FLAMEL TECHNOLOGIES SA
SC 13D/A, 2000-04-19
PHARMACEUTICAL PREPARATIONS
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                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                                  SCHEDULE 13D
                                 Amendment No. 3

                    Under the Securities Exchange Act of 1934

                            Flamel Technologies S.A.
                          ----------------------------
                                (Name of Issuer)

                                 Ordinary Shares
                    ----------------------------------------
                         (Title of Class of Securities)

                                   338488 10 9
                                   -----------
                                 (CUSIP Number)

                                 Eileen McCarthy
                       One Post Office Square, Suite 3800
                                Boston, MA 02109
                                 (617) 482-8020
         ---------------------------------------------------------------
           (Name, Address and Telephone Number of Person Authorized to
                       Receive Notices and Communications)

                                  April 6, 2000
              -----------------------------------------------------
             (Date of Event which Requires Filing of this Statement)

         If the filing person has  previously  filed a statement on Schedule 13G
to report the  acquisition  which is the subject of this  Schedule  13D,  and is
filing this schedule because of Rule 13d-1(b)(3) or (4), check the following box
[ ].

         Check the following box if a fee is being paid with this statement [ ].
(A fee  is not  required  only  if the  reporting  person:  (1)  has a  previous
statement on file  reporting  beneficial  ownership of more than five percent of
the class of  securities  described  in Item 1; and (2) has  filed no  amendment
subsequent  thereto  reporting  beneficial  ownership of five percent or less of
such class. (See Rule 13d-7).

         Note: Six copies of this statement,  including all exhibits,  should be
filed with the  Commission.  See Rule  13d-1(a) for other parties to whom copies
are to be sent.

         * The  remainder of this cover page shall be filled out for a reporting
person's  initial  filing on this  form with  respect  to the  subject  class of
securities,  and for any subsequent amendment containing information which would
alter the disclosures provided in a prior cover page.

         The information  required on the remainder of this cover page shall not
be deemed to be "filed" for the purpose of Section 18 of the Securities Exchange
Act of 1934,  as  amended  (the  "Exchange  Act") or  otherwise  subject  to the
liabilities  of that  section  of the  Exchange  Act but shall be subject to all
other provisions of the Exchange Act.

                        (Continued on following page(s))

                               Page 1 of 19 Pages


<PAGE>


CUSIP No. 0338488 10 9                  13D                   Page 2 of 19 Pages

- --------------------------------------------------------------------------------
  (1) Names of Reporting Persons. SS or I.R.S. Identification Nos. of
      Above Persons

      Alta Partners
- --------------------------------------------------------------------------------
  (2) Check The Appropriate Box If A Member Of A Group                 (a):
                                                                       (b))X
- --------------------------------------------------------------------------------
  (3) SEC Use Only

- --------------------------------------------------------------------------------
  (4) Source Of Funds*

      WC
- --------------------------------------------------------------------------------
  (5) Check Box If Disclosure Of Legal Proceedings Is Required Pursuant
      To Items 2(d) Or 2(e)

- --------------------------------------------------------------------------------
  (6) Citizenship Or Place Of Organization

      California
- --------------------------------------------------------------------------------
Number Of Shares                   (7)      Sole Voting Power         4,050,000
Beneficially Owned                                                See Footnote 1
By Each Reporting
Person With                        (8)      Shared Voting Power      -0-


                                   (9)      Sole Dispositive Power    4,050,000
                                                                  See Footnote 1

                                   (10)     Shared Dispositive Power -0-

  (11)   Aggregate Amount Beneficially Owned By Each Reporting Person

                  4,050,000  Please See Footnote 1
- --------------------------------------------------------------------------------
  (12)   Check If The Aggregate Amount In Row (11) Excludes Certain Shares*

- --------------------------------------------------------------------------------
  (13)   Percent Of Class Represented By Amount In Row (11)

                  20.4%
- --------------------------------------------------------------------------------
  (14)   Type Of Reporting Person

                  CO
- --------------------------------------------------------------------------------
                      *SEE INSTRUCTION BEFORE FILLING OUT!

Footnote  1:  Includes  1,875,000  shares of  ordinary  shares and  Warrants  to
purchase 1,050,000 shares of Class A (BSA) and 1,125,000 shares of Class B (BSA)
or Class C (BSA).  See  Exhibits E and F for terms for  exercising  the warrants
(BSA).


<PAGE>


CUSIP No. 0338488 10 9                  13D                   Page 3 of 19 Pages

- --------------------------------------------------------------------------------
  (1) Names of Reporting Persons. SS or I.R.S. Identification Nos. of
      Above Persons

      Alta BioPharma Partners, L.P.
- --------------------------------------------------------------------------------
  (2) Check The Appropriate Box If A Member Of A Group                 (a):
                                                                       (b))X
- --------------------------------------------------------------------------------
  (3) SEC Use Only

- --------------------------------------------------------------------------------
  (4) Source Of Funds*

      WC
- --------------------------------------------------------------------------------
  (5) Check Box If Disclosure Of Legal Proceedings Is Required Pursuant
      To Items 2(d) Or 2(e)

- --------------------------------------------------------------------------------
  (6) Citizenship Or Place Of Organization

      Delaware
- --------------------------------------------------------------------------------
Number Of Shares                   (7)      Sole Voting Power         2,517,428
Beneficially Owned                                                See Footnote 2
By Each Reporting
Person With                        (8)      Shared Voting Power      -0-


                                   (9)      Sole Dispositive Power    2,517,428
                                                                  See Footnote 2

                                   (10)     Shared Dispositive Power -0-

  (11)   Aggregate Amount Beneficially Owned By Each Reporting Person

                  2,517,428  See Footnote 2
- --------------------------------------------------------------------------------
  (12)   Check If The Aggregate Amount In Row (11) Excludes Certain Shares*

- --------------------------------------------------------------------------------
  (13)   Percent Of Class Represented By Amount In Row (11)

                  12.7%
- --------------------------------------------------------------------------------
  (14)   Type Of Reporting Person

                  PN
- --------------------------------------------------------------------------------
                      *SEE INSTRUCTION BEFORE FILLING OUT!

Footnote  2:  Includes  1,165,474  shares of  ordinary  shares and  Warrants  to
purchase  652,666 shares of Class A (BSA) and 699,288 shares of Class B (BSA) or
Class C (BSA). See Exhibits E and F for terms for exercising the warrants (BSA).


<PAGE>


CUSIP No. 0338488 10 9                  13D                   Page 4 of 19 Pages

- --------------------------------------------------------------------------------
  (1) Names of Reporting Persons. SS or I.R.S. Identification Nos. of
      Above Persons

      Alta Embarcadero BioPharma, LLC
- --------------------------------------------------------------------------------
  (2) Check The Appropriate Box If A Member Of A Group                 (a):
                                                                       (b))X
- --------------------------------------------------------------------------------
  (3) SEC Use Only

- --------------------------------------------------------------------------------
  (4) Source Of Funds*

      WC
- --------------------------------------------------------------------------------
  (5) Check Box If Disclosure Of Legal Proceedings Is Required Pursuant
      To Items 2(d) Or 2(e)

- --------------------------------------------------------------------------------
  (6) Citizenship Or Place Of Organization

      California
- --------------------------------------------------------------------------------
Number Of Shares                   (7)      Sole Voting Power            94,887
Beneficially Owned                                                See Footnote 3
By Each Reporting
Person With                        (8)      Shared Voting Power      -0-


                                   (9)      Sole Dispositive Power       94,887
                                                                  See Footnote 3

                                   (10)     Shared Dispositive Power -0-

  (11)   Aggregate Amount Beneficially Owned By Each Reporting Person

                  94,887  See Footnote 3
- --------------------------------------------------------------------------------
  (12)   Check If The Aggregate Amount In Row (11) Excludes Certain Shares*

- --------------------------------------------------------------------------------
  (13)   Percent Of Class Represented By Amount In Row (11)

                  .5%
- --------------------------------------------------------------------------------
  (14)   Type Of Reporting Person

                  CO
- --------------------------------------------------------------------------------
                      *SEE INSTRUCTION BEFORE FILLING OUT!

Footnote 3: Includes  43,929 shares of ordinary  shares and Warrants to purchase
24,600  shares  of Class A (BSA) and  26,358  shares of Class B (BSA) or Class C
(BSA). See Exhibits E and F for terms for exercising the warrants (BSA).


<PAGE>


CUSIP No. 0338488 10 9                  13D                   Page 5 of 19 Pages

- --------------------------------------------------------------------------------
  (1) Names of Reporting Persons. SS or I.R.S. Identification Nos. of
      Above Persons

      Flamel Chase Partners (Alta Bio), LLC
- --------------------------------------------------------------------------------
  (2) Check The Appropriate Box If A Member Of A Group                 (a):
                                                                       (b))X
- --------------------------------------------------------------------------------
  (3) SEC Use Only

- --------------------------------------------------------------------------------
  (4) Source Of Funds*

      WC
- --------------------------------------------------------------------------------
  (5) Check Box If Disclosure Of Legal Proceedings Is Required Pursuant
      To Items 2(d) Or 2(e)

- --------------------------------------------------------------------------------
  (6) Citizenship Or Place Of Organization

      Delaware
- --------------------------------------------------------------------------------
Number Of Shares                   (7)      Sole Voting Power         1,437,685
Beneficially Owned                                                See Footnote 4
By Each Reporting
Person With                        (8)      Shared Voting Power      -0-


                                   (9)      Sole Dispositive Power    1,437,685
                                                                  See Footnote 4

                                   (10)     Shared Dispositive Power -0-

  (11)   Aggregate Amount Beneficially Owned By Each Reporting Person

                  1,437,685  See Footnote 4
- --------------------------------------------------------------------------------
  (12)   Check If The Aggregate Amount In Row (11) Excludes Certain Shares*

- --------------------------------------------------------------------------------
  (13)   Percent Of Class Represented By Amount In Row (11)

                  7.2%
- --------------------------------------------------------------------------------
  (14)   Type Of Reporting Person

                  CO
- --------------------------------------------------------------------------------
                      *SEE INSTRUCTION BEFORE FILLING OUT!

Footnote 4: Includes  665,597 shares of ordinary shares and Warrants to purchase
372,734  shares of Class A (BSA) and 399,354  shares of Class B (BSA) or Class C
(BSA). See Exhibits E and F for terms of exercising the warrants (BSA).


<PAGE>


CUSIP No. 0338488 10 9                  13D                   Page 6 of 19 Pages

- --------------------------------------------------------------------------------
  (1) Names of Reporting Persons. SS or I.R.S. Identification Nos. of
      Above Persons

      Alta BioPharma Management, LLC
- --------------------------------------------------------------------------------
  (2) Check The Appropriate Box If A Member Of A Group                 (a):
                                                                       (b))X
- --------------------------------------------------------------------------------
  (3) SEC Use Only

- --------------------------------------------------------------------------------
  (4) Source Of Funds*

      WC
- --------------------------------------------------------------------------------
  (5) Check Box If Disclosure Of Legal Proceedings Is Required Pursuant
      To Items 2(d) Or 2(e)

- --------------------------------------------------------------------------------
  (6) Citizenship Or Place Of Organization

      Delaware
- --------------------------------------------------------------------------------
Number Of Shares                   (7)      Sole Voting Power         2,517,428
Beneficially Owned                                                See Footnote 5
By Each Reporting
Person With                        (8)      Shared Voting Power      -0-


                                   (9)      Sole Dispositive Power    2,517,428


                                   (10)     Shared Dispositive Power -0-

  (11)   Aggregate Amount Beneficially Owned By Each Reporting Person

                  2,517,428  See Footnote 5
- --------------------------------------------------------------------------------
  (12)   Check If The Aggregate Amount In Row (11) Excludes Certain Shares*

- --------------------------------------------------------------------------------
  (13)   Percent Of Class Represented By Amount In Row (11)

                  12.7%
- --------------------------------------------------------------------------------
  (14)   Type Of Reporting Person

                  CO
- --------------------------------------------------------------------------------
                      *SEE INSTRUCTION BEFORE FILLING OUT!

