The loan will be convertible into Praecis stock at the market
price existing on the date of issuance;
e. The loan is requested in writing no later than 30 days
following approval of the NDA;
f. Documentation reasonably satisfactory to Amgen (it being
understood that such documentation shall not include any
operating or financial covenants).
(iv) TERMINATION PURSUANT TO SECTION 20(C). Amgen may
terminate this Binding Agreement in Principle upon the terms and subject to the
conditions set forth in Section 20(c) hereof.
c) TERMINATION FOR DEFAULT.
(i) AMGEN DEFAULT. Upon any Default by Amgen hereunder, if
Praecis notifies Amgen of such Default and Amgen shall not have cured such
Default within 60 days, Praecis may terminate this Binding Agreement in
Principle.
16
<PAGE>
(ii) PRAECIS DEFAULT. Upon any Default by Praecis hereunder,
if Amgen notifies Praecis of such Default and Praecis shall not have cured the
Default within 60 days, Amgen may: (1) terminate this Binding Agreement in
Principle in whole or on a country by country basis, (2) terminate Praecis'
manufacturing rights and *** (in which case Amgen shall assume all of Praecis'
rights and obligations under then existing supply agreements to the extent such
rights and obligations are assignable) and/or terminate any or all of Praecis'
rights hereunder (other than rights to receive payments) and/or (3) deduct from
the profits/losses and royalties payable to Praecis any costs, liabilities,
damages***, or (4) terminate this Binding Agreement in Principle and retain all
licenses to Collaboration Technology granted hereunder, subject to continued
payment to Praecis of all payments payable hereunder.
d) BANKRUPTCY OR ACQUISITION. In the event Praecis shall declare or be
declared bankrupt, or upon the acquisition (directly or indirectly, by any third
party of 50% or more of the shares of capital stock) of Praecis by a third
party, Amgen may: (1) terminate this Agreement in whole or in part on a country
by country basis; or (2) terminate Praecis' manufacturing rights and ***(in
which case Amgen shall assume all of Praecis' rights and obligations under then
existing supply agreements to the extent such rights and obligations are
assignable) *** (other than rights to receive payments due hereunder), subject
to continued payment to Praecis of all payments payable by Amgen hereunder.
Notwithstanding the foregoing, in the case of an acquisition of Praecis by a
third party, Amgen shall not have the right set forth in (1) above. Any
termination under this subsection d) shall be made in an orderly and
businesslike manner.
e) INJUNCTION. This Binding Agreement in Principle will terminate
automatically in the event a final nonappealable order of any court or other
governmental body of competent jurisdiction shall have been issued prohibiting,
restraining or enjoining the transactions contemplated by this Binding Agreement
in Principle and all appeals or rights of appeal shall have been exhausted.
f) EFFECT OF TERMINATION. Upon termination of this Binding Agreement in
Principle in accordance with this Section 18, (i) except as otherwise provided
in Section 18(c)(ii) or Section 18(d), all licenses granted to Amgen hereunder
shall revert to Praecis and in such event Amgen shall assign (to the extent
permitted by law) to Praecis all regulatory filings, regulatory approvals,
clinical data and trademarks (including without limitation, trademarks owned by
Amgen) relating to Licensed Products, (ii) each party shall be responsible for
obligations of such party which accrued prior to such termination and (iii) each
party shall be liable for any breach by such party of this Binding Agreement in
Principle prior to such termination, except that if such termination is pursuant
to Section 18 b) iv), neither Praecis nor Amgen shall have liability for any
breach by it of any representation or warranty contained herein.
g) NO CONSEQUENTIAL DAMAGES. Neither party will be liable for
consequential
17
<PAGE>
damages incurred by the other party arising out of any breach of this Binding
Agreement in Principle.
19. INDEMNIFICATION. Amgen will indemnify Praecis and hold Praecis harmless from
all liability, loss, damage and cost arising out of (i) any claims of any nature
(other than claims by third parties relating to patent infringement) arising out
of the research, development, manufacturing, marketing and/or sale of Licensed
Products by, on behalf of or under authority of, Amgen and/or (ii) any
representation or warranty by Amgen set forth herein being untrue in any
material respect when made or failure by Amgen to perform any of its obligations
hereunder. Praecis will indemnify Amgen and hold Amgen harmless from all
liability, loss, damage and cost arising out of (i) any claims of any nature
(other than claims by third parties relating to patent infringement) arising out
of the research, development, manufacturing or promotion of Licensed Products
by, on behalf of or under authority of (other than Amgen, its Affiliates, or
sublicensees), Praecis and/or (ii) any representation or warranty of Praecis set
forth herein (subject to the first sentence of Section 20(c)) having been untrue
in any material respect when made or failure by Praecis to perform any of its
obligations hereunder. Each party will notify the other in the event it becomes
aware of a claim for which indemnification may be sought hereunder. For purposes
hereof, manufacturing and other activities or obligations to be performed or
provided by Praecis shall not be considered to be performed or provided on
behalf of, or under authority of, Amgen, its Affiliates or sublicensees.
20. REPRESENTATIONS AND WARRANTIES.
a) MUTUAL. Each of Praecis and Amgen represents and warrants to the
other that as of the Signing Date: i) it is duly incorporated, validly existing
and in good standing in its respective state of incorporation, ii) it has the
corporate power and authority to execute, deliver and perform this Binding
Agreement in Principle and its obligations hereunder, iii) this Binding
Agreement in Principle is a valid and binding obligation of such party,
enforceable against such party in accordance with its terms, except as such
enforceability may be limited by laws affecting creditors rights generally or by
the principles governing the availability of equitable remedies, iv) Praecis'
other material contractual obligations do not (1) materially impair the
performance by Praecis of any of its material obligations under this Binding
Agreement in Principal or (2) conflict with the rights granted to Amgen
hereunder, the effect of which would impair any such rights in any material
respect (provided that Praecis does not make the representation contained in
this clause (iv) with respect to Sections 10.01 and 10.02 of the IUF License
Agreement), v) there is not a legal or regulatory constraint on its ability to
carry out in all material respects its obligations hereunder.
b) PRAECIS. Praecis represents and warrants to Amgen that as of the
Signing Date:
(i) INTELLECTUAL PROPERTY. Praecis owns or possesses adequate
18
<PAGE>
licenses or other rights to use all the Praecis Patent Rights set forth in
Exhibit A. To the best knowledge of Praecis, the manufacture, use or sale of
Abarelix pursuant hereto will not infringe or conflict with any third party
right or patent and Praecis is not aware of any pending patent application that
if issued would be infringed by the manufacture, use or sale of Abarelix (alone
or in connection with the depot formulation described in the patent applications
referred to in Exhibit A) pursuant hereto. The Praecis Patent Rights set forth
in Exhibit A include all patent rights owned or controlled by Praecis which
claim or describe LHRH Antagonist Compounds and related methods. With respect to
the patent applications in Exhibit A, Praecis has no knowledge of any prior
patent or publication, public use, offer for sale or actual sale that would
invalidate the claims of such patent applications, and Praecis has no knowledge
of any actions taken by a patent office that would render such patent
unenforceable.
(ii) IUF LICENSE AGREEMENT. The IUF License Agreement is in
full force and effect. Praecis is in compliance in all material respects with
all of its obligations thereunder and has delivered to Amgen a true and complete
copy thereof together with all amendments. Neither Praecis nor, to the best
knowledge of Praecis, IUF is in breach of the IUF License Agreement.
(iii) ABARELIX. The data shown by Praecis to Amgen with
respect to the current Phase 2 study for Abarelix in prostate cancer is the
actual data from such study and is complete through the Signing Date. No patient
in any clinical trial of Abarelix has been shown to exhibit antibodies against
Abarelix.
(iv) MANUFACTURING. Praecis has entered into valid long term
contracts for the supply of Abarelix (including the depot formulation) with
three subcontractors identified to Amgen. Praecis, through these subcontractors,
has the ability to supply large scale commercial quantities of Abarelix
(including the depot formulation) consistent with the Long Range Plan and in
quality substantially similar to that used in the Phase 2 trials for Abarelix
for which Praecis has provided Amgen with clinical data.
(v) RESEARCH AND DEVELOPMENT. With respect to the NDA expected
to be filed for Abarelix following the completion of the upcoming Phase 3
studies in prostate cancer: (1) ***, (2) *** and (3) ***. Praecis has utilized a
sensitive, validated method to detect antibody formation in its clinical trials.
With respect to the ***, the minutes of such meeting prepared by Praecis and
provided to Amgen are accurate and complete.
c) AMGEN TERMINATION RIGHT. The representations and warranties in
Section 20 b) iv) and v) shall survive until April 5, 1999 (and thereafter shall
cease to be of any further force or effect). In order to give Amgen an
opportunity to complete its due diligence in order to verify the accuracy of
such representations and warranties, Praecis shall provide Amgen with access to
clinical investigators and make available to Amgen all information reasonably
requested, including all contract manufacturing sites and records, copies of
contracts with all contract manufacturers, copies of all
19
<PAGE>
correspondence to or from the FDA and copies of all notes from meetings with the
FDA, toxicology and other pre-clinical studies, clinical studies and QA/QC
records requested by Amgen. If based on such review Amgen reasonably determines
in good faith that any such representation or warranty in Section 20 b) iv) or
v) shall be inaccurate in any material respect as of the Signing Date, then on
or prior to April 5, 1999, Amgen may terminate this Binding Agreement in
Principle.
21. STANDSTILL. For a period of three years from the date that more than 50% of
Praecis' outstanding common stock is publicly traded on a national securities
exchange or the NASDAQ National Market, neither Amgen nor any of its
"affiliates" or representatives will directly or indirectly, (a) effect or seek,
offer or publicly propose to effect, or cause or participate in any way or
assist any person to effect or seek, offer or publicly propose to effect or
participate in, (i) any acquisition of any securities or material assets of
Praecis or any of its subsidiaries, (ii) any tender or exchange offer, merger or
other business combination involving Praecis or any of its subsidiaries; (iii)
any recapitalization, restructuring, liquidation, dissolution or other business
combination with respect to Praecis or its subsidiaries, (iv) any "solicitation"
of "proxies" or consents to vote any voting securities of the Company, (b) form,
join or in any way participate in a "group", or otherwise act, alone or in
concert with others, to seek to control or influence the management, Board of
Directors or policies of Praecis, (d) take any action which might force Praecis
to make a public announcement regarding any of the matters set forth in (a)
above; or (e) enter into any discussions or arrangements with any third party
with respect to any of the foregoing. (Certain terms used but not defined above
shall have the meaning given such terms in the Securities Exchange Act of 1934,
as amended, or the proxy rules of the Securities and Exchange Commission). The
foregoing restrictions shall apply only if and when more than 50% of Praecis'
outstanding common stock is publicly traded on a national securities exchange or
the NASDAQ National Market. In addition, nothing shall prevent Amgen from: (1)
purchasing, selling or holding less than 5% of Praecis common stock, or (2)
making offers or proposals at the request of the Board of Directors. The above
restrictions shall terminate immediately upon any of the following events: (i)
upon the announcement or disclosure or commencement by any third party (other
than one or more underwriters in a bonafide public offering) of any proposal or
offer to acquire, directly or indirectly, more than 30% of Praecis' outstanding
common stock, (ii) upon any acquisition or proposed acquisition by any third
party (other than one or more underwriters in a bonafide public offering) of
more than 30% of Praecis' outstanding common stock, or (iii) upon the proposal,
announcement, disclosure or initiation of any transaction of the type described
in subsection (a)(ii) or (iii) of the restrictions.
22. RIGHTS OF FIRST OFFER AND LAST REFUSAL. Amgen shall have a right of first
offer and last refusal during the Term to (1) any other Praecis products
intended to be sold to urologists or gynecologists and (2) all products in all
territories covered by the Synthelabo Agreement in the event that the Synthelabo
Agreement shall be terminated for any reason. Therefore, before offering to
dispose of any interest in (1) or (2) to any party, Praecis will first seek an
offer from Amgen. Following Amgen's submission of an offer, Praecis cannot
accept an offer from any third party on terms which, taken as a
20
<PAGE>
whole, are less favorable to Praecis than the Amgen offer. Should Amgen's offer
in clause (1) above be accepted by Praecis, then Praecis shall have the right to
co-promote such product with Amgen, with the size of the Praecis sales force
relative to the Amgen sales force to be determined proportional to the relative
value of the new product compared to the value of Abarelix. Co-promotion by
Praecis will be in accordance with Amgen's sales and marketing plan, under
Amgen's training and management and using Amgen's field sales materials.
23. CONFIDENTIALITY. Except to the extent expressly authorized by this Agreement
or otherwise agreed in writing, the parties agree that, for the term of this
Agreement and for five (5) years thereafter, Praecis and/or Amgen, as the case
may be (the "Receiving Party"), shall keep confidential and shall not publish or
otherwise disclose or use for any purpose other than as provided for in this
Agreement any proprietary data, information and/or materials furnished to it by
the other party (the "Disclosing Party") (together with all other data and
information deemed Confidential Information of either party herein,
"Confidential Information"), except, to the extent that it can be established:
(a) by the Receiving Party that Confidential Information was already known to
the Receiving Party, other than under an obligation of confidentiality, at the
time of disclosure by the Disclosing Party and such Receiving Party has
documentary evidence to that effect; (b) by the Receiving Party that
Confidential Information was generally available to the public or otherwise part
of the public domain at the time of its disclosure to the Receiving Party; (c)
by a party that Confidential Information became generally available to the
public or otherwise part of the public domain after its disclosure or
development, as the case may be, and other than through any act or omission of a
party in breach of this confidentiality obligation; or (d) by a party that
Confidential Information was disclosed to that party, other than under an
obligation of confidentiality, by a third party who had no obligation to the
Disclosing Party not to disclose such information to others.
