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EXHIBIT 10.11
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[CONFIDENTIAL TREATMENT HAS BEEN REQUESTED FOR THE PORTIONS OF THIS EXHIBIT
MARKED WITH ASTERIKS (***).]
Manufacturing Agreement
[CONFIDENTIAL TREATMENT HAS BEEN REQUESTED FOR INFORMATION REDACTED FROM THIS
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An agreement made on the 17th of March, 2000, between Pharmaceutics
International, Inc., of 10819 Gilroy Road, Suite 100, Hunt Valley, MD 21031
("PII") and Keryx Biopharmaceuticals, Inc., of 216 Jaffa Road, Jerusalem 94383
Israel ("Keryx"),
Whereas Keryx intends to commence clinical trials of its drug KRX-101 (also
known as sulodexide) *** contingent on FDA approval of its IND; and
Whereas Keryx requires the manufacture of the clinical trial materials ("CTM")
consisting of a certain number of gelcaps containing KRX-101, as well as gelcaps
containing a placebo, to conduct such clinical trials; and
Whereas PII has the necessary expertise to manufacture the gelcaps required by
Keryx.
It is hereby agreed by and between the parties:
1. Keryx's Responsibilities
1.1. Keryx shall be responsible for supplying PII with the following
items:
1.1.1. API - Sulodexide
1.1.2. Technology transfer document including manufacturing
process
1.1.3. Cleaning Method
1.1.4. Material Safety Data Sheet
1.1.5. Packaging protocol
1.2. Keryx shall supply all special assays required for the drug
substance (Factor Xa) and shall source an appropriate outside
testing laboratory.
1.3. Keryx shall be responsible for all analytical method development
(for drug product and drug substance) transfer.
2. PII's Responsibilities
2.1. Feasibility Batch
2.1.1. PII shall review the manufacturing protocol supplied by
Keryx.
2.1.2. PII shall purchase all excipients.
2.1.3. PII shall verify the cleaning method supplied by Keryx.
2.1.4. PII shall then manufacture a feasibility batch of
Sulodexide 50 mg and 100 mg of approximately ***
gelcaps of each strength to assess the manufacturing
parameters. The manufacture of the feasibility batch
shall be completed within two (2) weeks of the date on
which PII receives the Sulodexide material and the
technology transfer document including manufacturing
process.
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2.2. Manufacture of the CTM
2.2.1. PII shall manufacture up to *** gelcaps of each of
the following:
. Sulodexide - 50 mg
. Sulodexide - 100 mg
. Placebo - 50 mg
. Placebo - 100 mg
2.2.2. PII shall accept all the excipients, active
pharmaceutical ingredients and packaging components with
vendor Certificate of Analysis and perform full testing
(4 - 6 weeks).
2.2.3. PII shall prepare Master Batch Records for the clinical
supplies.
2.2.4. The CTM shall be manufactured, packaged and labeled by
PII under cGMP conditions as directed by Keryx in the
manufacturing protocol. Manufacturing staff of PII shall
wear respirators and Tyvex suits if appropriate.
2.2.5. Packing component shall be HDPE bottles and blister
packs and shall be packaged by PII in accordance with
the Keryx protocol.
2.2.6. The following in-process and finished-product tests
shall be performed under cGMP condition on the CTM of
each strength or as mutually agreed upon by the parties:
. Visual Inspection
. Shell Hardness
. Weight
. Fill weight
2.2.7. The following in-process and finished-product tests
shall be performed on the placebo CTM or as mutually
agreed upon by the parties:
. Visual Inspection
. Absence of active ingredients
. Hardness
. Weight
2.2.8. PII does anticipate using contract laboratories for some
of the activities (for Microbiology testing) in this
Agreement. PII shall be responsible for ensuring, in
writing, that any contract lab used complied with Good
Laboratory Practices and with all other relevant
requirements set forth in the Agreement between PII and
Keryx.
2.2.9. Manufacturing and packaging of the CTM shall be
completed and the CTM delivered with all appropriate FDA
and cGMP requirement documentation, to Keryx or its
designee(s) within 4 weeks after full testing is
complete.
3. Quality Assurance
3.1. At least five (5) U.S. working days prior to the scheduled
dispatch of each batch of finished gelcaps, PII shall send a
sample of the batch to Keryx, or to a third party designated in
writing by Keryx. Keryx shall have the sample tested by such
third party to ID and release tests.
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3.2. If, after conducting such testing, a sample is determined to
have failed to demonstrate the required activity, PII shall redo
the entire batch of gelcaps, at its own expense, within seven
(7) U.S. working days of its receipt of written notification by
Keryx of the negative test.