Footnote  5:  Includes  1,165,474  shares of  ordinary  shares and  Warrants  to
purchase  652,666 shares of Class A (BSA) and 699,288 shares of Class B (BSA) or
Class C (BSA). See Exhibits E and F for terms of exercising the warrants (BSA).


<PAGE>


CUSIP No. 0338488 10 9                  13D                   Page 7 of 19 Pages

- --------------------------------------------------------------------------------
  (1) Names of Reporting Persons. SS or I.R.S. Identification Nos. of
      Above Persons

      Alta/Chase BioPharma Management, LLC
- --------------------------------------------------------------------------------
  (2) Check The Appropriate Box If A Member Of A Group                 (a):
                                                                       (b))X
- --------------------------------------------------------------------------------
  (3) SEC Use Only

- --------------------------------------------------------------------------------
  (4) Source Of Funds*

      WC
- --------------------------------------------------------------------------------
  (5) Check Box If Disclosure Of Legal Proceedings Is Required Pursuant
      To Items 2(d) Or 2(e)

- --------------------------------------------------------------------------------
  (6) Citizenship Or Place Of Organization

      Delaware
- --------------------------------------------------------------------------------
Number Of Shares                   (7)      Sole Voting Power         1,437,685
Beneficially Owned                                                See Footnote 6
By Each Reporting
Person With                        (8)      Shared Voting Power      -0-


                                   (9)      Sole Dispositive Power    1,437,685
                                                                  See Footnote 6

                                   (10)     Shared Dispositive Power -0-

  (11)   Aggregate Amount Beneficially Owned By Each Reporting Person

                  1,437,685  See Footnote 6
- --------------------------------------------------------------------------------
  (12)   Check If The Aggregate Amount In Row (11) Excludes Certain Shares*

- --------------------------------------------------------------------------------
  (13)   Percent Of Class Represented By Amount In Row (11)

                  7.2%
- --------------------------------------------------------------------------------
  (14)   Type Of Reporting Person

                  CO
- --------------------------------------------------------------------------------
                      *SEE INSTRUCTION BEFORE FILLING OUT!

Footnote 6: Includes  665,597 shares of ordinary shares and Warrants to purchase
372,734  shares of Class A (BSA) and 399,354  shares of Class B (BSA) or Class C
(BSA). See Exhibits E and F for terms of exercising the warrants (BSA).


<PAGE>


CUSIP No. 0338488 10 9                  13D                   Page 8 of 19 Pages

- --------------------------------------------------------------------------------
  (1) Names of Reporting Persons. SS or I.R.S. Identification Nos. of
      Above Persons

      Jean Deleage
- --------------------------------------------------------------------------------
  (2) Check The Appropriate Box If A Member Of A Group                 (a):
                                                                       (b)X
- --------------------------------------------------------------------------------
  (3) SEC Use Only

- --------------------------------------------------------------------------------
  (4) Source Of Funds*

      AF
- --------------------------------------------------------------------------------
  (5) Check Box If Disclosure Of Legal Proceedings Is Required Pursuant
      To Items 2(d) Or 2(e)

- --------------------------------------------------------------------------------
  (6) Citizenship Or Place Of Organization

      U.S.A.
- --------------------------------------------------------------------------------
Number Of Shares                   (7)      Sole Voting Power         1
Beneficially Owned                                               See Footnote 7a
By Each Reporting
Person With                        (8)      Shared Voting Power       4,050,000
                                                                 See Footnote 7

                                   (9)      Sole Dispositive Power    1
                                                                 See Footnote 7a

                                   (10)     Shared Dispositive Power  4,050,000
                                                                 See Footnote 7

  (11)   Aggregate Amount Beneficially Owned By Each Reporting Person

                  4,050,001  See Footnote 7 and 8
- --------------------------------------------------------------------------------
  (12)   Check If The Aggregate Amount In Row (11) Excludes Certain Shares*

- --------------------------------------------------------------------------------
  (13)   Percent Of Class Represented By Amount In Row (11)

                  20.4%
- --------------------------------------------------------------------------------
  (14)   Type Of Reporting Person

                  IN
- --------------------------------------------------------------------------------
                      *SEE INSTRUCTION BEFORE FILLING OUT!

Footnote  7:  Includes  1,875,000  shares of  ordinary  shares and  Warrants  to
purchase 1,050,000 shares of Class A (BSA) and 1,125,000 shares of Class B (BSA)
or Class C (BSA).  See  Exhibits E and F for terms of  exercising  the  warrants
(BSA).

Footnote 7a: In addition  Jean Deleage owns 1 share of Flamel  Ordinary  Shares.
According to French law each  director on the Company  board must own 1 share of
the company's stock.


<PAGE>


CUSIP No. 0338488 10 9                  13D                   Page 9 of 19 Pages

- --------------------------------------------------------------------------------
  (1) Names of Reporting Persons. SS or I.R.S. Identification Nos. of
      Above Persons

      Garrett Gruener
- --------------------------------------------------------------------------------
  (2) Check The Appropriate Box If A Member Of A Group                 (a):
                                                                       (b)X
- --------------------------------------------------------------------------------
  (3) SEC Use Only

- --------------------------------------------------------------------------------
  (4) Source Of Funds*

      AF
- --------------------------------------------------------------------------------
  (5) Check Box If Disclosure Of Legal Proceedings Is Required Pursuant
      To Items 2(d) Or 2(e)

- --------------------------------------------------------------------------------
  (6) Citizenship Or Place Of Organization

      U.S.A.
- --------------------------------------------------------------------------------
Number Of Shares                   (7)      Sole Voting Power         1,000
Beneficially Owned
By Each Reporting
Person With                        (8)      Shared Voting Power       4,050,000
                                                                 See Footnote 8

                                   (9)      Sole Dispositive Power    1,000


                                   (10)     Shared Dispositive Power  4,050,000
                                                                 See Footnote 8

  (11)   Aggregate Amount Beneficially Owned By Each Reporting Person

                  4,051,000  See Footnote 8
- --------------------------------------------------------------------------------
  (12)   Check If The Aggregate Amount In Row (11) Excludes Certain Shares*

- --------------------------------------------------------------------------------
  (13)   Percent Of Class Represented By Amount In Row (11)

                  20.4%
- --------------------------------------------------------------------------------
  (14)   Type Of Reporting Person

                  IN
- --------------------------------------------------------------------------------
                      *SEE INSTRUCTION BEFORE FILLING OUT!

Footnote  8:  Includes  1,875,000  shares of  ordinary  shares and  Warrants  to
purchase 1,050,000 shares of Class A (BSA) and 1,125,000 shares of Class B (BSA)
or Class C (BSA).  See  Exhibits E and F for terms of  exercising  the  warrants
(BSA).  In addition,  Mr.  Gruener  owns 1,000  shares in his BEDCO  Pension and
Profit Sharing.


<PAGE>


CUSIP No. 0338488 10 9                  13D                  Page 10 of 19 Pages

- --------------------------------------------------------------------------------
  (1) Names of Reporting Persons. SS or I.R.S. Identification Nos. of
      Above Persons

      Daniel Janney
- --------------------------------------------------------------------------------
  (2) Check The Appropriate Box If A Member Of A Group                 (a):
                                                                       (b)X
- --------------------------------------------------------------------------------
  (3) SEC Use Only

- --------------------------------------------------------------------------------
  (4) Source Of Funds*

      AF
- --------------------------------------------------------------------------------
  (5) Check Box If Disclosure Of Legal Proceedings Is Required Pursuant
      To Items 2(d) Or 2(e)

- --------------------------------------------------------------------------------
  (6) Citizenship Or Place Of Organization

      U.S.A.
- --------------------------------------------------------------------------------
Number Of Shares                   (7)      Sole Voting Power         -0-
Beneficially Owned
By Each Reporting
Person With                        (8)      Shared Voting Power       4,050,000
                                                                 See Footnote 9

                                   (9)      Sole Dispositive Power    -0-


                                   (10)     Shared Dispositive Power  4,050,000
                                                                 See Footnote 9

  (11)   Aggregate Amount Beneficially Owned By Each Reporting Person

                  4,050,000  See Footnote 9
- --------------------------------------------------------------------------------
  (12)   Check If The Aggregate Amount In Row (11) Excludes Certain Shares*

- --------------------------------------------------------------------------------
  (13)   Percent Of Class Represented By Amount In Row (11)

                  20.4%
- --------------------------------------------------------------------------------
  (14)   Type Of Reporting Person

                  IN
- --------------------------------------------------------------------------------
                      *SEE INSTRUCTION BEFORE FILLING OUT!

Footnote  9:  Includes  1,875,000  shares of  ordinary  shares and  Warrants  to
purchase 1,050,000 shares of Class A (BSA) and 1,125,000 shares of Class B (BSA)
or Class C (BSA).  See  Exhibits E and F for terms of  exercising  the  warrants
(BSA).


<PAGE>


CUSIP No. 0338488 10 9                  13D                  Page 11 of 19 Pages

- --------------------------------------------------------------------------------
  (1) Names of Reporting Persons. SS or I.R.S. Identification Nos. of
      Above Persons

      Alix Marduel
- --------------------------------------------------------------------------------
  (2) Check The Appropriate Box If A Member Of A Group                 (a):
                                                                       (b)X
- --------------------------------------------------------------------------------
  (3) SEC Use Only

- --------------------------------------------------------------------------------
  (4) Source Of Funds*

      AF
- --------------------------------------------------------------------------------
  (5) Check Box If Disclosure Of Legal Proceedings Is Required Pursuant
      To Items 2(d) Or 2(e)

- --------------------------------------------------------------------------------
  (6) Citizenship Or Place Of Organization

      U.S.A.
- --------------------------------------------------------------------------------
Number Of Shares                   (7)      Sole Voting Power         -0-
Beneficially Owned
By Each Reporting
Person With                        (8)      Shared Voting Power       4,050,000
                                                                 See Footnote 10

                                   (9)      Sole Dispositive Power    -0-


                                   (10)     Shared Dispositive Power  4,050,000
                                                                 See Footnote 10

  (11)   Aggregate Amount Beneficially Owned By Each Reporting Person

                  4,050,000  See Footnote 10
- --------------------------------------------------------------------------------
  (12)   Check If The Aggregate Amount In Row (11) Excludes Certain Shares*

- --------------------------------------------------------------------------------
  (13)   Percent Of Class Represented By Amount In Row (11)

                  20.4%
- --------------------------------------------------------------------------------
  (14)   Type Of Reporting Person

                  IN
- --------------------------------------------------------------------------------
                      *SEE INSTRUCTION BEFORE FILLING OUT!

Footnote  10:  Includes  1,875,000  shares of  ordinary  shares and  Warrants to
purchase 1,050,000 shares of Class A (BSA) and 1,125,000 shares of Class B (BSA)
or Class C (BSA).  See  Exhibits E and F for terms of  exercising  the  warrants
(BSA).