Each party may disclose Confidential Information belonging to the other party to
the extent such disclosure is reasonably necessary in filing or prosecuting
patent applications, prosecuting or defending litigation or complying with
applicable governmental regulations. Amgen shall further have the right to
disclose Confidential Information owned by Praecis or jointly by Amgen and
Praecis in developing Licensed Products in connection with conducting
pre-clinical and clinical trials and commercializing and promoting Licensed
Products. Praecis, with Amgen's prior approval, shall have the right to disclose
Confidential Information owned by Amgen or jointly by Amgen and Praecis in
connection with Praecis' clinical development activities within the Development
Plan.
Data and information arising out of Praecis' activities under the Development
Plan will be Praecis Confidential Information and data and information arising
out of Amgen's activities under the Development Plan will be Amgen Confidential
Information.
24. PUBLICATION. Neither party will publish the structure of any Licensed
Product prior to publication of the structure in a patent application and
thereafter shall refrain
21
<PAGE>
from publishing without the approval of the other party if such publication will
materially aid competitors. Each party will submit to the other for review and
comment all proposed academic, scientific and medical publications relating to
Licensed Products and/or Collaboration Technology no less than ***days prior to
submission for publication. Following Amgen's assumption of final decision
making authority as set forth in Section 14c), Praecis shall not submit any such
publication without Amgen's prior written approval.
25. PUBLIC ANNOUNCEMENTS. The parties agree on the importance of coordinating
their public announcements respecting this Binding Agreement in Principle and
the subject matter thereof (other than academic, scientific or medical
publications which are subject to the publication provision set forth above).
Except as required by law, neither party will make any public announcement
regarding this Binding Agreement in Principle, Collaboration Technology or
Licensed Products (other than academic, scientific or medical publications which
are subject to the publication provisions set forth above) without giving the
other opportunity to review and comment.
In no event will either party use the name of the other in any press release or
public announcement without the prior approval of the named party.
26. [Intentionally omitted]
27. [Intentionally omitted]
28. DOCUMENTATION. The parties acknowledge and agree that this Binding
Agreement in Principle contains all of the essential terms of the transactions
contemplated hereby and is intended to be, and is, a legally binding agreement.
Amgen and Praecis will use good faith efforts to negotiate and execute
definitive agreements relating to the transactions set forth herein which will
include the terms set forth herein and such other terms as the parties may
mutually agree which, upon such execution, will supersede in its entirety this
Binding Agreement in Principle.
29. GOVERNING LAW. This Binding Agreement in Principle shall be governed by the
laws of the State of California, without reference to the conflicts of law
principles thereof.
30. MISCELLANEOUS. Neither this Binding Agreement in Principle nor the
activities contemplated hereunder shall be deemed to create a partnership or
joint venture for accounting or any other purposes and the parties shall be
independent with no right to bind or otherwise act as the agent for the other
party.
31. TRADEMARKS. Praecis hereby grants to Amgen exclusive royalty-free licenses
to use the Rel-Ease trademark and other trademarks owned by Praecis relating to
the Licensed Products in the Field throughout the Licensed Territory, such
license to cover the existing and all future forms of such trademark and
associated logos, subject to the same terms and conditions set forth in Article
8 of the Synthelabo Agreement.
22
<PAGE>
32. BUSINESS TRANSITION. It is anticipated that prior to January 1, 2002,
certain expertise possessed by Praecis personnel shall be utilized and be
reflected in FTE charges for the various expense items in the Annual Budget.
During this time period Amgen is expected to perform an increasing portion of
all activities as reflected in the Long Range Plan, but that some Praecis
employees will continue to participate in activities through 2001. After January
1, 2002, Amgen shall be solely responsible for substantially all activities
relating to the Licensed Products, excluding manufacturing and supply of the
depot formulation which shall remain the responsibility of Praecis. From and
after Amgen's assumption of manufacturing and supply responsibility pursuant to
Section 15f), Amgen shall have responsibility for supplying Praecis with
Licensed Product for the purpose of Praecis supplying Synthelabo with Licensed
Product under the Synthelabo Agreement (excluding the depot formulation which
shall remain the responsibility of Praecis). Amgen's supply of Praecis for
purposes of the preceding sentence shall be made: (1) at a price determined ***;
and (2) ***. After January 1, 2002, Praecis will make its personnel available to
Amgen at the then current FTE rate to participate in activities related to this
Binding Agreement in Principle, but only following reasonable advance notice by
Amgen and with due consideration for such employees' other responsibilities.
33. ENTIRE AGREEMENT OF THE PARTIES. This Binding Agreement in Principle
constitutes and contains the complete, final and exclusive understanding and
agreement of the parties and cancels and supersedes any and all prior
negotiations, correspondence, understandings and agreements, whether oral or
written, among the parties respecting the subject matter hereof.
34. OFFSET. A party (the "first party") shall be entitled to offset against any
payments due and payable to the other party hereunder all such amounts due and
payable hereunder but not yet paid by such other party to the first party.
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DEFINITIONS
AFFILIATE shall mean any person or entity that, directly or indirectly, through
one or more intermediaries, controls, is controlled by, or is under common
control with the person or entity specified. For the purposes of this
definition, control shall mean the direct or indirect ownership of at least 50%
of the shares of capital stock or other equity interest entitled to vote for the
election of directors or equivalent governing body.
ACTUAL EXPENSES shall mean all ***.
ACTUAL PROFITS shall be deemed to have occurred when Net Sales of Licensed
Products in a given calendar year exceed Actual Expenses in that calendar year.
COMMERCIALLY REASONABLE EFFORTS shall mean efforts and resources commonly used
in the research-based pharmaceutical industry for a product at a similar stage
in its product life of similar market potential taking into account efficacy and
side effects, the competitiveness of alternative products in the marketplace,
the patent and other proprietary position of the product, the likelihood of
regulatory approval given the regulatory structure involved, the profitability
of the product including the royalties payable to licensors of patent rights,
alternative products and other relevant factors. Commercially Reasonable Efforts
shall be determined on a market-by-market basis for a particular product, and it
is anticipated that the level of effort will change over time, reflecting
changes in the status of the product and the market involved.
COST OF SALES includes COGS ***.
CUMULATIVE ADJUSTED PROFIT shall be equal to ***
DEFAULT shall mean with respect to a party that (i) any representation or
warranty of such party shall have been untrue in any material respect when made
or (ii) such party shall have failed to perform any material obligation set
forth herein.
G & A shall mean general and administrative.
IMPROVEMENTS shall have the meaning set forth in the IUF License Agreement.
IUF LICENSE AGREEMENT shall mean the License Agreement dated as of October 17,
1996 between Indiana University Foundation ("IUF") and Praecis, as amended.
NET SALES shall mean ***.
PATENTED PRODUCT shall mean a Licensed Product the sale of which without a
license would infringe one or more claims of a valid, issued, and enforceable
(i.e., the patent is not expired and all maintenance fees due having been paid;
and there has been no determination which remains in effect of unenforceability
of the patent by a court of
24
<PAGE>
competent jurisdiction) patent included in the Collaboration Technology in the
country of sale. ***
PATENT RIGHT shall mean patent applications, patents issuing thereon and any
extensions or restorations by existing or future extension or restoration
mechanisms, including without limitation Supplementary Protection Certificates
or the equivalent thereof, renewals, continuations, continuations-in-part,
divisions, patents-of-addition, and/or reissues of any patent.
PIVOTAL TRIAL shall mean a clinical trial which, if the defined end-points are
met, is intended by Amgen and Praecis as of the start of such trial to be the
clinical trial which will constitute sufficient basis for receipt of marketing
approval in the United States.
PRAECIS IMPROVEMENTS shall mean all changes in composition, design or
manufacture of the Licensed Products by Praecis which result in enhancements or
alterations of any component of the Licensed Products with respect to, without
limitation, efficacy, safety, drug delivery profiles, stability, shelf-life,
dosage, cost, ease of use or styling.
R & D shall mean research and development.
SYNTHELABO AGREEMENT shall mean the License Agreement dated May 13, 1997 by and
between Praecis and Synthelabo, as amended by letter dated July 31, 1997 from
Synthelabo to Praecis.
UNPATENTED PRODUCT shall mean a Licensed Product the sale of which without a
license would not infringe one or more claims of a valid, issued and enforceable
(i.e., the patent is not expired and all maintenance fees due having been paid;
and there has been no determination which remains in effect of unenforceability
of the patent by a court of competent jurisdiction) patent included in the
Collaboration Technology in the country of sale. An Unpatented Product shall
become, and be, a Patented Product when, and for so long as, it meets the above
definition of Patented Product.
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<PAGE>
EXHIBIT A
PRAECIS PATENT RIGHTS
<TABLE>
<CAPTION>
- ---------------------------- ----------------------- ---------------------------------------------------- ------------------
SERIAL NO. FILING DATE TITLE PATENT NO./ISSUE
DATE
- ---------------------------- ----------------------- ---------------------------------------------------- ------------------
<S> <C> <C> <C>
US 08/480,494 6-7-95 LHRH Antagonist Peptides 5,843,901
12-1-98
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
US 08/573,109 12-15-95 Methods For Treating Prostate Cancer With LHRH-R 5,780,435
Antagonists 7-14-98
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
US 08/755,593 11-25-96 Methods For Treating Prostate Cancer With LHRH 5,843,902
Antagonists 12-1-98
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
PCT/US96/18911 *** Methods For Treating Prostate Cancer With LHRH
Antagonists
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
US 08/762,747 12-11-96 Pharmaceutical Formulations for Sustained Drug
Delivery
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
*** *** ***
- ---------------------------- ----------------------- ---------------------------------------------------- -------------------
</TABLE>
26
<PAGE>
EXHIBIT B
ANSWER 1 OF 1 REGISTRY COPYRIGHT 1999 ACS
<TABLE>
<S> <C>
RN 183552-38-7 ZREGISTRY
CN D-Alaninamide, N-acetyl-3-(2-napthalenyl) -D-alanyl-4-cholor-D-
Phehylalanyl-3-(3-pyridinyl) -D-alanyl-L-seryl-N-methly-L-tyrosyl-D-
Asparaginyl-L-leucyl-N6- (1-methylethyl) -L-lysyl-L-prolyl- (9CI) (CA
INDEX NAME)
OTHER NAMES:
CN Abarelix
CN PPI 149
CN R 3827
FS PROTEIN SEQUENCE; STEREOSEARCH
MF C72 H95 C1 N14 O14
CI COM
SR CAS Registry Services
LC STN Files: ADISINSIGHT, CA, CAPLUS, DDFU, DRUGU, DRUGUPDATES,
TOXLIT, USPATFULL
</TABLE>
Absolute stereochemistry.
PAGE 1-A
[CHEMICAL DIAGRAM]
PAGE 1-B
[CHEMICAL DIAGRAM]
2 REFERENCES IN FILE CA (1967 TO DATE)
2 REFERENCES IN FILE CAPLUS (1967 TO DATE)
27
<PAGE>
EXHIBIT C
COUNTRIES EXCLUDED FROM TERRITORY*
- ------------------------------------
*All countries not listed are included in the Territory
<TABLE>
- --------------------------------------------------------------------------------
<S> <C> <C> <C>
Austria Belgium Denmark Greece
- --------------------------------------------------------------------------------
Finland France Germany Luxembourg
- --------------------------------------------------------------------------------
Ireland Italy Liechtenstein Spain
- --------------------------------------------------------------------------------
Monaco Netherlands Norway Portugal
- --------------------------------------------------------------------------------
San Marino Sweden Switzerland United Kingdom
- --------------------------------------------------------------------------------
Vatican Iceland Andorra
- --------------------------------------------------------------------------------
Belize Costa Rica Guatemala Honduras
- --------------------------------------------------------------------------------
Mexico Nicaragua Panama San Salvador
- --------------------------------------------------------------------------------
Argentina Bolivia Brazil Chile
- --------------------------------------------------------------------------------
Columbia Ecuador French Guyana Guyana
- --------------------------------------------------------------------------------
Paraguay Peru Uruguay Venezuela
- --------------------------------------------------------------------------------
Albania Armenia Azerbaijan Belarusse
- --------------------------------------------------------------------------------
Bosnia/Herzegovina Bulgaria Croatia Czech Republic
- --------------------------------------------------------------------------------
Estonia Georgia Hungary Kazakhstan
- --------------------------------------------------------------------------------
Kyrgyzstan Latvia Lithuania Macedonia
- --------------------------------------------------------------------------------
Moldavia Poland Romania Russia
- --------------------------------------------------------------------------------
Slovakia Slovenia Tadzhikistan Turkmenistan
- --------------------------------------------------------------------------------
Ukrania Uzbekistan Yugoslavia
</TABLE>
28
<PAGE>
<TABLE>
- --------------------------------------------------------------------------------
<S> <C> <C> <C>
Algeria Benin Burkina Faso Cameroon
- --------------------------------------------------------------------------------
Central African Chad Congo Djibouti
Republic
- --------------------------------------------------------------------------------
Gabon Guinea Guinea Bissau Ivory Coast
- --------------------------------------------------------------------------------
Madagascar Mali Mauritania Morocco
- --------------------------------------------------------------------------------
Niger Rwanda Senegal Seychelles
- --------------------------------------------------------------------------------
Tunisia Zaire South Africa
- --------------------------------------------------------------------------------
Iran Iraq Israel Jordan
- --------------------------------------------------------------------------------
Kuwait Lebanon Oman Saudi Arabia
- --------------------------------------------------------------------------------
South Yemen Syria Turkey Yemen
- --------------------------------------------------------------------------------
Cyprus United Arab Emirates Bahrain
- --------------------------------------------------------------------------------
Malta Qatar
- --------------------------------------------------------------------------------
</TABLE>
29
<PAGE>
PRAECIS PHARMACEUTICALS
LONG RANGE PLAN - ** 1999-2008
MARCH 1999
EXHIBIT D ($MM)
**
30
<PAGE>
EXHIBIT E
[AMGEN INC. LETTERHEAD]
VIA FAX: 617-731-1908
February 26, 1999
Dr. Marc B. Garnick, MD
Executive Vice President and Chief Medical Officer
Praecis Pharmaceuticals Incorporated
1 Hampshire Street
Cambridge, MA 02139
Dear Marc:
RE: Collaboration of Amgen and Praecis on Abarelix Development
Thank you for your hospitality and patience in hosting the Amgen team on
February 24 at the Praecis office in Boston.