4. Cost
4.1. The total cost of $ *** including packaging in HPDE bottles,
shall be apportioned as follows:
<TABLE>
<CAPTION>
Activity Cost
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<S> <C> <C>
Section 2.1.3 Verification of Cleaning Method $ ***
Section 2.1.4 Feasibility Batches (50 mg/100 mg), Active and
Placebo (4 batches in total) $ ***
Section 2.2.1 Clinical Trial Material Manufacturing:
50 mg/100 mg 32,000 per batch $ ***
Matching Placebos (4 batches in total) $ ***
Section 2.2.5 Packaging in Bottles and Blister Packages TBC
Section 3 General Support $ ***
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Total $ ***
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</TABLE>
4.2. Payments are due fifteen (15) days from the date of each
invoice, except for the first payment, which shall be due five
(5) days from the date of the invoice. Amounts due shall be
invoiced on the following schedule:
<TABLE>
<CAPTION>
Invoice Issue Date Amount Due
<S> <C> <C>
Day I Initiation $ ***
Section 2.1.4 Completion of feasibility batches $ ***
Section 2.2.3 Completion of CTM batch records $ ***
Section 2.2.9 Release of batches $ ***
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Total $ ***
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</TABLE>
4.3. In addition to the above costs, Keryx shall pay to PII upon
receipt of PII's invoice by Keryx for all non-capital materials
(excipients, packaging components, HPLC columns, analytical
standards and tooling, if any) used in the study at ***. PII
shall obtain Keryx's prior written approval for any expenditures
greater than $5,000. For high priced items more than $5,000, PII
shall charge *** to Keryx, PII shall invoice Keryx for all
reasonable and normal out-of pocket travel related expenses,
including airfare, room & board, car rental and the like, of PII
during any technology transfer phase or project update meetings
requested in advance by Keryx. PII shall inform Keryx when non-
approvable invoices (under $5,000 items) reaches a total of
S5,000.
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5. Indemnification
5.1. Keryx shall indemnify and hold PII and PII's affiliates and its
and their directors, officers, employees and agents, harmless
from and against any and all costs and expenses (including
attorney's fees) incurred as a result of claims asserted or
suits brought against PII and PII's affiliates, and its and
their directors, officers, employees and agents arising out of
(i) any negligence or willful misconduct of Keryx in performing
the services hereunder, (ii) any misrepresentation by Keryx or
breach by Keryx of any covenant or agreement hereunder, or (iii)
any claim asserted by a third party that Keryx in performing the
services hereunder has infringed or misappropriated any
proprietary or confidential information or intellectual property
rights of such third party arising out of materials provided by
Keryx to PII.
5.2. PII shall indemnify and hold Keryx and Keryx's affiliates, and
its and their directors, officers, employees and agents,
harmless from and against any and all costs and expenses
(including attorney's fees) incurred as a result of claims
asserted or suits brought against Keryx and Keryx's affiliates,
and its and their directors, officers, employees and agents
arising out of (i) any negligence or willful misconduct of PII
in performing the services hereunder, (ii) any misrepresentation
by PII or breach by PII of any covenant or agreement hereunder,
or (iii) any claim asserted by a third party that PII in
performing the services hereunder has infringed or
misappropriated any proprietary or confidential information or
intellectual property rights of such third party.
5.3. In no event shall either party be liable to the other for
consequential or indirect damages, including without limitation
lost profits or revenues.
6. Termination
6.1. Keryx, but not PII, shall have the right to terminate this
Agreement at anytime and for any reason at the sole discretion
of Keryx.
6.2. Upon such termination, Keryx shall pay all costs incurred by PII
for work performed to the date of termination, provided PII
provides written evidence that such costs have been incurred and
work performed.
6.3. Within 10 days of the termination of this Agreement, PII shall
deliver to Keryx all data, information, reports and any and all
related documentation which were, or required to be, developed,
generated or derived, directly or indirectly, by PII (or by any
subcontractor or agent of PII) for Keryx during the course of
the project.
7. Ownership of Materials and Information
7.1. All data, information, reports and any and all related
documentation, which are developed, generated or derived,
directly or indirectly, by PII (or by any subcontractor or agent
of PII) for Keryx during the course of the project (the "Data"),
and all inventions,
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discoveries, formulae, procedures, processes, technology and any
other intellectual property, and any improvements thereto,
whether patentable or not, which result or evolve directly,
during the course of the project or as a result of the services
performed hereunder by PII (or by any subcontractor or agent or
PII) (the "Inventions"), shall be and remain the sole and
exclusive property of Keryx.
7.2. Neither PII nor its employees or agents shall have or acquire
any right, title or interest in such Data or Inventions, and PII
shall promptly disclose in writing to Keryx any Inventions,
shall assign any and all rights in any Data and Inventions to
Keryx and shall assist Keryx in performing its rights in such
Data and Inventions.
8. Nondisclosure
8.1. PII agrees that it will not use, provide to, disclose to, or
permit any third party to use any information, data, or
documents which were received from Keryx or which were
specifically developed or generated by PII or any third party in
this project for Keryx (the "Project Information").
8.2. PII acknowledges that the Project Information is highly
confidential, and PII agrees to return to Keryx all such Project
Information upon the termination of this Agreement or
completion of this project. PII's obligations with respect to
the Project Information shall survive this termination of this
Agreement and the completion of this project.
9. Miscellaneous
9.1. Independent Contractors: PII is providing the services set forth
in this Agreement as an independent contractor and, therefore,
neither it, its employees, its representatives nor its agents
shall have any authority to bind Keryx in any manner.
9.2. Governing Law: This Agreement and any disputes arising from it
shall be governed by the laws of the State of New York.
9.3. Entire Agreement: This Agreement constitutes the entire
agreement between the parties concerning the subject matter of
this Agreement and supersedes any prior understanding or write
or oral agreement. Its terms may be modified or amended only by
a writing signed by authorized signatories of each party.
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[LOGO OF PII]
AGREED AND ACCEPTED
PHARMACEUTICS INTERNATIONAL, INC.
/s/ Steve King
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Steve King
Vice President Business Development
April 3rd 2000
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Date
KERYX BIOPHARMACEUTICALS, INC.
/s/ Ira Weinstein
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Authorized Agent or Representative
Title: Treasurer
March 30, 2000
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Date
Keryx Biopharmaceuticals, Inc.
Billing Contact: Ira Weinstein
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