<PAGE>


CUSIP No. 0338488 10 9                  13D                  Page 12 of 19 Pages

- --------------------------------------------------------------------------------
  (1) Names of Reporting Persons. SS or I.R.S. Identification Nos. of
      Above Persons

      Guy Nohra
- --------------------------------------------------------------------------------
  (2) Check The Appropriate Box If A Member Of A Group                 (a):
                                                                       (b)X
- --------------------------------------------------------------------------------
  (3) SEC Use Only

- --------------------------------------------------------------------------------
  (4) Source Of Funds*

      AF
- --------------------------------------------------------------------------------
  (5) Check Box If Disclosure Of Legal Proceedings Is Required Pursuant
      To Items 2(d) Or 2(e)

- --------------------------------------------------------------------------------
  (6) Citizenship Or Place Of Organization

      U.S.A.
- --------------------------------------------------------------------------------
Number Of Shares                   (7)      Sole Voting Power         1,000
Beneficially Owned
By Each Reporting
Person With                        (8)      Shared Voting Power       4,050,000
                                                                 See Footnote 11

                                   (9)      Sole Dispositive Power    1,000


                                   (10)     Shared Dispositive Power  4,050,000
                                                                 See Footnote 11

  (11)   Aggregate Amount Beneficially Owned By Each Reporting Person

                  4,051,000  See Footnote 11
- --------------------------------------------------------------------------------
  (12)   Check If The Aggregate Amount In Row (11) Excludes Certain Shares*

- --------------------------------------------------------------------------------
  (13)   Percent Of Class Represented By Amount In Row (11)

                  20.4%
- --------------------------------------------------------------------------------
  (14)   Type Of Reporting Person

                  IN
- --------------------------------------------------------------------------------
                      *SEE INSTRUCTION BEFORE FILLING OUT!

Footnote  11:  Includes  1,875,000  shares of  ordinary  shares and  Warrants to
purchase 1,050,000 shares of Class A (BSA) and 1,125,000 shares of Class B (BSA)
or Class C (BSA).  See  Exhibits E and F for terms of  exercising  the  warrants
(BSA).  In addition Mr. Nohra owns 1,000 shares in his BEDCO  Pension and Profit
Sharing.


<PAGE>


CUSIP No. 0338488 10 9                  13D                  Page 13 of 19 Pages

- --------------------------------------------------------------------------------
  (1) Names of Reporting Persons. SS or I.R.S. Identification Nos. of
      Above Persons

      Marino Polestra
- --------------------------------------------------------------------------------
  (2) Check The Appropriate Box If A Member Of A Group                 (a):
                                                                       (b)X
- --------------------------------------------------------------------------------
  (3) SEC Use Only

- --------------------------------------------------------------------------------
  (4) Source Of Funds*

      AF
- --------------------------------------------------------------------------------
  (5) Check Box If Disclosure Of Legal Proceedings Is Required Pursuant
      To Items 2(d) Or 2(e)

- --------------------------------------------------------------------------------
  (6) Citizenship Or Place Of Organization

      U.S.A.
- --------------------------------------------------------------------------------
Number Of Shares                   (7)      Sole Voting Power         -0-
Beneficially Owned
By Each Reporting
Person With                        (8)      Shared Voting Power       4,050,000
                                                                 See Footnote 12

                                   (9)      Sole Dispositive Power    -0-


                                   (10)     Shared Dispositive Power  4,050,000
                                                                 See Footnote 12

  (11)   Aggregate Amount Beneficially Owned By Each Reporting Person

                  4,050,000  See Footnote 12
- --------------------------------------------------------------------------------
  (12)   Check If The Aggregate Amount In Row (11) Excludes Certain Shares*

- --------------------------------------------------------------------------------
  (13)   Percent Of Class Represented By Amount In Row (11)

                  20.4%
- --------------------------------------------------------------------------------
  (14)   Type Of Reporting Person

                  IN
- --------------------------------------------------------------------------------
                      *SEE INSTRUCTION BEFORE FILLING OUT!

Footnote  12:  Includes  1,875,000  shares of  ordinary  shares and  Warrants to
purchase 1,050,000 shares of Class A (BSA) and 1,125,000 shares of Class B (BSA)
or Class C (BSA).  See  Exhibits E and F for terms of  exercising  the  warrants
(BSA).


<PAGE>


Item 1. Security and Issuer.

                  This  Statement on Schedule D relates to the Ordinary  Shares,
$0.080 French franc par value per share (the "Shares"), of Flamel S.A., a French
Societe  Anonyme  organized  under  the  laws of The  Republic  of  France  (the
"Company").  The principal  executive offices of the Company are located at Parc
Club Du Moulin a Vent, 33, avenue de Dr. Georges Levy, Venissieux,  Cedex 69693,
France.

Item 2. Identity and Background.

                  (a) This Statement is filed by Alta BioPharma Partners,  L.P.,
a Delaware limited partnership ("Alta BioPharma"),  Alta Embarcadero  BioPharma,
LLC, a California  limited  liability  company  ("Embarcadero  LLC"), and Flamel
Chase Partners (Alta Bio),  LLC, a Delaware LLC ("Flamel Alta Bio") by virtue of
their  direct  beneficial  ownership  of Shares,  by Alta  BioPharma  Management
Partners,  LLC, a Delaware limited  liability  company ("Alta  Management"),  by
virtue  of being the sole  general  partner  of Alta  BioPharma,  by  Alta/Chase
BioPharma  Management  LLC, a Delaware  limited  liability  company  (Alta/Chase
Management) by virtue of being the sole managing member of Flamel Chase Partners
(Alta  Bio),  LLC  and  by  Alta  Partners,  a  California   corporation  ("Alta
Partners"),  by  virtue  of  being  the  management  advisory  company  of these
entities.  Alta  BioPharma,   Embarcadero  LLC,  Flamel  Chase  Alta  Bio,  Alta
Management, Alta/Chase Management and Alta Partners are collectively referred to
as the "Reporting  Persons." Jean Deleage,  Garrett  Gruener,  Dan Janney,  Alix
Marduel,  Guy  Nohra and  Marino  Polestra  (the  "Partners")  are the  managing
directors  of  Alta  Management,  Alta/Chase  Management  and  officers  of Alta
Partners.  By virtue of the  relationships  described above and their roles with
Alta  Partners,  each of the Partners  may be deemed to control  Alta  Partners,
Alta/Chase Management, Alta Management, and, therefore, may be deemed to possess
indirect beneficial ownership of the Shares held by each entity.  However,  none
of the Partners,  acting alone,  has voting or investment  power with respect to
the Shares  directly  beneficially  held by the entities  and, as a result,  the
Partners disclaim beneficial ownership of the Shares directly beneficially owned
by each entity, except to the extent of their pecuniary interest in each entity.
Embarcadero  LLC is a side  company that makes all  investments  pro rata to the
capital of Alta  BioPharma  with all  allocations  made to its members  based on
paid-in  capital.  Certain of the  Partners are members of  Embarcadero  LLC and
certain members of Embarcadero LLC are affiliates of Alta Partners.

                  (b)  The  principal   executive  offices  of  Alta  BioPharma,
Embarcadero LLC, Flamel Chase Alta Bio, Alta Management,  Alta/Chase  Management
and Alta Partners,  and the business address of each Partner, are located at One
Embarcadero Center, Suite 4050, San Francisco, California 94111.

                  (c) Alta Partners  provides  investment  advisory  services to
venture  capital firms.  Alta  BioPharma,  Flamel Chase Alta Bio and Embarcadero
LLC's  principal  business  is acting as venture  capital  investment  vehicles.
Alta/Chase  Management  and Alta  Management's  principal  business is acting as
managing  director of Flamel  Chase Alta Bio and Alta  BioPharma,  respectively.
Each of the  Partners'  principal  business is acting as a managing  director of
Alta Management and Alta/Chase Management and as an officer of Alta Partners.

                  (d) None of the Reporting  Persons or, to the knowledge of the
Reporting  Persons,  any of the  Partners,  has  been  convicted  in a  criminal
proceeding  in the past five  years  (excluding  traffic  violations  or similar
misdemeanors).

                  (e) During the past five years,  none of the Reporting Persons
or, to the knowledge of the Reporting Persons,  and none of the Partners,  was a
party to a civil  proceeding of a judicial or  administrative  body of competent
jurisdiction  as a result of which such  person was or is subject to a judgment,
decree  or final  order  enjoining  future  violations  of,  or  prohibiting  or
mandating activities subject to, federal or state securities laws of finding any
violation with respect to such laws.


<PAGE>


                  (f) Alta Partners is a California corporation.  Alta BioPharma
is a Delaware  limited  partnership.  Embarcadero  LLC is a  California  limited
liability  corporation.  Flamel Chase Alta Bio is a Delaware  limited  liability
company.   Alta  Management  and  Alta/Chase  Management  are  Delaware  limited
liability companies. Each of the Partners is a citizen of the United States.

                  (g) Jean Deleage, a Director of Flamel Technologies  through a
relationship with Burr, Egan, Deleage & Co., a separate reporting entity, is and
expects to continue as a Director of Flamel Technologies  representing both Alta
Partners and Burr,  Egan,  Deleage & Co. Mr. Jean Deleage,  is Vice President of
Burr, Egan, Deleage & Co. and a general partner of Alta IV Management  Partners,
L.P. (which is the general partner of Alta IV Limited  Partnership,  L.P.). As a
general  partner of the fund,  he may be deemed to share  voting and  investment
powers for the shares  held by the fund.  Mr.  Deleage  owns one share of Common
Stock of Flamel  Technologies  stock. He disclaims  beneficial  ownership of all
such shares held by all of the funds affiliated with Burr,  Egan,  Deleage & Co.
except to the extent of his proportionate pecuniary interests therein.

Item 3. Source and Amount of Funds or Other Consideration.

                  The  total  amount  of funds  required  by Alta  BioPharma  to
acquire the 2,517,428  shares (13)of  Ordinary  Shares reported in Item 5(a) was
$4,493,445.17(13a),  the total amount of funds  required by  Embarcadero  LLC to
acquire  the  94,887(14)  shares of  Ordinary  Shares  reported in Item 5(a) was
$169,366.95(14a) and the total amount of funds required by Flamel Chase Alta Bio
to acquire the 1,437,685(15) shares of Ordinary Shares reported in Item 5(a) was
$2,566,186.53(15a).  Such funds were provided by each entity's capital available
for investment.

Item 4. Purpose of Transaction.

                  Alta  BioPharma,  Embarcadero  LLC,  and Flamel Chase Alta Bio
acquired  the  Ordinary  Shares  reported  in Item  5(c)  for  investment  only.
Depending upon their evaluation of the Company's investments and prospects,  and
upon future developments (including,  but not limited to, market for the Shares,
the effective yield on the Shares,  availability of funds,  alternative  uses of
funds,  and money,  stock market and general economic  conditions),  each of the
Reporting Persons may from time to time purchase the Ordinary Shares, dispose of
all or a  portion  of the  Ordinary  Shares  that it holds,  or cease  buying or
selling Ordinary Shares. Any such additional  purchases or sales of the Ordinary
Shares may be in open market or privately negotiated transactions or otherwise.

                  On April 6, 2000, Alta  BioPharma,  Embarcadero LLC and Flamel
Chase Alta Bio entered into a Securities  Purchase  Agreement  (the  "Securities
Purchase Agreement") dated February 29, 2000, with the Company pursuant to which
Alta  BioPharma,  Embarcadero  LLC and Flamel  Chase Alta Bio  acquired,  for an
aggregate  purchase price of  $7,228,998.65(16),  a total of 1,875,000 shares of
Ordinary Shares and Warrants to

- --------

(13)  Includes  1,165,474  shares of  Ordinary  Stock and  Warrants  to purchase
652,666  shares of Class A (BSA) and 699,288  shares of Class B (BSA) or Class C
(BSA).  See  Exhibits E and F for terms of  exercising  warrants.