I have attached draft minute to document the results of our conversations.
Please let me know if you have any corrections. As we discussed, a proposed
agenda for our planned meeting in Boston on Monday is attached.
Best regards
William Sheridan
cc: C. Bubser, M. Foote, D. Alu, D. Menchaca, H. Movahhed, J. O'Connor, D.
Perry, G. Schwab, T. Ulich
31
<PAGE>
DRAFT
Minutes of Discussion between Amgen and Praecis staff held in Boston February
24th, 1999, 1:00pm - 4:30pm
Attendees:
a) Section 1 A only.
Praecis: M. Campion, E. Cole, T. English, M. Garnick, M. Gray, C. Kelley, B.
Kuca, K. Martha, C. Molineaux
Amgen: C. Bubser, M. Foote, H. Movahhed, G. Schwab, B. Sheridan
PPD by phone: R. Crawley, J. Conway, T. Hopkins, C. Philput, K. Ferriter
b) All other sections - Continued discussions between M. Garnick and W.
Sheridan, 4:30-9:45pm.
I. PRIORITIES FOR ONGOING CLINICAL PROGRAM AND PRECLINICAL SUPPORT
***
(BALANCE OF OUTLINE IS CONFIDENTIAL.)
32
<PAGE>
Appendix 1
Prostate Cancer NDA - Clinical Components
***
***
33
<PAGE>
Appendix 3
Proposed Agenda for Abarelix R&D Offsite Meeting
Boston
Monday, March 1, 1999
Amgen Attendees:
Chris Bubser - Marketing Planning and Development, David Lau - Pharmacokinetic
and Drug Metabolism, Dora Menchaca - Clinical Research, Hassan Movahhed -
Clinical Affairs, Doug Perry - Marketing Planning and Development, Bill Sheridan
- - Product Development, Gisela Schwab - Clinical Research
Praecis Attendees:
Marc Garnick, C. Molineaux, M. Campion, Marc Silver, B. Cooper, Janice Swirski,
Kip Martha, Michelle Gray
1. Welcome and Introductions M. Garnick
2. Questions and Clarifications to Minutes of February 24 Meeting All
................................................................................
3. NDA filing
................................................................................
- - Amgen International Clinical Safety Department contact for Praecis (H.
Movahhed)
- - ***
- - ***
4. Package Insert and Preferred Product Profile C.
Bubser
................................................................................
5. Main Item: Abarelix Product Development Plan
................................................................................
a) new prostate cancer studies
b) endometriosis NDA plan
c) BPH
d) PIN
e) ***
f) ***
g) summary of timelines
h) summary of costs
i) requirements international filings in Canada and Australia (brief)
j) development of Abarelix in Japan (very brief)
6. Investigator Meetings, Scientific Meetings, Advisory Panel Workshops,
Regulatory Meetings
..........................................................................
-plans and schedules
34
<PAGE>
EXHIBIT F
REPAYMENT SCHEDULE
INTEREST
Beginning January 30, 2001 and on January 30 in each year thereafter, Praecis
will repay to Amgen all accrued but unpaid interest (through December 31 of the
prior year), if any, provided that the final interest payment shall be made on
January 30, 2009.
PRINCIPAL
Beginning January 1, 2004, within 30 days after the end of each quarter, Praecis
will repay to Amgen principal on a quarterly basis. The principal payments shall
be equal to a minimum of 20% of Praecis' share of profits from the sales of
Licensed Products. All payments will be applied first to accrued but unpaid
interest and then to principal. All principal balances will be repaid by
December 31, 2008.
35
<PAGE>
EXHIBIT 10.9
CONFIDENTIAL TREATMENT HAS BEEN REQUESTED FOR CERTAIN
PORTIONS OF THIS DOCUMENT. SUCH PORTIONS HAVE BEEN
REDACTED AND MARKED WITH ASTERISKS (**). THE NON-
REDACTED VERSION OF THIS DOCUMENT HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO
AN APPLICATION FOR CONFIDENTIAL TREATMENT.
EXECUTION COPY
COLLABORATION AND LICENSE AGREEMENT
by and between
PHARMACEUTICAL PEPTIDES, INC.
and
BOEHRINGER INGELHEIM INTERNATIONAL GmbH
dated as of August 1, 1996
<PAGE>
TABLE OF CONTENTS
ARTICLE 1. DEFINITIONS..............................................1
1.1 AAI................................................1
1.2 Abandonment Date...................................1
1.3 Affiliate..........................................1
1.4 Applicable Base Royalty Rate.......................2
1.5 BI Compound........................................2
1.6 BI Patent Rights...................................2
1.7 BI Product.........................................2
1.8 Develop or Development.............................2
1.9 Designated BI Compound.............................2
1.10 Effective Date....................................2
1.11 Exchange Information..............................3
1.12 Exclusivity Period................................3
1.13 First Commercial Sale.............................3
1.14 FTE...............................................3
1.15 Indemnitee........................................3
1.16 Indemnitor........................................3
1.17 Information.......................................3
1.18 Licensed Diagnostic Compound......................3
1.19 Marketing Authorization...........................3
1.20 Net Sales.........................................3
1.21 Patent Expiration Date............................4
1.22 Phase 0...........................................4
1.23 Phase I...........................................5
1.24 Phase II..........................................5
1.25 Phase III.........................................5
1.26 PPI Change of Control Transaction.................5
1.27 PPI Compound......................................5
1.28 PPI Information...................................5
1.29 PPI Patent Rights.................................6
1.30 PPI Product.......................................6
1.31 Publishing Party..................................6
1.32 Recognized Agent..................................6
1.33 Reviewing Party...................................7
1.34 Sale Date.........................................7
1.35 SAR Information...................................7
1.36 Screening Data....................................7
1.37 Screening Program.................................7
1.38 Screening Term....................................7
1.39 Screening Term Year...............................7
1.40 SEC...............................................7
1.41 Section 10.4.1(a) Notice..........................7
1.42 Territory.........................................7
1.43 Third Party.......................................7
i
<PAGE>
1.44 Third Party AD Product............................7
1.45 Work Plan.........................................8
1.46 ***% Royalty Rate.................................8
1.47 ***% Royalty Rate.................................8
ARTICLE 2. SCREENING PROGRAM........................................8
2.1 Screening Services.................................8
2.2 Payments...........................................8
2.3 Expense Reimbursement..............................9
2.4 Screening Term.....................................9
2.5 Exclusivity.......................................10
ARTICLE 3. LICENSE GRANTS; DEVELOPMENT, MANUFACTURING
AND MARKETING OF BI PRODUCTS........................11
3.1 Grant of License Rights by PPI to BI..............11
3.2 Sublicense Rights.................................12
3.3 Diligence; Limit on Sales to
Recognized Agents..............................12
3.4 Failure to Market Due to Currency
Difficulties...................................12
3.5 Future License Rights.............................13
3.5.1 PPI's Future License Right..............13
3.5.2 BI's Right of First
Refusal...............................14
ARTICLE 4. EXCHANGE OF INFORMATION.................................15
4.1 Information to be Provided........................15
4.2 Information Not Required to be
Provided; Restriction on Certain
Research Activities............................16
ARTICLE 5. INTELLECTUAL PROPERTY RIGHTS............................16
ARTICLE 6. ROYALTIES...............................................17
6.1 Royalties on Net Sales............................17
6.1.1 Royalty Rate............................17
6.1.2 Third Party Patents;
Combination BI Products; Bundled
Products ...............................19
6.1.3 Sublicense Royalties....................19
6.2 Royalty Reports; Exchange Rates...................20
6.3 Audits............................................20
6.4 Royalty Payment Terms.............................21
6.5 Withholding Taxes.................................21
6.6 Application for Tax Exemption.....................22
6.7 Interest on Late Payments.........................22
ii
<PAGE>
6.8 Duration of Royalties; Step Down..................22
ARTICLE 7. CONFIDENTIALITY.........................................23
7.1 Nondisclosure Obligations.........................23
7.1.1 General.................................23
7.1.2 Limitations.............................23
7.2 Terms of this Agreement...........................24
7.3 Publications......................................25
7.3.1 Procedure...............................25
7.3.2 Delay...................................25
7.3.3 Resolution..............................25
7.4 Injunctive Relief.................................26
ARTICLE 8. REPRESENTATIONS AND WARRANTIES..........................26
ARTICLE 9. INDEMNITY...............................................26
9.1 BI Indemnity Obligations..........................26
9.2 PPI Indemnity Obligations.........................27
9.3 Procedure.........................................27
9.4 Insurance.........................................28
ARTICLE 10. TERMINATION............................................28
10.1 Termination......................................28
10.1.1 Material Breach........................28
10.1.2 Failure of BI to Pay...................28
10.1.3 Failure of BI to Use
Diligent Efforts.....................29
10.1.4 Bankruptcy...............................29
10.1.5 Change of Control........................29
10.2 Effect of Termination Generally..................29
10.2.1 Existing Obligations.....................29
10.2.2 Survival.................................29
10.3 Effect of Termination by PPI.....................30
10.3.1 Termination by PPI Prior
to Commencement of Phase III..........30
10.3.2 Termination By PPI After
Commencement of Phase III.............30
10.4 Effect of Termination by BI......................30
10.4.1 Termination for PPI Breach...............30
10.4.2 Termination for Change of
Control...............................32
ARTICLE 11. MISCELLANEOUS..........................................32
11.1 Force Majeure....................................32
11.2 Assignment.......................................33
11.3 Severability.....................................33
iii
<PAGE>
11.4 Notices..........................................34
11.5 Applicable Law...................................35
11.6 Dispute Resolution; Choice of
Forum......................................35
11.7 Arbitration......................................35
11.8 Entire Agreement.................................35
11.9 Headings.........................................36
11.10 Independent Contractors.........................36
11.11 Agreement Not to Solicit
Employees..................................36
11.12 Exports.........................................36
11.13 Waiver..........................................37
11.14 Counterparts....................................37
Appendix A - PPI Patent Rights
Appendix B - Recognized Agents of BI
Appendix C - Work Plan
iv
<PAGE>
COLLABORATION AND LICENSE AGREEMENT
This COLLABORATION AND LICENSE AGREEMENT (the "Agreement") is made
as of August 1, 1996, by and between Pharmaceutical Peptides, Inc., a Delaware
corporation having its principal place of business at One Hampshire Street,
Cambridge, Massachusetts 02139-1572 ("PPI"), and Boehringer Ingelheim
International GmbH, a limited liability company organized under the laws of the
Federal Republic of Germany having its principal place of business at D-55216
Ingelheim Rhein Germany ("BI").
WHEREAS, PPI is the owner of certain proprietary screening
technology which enables PPI to identify compounds as lead candidates for
discovery program for compounds and drug development; and
WHEREAS, PPI has a discovery program for compounds which exhibit
A(beta) peptide amyloid aggregation inhibition activity with a view to
developing and commercializing such compounds as pharmaceutical products; and
WHEREAS, BI possesses certain compounds which it desires to have
screened by PPI in order to identify if any such compounds or their derivatives
exhibit A(beta) peptide amyloid aggregation inhibition activity with a view to
developing and commercializing such compounds as pharmaceutical products;
NOW, THEREFORE, in consideration of the foregoing, and the
representations, warranties and agreements contained herein, and for other good
and valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, the parties hereto agree as follows:
ARTICLE 1. DEFINITIONS
1.1 "AAI" shall mean amyloid aggregation inhibition.
1.2 Abandonment Date" shall have the meaning set forth in Section
3.5.
1.3 "Affiliate" shall mean any corporation or other entity which
controls, is controlled by, or is under
<PAGE>
common control with a party to this Agreement. A corporation or other entity
shall be regarded as in control of another corporation or entity if it owns or
directly or indirectly controls more than fifty percent (50%) of the voting
stock or other ownership interest of the other corporation or entity, or if it
possesses, directly or indirectly, the power to direct or cause the direction of
the management and policies of the corporation or other entity or the power to
elect or appoint fifty percent (50%) or more of the members of the governing
body of the corporation or other entity.
1.4 "Applicable Base Royalty Rate" shall have the meaning set forth
in Section 6.1.
1.5 "BI Compound" shall mean and include any of (i) any compound
which is screened by PPI pursuant to Article 2 hereof and exhibits AAI activity
in any of such screens or (ii) any compound which is developed by BI utilizing,
or is based upon, any PPI Information.
1.6 "BI Patent Rights" shall mean all patents, patent applications,
patent extensions, certificates of invention or applications for certificates of
invention, together with any divisions, continuations or continuations-in-part
thereof, which are owned or controlled by, or licensed (or sublicensed) to, BI
with respect to any Designated BI Compound. BI agrees to provide a list to PPI
of BI Patent Rights at least annually.
1.7 "BI Product" shall mean any pharmaceutical preparation or
product containing a BI Compound, whether as the sole active ingredient or mixed
with any other active ingredient.