(13a) Includes warrant cost of $3,032.68.

(14) Includes  43,929 shares of Ordinary  Stock and Warrants to purchase  24,600
shares of Class A (BSA) and 26,358 share of Class B (BSA) or Class C (BSA).  See
Exhibits E and F for terms of the exercising warrants.

(14a) Includes warrant cost of $114.31.

(15) Includes  665,597  shares of Ordinary Stock and Warrants for 372,734 shares
of Class A (BSA)  and  399,354  shares  of  Class B (BSA) or Class C (BSA).  See
Exhibits E and F for terms of exercising the warrants.

(15a) Includes warrant cost of $1,731.93.

(16) Includes warrant costs of $4,878.92.

<PAGE>


purchase 1,050,000 shares of Class A (BSA) and 1,125,000 shares of Class B (BSA)
or Class C (BSA)(17).  The entities  also  entered  into a  Registration  Rights
Agreement.

Item 5. Interest in Securities of the Issuer.

                  (a) Alta BioPharma is the direct beneficial owner of 2,517,428
shares(18)  or  approximately  12.7% of the  shares  deemed  outstanding  by the
Company  (19,878,215(19))  as of April 6,  2000.  Flamel  Chase  Alta Bio is the
direct   beneficial  owner  of  1,437,685(20)   shares  of  Ordinary  Shares  or
approximately 7.2% of the shares deemed outstanding by the Company  (19,878,215)
as of  April  6,  2000.  Embarcadero  LLC  is the  direct  beneficial  owner  of
94,887(21)  shares of Ordinary Shares or approximately  .5% of the shares deemed
outstanding by the Company (19,878,215) as of April 6, 2000.

                  (b) Each entity has the power to direct the disposition of and
vote the stock held by it. By virtue of the  relationships  previously  reported
under Item 2 of this Statement, Alta Management,  Alta/Chase Management and Alta
Partners may be deemed to have indirect beneficial ownership of the shares owned
by such entities.

                  (c) On April 6, 2000 Alta  BioPharma,  Flamel  Chase Alta Bio,
and Embarcadero LLC acquired the Shares described in Item 3 of this Statement in
a privately negotiated transaction with the Company for aggregate  consideration
of $4,493,445.17, $2,566,186.53 and $169,366.95, respectively.

                      Except as set forth above,  neither the Reporting  Persons
nor the Partners have effected any  transaction in the Shares during the past 60
days.

                  (d) Alta BioPharma,  Flamel Chase Alta Bio and Embarcadero LLC
each have the right to receive  dividends and proceeds from the sale of Ordinary
Shares  held by it. By virtue of the  relationships  reported  in Item 2 of this
Statement,  Alta  Management,  Alta/Chase  Management  and Alta  Partners may be
deemed to have the power to direct the  receipt of  dividends  and the  proceeds
from the sale of the Ordinary Shares held by each entity.

Item 6. Contracts, Arrangements, Understandings or Relationships with Respect to
Securities of the Issuer.

                  The Flamel S.A.  Securities  Purchase Agreement dated February
29, 2000 and the Flamel  Technologies S.A.  Registration  Rights Agreement dated
April 5, are hereby incorporated in their entirety by this reference.

- ---------

(17) Please see Exhibits E and F for terms to exercise the warrants.

(18)  Includes  1,165,474  shares of  Ordinary  Shares and  Warrants to purchase
652,666  shares of Class A (BSA) and 699,288  shares of Class B or C (BSA).  See
Exhibits E and F for terms for exercising the warrants.

(19) Includes  16,190,965  outstanding  Ordinary Shares and Warrants to purchase
3,687,250 shares of Class A, B and/or C (BSA). See Exhibits E and F for terms of
warrants.

(20) Includes  665,597 shares of Ordinary Stock and Warrants to purchase 372,734
shares of Class A (BSA) and 399,354 shares of Class B or C (BSA). See Exhibits E
and F for terms to  exercise  warrants.

(21) Includes  43,929 shares of Ordinary  Stock and Warrants to purchase  24,600
shares of Class A (BSA) and 26,358 shares of Class B or C (BSA).  See Exhibits e
and F for terms to exercise warrants.

<PAGE>


Item 7.  Material to be Filed as Exhibits.

         Exhibit A: Joint Filing Statement.

         Exhibit B: Flamel S.A. Securities Purchase Agreement dated February 29,
         2000.

         Exhibit C: Flamel S.A.  Registration  Rights  Agreement  dated April 5,
         2000.

         Exhibit  D: No Exhibit

         Exhibit E:  Certificates  for Class A  Warrants,  Class B Warrants  and
         Class C Warrants (Free French Translation).

         Exhibit  F: Press  Release  issued by Flamel  Technologies  on March 1,
         2000.


<PAGE>


Signature

<TABLE>
                  After  reasonable  inquiry and to the best of my knowledge and
belief,  I certify  that the  information  set forth in this  statement is true,
complete and correct.

Date:  April 17, 2000

<S>                                                           <C>
Alta Partners                                                 Alta BioPharma Partners, L.P.

By:               /s/  Eileen McCarthy                        By:      Alta BioPharma Management, LLC
         -------------------------------                               Its General Partner
         Eileen McCarthy, Vice President

Alta BioPharma Management, LLC                                By:          /s/ Eileen McCarthy
                                                                       ----------------------------
                                                                       Eileen McCarthy, Member

By:               /s/ Eileen McCarthy                         Flamel Chase Partners (Alta Bio), LLC
         -------------------------------
         Eileen McCarthy, Member

                                                              By:      Alta/Chase BioPharma Management, LLC
Alta/Chase BioPharma Management, LLC                                   Its Managing Member

By:               /s/ Eileen McCarthy                         By:            /s/ Eileen McCarthy
         -------------------------------                               ----------------------------
         Eileen McCarthy, Member                                       Eileen McCarthy, Member

Alta Embarcadero BioPharma, LLC

By:               /s/ Eileen McCarthy
         -------------------------------
         Eileen McCarthy, Member

         /s/ Jean Deleage                                              /s/ Guy Nohra
- ---------------------------------                             ------------------------------------
Jean Deleage                                                  Guy Nohra

         /s/ /Garrett Gruener                                          /s/ Marino Polestra
- ---------------------------------                             ------------------------------------
Garrett Gruener                                               Marino Polestra

         /s/ Daniel Janney                                             /s/ Alix Marduel
- ---------------------------------                             ------------------------------------
Daniel Janney                                                 Alix Marduel
</TABLE>


<PAGE>


                                    EXHIBIT A

                             Joint Filing Statement

<TABLE>
         We, the  undersigned,  hereby  express our agreement  that the attached
Schedule 13D is filed on behalf of each of us.

Date:  April 17, 2000

<S>                                                           <C>
Alta Partners                                                 Alta BioPharma Partners, L.P.

By:               /s/  Eileen McCarthy                        By:      Alta BioPharma Management, LLC
         -------------------------------                               Its General Partner
         Eileen McCarthy, Vice President

Alta BioPharma Management, LLC                                By:          /s/ Eileen McCarthy
                                                                       ----------------------------
                                                                       Eileen McCarthy, Member

By:               /s/ Eileen McCarthy                         Flamel Chase Partners (Alta Bio), LLC
         -------------------------------
         Eileen McCarthy, Member

                                                              By:      Alta/Chase BioPharma Management, LLC
Alta/Chase BioPharma Management, LLC                                   Its Managing Member

By:               /s/ Eileen McCarthy                         By:            /s/ Eileen McCarthy
         -------------------------------                               ----------------------------
         Eileen McCarthy, Member                                       Eileen McCarthy, Member

Alta Embarcadero BioPharma, LLC

By:               /s/ Eileen McCarthy
         -------------------------------
         Eileen McCarthy, Member

         /s/ Jean Deleage                                              /s/ Guy Nohra
- ---------------------------------                             ------------------------------------
Jean Deleage                                                  Guy Nohra

         /s/ /Garrett Gruener                                          /s/ Marino Polestra
- ---------------------------------                             ------------------------------------
Garrett Gruener                                               Marino Polestra

         /s/ Daniel Janney                                             /s/ Alix Marduel
- ---------------------------------                             ------------------------------------
Daniel Janney                                                 Alix Marduel
</TABLE>


<PAGE>


                                    EXHIBIT B

                                                                  Execution Copy

================================================================================


                          SECURITIES PURCHASE AGREEMENT

                                 ORDINARY SHARES

                                       AND

                              WARRANTS TO PURCHASE

                                 ORDINARY SHARES

                                       OF

                            FLAMEL TECHNOLOGIES S.A.


                          DATED AS OF FEBRUARY 29, 2000


================================================================================


<PAGE>


                          SECURITIES PURCHASE AGREEMENT

         THIS SECURITIES  PURCHASE AGREEMENT (this  "Agreement"),  is made as of
this 29th day of February, 2000, by and among FLAMEL TECHNOLOGIES S.A., a French
societe  anonyme (the  "Company"),  BIOTECHNOLOGY  VALUE FUND,  L.P., a Delaware
limited  partnership,  BIOTECHNOLOGY  VALUE FUND II,  L.P.,  a Delaware  limited
partnership,  INVESTMENT  10  L.L.C.,  an  Illinois  limited  liability  company
(collectively,  the "BVF Investors"),  and ALTA BIOPHARMA  PARTNERS,  a Delaware
limited  partnership,  Alta  Embarcadero  Biopharma,  LLC, a California  limited
liability company, and Flamel Chase Partners (AltaBio),  LLC, a Delaware limited
liability company (collectively "Alta"); Chase EUROPEAN EQUITY ASSOCIATES,  LLC,
a  Delaware  limited  liability  company  ("Chase"  and,  together  with the BVF
Investors, and Alta, the "Investors").

                              W I T N E S S E T H:

         WHEREAS, the Investors desire to invest 83,717,750 French francs in the
Company in exchange for the  Company's  Ordinary  Shares (the  "Common  Stock"),
Class A bons de  souscription  to purchase the Company's  Common Stock (each,  a
"Class A Warrant" and  collectively,  the "Class A  Warrants"),  Class B bons de
souscription  to purchase the Company's  Common Stock (each, a "Class B Warrant"
and  collectively,  the "Class B Warrants") and Class C bons de  souscription to
purchase the Company's Common Stock (each, a "Class C Warrant" and collectively,
the "Class C Warrants"  and,  together with the Class A Warrants and the Class B
Warrants, the "Warrants") entitling the holders to purchase shares of the Common
Stock (the "Warrant Shares"); and

         WHEREAS,  the Company  and the  Investors  desire to set forth  certain
matters to which they have agreed relating to the Warrants and the Common Stock.

         NOW  THEREFORE,  in  consideration  of  the  premises  and  the  mutual
covenants contained in this Agreement, the parties agree as follows:

                                   Article I.

                 ISSUANCE AND TERMS OF WARRANTS AND COMMON STOCK

1.1.     Authorization of Securities.

         Subject to the terms and conditions of this Agreement,  the Company has
authorized,  or  prior  to  the  Closing  (as  hereinafter  defined)  will  have
authorized,  the issuance of the Common Stock and the Warrants  pursuant to this
Agreement.

1.2.     Purchase and Sale of Warrants and Common Stock.

         Subject to the terms and  conditions of this  Agreement and in reliance
upon the  representations  and warranties of the Company contained  herein,  the
Investors severally agree to purchase from the Company and the Company agrees to
sell to each of the Investors on the


<PAGE>


Closing  Date  (as  hereinafter  defined)  for an  aggregate  purchase  price of
83,717,750  French  francs  (i) the  number of shares of Common  Stock set forth
opposite each Investor's name on Exhibit A hereto,  aggregating 3,212,500 shares
of Common  Stock;  (ii) the number of Class A Warrants set forth  opposite  each
Investor's  name on Exhibit A hereto;  (iii) the number of Class B Warrants  set
forth opposite each Investor's name on Exhibit A hereto,  and (iv) the number of
Class C Warrants set forth opposite each Investor's name on Exhibit A hereto.

1.3.     Payment.

         Each of the  Investors  agrees to make  payment of the amount set forth
opposite  its name on Exhibit A hereto in  exchange  for the number of shares of
Common Stock and the number of Warrants,  in each case,  set forth  opposite its
name in such Exhibit A and delivered at the Closing (as hereinafter defined), by
certified check or wire transfer on the Closing Date to an account  specified by
the Company.

                                   ARTICLE II.

                                     CLOSING

2.1.     Closing.

         Subject to the  satisfaction  of the conditions set forth in Articles V
and VI hereof,  the closing (the "Closing") shall take place at a place and time
(the "Closing Date")  mutually  agreed by the Company and the Investors,  but in
any event no later than March 31, 2000.  At the Closing,  (a) the Company  shall
deliver to the  Investors  one or more stock  certificates  registered  in their
names for an aggregate of 3,212,500  shares of Common Stock, and (b) the Company
shall deliver to the Investors one or more Warrants registered in their names to
purchase the number of shares indicated therein, in each case against payment to
the Company of the purchase price therefor pursuant to Section 1.3.

2.2.     Legend.

         The  certificates  representing the Warrants and the Common Stock shall
be subject to a legend restricting transfer under the Securities Act of 1933, as
amended (the "Securities Act"), such legend to be substantially as follows:

                  "THE SECURITIES  EVIDENCED HEREBY HAVE NOT
                  BEEN  REGISTERED  UNDER THE SECURITIES ACT
                  OF 1933.  THESE SECURITIES MAY NOT BE SOLD
                  OR  OTHERWISE  TRANSFERRED  BY ANY  PERSON
                  UNLESS  (1)  EITHER  (A)  A   REGISTRATION
                  STATEMENT WITH RESPECT TO SUCH  SECURITIES
                  SHALL BE  EFFECTIVE  UNDER THE  SECURITIES
                  ACT OF 1933  ("ACT"),  OR (B) THE  COMPANY
                  SHALL  HAVE   REASONABLY   REQUESTED   AND
                  RECEIVED    AN    OPINION    OF    COUNSEL
                  SATISFACTORY  TO IT THAT AN EXEMPTION FROM
                  REGISTRATION   UNDER   SUCH  ACT  IS  THEN
                  AVAILABLE,  AND

                                       -2-

<PAGE>

                  (2) THERE SHALL HAVE BEEN  COMPLIANCE WITH
                  ALL APPLICABLE STATE SECURITIES LAWS."

                                  ARTICLE III.

                  REPRESENTATIONS AND WARRANTIES OF THE COMPANY

         The Company hereby represents and warrants to the Investors that, as of
the date of this Agreement, the following are true and correct:

3.1.     Organization and Standing of the Company.

         The Company is a corporation  duly organized,  validly  existing and in
good  standing  under the laws of the  Republic of France.  The Company has full
corporate  power  and  authority  to  enter  into,  deliver,   and  perform  its
obligations  and  undertakings  under  this  Agreement.   The  Company  is  duly
authorized  to conduct its  business and is in good  standing  under the laws of
each jurisdiction where such qualification is required, except where the lack of
such  qualification  would not have a material  adverse  effect on the business,
financial condition,  operations,  results of operations, or future prospects of
the Company.  The Company has full corporate power and authority to carry on the
business in which it is engaged and to own and use the  properties  owned and as
used by it.

3.2.     Capitalization.

         As of the date hereof,  the Company's entire  authorized  capital stock
consists of: (i) 12,939,215 Ordinary Shares, nominal value 0.80 French Franc per
Ordinary Share, of which 12,939,215 shares are validly issued and outstanding on
the date hereof. On or before the Closing, the Company's  shareholders will have
authorized a capital  increase to permit the issuance of the Common  Stock,  the
Warrants and the Warrant  Shares.  Subsequent to the Closing,  the Company shall
complete  publication  requirements  and file the  resolutions  of the  Board of
Directors  and the  Company's  shareholders  so that the  Company's  statuts are
amended to reflect such capital  increase.  The issuance of all presently issued
and  outstanding  shares was duly  authorized and all such shares are fully paid
and non-assessable. All such issued and outstanding shares have the preferences,
voting powers,  qualifications  and special or relative rights or privileges set
forth in the Company's statuts,  as in effect on the date hereof.  Other than as
indicated in the SEC Reports (as hereinafter defined), the Company does not have
outstanding any option,  warrant,  purchase  right,  subscription  right,  stock
appreciation right, phantom stock right, profit  participation right,  agreement
or other  commitment to issue or to acquire any shares of its capital stock,  or
any securities or obligations  convertible  into or exchangeable for its capital
stock,  and the Company  has not given any person any right to acquire  from the
Company or sell to the  Company any shares of its  capital  stock.  There are no
voting trusts,  proxies,  or other agreements or understandings  with respect to
the voting of the capital stock of the Company.

                                      -3-

<PAGE>


3.3.     Validity of this Agreement.

         Subject to  shareholder  approval,  the  execution  and delivery by the
Company of this Agreement and the  performance by the Company of its obligations
under this Agreement,  and the issuance,  sale and delivery of the Common Stock,
the Warrants and the Warrant  Shares,  have been duly authorized and approved by
all  necessary  corporate  action.  This  Agreement  has been duly  executed and
delivered by the Company and  constitutes a valid and binding  obligation of the
Company,   enforceable   in  accordance   with  its  terms  subject  to,  as  to
enforceability,  to  bankruptcy,  insolvency,  reorganization  and other laws of
general applicability  relating to or affecting creditors' rights and to general
principles  of  equity.  The  execution  and  delivery  by the  Company  of this
Agreement  and the  performance  by the  Company of its  obligations  under this
Agreement and the issuance,  sale and delivery of the Common Stock, the Warrants
and the Warrant  Shares will not (i) conflict  with,  or result in any breach of
any of the terms of, or  constitute a default  under,  the statuts when the same
will have been amended to authorize the Common Stock, (ii) conflict with, result
in a breach of or violation or  imposition  of any lien,  charge or  encumbrance
upon any property or assets of the Company or any of its  subsidiaries  pursuant
to,  constitute a default under,  result in the  acceleration  of, create in any
party the right to  accelerate,  terminate,  modify,  or cancel,  or require any
notice  under,  any  agreement,  instrument,  covenant or other  restriction  or
arrangement  to  which  the  Company  is a party  or by  which  it or any of its
properties or assets is bound or any statute law,  rule,  regulation,  judgment,
order or decree  applicable  to the  Company or any of its  subsidiaries  of any
court, regulatory body, administrative agency,  governmental body, arbitrator or
other authority having  jurisdiction over the Company or any of its subsidiaries
or any of its or their properties.

3.4.     Governmental Consent, Etc.

         Except for (i) the filing of the  amendment  to the  Company's  statuts
referenced in Section 7.5, (ii) the shareholder  approval referenced in Sections
5.1(e)  and  6.1(e),  and  (iii)  filings,  consents,   permits,  approvals  and
authorizations  which will be obtained  by the Company  prior to the Closing and
which are set forth on  SCHEDULE  3.4, no consent,  approval,  authorization  or
other order of,  action by,  filing with, or  notification  to any  governmental
authority is required  under  existing law or regulation in connection  with the
execution,  delivery and  performance  of the Agreement or the offer,  issuance,
sale or delivery  of the Common  Stock,  the  Warrants  and the  Warrant  Shares
pursuant to Section 1.3  pursuant to the  Agreement or the  consummation  of any
other transactions contemplated thereby.

3.5.     Valid Issuance of Securities.

         When issued and delivered  against payment  therefor in accordance with
the terms and conditions of this Agreement,  the Common Stock,  the Warrants and
the Warrant Shares,  shall be (i) duly authorized and validly issued, fully paid
and non-assessable and (ii) not subject to any preemptive rights,  liens, claims
or  encumbrances,  or other  restrictions  on  transfer or other  agreements  or
understandings  with  respect to the voting of the Common  Stock or the  Warrant
Shares, except as set forth in this Agreement.

                                      -4-

<PAGE>

3.6.     Financial Statements.

         The  audited  financial  statements  of the  Company  contained  in the
Company's  Annual  Report on Form 20-F for the year  ended  December  31,  1998,
including the notes relating thereto,  and the unaudited financial statements of
the Company  contained in the  Company's  Quarterly  Reports on Form 6-K for the
quarters ended March 31, 1999,  June 30, 1999 and September 30, 1999,  including
the notes thereto,  disclose all material  liabilities of the Company as of such
dates. Such financial  statements,  including the notes relating  thereto,  have
been prepared in accordance with U.S. generally accepted  accounting  principles
consistently applied throughout the periods involved.  Said financial statements
and related  notes  fairly  present the  financial  position  and the results of
operations and cash flow of Company as of the  respective  dates thereof and for
the periods indicated.

3.7.     Accuracy and Completeness of Information.

         American Depositary Shares representing the Common Stock are registered
pursuant to Section 12(g) of the Exchange Act (as hereinafter  defined).  Copies
of all  reports  filed by the  Company  with the United  States  Securities  and
Exchange  Commission (the "Commission")  pursuant to the Securities Exchange Act
of 1934, as amended (the "Exchange  Act") during the period from January 1, 1999
to the date of this  Agreement  (the  "Furnished  SEC  Reports")  have been made
available  to the  Investors.  Since June 12,  1996,  the Company has filed each
statement,  annual,  quarterly,  and other report,  and  registration  statement
required to be filed by the Company with the Commission (the "SEC Reports").  No
SEC Report at the time filed contained any untrue  statement of a material fact,
or  omitted  to state  any such  material  fact  necessary  in order to make the
statements  contained  therein,  in light of the circumstances  under which they
were made, not misleading,  and the SEC Reports,  collectively,  subject in each
case to  statements  which have been  corrected,  supplemented  or  remedied  by
subsequent  filings  with the  Commission  or by  information  contained  in the
disclosure  schedules  referenced  in this  Agreement  do not contain any untrue
statement of a material  fact, or omit to state any such material fact necessary
in order to make the statements contained therein, in light of the circumstances
under  which they were made,  not  misleading.  Except as  disclosed  in the SEC
Reports and as set forth on SCHEDULE 3.7 as of each date this representation and
warranty is made or deemed made, there is no fact relating to the Company or any
of its subsidiaries or their respective businesses (other than facts relating to
the economy in general)  known to the Company or any of its  subsidiaries  which
has, or could reasonably be expected to have, a Material Adverse Effect.

         For purposes of this Agreement,  each of "Material  Adverse Change" and
"Material  Adverse Effect" means any material adverse change, or any development
that could reasonably be expected to result in a material adverse change, in the
condition,  financial or otherwise, or in the earnings, business,  operations or
prospects,  whether or not arising from  transactions  in the ordinary course of
business, of the Company and its subsidiaries, taken as a whole.

                                      -5-

<PAGE>

3.8.     Adverse Changes.

         Since September 30, 1999 and except as set forth on SCHEDULE 3.8, there
has not been any Material Adverse Change.

3.9.     No Violation.

         Neither the  execution  and delivery by the Company of this  Agreement,
nor the  consummation of the transactions  contemplated  hereby will violate any
constitution, statute, rule, injunction, judgment, order, decree, ruling, charge
or other restriction of any government,  governmental  agency, or court known to
the Company to which the Company is subject,  or,  after  obtaining  shareholder
approval  and  amending  the  statuts  to  authorize  the  Common  Stock and the
Warrants, any provision of its statuts.