1.8 "Develop" or "Development" shall mean all work involved in
Phases O, I, II and III, as applicable, with respect to a BI Compound or a BI
Product.
1.9 "Designated BI Compound" shall mean any BI Compound referred to
in clause (i) of the definition of BI Compound (Section 1.5) which exhibits AAI
activity in each of the Nucleation Assay and the Neurotoxicity Assay referred to
in Section I of the Work Plan.
1.10 "Effective Date" shall mean the date first written above.
2
<PAGE>
1.11 "Exchange Information" shall have the meaning set forth in
Section 4.1.
1.12 "Exclusivity Period" shall have the meaning set forth in
Section 2.5.
1.13 "First Commercial Sale" shall mean the first sale for use or
consumption by the general public of a BI Product, PPI Product or a product
containing a Licensed Diagnostic Compound, as applicable, in any country based
upon the required marketing and pricing approval granted by the governing health
authority of such country.
1.14 "FTE" shall mean a full time professional employee dedicated to
the Screening Program.
1.15 "Indemnitee" shall have the meaning set forth in Section 9.3.
1.16 "Indemnitor" shall have the meaning set forth in Section 9.3.
1.17 "Information" shall have the meaning set forth in Section 7.1.
1.18 "Licensed Diagnostic Compound" shall have the meaning set forth
in Section 3.5.1.
1.19 "Marketing Authorization" shall mean all allowances and
approvals (including pricing and reimbursement approvals) granted by the
appropriate federal, state and local regulatory agencies, departments, bureaus
or other governmental entities within a country necessary to market and sell a
BI Product.
1.20 "Net Sales" shall mean the invoiced sales price per unit for
each of the BI Products or PPI Products, as applicable, billed to independent
customers or Recognized Agents by a party or its Affiliates, or permitted
sublicensees of either party, less, to the extent such amounts are included in
the invoiced sales price, actual (a) credited allowances to such independent
customers for such BI Products or PPI Products which were spoiled, damaged,
out-dated or returned; (b) freight and insurance costs incurred in transporting
BI Products or PPI Products to such customers; (c) quantity and other trade
discounts
3
<PAGE>
actually allowed and taken; (d) sales, use, value added and other taxes or
governmental charges incurred in connection with the sale, exportation or
importation of the BI Products or PPI Products in finished packaged form; and
(e) charge back payments and/or rebates provided to managed health care
organizations or federal, state and local governments, their agencies,
purchasers and reimburses, including reimbursements to social security
organizations. The transfer of the BI Products or PPI Products by a party or one
of its Affiliates to (i) another Affiliate of such party or (ii) a permitted
sublicensee of such party shall not be considered a sale; in such cases, Net
Sales shall be determined based on the invoiced sales price by the Affiliate or
permitted sublicensee to its customer, less the deductions allowed under this
Section. Every other commercial use or disposition of BI Products or PPI
Products by a party, its Affiliates or permitted sublicensees, other than
reasonable quantities of promotional samples or bona fide sale to a bona fide
customer, shall be considered a sale of the BI Products or PPI Products at the
weighted average Net Sales price then being invoiced by the seller in arm's
length transactions.
A party or its Affiliates shall be deemed to have sold a "Bundled
Product" if the BI Products or PPI Products are sold by a party or its
Affiliates pursuant to an agreement with an independent customer or a Recognized
Agent specifying, for a combination of products or services, (i) a single
price, (ii) other terms of purchase not separately identifying either a price
per product or the effective deductions referred to above per product or (iii) a
price for units of the BI Products or PPI Products which is discounted below a
party's or its Affiliates' standard invoice price per unit of the BI Products or
PPI Products by at least five percentage points more than the amount that any
other product of service in the Bundled Product is discounted below such other
product's or service's standard invoice price.
1.21 "Patent Expiration Date" shall have the meaning set forth in
Section 6.8
1.22 "Phase 0" shall mean that portion of Development which starts
after a candidate has been selected and approved by BI or a Third Party licensee
thereof for start of development as a product as evidenced by the approval in
writing of such start of development by
4
<PAGE>
BI's International Steering Committee or equivalent body. Phase 0 generally
includes toxicological and pharmacological studies as well as drug substance
and drug product formulation and manufacturing development necessary to obtain
the permission of regulatory authorities to begin and continue human clinical
testing.
1.23 "Phase I" shall mean that portion of Development which starts
with the first introduction into humans of a product with the purpose of
determining safety, metabolism, absorption, elimination and other
pharmacological action in humans as well as additional development work on
animal toxicity, metabolism, drug substance and drug product formulation and
manufacturing development to ensure continuation of human clinical testing.
1.24 "Phase II" shall mean that portion of Development which
includes initial trials on a limited number of patients for the purposes of
determining dose and evaluating safety and preliminary efficacy data in the
proposed therapeutic indication as well as additional development work on animal
toxicity, metabolism, drug substance and drug product formulation and
manufacturing development to ensure continuation of human clinical testing.
1.25 "Phase III" shall mean that portion of Development which
includes continued trials in sufficient numbers of patients to establish safety
and efficacy to support Marketing Authorization in the proposed indication. In
addition, all other development work on animal toxicity, metabolism, drug
substance and drug product formulation and manufacturing development will be
finalized.
1.26 "PPI Change of Control Transaction" shall mean any transaction
described in Section 10.1.5.
1.27 "PPI Compound" shall mean any compound owned by or licensed
(with the right to sublicense) to PPI which exhibits AAI activity.
1.28 "PPI Information" shall mean information, knowledge and
know-how (i) possessed by PPI before the Effective Date relating to the
Screening Program or (ii) generated solely by PPI personnel during the Screening
Program, including but not limited to screening methods and results during the
Screening Term in the course of performing the Screening Program, as well as SAR
Information with
5
<PAGE>
respect to PPI Compounds, which in each case is disclosed to BI hereunder.
1.29 "PPI Patent Rights" shall mean (i) the specific composition of
matter claims and the specific methods claims listed on Appendix A hereto (under
the heading "Claims Included") contained in the patent application and the
continuation in part thereof listed on Appendix A, as such claims are pending in
said applications as of the Effective Date, (ii) the claims referred to in
clause (i) to the extent granted in any resultant U.S. letters patent, (iii) the
claims referred to in clauses (i) and (ii) to the extent contained in any
corresponding Patent Co-operation Treaty applications, European Patent
Convention applications or applications under similar administrative
international conventions, or in any corresponding national patents and patent
applications, (iv) equivalents of the claims referred to in clauses (i), (ii)
and (iii) and (v) any divisional, continuation, substitution, reissue,
extension, supplementary protection certificate or other application solely to
the extent based on the claims referred to in clauses (i) through (iv). PPI
Patent Rights shall exclude all other claims set forth on Appendix A hereto
under the heading "Claims Excluded."
1.30 "PPI Product" shall mean any pharmaceutical preparation
containing a PPI Compound, whether as the sole active ingredient or mixed with
any other active ingredient and which is intended for prophylactic or
therapeutic purposes.
1.31 "Publishing Party" shall have the meaning set forth in Section
7.3.
1.32 "Recognized Agent" shall mean an entity, other than an
Affiliate of PPI or BI, as applicable, through which PPI or BI, as applicable,
distributes and sells its products in a particular country or region. From and
after the First Commercial Sale of a BI Product, PPI Product or a product
containing a Licensed Diagnostic Compound, the selling party will provide the
other party with a complete list of its Recognized Agents and will update such
list at least once annually.
1.33 "Reviewing Party" shall have the meaning set forth in Section
7.3.
6
<PAGE>
1.34 "Sale Date" shall have the meaning set forth in Section 6.8.
1.35 "SAR Information" shall mean and include structure activity
relationships information, and information with respect to chemical structure,
in each case with respect to PPI Compounds, whether in existence on the
Effective Date or generated thereafter.
1.36 "Screening Data" shall have the meaning set forth in Section
7.3.
1.37 "Screening Program" shall mean the collaboration by PPI and BI
during the Screening Term provided for in Article 2.
1.38 "Screening Term" shall mean the two-year period commencing on
the Effective Date, as extended pursuant to Section 2.4 hereof, unless this
Agreement is earlier terminated in accordance with Article 10 below, in which
event the Screening Term shall terminate on the effective date of such
termination.
1.39 "Screening Term Year" shall have the meaning set forth in
Section 2.3.
1.40 "SEC" shall mean the United States Securities and Exchange
Commission.
1.41 "Section 10.4.1(a) Notice" shall have the meaning set forth in
Section 10.4.
1.42 "Territory" shall mean all countries and territories in the
world.
1.43 "Third Party" shall mean any entity other than PPI and BI,
their respective Affiliates and Recognized Agents.
1.44 "Third Party AD Product" shall mean a pharmaceutical product
(other than a BI Product or a PPI Product) for the prevention or treatment of
Alzheimer's Disease which achieves its prophylactic or therapeutic effect
through A(beta) peptide AAI activity.
1.45 "Work Plan" shall mean the description of, and certain terms
and conditions applicable to, the
7
<PAGE>
screening services to be carried out by PPI pursuant to this Agreement,
including the scope and timing of such work, the in vitro and in vivo assays to
be utilized by PPI in performing such work, the anticipated annual capital
budget (and particular items of equipment to be purchased by PPI) in connection
with performing such work, as set forth in Appendix B, as it may be amended by
mutual agreement of the parties from time to time.
1.46 "***% Royalty Rate" shall have the meaning set forth in Section
6.1.
1.47 "***% Royalty Rate" shall have the meaning set forth in Section
6.1.
ARTICLE 2. SCREENING PROGRAM
2.1 Screening Services. Subject to and in accordance with the terms
and provisions of the Work Plan, during the Screening Term, PPI shall screen
compounds provided by BI.
2.2 Payments. Subject to the last two sentences of Section 11.1, BI
shall pay PPI *** Approximately 15 lines omitted ***. In the event the
conditions for payment in the preceding sentence are not met on the first
anniversary of the Effective Date for reasons associated with the nature of the
compounds provided by BI (PPI agreeing to use best efforts, but without
incurring significant additional expense or materially adversely delaying the
Work Plan, to minimize or eliminate any such reasons) or because of delays to
the Work Plan caused by BI, BI agrees to make such payment on such first
anniversary, provided PPI is then in compliance in all material respects with
the terms and provisions of this Agreement (other than any non-compliance for
reasons associated with the nature of the compounds provided by BI or because of
delays to the Work Plan caused by BI).
2.3 Expense Reimbursement.
(a) BI shall reimburse PPI for the following expenses in
respect of each consecutive twelve-month period during the Screening Term (a
"Screening Term Year"): (i) $250,000 per FTE; provided, that BI shall not be
8
<PAGE>
required to reimburse PPI for more than four FTEs, and (ii) actual amounts
expended for capital budget items as set forth in the Work Plan; provided,
however, that BI shall not be required to reimburse PPI pursuant to this Section
2.3 for expenses in excess of an aggregate of $2.5 million in respect of the
first two Screening Term Years and an aggregate of $1.25 million in respect of
any Screening Term Year.
(b) BI shall reimburse PPI at the end of each quarter for
expenses incurred by PPI during such quarter pursuant to paragraph (a) above,
such reimbursement payments to be received by PPI within fifteen days of BI's
receipt of a reasonably itemized invoice for such expenses prepared by PPI. For
purposes of this clause (b), expenses incurred by PPI for any FTE hired prior to
the Effective Date shall be deemed to be reimbursable expenses under paragraph
(a) above and shall be included in the first quarterly invoice prepared by PPI.
2.4 Screening Term.
(a) BI shall have the option, exercisable on any number of
occasions by delivering written notice to PPI not later than six months prior to
the expiration of the Screening Term then in effect, to extend such Screening
Term for an additional one (1) year period commencing on the later of the
expiration of the Screening Term then in effect or the expiration of any
extension thereof pursuant to subsection 2.4(b), provided that on or prior to
the commencement of such additional one (1) year period (i) BI pays (and
delivery of such notice shall constitute BI's agreement to pay) PPI $ 1
million in cash and (ii) the parties have agreed in writing to an amended Work
Plan.
(b) Notwithstanding subsection 2.4(a), if (i) BI is in
compliance with the terms and provisions of this Agreement (including without
limitation the Work Plan), and (ii) at the expiration of the Screening Term then
in effect, PPI has not completed the screening contemplated by the Work Plan
then in effect, then (A) PPI shall, if BI so requests by written notice to PPI
within fifteen (15) days after expiration of the Screening Term then in effect,
complete any such screening and the Screening Term shall be automatically
extended until the completion of such screening and (B) BI shall not be required
to pay PPI the $ 1 million in cash referred to in subsection 2.4(a) in
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respect of the extension of the Screening Term pursuant to this subsection
2.4(b) or to reimburse PPI in accordance with Section 2.3 for expenses incurred
by PPI during such extension.
2.5 Exclusivity.
(a) So long as (i) the Screening Term is in effect and BI has
supplied PPI with compounds in accordance with the Work Plan or (ii) BI is
pursuing Development or marketing of any BI Compound or BI Product with diligent
efforts at least consistent with those of BI with respect to other BI products
with similar commercial potential (the "Exclusivity Period"), PPI shall not
screen any Third Party compounds for A(beta) peptide AAI activity; provided,
however, that this restriction on screening during the Exclusivity Period only
applies to screening of compounds as potential prophylactics or therapeutics.
Without limitation of the foregoing restriction, PPI covenants and agrees with
BI that during the Exclusivity Period, if PPI enters into any agreement with a
Third Party to screen compounds of such Third Party for AAI activity, such
agreement shall provide that such Third Party shall not (i) utilize any
information provided by PPI to such Third Party in connection with the
development of, or (ii) develop, any such Third Party compound for use as a
prophylactic or therapeutic product for Alzheimer's Disease. PPI shall use its
reasonable efforts to enforce any such provision in any such agreement with such
a Third Party. For purposes of this Section 2.5(a), "Third Party" includes any
Recognized Agent of PPI.
(b) During the Exclusivity Period, BI shall not provide any
compounds to any Third Party for screening for A(beta) peptide AAI activity.
Without limitation of the foregoing restriction, BI covenants and agrees with
PPI that during the Exclusivity Period, if BI provides any compounds to any
Third Party for screening for AAI activity, BI will not, and will obtain an
agreement from such Third Party that such Third Party will not, (i) utilize any
information provided to or by such Third Party pursuant to such arrangement in
connection with the development of, or (ii) develop, any such compounds for use
as a prophylactic, therapeutic or diagnostic product for Alzheimer's Disease. BI
shall use its reasonable efforts to enforce any such provision in any such
agreement with such a Third Party. For purposes of this Section 2.5(b), "Third
Party" includes any Recognized Agent of BI.
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ARTICLE 3. LICENSE GRANTS; DEVELOPMENT,
MANUFACTURING AND MARKETING OF BI PRODUCTS
3.1 Grant of License Rights by PPI to BI. Subject to the terms and
conditions of this Agreement, PPI hereby grants to BI an exclusive (except as to
PPI, its Affiliates and their respective sublicensees) right and license in the
Territory during the Exclusivity Period, under the PPI Information and the PPI
Patent Rights, to develop BI Compounds, and to develop, manufacture or have
manufactured, use and sell or have sold BI Compounds as incorporated into a BI
Product, in each case solely for use (i) as a prophylactic or therapeutic or
(ii) as a diagnostic solely to the extent that any such BI Compound is required
as a diagnostic in order to commercialize a BI Compound, and sell the
corresponding BI Product, as a prophylactic or therapeutic. It is understood
that BI will have no right to, and BI agrees that it will not, develop,
manufacture or have manufactured, use, sell or have sold any BI Compound or BI
Product for use as a diagnostic, except as and to the extent that such BI
Compound or BI Product is required as a diagnostic in order for BI to
commercialize a BI Compound, and for BI to sell the corresponding BI Product,
as a prophylactic or therapeutic.
3.2 Sublicense Rights. BI shall have the right to grant sublicenses
with respect to the license granted in Section 3.1 to Affiliates of BI, BI's
Recognized Agents and third parties.
3.3 Diligence; Limit on Sales to Recognized Agents. BI shall (i) use
diligent efforts at least consistent with BI's normal business practices with
respect to other BI products with similar commercial potential, to (A) Develop
BI Compounds (and shall immediately advise PPI in writing if a BI Compound has
been selected and approved for start of development as described in the
definition of Phase 0 (Section 1.22)), manufacture, market and distribute the
corresponding BI Products throughout the Territory and obtain all requisite
regulatory licenses, permits or approvals relating thereto and (B) obtain and
enforce patent and other relevant intellectual property protection in the
Territory for BI Compounds and BI Products with respect to which BI is required
to use diligent efforts pursuant to clause (A) immediately above, and (ii)
provide PPI on a semi-annual basis with status reports in reasonable detail
with respect to such activities. BI covenants
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and agrees with PPI that in no event will the amount of Net Sales in any year of
any BI Product in the Territory to BI's Recognized Agents exceed 10% of the
total amount of Net Sales of such BI Product in the Territory during such year.
3.4 Failure to Market Due to Currency Difficulties. It shall not be
considered a breach of BI's obligations under Section 3.3 if BI reduces or
halts shipments of BI Products to a country which by law, regulation or fiscal
policy, has restricted or forbidden the transfer of funds of a convertible
currency to Germany, provided that BI notifies PPI of any such circumstance and
resumes the obligations to market the BI Products in such country promptly after
such circumstance no longer exists. BI shall, however, remain obligated to pay
royalties to PPI on its Net Sales, if any, in such country as provided in
Article 6.
3.5 Future License Rights.
3.5.1 PPI's Future License Right. In the event (i) BI has not,
within *** after the end of the Screening Term, either (A) commenced Development
of at least one BI Compound or (B) granted a license to at least one BI Compound
to a Third Party which is financially and otherwise reasonably capable of
pursuing the development and commercialization of such BI Compound and which
imposes on such Third Party diligence obligations no less stringent than those
imposed upon BI pursuant to this Agreement, or (ii) if after commencing such
Development or granting such a license to such a Third Party, BI or such Third
Party ceases to pursue such Development or such license is terminated, PPI
shall have the right to obtain an exclusive royalty-bearing license in the
Territory, with the right to grant sublicenses, under any and all applicable BI
Patent Rights and BI know-how, on royalty and other customary terms to be
negotiated in good faith by the parties hereto, to use, develop, manufacture and
have manufactured, any one BI Compound, and to use, manufacture, have
manufactured, distribute for sale, sell and have sold, any corresponding BI
Product. PPI shall have the same license right, to the same extent set forth in
the immediately preceding sentence, with respect to any BI Compound, and
corresponding BI Product, which PPI determines it will seek to develop and
commercialize as a diagnostic, other than any such BI Compound which is required
by BI as a diagnostic in order
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to commercialize any BI Compound, and sell the corresponding BI Product, as a
prophylactic or therapeutic, and of which BI or a Third Party licensee thereof
has commenced and not ceased Development (any such BI Compound as to which PPI
makes such a determination being referred to as a "Licensed Diagnostic
Compound"). BI or any Third Party referred to above shall be deemed to have
ceased Development of a BI Compound if, (i) in the case of BI, it fails to meet
the diligence requirements set forth in Section 3.3 above with respect to
Development of such BI Compound or, in the case of such Third Party it fails to
meet the analogous diligence requirements in the applicable license to such
Third Party or (ii) BI or any Third Party referred to above abandons Development
of such BI Compound or the license held by such Third Party terminates prior to
the Development and commercialization of such BI Compound (the date of any such
cessation or abandonment being referred to herein as an "Abandonment Date"). In
order that PPI may realize the benefits of this Section 3.5.1, (i) BI shall
promptly provide PPI with such information as PPI may reasonably require and
request with respect to each Designated BI Compound if BI has not taken either
of the actions referred to in clause (i) of the first sentence of this Section
3.5.1 within the time period specified in such clause and (ii) BI shall promptly
notify PPI in writing after becoming aware of the occurrence of an Abandonment
Date. Upon the occurrence of an Abandonment Date, or, with respect to any
Licensed Diagnostic Compound, upon notice from PPI that it will seek to develop
such Licensed Diagnostic Compound, BI shall promptly provide PPI with such
information as PPI may reasonably require and request with respect to the BI
Compound which is the subject of such Abandonment Date and/or with respect to
such Licensed Diagnostic Compound, subject to PPI's execution of an appropriate
confidentiality agreement reasonably acceptable to BI, and within fifteen (15)
days of the written request of PPI, the parties shall commence good faith
negotiations with respect to the royalty and other terms of the license of such
BI Compound(s) and/or Licensed Diagnostic Compound(s) to PPI in accordance with
this Section 3.5.1. If within sixty (60) days of the commencement of such
negotiations the parties have not entered into a definitive license agreement
with respect to such BI Compound(s) and/or Licensed Diagnostic Compound(s), the
terms of such license agreement shall be determined by binding arbitration in
accordance with Section 11.7 hereof, and the par-
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ties shall be obligated to promptly execute and deliver a definitive license
agreement containing such terms.
3.5.2 BI's Right of First Refusal. BI shall, subject to and in
accordance with the provisions set forth below, have a right of first
negotiation to obtain an exclusive royalty-bearing license in the Territory with
respect to any PPI Compound, solely for use as a prophylactic or therapeutic
for Alzheimer's Disease, which PPI has determined to seek to license to a Third
Party. PPI shall promptly notify BI of such determination (a "PPI License
Notice"), and BI shall have twenty (20) days after receipt of a PPI License
Notice to notify PPI (an "Initial BI License Response Notice") that it may seek
to enter into such negotiations and, as part of such Initial BI License Response
Notice, to request such information with respect to such PPI Compound as it
reasonably requires to determine whether to enter into such negotiations. If BI
has timely delivered an Initial BI License Response Notice, PPI shall promptly
provide such information with respect to such PPI Compound as BI has requested
in the Initial BI License Response Notice and is available to PPI, subject to
BI's execution of an appropriate confidentiality agreement reasonably acceptable
to PPI. BI shall have thirty (30) days after PPI's substantial compliance with
the information request included as part of the Initial BI License Response
Notice to notify PPI in writing that it has determined to enter into such
negotiations (a "BI Negotiation Notice"). If BI has not timely delivered a BI
Negotiation Notice, PPI shall be free to enter into an agreement with a Third
Party to license such PPI Compound on such terms and conditions as PPI shall
determine. If BI timely delivers a BI Negotiation Notice, then for a period of
sixty (60) days after PPI's receipt of such BI Negotiation Notice, PPI will
negotiate exclusively with BI with respect to the terms of such a license. If at
the end of such sixty (60) day period the parties have not entered into a
definitive license agreement with respect to such PPI Compound, then PPI shall
be free to enter into an agreement with a Third Party to license such PPI
Compound, provided that the terms of such license agreement shall not, taken as
a whole, be materially more favorable to such Third Party than the terms, if
any, last offered in writing by BI to PPI during the aforesaid sixty (60) day
period, unless PPI has first offered BI in writing the opportunity to enter into
the license agreement containing such more favorable terms and BI has not
executed and delivered such
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license agreement within twenty (20) days after receipt of such written offer
from PPI.
ARTICLE 4. EXCHANGE OF INFORMATION
4.1 Information to be Provided. During the Screening Term, each
party shall promptly provide the other party with information and results
generated from the Screening Program (the "Exchange Information"), and, without
limiting the generality of the foregoing, PPI shall promptly provide BI with SAR
Information to the extent reasonably necessary to facilitate BI's selection of a
BI Compound for Development; provided, however, that PPI shall not be required
to provide BI with any clinical data relating to any PPI Compound. However, PPI
agrees to provide BI with copies of its clinical plans and protocols relating to
clinical trials with respect to each PPI Compound, and PPI agrees, and BI shall
have the right for a sixty (60) day period after receipt of such clinical plans
or protocols, to negotiate in good faith the financial and other terms and
conditions upon which BI would gain access to such clinical data.
4.2 Information Not Required to be Provided; Restriction on
Certain Research Activities. Notwithstanding Section 4.1 or any other
provision of this Agreement, (i) so long as the withholding of Exchange
Information does not materially adversely affect the Screening Program,
neither party shall be required to provide the other party with general,
enabling technology or with other general technical information or know-how
which is applicable outside the scope of the Screening Program and (ii)
neither party will analyze the chemical and/or physical properties of any
compound provided by such party to the other party hereunder or otherwise
undertake any analysis of such compound to derive or elucidate such
structural information; provided, that upon BI's selection of a BI Compound
for Development, or PPI's exercise of its license rights with respect to a BI
Compound (including a Licensed Diagnostic Compound) pursuant to Section
3.5.1, BI shall promptly disclose to PPI structural information with respect
to such BI Compound(s).
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ARTICLE 5. INTELLECTUAL PROPERTY RIGHTS
Except to the extent expressly set forth in this Agreement, (a) all
right, title and interest in PPI Patent Rights, other patent or intellectual
property rights of any kind relating to any PPI Compounds, all PPI Information
and any PPI Compounds shall be and remain vested solely and exclusively in PPI,
(b) all right, title and interest in all BI Patent Rights, BI Information and
BI Compounds shall be and remain vested solely and exclusively in BI and (c)
under no circumstances shall a party hereto, as a result of this Agreement,
obtain any ownership interest in or other right to any technology, know-how,
patents, pending patent applications, products or biological materials of the
other party, including items owned, controlled or developed by the other party,
or transferred by the other party to said party, at any time pursuant to this
Agreement.
ARTICLE 6. ROYALTIES
6.1 Royalties on Net Sales.
6.1.1 Royalty Rate.
(a) In consideration of the rights granted to BI under
Section 3.1, with respect to any BI Product, BI shall pay PPI (i) a royalty in
the amount equal to ***% of annual Net Sales of such BI Product (the "***%
Royalty Rate") up to $***, and (ii) a royalty in the amount equal to ***% of
that portion of annual Net Sales of such BI Product (the "***% Royalty Rate")
greater than $***. Each of the ***% Royalty Rate and the ***% Royalty Rate are
referred to herein as the "Applicable Base Royalty Rate." The Applicable Base
Royalty Rate is subject to increase as provided in Section 6.1.1(b), and to
reduction as provided in Section 6.1.1(c) and Section 6.8.
(b) If, within three years after PPI's First Commercial Sale
of a PPI Product in a country, BI introduces a BI Product to the market in such
country, the Applicable Base Royalty Rate with respect to Net Sales of such BI
Product in such country for the first and second consecutive twelve-month
periods, respectively, commencing on the First Commercial Sale of such BI
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Product in such country, shall be the Applicable Base Royalty Rate with respect
to such Net Sales, plus ***% and ***%, respectively; provided, however, that the
maximum amount of additional royalties (over and above the amount of royalties
payable pursuant to paragraph (a) above) which BI shall be obligated to pay PPI
pursuant to this paragraph (b) shall not exceed 50% of the Net Sales of such PPI
Product in such country during the consecutive twelve calendar months
immediately preceding the First Commercial Sale of such BI Product in such
country.