3.10.    All Necessary Permits, Etc.

         The  Company  and each  subsidiary  possesses  such  valid and  current
certificates,  authorizations  or  permits  issued  by  the  appropriate  state,
federal,  foreign,  EU or  French  provincial,  municipal  or  local  regulatory
agencies  or bodies as are  necessary  to conduct  their  respective  businesses
except where the lack of such certificate,  authorization or permit individually
or in the aggregate would not have a Material Adverse Effect on the Company, and
neither the Company nor any  subsidiary  has received any notice of  proceedings
relating to the revocation or modification of, or non-compliance  with, any such
certificate  authorization or permit which,  singly or in the aggregate,  if the
subject  of an  unfavorable  decision,  ruling  or  finding,  would  result in a
Material Adverse Change.

3.11.    Title to Properties.

         The Company and each of its  subsidiaries has good and marketable title
to all the  properties  and  assets  reflected  as owned by it in the  financial
statements  referred  to in  Section  3.6 in each  case  free  and  clear of any
security interests,  mortgages, liens, encumbrances,  equities, claims and other
defects, except such as do not materially and adversely affect the value of such
property  and do not  materially  interfere  with the use made or proposed to be
made of such  property by the  Company or such  subsidiary.  The real  property,
improvements, equipment and personal property held under lease by the Company or
any subsidiary are held under valid and enforceable leases, with such exceptions
as are not  material  and do not  materially  interfere  with  the  use  made or
proposed to be made of such real property,  improvements,  equipment or personal
property by the Company or such subsidiary.

3.12.    Securities Laws.

         All  notices,  filings,   registrations  or  qualifications  under  any
applicable  securities  laws,  including state  securities or "blue sky" laws or
French laws which are required in connection with the offer,  issue and delivery
of the Common Stock,  the Warrants and the Common Stock into which such Warrants
are convertible pursuant to this Agreement have been or will be timely completed
by the Company.

                                      -6-

<PAGE>


3.13.    Relationship to the Regulated Holder.

         Except as previously disclosed,  neither the Company nor its subsidiary
(i) offers or  markets,  directly  or through  any  arrangement,  any product or
service of The Chase  Manhattan  Corporation or (ii) permits any of its products
or services,  to the extent within its  knowledge and control,  to be offered or
marketed, directly or through any arrangement, by or through The Chase Manhattan
Corporation.  Except  as  previously  disclosed,  neither  the  Company  nor its
subsidiary  currently  has or expects to have any  extension  of credit from any
depository institution owned by The Chase Manhattan Corporation.

3.14.    U.S. Activities.

         The Company  hereby  represents and warrants that it does not presently
engage in business in the United States  within the meaning of Section  211.2(g)
of Regulation K of the Board of Governors of the Federal Reserve System nor does
it presently have nay intention to do so.

                                   ARTICLE IV.

                 REPRESENTATIONS AND WARRANTIES OF THE INVESTORS

         Each of the Investors  hereby  acknowledges,  represents,  warrants and
agrees as follows:

4.1.     Authority of Investors, Validity of this Agreement.

         Each of the Investors  has all  requisite  power and authority to enter
into this  Agreement  and  perform its  obligations  hereunder.  The  execution,
delivery and  performance  by each of the Investors of this  Agreement,  and the
purchase of the  Warrants and the Common  Stock  pursuant  hereto have been duly
authorized and approved by all necessary  corporate  action.  This Agreement has
been duly executed and delivered and constitutes a valid and binding  obligation
of  each of the  Investors,  enforceable  in  accordance  with  its  terms.  The
execution,  delivery and  performance  of this Agreement and the purchase of the
Warrants and the Common Stock will not  conflict  with,  or result in a material
breach of any of the terms of, or  constitute  a  material  default  under,  any
charter, by-law, agreement,  instrument,  covenant or other restriction to which
any of the  Investors  is a party  or by which  it or any of its  properties  or
assets is bound.

4.2.     Investment Representations.

         Each of the Investors  hereby  acknowledges,  represents,  warrants and
agrees as follows:

         (a)  Each of the  Investors  has  had the  opportunity  to  review  the
Furnished SEC Reports and the financial  statements  contained therein.  Each of
the Investors  acknowledges that the Company has made available to the Investors
documents and information that it has requested  relating to the Company and has
provided answers to the Investors'  questions concerning the Company, the Common
Stock and the Warrants.

                                      -7-

<PAGE>


         (b) Each of the  Investors  is an  "accredited  investor" as defined in
Rule 501(a)(3) of the Securities Act.

         (c) Each of the Investors understands that the offering of the Warrants
and the Common Stock has not been  registered  under the  Securities  Act or the
securities  laws of any state or other  jurisdiction  and that such Warrants and
the Common Stock must be held indefinitely unless an exemption from registration
is available.  Each of the Investors  understands  that the offering and sale of
the  Warrants  and the Common  Stock is intended to be exempt from  registration
under the  Securities  Act.  Each of the  Investors  covenants  that it will not
transfer the Warrants or the Common Stock in violation of the  provisions of any
applicable Federal or state securities statute.

         (d)  Subject to the  Investors'  registration  rights  relating  to the
Common Stock  (including the Common Stock  underlying the Warrants)  pursuant to
the terms of the  Registration  Agreement  referred to in Section 5.1(j) hereof,
each of the  Investors  is  acquiring  the  Warrants  and the  Common  Stock for
investment, and not with a view to the resale or distribution thereof; it has no
present  intention  of  selling,  negotiating,  or  otherwise  disposing  of the
Warrants and the Common Stock.  Each of the Investors'  financial  condition and
investments are such that it is in a financial position to hold the Warrants and
the Common Stock for an indefinite  period of time and to bear the economic risk
of, and withstand a complete  loss of, such  Warrants and the Common  Stock.  In
addition,  by virtue of its  expertise,  the  advice  available  to it,  and its
previous investment  experience,  each of the Investors has sufficient knowledge
and experience in financial and business matters,  investments,  securities, and
private  placements  and the  capability to evaluate the merits and risks of the
transactions contemplated by this Agreement.

                                   ARTICLE V.

                      CONDITIONS TO INVESTORS' OBLIGATIONS

5.1.     Conditions to Closing.

         The  obligation  of the  Investors to purchase and pay for the Warrants
and the Common Stock, on the Closing Date is subject to the following:

         (a) Representations and Warranties.  The representations and warranties
of the Company made herein shall be true,  correct and complete on and as of the
Closing  Date with the same  force and effect as if they had been made on and as
of the Closing Date.

         (b) Performance. All covenants,  agreements and conditions contained in
this  Agreement to be  performed or complied  with by the Company on or prior to
the Closing Date shall have been performed or complied with.

         (c) Opinion of Company's Counsel. The Investors shall have received (i)
an opinion of Willkie Farr & Gallagher,  special counsel to the Company, in form
and substance reasonably satisfactory to the Investors,  dated the Closing Date,
as to the matters  set forth on SCHEDULE  5.1(C) and (ii) an opinion of Sokolow,
Dunaud,  Mercadier  &  Carreras,  French  counsel  to the

                                      -8-

<PAGE>


Company, in form and substance reasonably  satisfactory to the Investors,  dated
the Closing Date, as to the matters set forth on SCHEDULE 5.1(C).

         (d)  Corporate  Proceedings,  Consents,  etc. All  corporate  and other
proceedings  to be  taken  and  all  waivers  and  consents  to be  obtained  in
connection with the transactions  contemplated by this Agreement shall have been
taken or  obtained  and all  documents  incident  thereto  shall  be  reasonably
satisfactory  in form and substance to the Investors and their counsel,  each of
whom shall have received all such originals or certified or other copies of such
documents as each may reasonably request.

         (e) Shareholder Approval.  The Company shall have obtained any required
approval of its shareholders  representing at least two-thirds of the votes cast
by the then  outstanding  shares of  Common  Stock to the  authorization  of the
Common Stock and the Warrants.

         (f) No Proceeding.  No action, suit,  investigation or proceeding shall
be pending or threatened  before any court or  governmental  agency to restrain,
prohibit,  collect damages as a result of or otherwise  challenge this Agreement
or any transaction contemplated hereby or thereby.

         (g) No Law Prohibiting or Restricting  Such Sale. There shall not be in
effect any law,  rule or regulation  prohibiting  or  restricting  such sale, or
requiring  any  consent  or  approval  of any person  which  shall not have been
obtained to issue the Common Stock, the Warrants, or the Common Stock into which
the Warrants are convertible.

         (h) Officer's  Certificate Delivered by Company. The Company shall have
delivered to the Investors a  certificate,  dated the Closing Date and signed by
the Chief Executive Officer or the President of the Company,  to the effect that
each of the  conditions to be satisfied by the Company  pursuant to this Section
5.1 on or before the Closing Date has been duly satisfied.

         (i) Registration Rights Agreement.  The Company and the Investors shall
have  executed  and  delivered  a  Registration  Rights  Agreement  in form  and
substance as set forth on Exhibit C hereto.

         (j) Warrants.  The Company shall have executed and delivered a document
evidencing  the Class A Warrants in form and  substance  as set forth on Exhibit
B-1 hereto,  the Class B Warrants in form and  substance as set forth on Exhibit
B-2  hereto  and the  Class C  Warrants  in form and  substance  as set forth on
Exhibit B-3 hereto.

         (k) No  Material  Adverse  Change.  There  shall have been no  Material
Adverse Change in the Company since the date of signing of this Agreement.

         (l) Legal Matters. All material matters of a legal nature which pertain
to this  Agreement  and the  transactions  contemplated  hereby  shall have been
reasonably approved by counsel to the Investors.

                                      -9-

<PAGE>


         Notwithstanding  the  foregoing,  no  Investor  shall  be  required  to
purchase and pay for Warrants  and the Common  Stock if another  Major  Investor
defaults in its obligation to purchase and pay for the Warrants and Common Stock
set forth  opposite its name on Exhibit A hereto.  For purpose of the  foregoing
sentence,  the BVF Investors  and Alta shall be deemed to be "Major  Investors."
Nothing  contained  herein shall relieve such other defaulting Major Investor of
any liability it may have for damages caused by its default in its obligation to
purchase and pay for Warrants and Common Stock.

                                   ARTICLE VI.

                     CONDITIONS TO THE COMPANY'S OBLIGATIONS

6.1.     Conditions to Closing.

         The  obligation  of the  Company to issue the  Warrants  and the Common
Stock,  respectively,  to the  Investors  on the Closing  Date is subject to the
following:

         (a) Representations and Warranties.  The representations and warranties
of the Investors made herein shall be true, correct and complete in all respects
on and as of the Closing Date with the same force and effect as if they had been
made on and as of the Closing Date.

         (b) Payment.  The  Investors  shall have  tendered the payments for the
purchase  price of the Common Stock and the Warrants as set forth in Section 1.3
to an account specified by the Company.

         (c) No Proceeding.  No action, suit,  investigation or proceeding shall
be pending or threatened  before any court or  governmental  agency to restrain,
prohibit,  collect damages as a result of or otherwise  challenge this Agreement
or any transaction contemplated hereby or thereby.

         (d) No Law Prohibiting or Restricting  Such Sale. There shall not be in
effect any law,  rule or regulation  prohibiting  or  restricting  such sale, or
requiring  any  consent  or  approval  of any person  which  shall not have been
obtained to issue the Warrants and the Common Stock.