(c) If (i) in any calendar year commencing after the end of
the first full calendar year following the First Commercial Sale of a BI
Product in a country, Net Sales of such BI Product in the Territory are less
than $*** and (ii) in such country the number of units of a Third Party AD
Product sold in such country during such year exceeds ***%, ***%, ***%, ***% or
***%, respectively, of the number of units of such BI Product sold in such
country during such year, the Applicable Base Royalty Rate with respect to Net
Sales of such BI Product in such country during such year shall be reduced by
***%, ***%, ***%, ***% or ***%, respectively, provided that in no event shall
such Applicable Base Royalty Rate be reduced by more than ***% (including
pursuant to the operation of Section 6.1.1(c), alone or together with Section
6.8.) The percentage reduction(s) (if any) of the Applicable Base Royalty Rate
in any country in respect of any year pursuant to this Section 6.1.1(c) shall
be set forth in the quarterly royalty report of BI for the last quarter of such
year contemplated by Section 6.2. If any such reduction is applicable, then the
amount of any royalties previously paid by BI during such year in excess of the
amount which would have been payable based on the Applicable Base Royalty Rate,
as so reduced, shall be an offset against the amount of royal ties payable by BI
in respect of the last quarter of such year (calculated without giving effect to
any such reduction) and, as necessary, against the amount of royalties
otherwise payable thereafter; provided that BI shall not be entitled to offset
more than ***% of the amount of royalties which would otherwise be payable to
PPI in any fiscal quarter.
(d) With respect to any BI Compound or BI Product, promptly
after completion of Phase II and pro-
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vided a PPI Change of Control Transaction has not occurred, BI shall provide
PPI with all information relating to the Development thereof, all data,
clinical results and protocols for the commencement of Phase III with respect
thereto, and, whether or not a PPI Change of Control Transaction has occurred, a
detailed budget which sets forth a fair and reasonable estimate of the costs
associated with such Phase III. Within ninety (90) days of receipt of such
information, PPI may elect by written notice to BI to reimburse BI on a
quarterly basis for ***%, ***% or ***% of the actual Phase III Development costs
paid by BI, and, from and after delivery of such notice by PI, the royalty rate
payable by BI with respect to Net Sales of a BI Product shall be the rate which
would otherwise be applicable pursuant to Sections 6.1(a), (b) and (c), plus
***%, ***% or ***%, respectively (such applicable additional percentage being
referred to as the "PPI Investment Percentage Royalty Rate Increase"), and PPI
shall be obligated to make such reimbursement payments within fifteen (15) days
after receiving an invoice therefor containing a reasonable itemization of
such costs. It is understood and agreed that BI shall have sole responsibility
with respect to any decision regarding the Phase III referred to in this
Section 6.1.1(d).
6.1.2 Third Party Patents; Combination BI Products; Bundled
Products.
(a) If BI, its Affiliates or sublicensees can demonstrate
that, in order to operate under or exploit any license granted under Section
3.1 in any country they must make payments (including without limitation
royalties, option fees or license fees) to one or more Third Parties to obtain a
license or similar right in the absence of which the BI Product could not be
legally manufactured or sold in such country, BI and PPI shall enter into good
faith negotiations with a view to agreeing on a reasonable amount that BI may
deduct from the royalties payable to PPI hereunder in respect of Net Sales of
such BI Product in such country in any given quarter.
(b) If a BI Product contains an active ingredient in addition
to a BI Compound, then BI and PPI shall enter into good faith negotiations with
a view to agreeing on an appropriate reduction in the Applicable
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Base Royalty Rate with respect to Net Sales of such BI Product.
(c) If a Bundled Product (as defined in Section 1.20) is sold,
the parties will promptly negotiate mutually agreeable royalty terms with
respect to sales of such Bundled Product. If within sixty (60) days of the
commencement of such negotiations, such royalty terms have not been agreed to in
writing by the parties, such royalty terms shall be determined by binding
arbitration in accordance with Section 11.7 hereof.
6.1.3 Sublicense Royalties. If BI grants a sublicense
hereunder to any Third Party to make, have made, use, distribute for sale or
sell the BI Products in any country, BI shall pay to PPI royalties on Net Sales
of the BI Products sold by such Third Party in such country at the royalty rate
set forth in Section 6.1.1 that would be applicable had such sales been made by
BI.
6.2 Royalty Reports; Exchange Rates. Following the First Commercial
Sale of any BI Product in any country, BI shall within thirty (30) days after
each calendar quarter furnish to PPI a written quarterly report showing: (i) the
gross sales of the BI Product sold by BI, its Affiliates and sublicensees,
including sales by BI to Recognized Agents during the reporting period and the
calculation of Net Sales from such gross sales; (ii) withholding taxes, if any,
required by law to be deducted in respect of such sales; and (iii) the exchange
rates used in determining the amount of United States dollars. All sales in
currencies other than United States dollars shall first be converted into German
marks and then into United States dollars using in both cases the average
monthly exchange rates as published regularly by Deutsche Bank in Frankfurt am
Main, Germany, and as customarily used by BI in its accounting system. If no
royalty is due for any royalty period hereunder, BI shall so report. BI shall
keep complete and accurate records in sufficient detail to properly reflect all
gross sales and Net Sales and to enable the royalties payable hereunder to be
determined.
6.3 Audits. Upon the written request of PPI, BI shall permit an
independent public accountant selected by PPI and acceptable to BI, which
acceptance shall not be unreasonably withheld, to have access during normal
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business hours to such records of BI as may be reasonably necessary to verify
the accuracy of the royalty reports described herein, in respect of any fiscal
year ending not more than thirty-six (36) months prior to the date of such
request. All such verifications shall be conducted at PPI's expense and not more
than once in each calendar year. In the event such PPI representative concludes
that additional royalties were owed to PPI during such period, the additional
royalty shall be paid by BI within thirty (30) days of the date PPI delivers to
BI such representative's written report so concluding. The fees charged by such
representative shall be paid by PPI unless the audit discloses that the
royalties payable by BI for the audited period are incorrect by more than five
percent (5%), in which case BI shall pay the reasonable fees and expenses
charged by such representative. BI shall include in each Third Party sublicense
granted by it pursuant to this Agreement a provision requiring the sublicensee
to make reports to BI, to keep and maintain records of sales made pursuant to
such sublicense and to grant access to such records by PPI's representatives to
the same extent required of BI under this Agreement. PPI agrees that all
information subject to review under this Section 6.3 or under any sublicense
agreement is confidential and that PPI shall cause its representatives to
retain all such information in confidence.
6.4 Royalty Payment Terms. Royalties shown to have accrued by each
royalty report provided for under this Agreement shall be due thirty (30) days
after the end of each calendar quarter. Payment of royalties in whole or in part
may be made in advance of such due date. Royalties determined to be owing with
respect to any prior quarter shall be added, together with interest thereon
accruing under this Agreement from the date of the report for the quarter for
which such amounts are owing, to the next quarterly payment hereunder.
6.5 Withholding Taxes. BI shall deduct any withholding taxes from
the payments agreed upon under this Agreement and pay them to the proper tax
authorities required by the laws of the Federal Republic of Germany applicable
at the date of payment. BI shall not deduct any other withholding or any other
governmental charges from the payments agreed upon under this Agreement,
including but not limited to any such taxes or charges incurred as a result of
an assignment or sublicense by BI
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to any Affiliate or any Third Party, except as noted above. BI shall maintain
official receipts of payment of any withholding taxes and forward these receipts
to PPI.
The parties will exercise their best efforts to ensure that any withholding
taxes imposed are reduced as far as possible under the provisions of the current
or any future double taxation agreement between the United States and the
Federal Republic of Germany. According to existing German Law, this reduction
requires that the German Bundesamt fur Finanzen issue a Certificate of Tax
Exemption. In order to achieve such reduction, PPI shall provide BI with an
application for a certificate of tax exemption for royalties under the US-German
Double Taxation Treaty performed on the official German form (Application for
Tax Exemption) and signed by PPI. The Certification of Filing a Tax Return (IRS
Form 6166) must be enclosed with the Application For Tax Exemption. BI shall
provide PPI with the official German form. Once every three years after PPI
first provides BI with an Application For Tax Exemption, it will provide BI with
a new such Application unsolicited which complies with the above mentioned
prerequisites.
6.6 Application for Tax Exemption. The payments are not due until
PPI provides BI with the Application for Tax Exemption fulfilling the
prerequisites set out in Section 6.5 of this Agreement. Payments arising after
expiration of any Certification of Tax Exemption are not due until the next
Application for Tax Exemption is filed with BI. Notwithstanding the preceding
provisions of this Section 6.6, in the event of any extended delay in approval
or effectiveness of the Application for Tax Exemption, PPI may require payment
of any amounts due pursuant to this Agreement after deduction of any applicable
withholding taxes. PPI shall be notified by BI of any changes regarding the
filing of Applications for Tax Exemption.
6.7 Interest on Late Payments. Any payments by BI to PPI that are
not paid on or before the date such payments are due under this Agreement shall
bear interest, to the extent permitted by applicable law, at two (2) percentage
points above the Prime Rate of interest declared from time to time by The First
National Bank of Boston in Boston, Massachusetts, calculated on the number of
days payment is delinquent.
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6.8 Duration of Royalties; Step Down. If (a) the expiration date of
the last to expire of the PPI Patent Rights in any country (with respect to such
country, the "Patent Expiration Date") occurs prior to the date which is ten
(10) years after the First Commercial Sale of a BI Product in such country (with
respect to such country, the end of such tenth year being referred to herein as
the "Sale Date"), (i) the Applicable Base Royalty Rate with respect to Net Sales
of such BI Product in such country shall (A) decrease by ***% on such Patent
Expiration Date (unless, with respect to the year in which the Patent Expiration
Date occurs in such country and any subsequent year, the Applicable Base Royalty
Rate with respect to Net Sales of such BI Product in such country for such year
has already been reduced pursuant to Section 6.1.1(c)) and (B) decrease by an
additional ***% (or such lesser percentage such that, together with any
reduction of the Applicable Base Royalty Rate pursuant to Section 6.1.1(c), the
Applicable Base Royalty Rate with respect to Net Sales of such BI Product in
such country in the year in which the Sale Date occurs and any subsequent year
is decreased by ***%) on such Sale Date and (ii) any PPI Investment Percentage
Royalty Rate Increase in effect with respect to Net Sales of such BI Product in
such country shall decrease by ***% on such Sale Date, and (b) if the Sale Date
occurs prior to the Patent Expiration Date, (i) the Applicable Base Royalty Rate
with respect to Net Sales of such BI Product in such country shall decrease by
***% (or such lesser percentage such that, together with any reduction of the
Applicable Base Royalty Rate pursuant to Section 6.1.1(c), the Applicable Base
Royalty Rate with respect to Net Sales of such BI Product in such country in the
year in which the Sale Date occurs and any subsequent year is decreased by ***%)
on such Sale Date and (ii) any PPI Investment Percentage Royalty Rate Increase
in effect with respect to Net Sales of such BI Product in such country shall
decrease by ***% on such Sale Date; provided, that in no event shall the
Applicable Base Royalty Rate be decreased by more than ***% (including pursuant
to the operation of Section 6.1.1(c), alone or together with this Section 6.8),
and provided further that no royalties with respect to Net Sales of a BI Product
in a country shall be payable in accordance with this Article 6 after the date
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which is fifteen (15) years after the First Commercial Sale of a BI Product in
such country.
ARTICLE 7. CONFIDENTIALITY
7.1 Nondisclosure Obligations.
7.1.1 General. Except as otherwise provided in this Article 7,
both parties shall maintain in strict confidence and use only for purposes
specifically authorized under this Agreement (i) information and data received
from the other party resulting from or related to the Screening Program
(including without limitation SAR Information and PPI Information) or the
Development of any BI Product and (ii) all information and data not described in
clause (i) but supplied by the other party under this Agreement and marked
"Confidential." For purposes of this Article 7, information and data described
in clause (i) or (ii) shall be referred to as "Information."
7.1.2 Limitations. To the extent it is reasonably necessary or
appropriate to fulfill its obligations or exercise its rights under this
Agreement, a party may disclose Information it is otherwise obligated under this
Section not to disclose to its Affiliates, sublicensees, consultants, outside
contractors and clinical investigators, on a need-to-know basis on condition
that such entities or persons agree to keep the Information confidential to the
same extent as such party is required to keep the Information confidential; and
a party or its sublicensees may disclose such Information to government or other
regulatory authorities to the extent that such disclosure is reasonably
necessary to obtain patents or authorizations to conduct clinical trials of, and
to commercially market, the BI Products. The obligation not to disclose
Information shall not apply to any part of such Information that: (i) is or
becomes part of the public domain other than by unauthorized acts of the party
obligated not to disclose such Information or its Affiliates or sublicensees;
(ii) can be shown by written documents to have been disclosed to the receiving
party or its Affiliates or sublicensees by a Third Party, provided such
Information was not obtained by such Third Party directly or indirectly from the
other party under this Agreement pursuant to a confidentiality agreement; (iii)
prior to disclosure under this Agree-
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ment, was already in the possession of the receiving party or its Affiliates or
sublicensees, provided such Information was not obtained directly or indirectly
from the other party under this Agreement pursuant to a confidentiality
agreement; (iv) can be shown by written documents to have been independently
developed by the receiving party or its Affiliates without breach of any of the
provisions of this Agreement; or (v) is disclosed by the receiving party
pursuant to interrogatories, requests for information or documents, subpoena,
civil investigative demand issued by a court or governmental agency or as
otherwise required by law; provided, that the receiving party notifies the other
party immediately upon receipt thereof (and provided that the disclosing party
furnishes only that portion of the Information which it is advised by counsel is
legally required).
7.2 Terms of this Agreement. PPI and BI each agree not to disclose
any terms or conditions of this Agreement to any Third Party without the prior
written consent of the other party, except as required by applicable law,
including without limitation the rules and regulations of the SEC governing
disclosure to shareholders or potential investors. If PPI determines that it is
required to file with the SEC or other governmental agency this Agreement for
any reason, PPI shall request confidential treatment of such portions of this
Agreement as it and BI shall together determine. Notwithstanding the foregoing,
prior to execution of this Agreement, PPI and BI shall agree upon the substance
of information that can be used as a routine reference in the usual course of
business to describe the terms of this Agreement, and PPI and BI may disclose
such information, as modified by mutual agreement from time to time, without the
other party's consent.
7.3 Publications.
7.3.1 Procedure. Each party recognizes the mutual interest in
avoiding premature publication of information and data with respect to the
results of the Screening Program ("Screening Data"). In the event that, either
party, its employees or consultants or any other Third Party under contract to
such party wishes to make a publication (including any oral disclosure made
without obligation of confidentiality) disclosing any Screening Data (the
"Publishing Party"), such party shall transmit
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to the other party (the "Reviewing Party") a copy of the proposed written
publication at least forty-five (45) days prior to submission for publication,
or an abstract of such oral disclosure at least thirty (30) days prior to
submission of the abstract or the oral disclosure, whichever is earlier. The
Reviewing Party shall have the right (a) to propose modifications to the
publication for patent reasons, (b) to request a delay in publication or
presentation in order to protect patentable information, or (c) to request that
the information be maintained as a trade secret and, in such case, the
Publishing Party shall not make such publication.
7.3.2 Delay. If the Reviewing Party requests a delay as
described in subsection 7.3.1.(b), the Publishing Party shall delay submission
or presentation of the publication for a period of ninety (90) days to enable
patent applications protecting each party's rights in such information to be
filed.
7.3.3 Resolution. Upon the receipt of written approval of the
Reviewing Party, the Publishing Party may proceed with the written publication
or the oral presentation.
7.4 Injunctive Relief. The parties hereto understand and agree that
remedies at law may be inadequate to protect against any breach of any of the
provisions of this Article 7 by either party or their employees, agents,
officers or directors or any other person acting in concert with it or on its
behalf. Accordingly, each party shall be entitled to the granting of injunctive
relief by a court of competent jurisdiction against any action that constitutes
any such breach of this Article 7.
ARTICLE 8. REPRESENTATIONS AND WARRANTIES
Each party represents and warrants to the other that it has the
legal right and power to enter into this Agreement, to extend the rights and
licenses granted to the other in this Agreement, and that the performance of
such obligations will not conflict with its charter documents or any agreements,
contracts or other arrangements to which it is a party. BI further represents
and warrants to, and covenants with, PPI that (a) BI is a
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limited liability company duly organized, validly existing and in good standing
under applicable German law and has taken all necessary action to authorize the
execution, delivery and performance of this Agreement and (b) upon the
execution and delivery of this Agreement, this Agreement shall constitute a
valid and binding obligation of BI enforceable in accordance with its terms,
except as enforceability may be limited by applicable bankruptcy, insolvency,
reorganization, moratorium or similar laws affecting creditors' and contracting
parties' rights generally and except as enforceability may be subject to general
principles of equity (regardless of whether such enforceability is considered in
a proceeding in equity or at law).
ARTICLE 9. INDEMNITY
9.1 BI Indemnity Obligations. BI agrees to defend, indemnify and
hold PPI, its Affiliates and their respective employees and agents harmless from
all claims, losses, damages or expenses arising as a result of: (a) actual or
asserted violations of any applicable law or regulation by BI, its Affiliates or
sublicensees in connection with the manufacture, distribution or sale or use of
any BI Compounds or BI Products; (b) claims for bodily injury, death or property
damage attributable to the manufacture, distribution, sale or use of BI Com
pounds or BI Products by BI, its Affiliates or sublicensees; or (c) a BI
Product recall ordered by a governmental agency or required by a confirmed BI
Product failure as reasonably determined by the parties hereto.
9.2 PPI Indemnity Obligations. PPI, its Affiliates and their
respective employees and agents shall not be entitled to the indemnities set
forth in Section 9.1 to the extent the loss, damage or expense for which
indemnification is sought was caused by the negligence, willful misconduct or
material breach of this Agreement by PPI or its Affiliates or sublicensees.
Further, should BI be found responsible for claims, losses or expenses caused by
any such negligence, willful misconduct or breach by PPI or its Affiliates and
not attributable to other causes for which BI is responsible, BI shall be
entitled to an indemnity from PPI to the same extent as PPI would be so entitled
from BI under Section 9.1 above.
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9.3 Procedure. A party or any of its Affiliates or their respective
employees or agents (the "Indemnitee") that intends to claim indemnification
under this Article 9 shall promptly notify the other party (the "Indemnitor") of
any loss, claim, damage, liability or action in respect of which the Indemnitee
intends to claim such indemnification, and the Indemnitor shall assume the
defense thereof with counsel mutually satisfactory to the parties; provided,
however, that an Indemnitee shall have the right to retain its own counsel,
with the fees and expenses to be paid by the Indemnitor, if representation of
such Indemnitee by the counsel retained by the Indemnitor would be inappropriate
due to actual or potential differing interests between such Indemnitee and any
other party represented by such counsel in such proceedings. The indemnity
agreement in this Article 9 shall not apply to amounts paid in settlement of any
loss, claim, damage, liability or action if such settlement is effected without
the consent of the Indemnitor, which consent shall not be unreasonably
withheld. The failure to deliver notice to the Indemnitor within a reasonable
time after the commencement of any such action, if prejudicial to its ability
to defend such action, shall relieve such Indemnitor of any liability to the
Indemnitee under this Article 9, but the omission so to deliver notice to the
Indemnitor will not relieve it of any liability that it may have to any
Indemnitee otherwise than under this Article 9. The Indemnitee under this
Article 9, its employees and agents, shall cooperate fully with the Indemnitor
and its legal representatives in the investigation of any action, claim or
liability covered by this indemnification. In the event that each party claims
indemnity from the other and one party is finally held liable to indemnify the
other, the Indemnitor shall additionally be liable to pay the reasonable legal
costs and attorneys' fees incurred by the Indemnitee in establishing its claim
for indemnity.
9.4 Insurance. BI shall maintain appropriate product liability
insurance with respect to the Development, manufacture and sales of BI Products
by BI in such amount as BI customarily maintains with respect to sales of
similar products. BI shall maintain such insurance for so long as it continues
to manufacture or sell BI Products, and thereafter for so long as BI maintains
insurance for itself covering such manufacture or sales.
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ARTICLE 10. TERMINATION
10.1 Termination. This Agreement may be terminated in the following
circumstances:
10.1.1 Material Breach. By a party upon written notice to the
other party by reason of a material breach by such other party not described in
Section 10.1.2 or 10.1.3 that the breaching party fails to remedy within ninety
(90) days after written notice thereof by the non-breaching party;
10.1.2 Failure of BI to Pay. By PPI, if BI fails to make (i)
any payment to PPI required under Section 2.2 or 2.3 within fifteen (15) days
after such payment becomes payable or (ii) any royalty payment under Section 6.1
within thirty (30) days after such payment becomes payable, and, in either such
case, such failure is not remedied within thirty (30) days after notice thereof
from PPI;
10.1.3 Failure of BI to Use Diligent Efforts. By PPI, if BI
fails to use diligent efforts as required by Section 3.3, and BI fails to remedy
or take reasonable action to initiate a remedy of such default within ninety
(90) days after the notice thereof by PPI;
10.1.4 Bankruptcy. By either party upon bankruptcy,
insolvency, dissolution or winding up of the other; and
10.1.5 Change of Control. By BI if, prior to the end of the
Screening Term, a transaction with a Third Party is consummated involving (a)
the acquisition, merger or consolidation of PPI and (i) PPI is not the
acquiring, surviving or continuing corporation or (ii) PPI is the surviving or
continuing corporation, but, in connection with such transaction, the then out
standing shares of the capital stock of PPI were changed into or exchanged for
stock or other securities of such Third Party or cash or other property or the
then out standing shares of the capital stock of PPI represented less than fifty
percent (50%) of the outstanding shares and share equivalents of the surviving
or continuing corporation immediately after consummation of such transaction or
(b) the sale or other disposition of more than fifty percent (50%) of the voting
capital stock of PPI or
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all or substantially all of the assets of PPI to a Third Party, and such Third
Party is a major pharmaceutical company that is in competition with BI.
10.2 Effect of Termination Generally.
10.2.1 Existing Obligations. Termination pursuant to Section
10.1 of this Agreement for any reason shall not relieve the parties of any
obligation accruing prior to such termination.
10.2.2 Survival. Except as otherwise expressly provided below
in this Article 10, the provisions of Sections 2.2 and 2.3 (with respect only
to payments and expense reimbursement payments accrued at the time of
termination but not yet paid), Article 3, Articles 5 through 9, this Section
10.2, Section 10.3 (if this Agreement is terminated by PPI pursuant to Section
10.1), Section 10.4.1 (if this Agreement is terminated by BI pursuant to Section
10.1.1), Section 10.4.2 (if this Agreement is terminated pursuant to Section
10.1.5) and Article 11 (as applicable to such surviving provisions) shall
survive termination of this Agreement pursuant to Section 10.1.
10.3 Effect of Termination by PPI.
10.3.1 Termination By PPI Prior to Commencement of Phase III.
In the event that this Agreement is terminated by PPI pursuant to Section 10.1
prior to the time that a BI Compound or BI Product enters Phase III (such time
being referred to as the "Phase III Initiation Date"), then (i) all licenses
and rights granted to BI hereunder shall terminate, except to the extent PPI
otherwise determines and advises BI in writing, and BI will immediately cease
Development of any BI Compound, (ii) BI shall, (a) to the extent legally
permissible, take all action reasonably necessary to assign all of its right,
title and interest in and transfer possession and control to PPI of the
regulatory filings prepared by BI, and regulatory approvals received by BI, to
the extent that such filings and approvals relate to a BI Compound and/or any BI
Product and (b) grant PPI, and take any other action necessary to provide PPI
with, a worldwide, perpetual, exclusive, fully-paid and royalty free right and
license, with the right to grant sublicenses, under any and all applicable BI
Patent Rights and BI know-how
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to develop such BI Compound, and to develop, manufacture or have manufactured,
use and sell or have sold such BI Compound as incorporated into a BI Product and
(iii) PPI shall retain any and all remedies which may be available to it at law
or in equity.
10.3.2 Termination By PPI After Commencement of Phase III. In
the event that PPI is entitled to terminate this Agreement pursuant to Section
10.1 after the Phase III Initiation Date, then from and after the time such
right of termination first arises, (i) the Applicable Base Royalty Rate
applicable to Net Sales of any BI Product in any country shall be *** times such
Applicable Base Royalty Rate as would have otherwise applied and (ii) PPI shall
retain any and all remedies which may be available to it at law or in equity.
10.4 Effect of Termination by BI.
10.4.1 Termination for PPI Breach. (a) In the event that BI is
entitled to terminate this Agreement pursuant to Section 10.1.1, BI may elect,
by notice to PPI (a "Section 10.4.1(a) Notice") not later than thirty (30) days
after such right first arises, to either (i) terminate this Agreement, in which
case all licenses and rights granted to BI shall terminate, except to the extent
the parties otherwise agree in writing, and BI will immediately cease
Development of any BI Compound and will cease to manufacture and sell any BI
Products except as provided in this Section 10.4.1(a) and except as the parties
otherwise agree in writing, and BI shall retain any and all remedies which may
be available to it at law or in equity or (ii) pursue the remedy set forth in
Section 10.4.1(b) below (it being understood and agreed that if BI fails to
deliver to PPI a Section 10.4.1(a) Notice within the required thirty (30) day
period, BI shall be deemed to have elected such remedy set forth in Section
10.4.1(b) below). If BI elects to terminate this Agreement pursuant to clause
(i) above, then (x) BI may dispose of its inventory of BI Products on hand as of
the effective date of termination, and may fill any orders for twelve (12)
months after the effective date of termination and (y) within thirty (30) days
after disposition of such inventory and fulfillment of such orders (and in any
event within seven (7) months after termination) BI will forward to PPI a final
report and, subject to Section 10.5, if applicable, pay all royalties due for
Net Sales in such period.
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(b) If BI elects, pursuant to Section 10.4.1, to pursue the remedy
set forth in this paragraph (b), then (i) BI shall have the right and option, if
it has obtained a final judgment or award of monetary damages and/or costs
against PPI based on such breach, (A) to offset the amount of such damages
and/or costs against any amounts would otherwise be payable to PPI under Article
2 or Article 6 and (B) if the breach which gave rise to BI's right to terminate
this Agreement was PPI's material breach of BI's right to exclusivity pursuant
to Section 2.5 or Section 3.1, (1) BI may cease paying royalties to PPI
hereunder (and in such event BI shall be deemed to have a paid-up and royalty
free license equivalent to that set forth in Section 3.1 hereof), (2) PPI's
rights pursuant to Section 3.5.1 shall automatically terminate, if such breach
occurs prior to the Phase III Initiation Date or equivalent development stage of
a Licensed Diagnostic Compound and (3) the parties acknowledge and agree that if
such breach occurs after the Phase III Initiation Date or equivalent development
stage of a Licensed Diagnostic Compound, the royalties which would otherwise be
payable by PPI to BI pursuant to the license agreement referred to in Section
3.5.1 (or which would be considered customary for purposes of the license
negotiation referred to in such Section) shall be multiplied by 3, and (ii) BI
shall retain any and all remedies (other than termination of this Agreement)
which may be available to it at law or in equity.
10.4.2 Termination for Change of Control. In the event that BI
is entitled to terminate this Agreement pursuant to Section 10.1.5, BI may
terminate this Agreement, in which case all licenses and rights granted to BI
shall terminate, except to the extent PPI otherwise determines and advises BI in
writing, and BI will immediately cease Development of any BI Compound.