         (e) Shareholder Approval.  The Company shall have obtained any required
approval of its shareholders  representing at least two-thirds of the votes cast
by the then  outstanding  shares of  Common  Stock to the  authorization  of the
Common Stock and the Warrants.

         (f) Investors'  Certificates  Delivered by the  Investors.  Each of the
Investors  shall have delivered to the Company a certificate,  dated the Closing
Date and signed by a duly  authorized  representative  of the  Investor,  to the
effect  that each of the  conditions  pursuant  to Section  6.1(a) and (b) on or
before the Closing Date has been duly satisfied.

                                      -10-

<PAGE>

                                  ARTICLE VII.

                            COVENANTS OF THE COMPANY

         The Company hereby covenants to such Investors as follows:

7.1.     Furnishing of Information.

         The Company  covenants to timely file (or obtain  extensions in respect
thereof) all reports  required to be filed by the Company  after the date hereof
pursuant to Section  13(a) or 15(d) of the Exchange Act and under French law and
to promptly  furnish the  Investors  with true and  complete  copies of all such
filings.  If the Company is not at the time required to file reports pursuant to
such  sections or under French law, it will prepare and furnish to the Investors
annual and quarterly  reports  comparable to those  required by Section 13(a) or
15(d) of the Exchange  Act in the time period that such filings  would have been
required to have been made under the Exchange Act.

7.2.     Information with Respect to the Securities.

         The Company  covenants to provide  such  information  as is  reasonably
requested  by any of the  Investors  related to the terms of the  Common  Stock,
Warrants or Warrant Shares.

7.3.     Shareholder Approval.

         The Company shall use best efforts to convene the shareholders  meeting
to seek the  approval  described in Section  5.1(e)  hereof prior to the Closing
Date.  Subject to the fiduciary duties of the Company's Board of Directors,  the
Company shall include in the materials prepared for the shareholders meeting the
recommendation  of the  Company's  Board  of  Directors  to vote in favor of the
transactions contemplated herein.

7.4.     Investor's Rights.

         Notwithstanding   anything  to  the  contrary  in  the  foregoing,  the
Investors shall be entitled to such information, privileges, rights and benefits
accorded to them as holders of the Common Stock under  applicable  law and under
the Company's statuts, as amended.

7.5.     Filing for Amendment to Statuts.

         Within six weeks of the  Closing  Date,  the  Company  shall  cause all
required  documents to be filed with Registre du Commerce to cause the amendment
to the Company's statuts.

7.6.     Election of Director.

         Upon the written  request of the BVF Investors,  the Company shall take
all action within its power to cause a person designated by the BVF Investors to
be elected to the Board of Directors of the Company as soon as practicable.

                                      -11-

<PAGE>


7.7.     Regulatory Matters Generally.

         Upon request the Company  shall  provide to the  Regulated  Holder such
information  within the  Company's  possession  as is  necessary  to resolve the
Regulatory  Problem,  provided  that  if  such  information  is  proprietary  or
confidential  satisfactory  arrangements  are  made for the  protection  of such
information.  The "Regulated Holder" is Chase and any other Investor  affiliated
with  Chase.  A  "Regulatory  Problem"  is a set of  circumstances  in which the
Regulated Holder's ownership of its shares of Common Stock or Warrants (i) gives
rise to a violation of a banking law or regulation of a federal  banking  agency
or gives  rise to a  reasonable  belief  by the  Regulated  Holder  that  such a
violation is likely to occur or (ii) gives rise to a limitation in law that will
impair  materially  the  ability of the  Regulated  Holder or any  Affiliate  to
conduct  its  business  or gives rise to a  reasonable  belief by the  Regulated
Holder that such a limitation  is likely to arise.  "Affiliate"  has the meaning
given in Regulation Y of the Board of Governors of the Federal Reserve System.

7.8.     Notification.

         The Company shall notify the Regulated Holder promptly at any time that
the Company comes to believe that any  representation  contained in Section 3.13
or Section 3.14 no longer is true.

                                  ARTICLE VIII.

                          SURVIVAL AND INDEMNIFICATION

8.1.     Survival.

         Notwithstanding  any  examination  made by or on  behalf  of any  party
hereto,  the  knowledge  of any  party  or the  acceptance  by any  party of any
certificate or opinion,  each  representation,  warranty  contained herein shall
survive the Closing for a period of two years,  and each covenant  shall survive
for the period indicated therein.

8.2.     Indemnification.

         (a) The Company  agrees to indemnify and hold  harmless each  Investor,
its shareholders,  officers,  directors,  employees,  agents and representatives
against any damage,  claim, loss,  liability and expense  (including  reasonable
counsel fees and expenses) which may be suffered or incurred by any of them as a
result of a breach of any  representation  or warranty  or covenant  (including,
without  limitation,  pursuant  to  Section  9.16)  made by the  Company in this
Agreement.

         (b) The  Investors,  jointly  and  severally,  agree to  indemnify  the
Company  and  its  shareholders,  officers,  directors,  employees,  agents  and
representatives  against any damages,  claims, losses,  liabilities and expenses
(including  reasonable counsel fees and other expenses) which may be suffered or
incurred  by it as a result of any breach of any  representation,  warranty,  or
covenant made by the Investors in this Agreement.

                                      -12-

<PAGE>


         (c) In case any proceeding  (including any governmental  investigation)
shall be instituted  involving  any person in respect of which  indemnity may be
sought  pursuant to this Section,  such person (the  "indemnified  party") shall
promptly  notify the  person  against  whom such  indemnity  may be sought  (the
"indemnifying   party")  in  writing  of  the   occurrence   of  the  facts  and
circumstances  giving rise to such  claim.  The failure of any person to deliver
the  notice  required  by this  Section  8.2(c)  shall not in any way affect the
indemnifying party's indemnification obligation hereunder except and only to the
extent that the indemnifying party is actually  prejudiced  thereby. In case any
such  proceeding  shall be brought  against any  indemnified  party and it shall
notify the  indemnifying  party of the  commencement  thereof,  the indemnifying
party shall be entitled to participate  therein and, to the extent that it shall
wish, jointly with any other indemnifying  party similarly  notified,  to assume
the defense thereof,  with counsel  satisfactory to such  indemnified  party and
shall pay as  incurred  the fees and  expenses of such  counsel  related to such
proceeding.  In any such proceeding,  any indemnified party shall have the right
to  retain  its  own  counsel  or pay  its  own  expenses.  Notwithstanding  the
foregoing, the indemnifying party shall pay as incurred the fees and expenses of
the counsel retained by the indemnified  party in the event (i) the indemnifying
party and the  indemnified  party shall have mutually agreed to the retention of
such counsel or (ii) the named parties to any such  proceedings  (including  any
impleaded parties) include both the indemnifying party and the indemnified party
and  representation  of both parties by the same counsel would be  inappropriate
due to actual or potential  differing  interests  between them. The indemnifying
party shall not be liable for any settlement of any proceeding  effected without
its  written  consent  but if settled  with such  consent or if there be a final
judgment for the  plaintiff,  the  indemnifying  party  agrees to indemnify  the
indemnified  party  from and  against  any loss or  liability  by reason of such
settlement or judgment and the indemnifying party shall obtain a full release of
the indemnified party.

                                   ARTICLE IX.

                                  MISCELLANEOUS

9.1.     Notices.

         All  notices,  requests,  consents and other  communications  hereunder
shall be in writing,  shall be addressed to the  receiving  party's  address set
forth  below  or to such  other  address  as a party  may  designate  by  notice
hereunder,  and shall be either (i) delivered by hand,  (ii) made by telecopy or
facsimile  transmission,  (iii)  sent by  overnight  courier,  or  (iv)  sent by
registered mail, return receipt requested, postage prepaid.

If to the
BVF Investors:             c/o BVF Partners, L.P.
                           One Sansome Street, 39th Floor
                           San Francisco, CA 94104
                           Attn.: Mr.  Mark Lampert
                           Fax: (415) 288-2394

With a copy to:            Sidley & Austin

                                      -13-

<PAGE>

                           875 Third Avenue
                           New York, NY  10022
                           Attn.: Paul K. Risko, Esq.
                           Fax: (212) 906-2021

If to Alta:                One Embarcadero Center
                           Suite 4050
                           San Francisco, CA 94111
                           Attn.: Mr. Dan Janney
                           Fax: (415) 362-6178

If to Chase:               380 Madison Avenue, 12th Floor
                           New York, NY 10017-2951
                           Attn.: Mr. Damion Wicker
                           Fax: (212) 622-3771

If to the Company:         Flamel Technologies S.A.
                           33 Avenue du Docteur Georges Levy
                           69693 Venissieux Cedex, France
                           Attn.: Gerard Soula, D.Sc.
                           Fax: (33) 4-72-78-34-25

With a copy to:            Willkie Farr & Gallagher
                           787 Seventh Avenue
                           New York, New York  10019
                           Attn.: Peter H. Jakes, Esq.
                           Fax: (212) 728-8111

                           and

                           Sokolow, Dunaud, Mercadier & Carreras
                           55 Avenue Kleber
                           75116 Paris, France
                           Attn.: Francoise Monod, Esq.
                           Fax: (33) 1-53-65-70-50

All notices,  requests,  consents and other  communications  hereunder  shall be
deemed to have been  given  either (i) if by hand,  at the time of the  delivery
thereof to the  receiving  party at the  address of such party set forth  above,
(ii) if made by telecopy or facsimile  transmission,  one (1) day after the time
that  receipt  thereof  has been  acknowledged  by  electronic  confirmation  or
otherwise,  (iii)  if  sent by  overnight  courier,  on the  next  business  day
following  the day such notice is delivered to the courier  service,  or (iv) if
sent by registered  mail, on the 5th business day following the day such mailing
is made.

                                      -14-

<PAGE>

9.2.     Entire Agreement.

         This Agreement,  including  exhibits,  or other  documents  referred to
herein,  and the  Confidentiality  Agreement,  dated  November 15, 1999,  by and
between the Company and BVF, Inc. embody the entire agreement and  understanding
between  the  parties  hereto  with  respect to the  subject  matter  hereof and
supersede all prior oral or written  agreements and  understandings  relating to
the subject matter hereof. No statement,  representation,  warranty, covenant or
agreement of any kind not expressly set forth in this Agreement shall affect, or
be used to interpret,  change or restrict,  the express terms and  provisions of
this Agreement.

9.3.     Amendments.

         The terms and  provisions of the Agreement may be modified,  amended or
waived, or consent for the departure therefrom granted,  only by written consent
of the Company and the  Investors.  No such waiver or consent shall be deemed to
be or shall  constitute  a waiver or consent  with respect to any other terms or
provisions  of this  Agreement,  whether  or not  similar.  Each such  waiver or
consent shall be effective only in the specific instance and for the purpose for
which it was given, and shall not constitute a continuing waiver or consent.

9.4.     Assignment.

         Neither this Agreement nor any or all of the rights and  obligations of
a party hereunder shall be assigned,  delegated,  sold, transferred or otherwise
disposed of by operation of law or  otherwise,  to any third person  without the
prior  written  consent  of the  other  party,  and  any  attempted  assignment,
delegation,  sale,  transfer,  or  other  disposition,  by  operation  of law or
otherwise,  of this Agreement or of any rights or obligations hereunder contrary
to this Section 9.4 shall be void and without force or effect.  Each party shall
be  responsible  for  the  compliance  by its  Affiliates  with  the  terms  and
conditions of this Agreement.

9.5.     Benefit.

         All statements,  representations,  warranties, covenants and agreements
in this Agreement  shall be binding on the parties hereto and shall inure to the
benefit of the respective successors and permitted assigns of each party hereto.
Nothing in this Agreement shall be construed to create any rights or obligations
except among the parties hereto,  and no person or entity shall be regarded as a
third-party beneficiary of this Agreement.