ARTICLE 11. MISCELLANEOUS
11.1 Force Majeure. Neither party shall be held liable or
responsible to the other party nor be deemed to have defaulted under or breached
this Agreement for failure or delay in fulfilling or performing any term of this
Agreement when such failure or delay is caused by or results from causes beyond
the reasonable control of the affected party, including but not limited to fire,
floods, embargoes, war, acts of war (whether war is declared or
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not), insurrections, riots, civil commotions, strikes, lockouts or other labor
disturbances, acts of God or acts, omissions or delays in acting by any
governmental authority or the other party; provided, however, that the party so
affected shall use reasonable commercial effects to avoid or remove such causes
of non-performance, and shall continue performance hereunder with reasonable
dispatch whenever such causes are removed. Either party shall provide the other
party with prompt written notice of any delay or failure to perform that occurs
by reason of force majeure. The parties shall mutually seek a resolution of the
delay or the failure to perform as noted above. It is understood and agreed that
if this Section 11.1 is applicable to a party's failure or delay in performing
its obligations under the Work Plan, the other party will not be obligated
thereunder until the first party has so performed, and if such failure or delay
is by PPI, BI will not be obligated to pay PPI the payment required by Section
2.2(b) until such failure or delay is cured. It is further agreed that if such
failure or delay by either party continues for more than twelve consecutive
months, the other party shall have the right to terminate this Agreement with
the effect provided in Section 10.3.1. (if such failure or delay is by BI) or
Section 10.4.1 (if such failure or delay is by PPI).
11.2 Assignment. This Agreement may not be assigned or otherwise
transferred by either party without the consent of the other party; provided,
however, that either PPI or BI may, without such consent, assign its rights and
obligations under this Agreement (i) in connection with a corporate
reorganization, to any Affiliate, all or substantially all of the equity
interest of which is owned and controlled by such party or its direct or
indirect parent corporation, or (ii) in connection with a merger, consolidation
or sale of substantially all of such party's assets to an unrelated third party;
provided, however, that such party's rights and obligations under this Agreement
shall be assumed (by operation of law or otherwise) by its successor in interest
in any such transaction and shall not be transferred separate from all or
substantially all of its other business assets, including those business assets
that are the subject of this Agreement. Any purported assignment in violation
of the preceding sentence shall be void. Any permitted assignee
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shall assume all obligations of its assignor under this Agreement.
11.3 Severability. Each party hereby agrees that it does not intend
to violate any public policy, statutory or common laws, rules, regulations,
treaty or decision of any government agency or executive body thereof of any
country or community or association of countries. Should one or more provisions
of this Agreement be or become invalid, the parties hereto shall substitute, by
mutual consent, valid provisions for such invalid provisions which valid
provisions in their economic effect are sufficiently similar to the invalid
provisions that it can be reasonably assumed that the parties would have entered
into this Agreement with such valid provisions. In case such valid provisions
cannot be agreed upon, the invalidity of one or several provisions of this
Agreement shall not affect the validity of this Agreement as a whole, unless the
invalid provisions are of such essential importance to this Agreement that it is
to be reasonably assumed that the parties would not have entered into this
Agreement without the invalid provisions.
11.4 Notices. Any consent, notice or report required or permitted to
be given or made under this Agreement by one of the parties hereto to the other
shall be in writing, delivered personally or by facsimile (and promptly
confirmed by telephone, personal delivery or courier) or courier, postage
prepaid (where applicable), addressed to such other party at its address
indicated below, or to such other address as the addressee shall have last
furnished in writing to the addressor and shall be effective upon receipt by the
addressee.
If to PPI: Pharmaceutical Peptides, Inc.
One Hampshire Street
Cambridge, Massachusetts 02139
Attention: President
Telephone: (617) 494-8400
Telecopy: (617) 494-8414
with copy to: Skadden, Arps, Slate, Meagher & Flom
One Beacon Street, 31st Floor
Boston, Massachusetts 02108
Attention: Kent A. Coit, Esq.
Telephone: (617) 573-4835
Telecopy: (617) 573-4822
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If to BI: Boehringer Ingelheim International GmbH
Postbox 200
D-55216 Ingelheim, Rhein
Germany
Attention: Corporate Licensing
Telephone: 011 49 61 32 77 34 08
Telecopy: 011 49 61 32 77 35 83
with a copy to: Boehringer Ingelheim International GmbH
Postbox 200
D-55216 Ingelheim, Rhein
Germany
Attention: Head of Legal Department
Telephone: 011 49 61 32 77 21 06
Telecopy: 011 49 61 32 77 35 83
11.5 Applicable Law. This Agreement shall be governed by and
construed in accordance with the laws of the State of New York, without giving
effect to the conflicts of law provisions thereof.
11.6 Dispute Resolution; Choice of Forum. Any disputes arising
between the parties relating to, arising out of or in any way connected with
this Agreement or any term or condition hereof, or the performance by either
party of its obligations hereunder, whether before or after the termination
pursuant to Section 10.1 of this Agreement, shall be promptly presented to the
Chief Executive Officer of PPI and the Member of the Corporate Board of BI
responsible for Pharmaceuticals for resolution and if they or their designees
cannot promptly resolve such disputes, then either party shall have the right to
bring an action to resolve such dispute before a court of competent
jurisdiction. The parties hereby submit to the exclusive jurisdiction of the
federal or state courts located within the State or City of New York for the
conduct of any suit, action or proceeding arising out of or relating to this
Agreement.
11.7 Arbitration. If the parties are unable to enter into the
definitive license agreement referenced in Section 3.5.1 within the time period
specified in such Section, or are unable to reach agreement on royalty terms for
a Bundled Product as provided in Section 6.1.2(c) within the time period
specified in such Section, the terms of such license agreement or such royalty
terms, as applicable, shall be settled by arbitration. Such arbitra-
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tion shall be conducted in the City of New York, in accordance with the
Commercial Arbitration rules then pertaining to the American Arbitration
Association with a panel of three (3) arbitrators. The arbitrators shall be
selected from the National Panel of Arbitrators of the American Arbitration
Association. The laws of the State of New York shall apply to the arbitration
proceedings. The decision of the arbitrators with respect to the terms of such
license agreement, or such royalty terms, as applicable, shall be final and
binding on the parties and their legal successors.
11.8 Entire Agreement. This Agreement, together with the appendices
hereto contains the entire understanding of the parties with respect to the
subject matter hereof and supersedes the Confidentiality Agreement dated August
8, 1995 between PPI and BI. All express or implied agreements and
understandings, either oral or written, heretofore made are expressly merged in
and made a part of this Agreement. This Agreement may be amended, or any term
hereof modified, only by a written instrument duly executed by both parties
hereto.
11.9 Headings. The captions to the several Articles and Sections
hereof are not a part of this Agreement, but are merely guides or labels to
assist in locating and reading the several Articles and Sections hereof.
11.10 Independent Contractors. It is expressly agreed that PPI and
BI shall be independent contractors and that the relationship between the two
parties shall not constitute a partnership, joint venture or agency. Neither PPI
nor BI shall have the authority to make any statements, representations or
commitments of any kind, or to take any action, which shall be binding on the
other, without the prior consent of the other party to do so.
11.11 Agreement Not to Solicit Employees. During the term of this
Agreement and for a period of two (2) years following the termination of this
Agreement, PPI and BI agree not to seek to persuade or induce any employee of
the other company who is or was involved in the collaboration provided for
herein to discontinue his or her employment with that company in order to
become employed by or associated with any business, enterprise or effort that is
associated with its own business.
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11.12 Exports. The parties acknowledge that the export of technical
data, materials or products is subject to the exporting party receiving any
necessary export licenses and that the parties cannot be responsible for any
delays attributable to export controls which are beyond the reasonable control
of either party. PPI and BI agree not to export or re-export, directly or
indirectly, any information, technical data, the direct product of such data,
samples or equipment received or generated under this Agreement in violation of
any governmental regulations which may be applicable, including, but not limited
to, the Export Administration Act of 1979, as amended, its rules and
regulations, including, but not limited to, Part 779 of the United States Export
Control Regulations, published by the United States Department of Commerce, and
other applicable export control laws. PPI and BI agree to obtain similar
covenants from their licenses, sublicenses and contractors with respect to the
subject matter of this Section 11.12.
11.13 Waiver. The waiver by either party hereto of any right
hereunder or the failure to perform or of a breach by the other party shall not
be deemed a waiver of any other right hereunder or of any other breach or
failure by said other party whether of a similar nature or otherwise.
11.14 Counterparts. This Agreement may be executed in two
counterparts, each of which shall be deemed an original and together shall
constitute one and the same instrument.
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IN WITNESS WHEREOF, the parties have executed this Agreement as of
the date first set forth above.
PHARMACEUTICAL PEPTIDES, INC.
By /s/ Joseph M. Limber
------------------------------
Name: Joseph M. Limber
Title: President/COO
BOEHRINGER INGELHEIM
INTERNATIONAL GmbH
By /s/ Hohbach Muller
------------------------------
Name: Hohbach Muller
Title: Authorized Signatories
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APPENDIX A
- --------------------------------------------------------------------------------
Patent Application Claims Included Claims Excluded
------------------ --------------- ---------------
- --------------------------------------------------------------------------------
U.S. Patent Appli- Compositions of Compositions of
cation Serial No. Matter: Matter:
08/404,831
13-17 and 30-32 1-12 and 20-29
Methods: Methods:
18-19, 37-44, 50-52 33-36, 45-49 and
and 59-62 53-58
- --------------------------------------------------------------------------------
U.S. Continuation- Compositions of Compositions of
in-Part Patent Matter: Matter:
Application
Serial No. 14-18 and 32-34 1-13 and 21-31
08/475,579
Methods: Methods:
19-20 and 40-47 35-39
- --------------------------------------------------------------------------------
<PAGE>
APPENDIX B
WORK PLAN UNDER THE
COLLABORATION AND LICENSE AGREEMENT
DATED AS OF AUGUST 1, 1996
BY AND BETWEEN
PHARMACEUTICAL PEPTIDES, INC.
AND
BOEHRINGER INGELHEIM INTERNATIONAL GmbH
This is the Work Plan referred to in, and which forms a part of, the
Collaboration and License Agreement dated as of August 1, 1996 by and between
Pharmaceutical Peptides, Inc. and Boehringer Ingelheim International GmbH (the
"Collaboration Agreement"). Capitalized terms used but not defined herein have
the respective meanings ascribed thereto in the Collaboration Agreement.
I. Screening Program
During the Screening Term, PPI will employ exclusively assays A-D as described
below to screen for A(beta) peptide polymerization inhibition activity for
50,000 compounds selected and supplied by BI. *** Depending on activity levels
seen in Assay A, PPI may require additional material for Assays B-D and
subsequent in vivo assays. PPI will deliver to BI SAR data on existing PPI
Compounds within 6 weeks of the Effective Date. BI will deliver to PPI at least
13,000, 25,000, 37,500, and 50,000 compounds within 2.0, 5.0, 12.0, and 16.0
months respectively, of the Effective Date and PPI anticipates, barring any
unforeseen technical issues, screening 25,000 compounds in its Nucleation Assay
within 12 months and 50,000 compounds in its Nucleation Assay within 24 months
of the Effective Date. Compounds jointly designated will be further screened in
secondary assays described below.
Assay Functional Measurement Manpower
- ----- ---------------------- --------
A. Nucleation Assay *** *** FTE
B. Extension Assay *** *** FTE
C. Neurotoxicity *** *** FTE
D. Specificity *** *** FTE
<PAGE>
PPI will make available *** FTE's to the Screening Program immediately following
the Effective Date. These FTE's will either be new hires or redeployments of
existing personnel. PPI anticipates that it will be evaluating BI compounds in
assays A-D within 6 weeks of first receiving compounds from BI. All Applicable
data will be supplied to BI in PC compatible form (e.g. ASCI II or Excel files).
All BI compounds will be handled or disposed of in accordance with BI's written
instructions.
A. Nucleation Assay: A rapid high-throughput primary screen
The nucleation assay *** Approximately 13 lines omitted ***
B. Extension Assay: ***
The extension assay *** Approximately 6 lines omitted ***
C. Neurotoxicity Assay: in vitro Cellular Efficacy
*** Approximately 10 lines omitted ***
D. ***: Amyloid Specificity Assays
*** Approximately 9 lines omitted ***
II. Development of Animal Model for A(beta)Peptide Polymerization Inhibitors
Assay Functional Measurement Manpower
----- ---------------------- --------
Animal Model *** ***
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PPI will dedicate *** to the development of an animal model immediately
following the Effective Date. *** will either be *** new hire or a redeployment
of *** The *** for assay 5 will be active in the identification, in-house
development, and validation of an efficacy model for testing A(beta) peptide
polymerization inhibitors.
*** Approximately 9 lines omitted ***
III. Capital Budget Items
Capital Budget items include dedicated equipment and assay specific supplies
purchased during the Screening Program. These will include but not be limited
to:
Dedicated Equipment
o 2 rotary shakers
o Plate-reader flourimeter
o Spectrophotometer (96-well Plate Reader)
o Spectrophotometer (Cuvette)
o Computers (data management, direct connection to flourimeter)
o Cryostat
o Stereotaxtic Apparatus
Assay Specific Supplies
o Pipet tips
o Multi-pipettors
o Low-Bind 96 well plates
o Standard 96 well plates
o Reservoirs
o Computer Software
o Disposable Cuvettes
o Tissue Culture Media and Supplies
o Histochemical Supplies
o Animal Purchase Costs/Supplies/Housing
<PAGE>
o Osmotic Pumps
*** Approximately 4 lines omitted ***