9.6.     Governing Law.

         This Agreement and the rights and obligations of the parties  hereunder
shall be  construed in  accordance  with and governed by the law of the State of
New York.

9.7.     Severability.

         In the event that any court of competent  jurisdiction  shall determine
that any provision, or any portion thereof, contained in this Agreement shall be
unreasonable  or  unenforceable  in any

                                      -15-

<PAGE>


respect,  then such  provision  shall be deemed  limited to the extent that such
court deems it  reasonable  and  enforceable,  and as so limited shall remain in
full  force  and  effect.  In the  event  that such  court  shall  deem any such
provision, or portion thereof, wholly unenforceable, the remaining provisions of
this  Agreement  shall be  interpreted as if such provision were so excluded and
shall nevertheless remain in full force and effect.

9.8.     Headings and Captions.

         The headings and captions of the various subdivisions of this Agreement
are for convenience of reference only and shall in no way modify,  or affect the
meaning or construction of any of the terms or provisions hereof.

9.9.     No Waiver of Rights, Powers and Remedies.

         No failure or delay by a party hereto in exercising any right, power or
remedy  under this  Agreement,  and no course of  dealing  between  the  parties
hereto,  shall  operate  as a waiver of any such  right,  power or remedy of the
party.  No single or partial  exercise of any right,  power or remedy under this
Agreement by a party hereto,  nor any abandonment or  discontinuance of steps to
enforce  any such right,  power or remedy,  shall  preclude  such party from any
other or further exercise  thereof or the exercise of any other right,  power or
remedy  hereunder.  The  election  of any  remedy  by a party  hereto  shall not
constitute  a waiver  of the  right  of such  party to  pursue  other  available
remedies.  No notice to or demand on a party not expressly  required  under this
Agreement  shall entitle the party  receiving such notice or demand to any other
or further  notice or demand in similar or other  circumstances  or constitute a
waiver of the rights of the party  giving  such notice or demand to any other or
further action in any circumstances without such notice or demand.

9.10.    Expenses.

         Except as provided in Section  8.2,  each of the parties  shall pay its
own  fees  and  expenses  (including  the  fees of any  attorneys,  accountants,
appraisers or others  engaged by such party) in connection  with this  Agreement
and the transactions  contemplated  hereby;  provided that the Company shall pay
such fees and expenses  (including  attorney's  fees) of the BVF Investors up to
$15,000.

                                      -16-

<PAGE>


9.11.    Brokers.

         Each of the parties hereto represents and warrants to the other that no
broker,  finder or financial  consultant  has acted on its behalf in  connection
with this Agreement or the transactions  contemplated hereby in such a way as to
create  any  liability  on the  other.  Each of the  parties  hereto  agrees  to
indemnify and save the other harmless from any claim or demand for commission or
other compensation by any other broker, finder,  financial consultant or similar
agent  claiming to have been  employed by or on behalf of such party and to bear
the cost of legal expenses incurred in defending against any such claim.

9.12.    Confidentiality.

         The Investors  acknowledge  and agree that any information or data they
have  acquired  from the  Company,  which is  clearly  designated  in writing as
confidential and is not otherwise properly in the public domain, was received in
confidence.  Each  of the  Investors  agrees  not  to  divulge,  communicate  or
disclose, except as may be required by law or upon the advice of its accountants
or for the performance of this Agreement, or use to the detriment of the Company
or for the  benefit of any other  person or persons,  or misuse in any way,  any
confidential information of the Company.

9.13.    Counterparts.

         This  Agreement  may be  executed in one or more  counterparts,  and by
different parties hereto on separate counterparts, each of which shall be deemed
an  original,  but all of  which  together  shall  constitute  one and the  same
instrument.

9.14.    Further Assurances.

         In case at any time after the Closing any further  action is  necessary
or desirable to carry out the  purposes of this  Agreement,  the Company and the
Investors  will take such  further  action  as the  other  party may  reasonably
request,  all at the sole cost and expense of the  requesting  party (unless the
requesting party is entitled to indemnification therefor under Article VIII).

9.15.    Consent to Jurisdiction.

         To the extent that the Company or the  Investors  have or may hereafter
become  entitled  to any right of  immunity,  on the grounds of  sovereignty  or
otherwise,   from  any  legal  action,  suit  or  proceeding,   from  setoff  or
counterclaim,  from the jurisdiction of any court, from service or process, from
attachment  upon or prior to judgment,  from  attachment  in aid of execution of
judgment,  or from  execution of judgment,  or other legal process or proceeding
for the  giving of any relief or for the  enforcement  of any  judgment,  in any
jurisdiction  in which  proceedings may at any time be commenced with respect to
the  obligations  and  liabilities  of the Company or the  Investors  under this
Agreement,  the Company and the Investors hereby irrevocably and unconditionally
waive,  and agree not to plead or claim,  any such  immunity and consent to such
relief and enforcement.  The Company hereby  irrevocably waives its rights under
the  provisions  of Article 14 and  Article 15 of the  French  Civil  Code.  The
Company  hereby  irrevocably

                                      -17-

<PAGE>

consents and submits to the jurisdiction of the courts of the State of New York,
New York  County,  and in the  United  States  District  Court for the  Southern
District of New York in personam generally and unconditionally in respect of any
such suit or proceeding.

9.16.    Break-Up Fee.

         If (i) (x) the  Company's  shareholders  do not  vote  to  approve  the
transactions  contemplated  by this  Agreement  or (y) if the  Company  fails to
consummate  the sale of the Common  Stock and the  Warrants to the  Investors as
contemplated by this Agreement by March 31, 2000 and (ii) within eighteen months
of the date hereof, the Company enters into agreement for the sale of its equity
securities or other  securities  convertible into or exchangeable for its equity
securities  (whether by private placement or public offering) or the acquisition
of the Company or the merger or consolidation of the Company with another entity
(each,  an  "Alternative  Transaction"),  then  it will  be a  condition  to the
consummation of the Alternative  Transaction by the Company that (a) each of the
Investors  shall have been issued that number of warrants in form and  substance
as set forth on Exhibit B-1 hereto to purchase Common Stock at an exercise price
of 39.10 French francs per share of Common Stock as set forth  opposite its name
under the column  "Class A Warrants" on Exhibit A, and (b) such  warrants  shall
have the benefit of, and be included under,  any  registration  rights agreement
entered  into in  connection  with such  Alternative  Transaction.  The  Company
acknowledges that the agreements  contained in this Section 9.16 are an integral
part of the transactions  contemplated  hereby, and that without such agreements
the Investors would not enter into this Agreement.

                   [REMAINDER OF PAGE IS INTENTIONALLY BLANK]

                                      -18-

<PAGE>


         IN WITNESS  WHEREOF,  the  undersigned  have executed  this  Securities
Purchase Agreement as of this 29th day of February, 2000.

                      FLAMEL TECHNOLOGIES S.A.


                      By:
                               -------------------------------------------------
                               Name:  Gerard Soula
                               Title:   Chief Executive Officer

                      BIOTECHNOLOGY VALUE FUND, L.P.

                      By:      BVF PARTNERS L.P., its General Partner

                               By:      BVF, INC., its General Partner

                                        By:
                                                 -------------------------------
                                                 Mark N. Lampert
                                                 President

                      BIOTECHNOLOGY VALUE FUND II, L.P.

                      By:      BVF PARTNERS L.P., its General Partner

                               By:      BVF, INC., its General Partner

                                        By:
                                                 -------------------------------
                                                 Mark N. Lampert
                                                 President

                      INVESTMENT 10 L.L.C.

                      By:      BVF PARTNERS, L.P., its Investment Advisor

                               By:      BVF, INC., its General Partner

                               By:
                                        ----------------------------------------
                                        Mark N. Lampert
                                        President

                      ALTA BIOPHARMA PARTNERS LP

                               By:
                                   ---------------------------------------------
                                   Name:

                                      -19-

<PAGE>


                                   Title:

                      ALTA EMBARCADERO BIOPHARMA, LLC


                      By:
                          ------------------------------------------------------
                          Name:
                          Title:

                      FLAMEL CHASE PARTNERS (ALTA BIO), LLC



                      By:
                          ------------------------------------------------------
                          Name:
                          Title:



                      CHASE EUROPEAN EQUITY ASSOCIATES, LLC

                      By: Chase Capital Partners, its Manager

                          By:
                             ---------------------------------------------------
                             Name:
                             Title:

                                      -20-

<PAGE>


<TABLE>
                                    EXHIBIT A

INVESTORS:

<CAPTION>
- --------------------------------------------- -------------- ---------------- ----------------- --------------- -------------------
NAME                                            ORDINARY         CLASS A          CLASS B          CLASS C        PURCHASE PRICE
                                                 SHARES         WARRANTS          WARRANTS         WARRANTS           (FrF)
- --------------------------------------------- -------------- ---------------- ----------------- --------------- -------------------
<S>                                              <C>               <C>                 <C>             <C>        <C>
AltaBioPharma Partners, LP                       1,165,474         652,666             699,288         699,288       30,372,252.44
Alta Embarcadero BioPharma, LLC                     43,929          24,600              26,358          26,358        1,144,789.74
Biotechnology Value Fund, L.P.                     375,000         210,000             225,000         225,000        9,772,500.00
Biotechnology Value Fund II, L.P.                  812,500         455,000             487,500         487,500       21,173,750.00
Chase European Equity Associates, LLC               87,500          49,000              52,500          52,500        2,280,250.00
Flamel Chase Partners (Alta Bio), LLC              665,597         372,734             399,354         399,354       17,345,457.82
Investment 10 L.L.C.                                62,500          35,000              37,500          37,500        1,628,750.00
                                                 ---------       ---------           ---------       ---------    ----------------
                                    Total:       3,212,500       1,799,000           1,927,500       1,927,500    FrF83,717,750.00
                                    =====        =========       =========           =========       =========    ================

- --------------------------------------------- -------------- ---------------- ----------------- --------------- -------------------
</TABLE>


<PAGE>

                                                                    SCHEDULE 3.7

(1) The Company's cash balances have continued to decline over time.

(2) Barbara  Sherrill  resigned from her position as Chief Financial  Officer of
the Company as of December 3, 1999.

(3) Bruce Morra resigned from his position as President of Flamel  Technologies,
Inc., the Company's subsidiary, as of January 31, 2000.

(4) The Company intends to dissolve its only  subsidiary,  Flamel  Technologies,
Inc. in the first half of 2000.

<PAGE>


                                                                    SCHEDULE 3.8

(1) The Company's cash balances have continued to decline over time.

(2) Barbara Sherrill resigned from her position as Chief Financial Officer as of
December 3, 1999.

(3) Bruce Morra resigned from his position as President of Flamel  Technologies,
Inc., the Company's subsidiary, as of January 31, 2000.

(4) The Company intends to dissolve its only  subsidiary,  Flamel  Technologies,
Inc. in the first half of 2000.


<PAGE>

<TABLE>
                                              Table of Contents

<CAPTION>
                                                                                                                Page
                                                                                                                ----

<S>                                                                                                              <C>
ARTICLE I.  ISSUANCE AND TERMS OF WARRANTS AND COMMON STOCK.......................................................1

   1.1. Authorization of Securities...............................................................................1
   1.2. Purchase and Sale of Warrants and Common Stock............................................................1
   1.3. Payment...................................................................................................2

ARTICLE II.  CLOSING..............................................................................................2

   2.1. Closing...................................................................................................2
   2.2. Legend....................................................................................................2

ARTICLE III.  REPRESENTATIONS AND WARRANTIES OF THE COMPANY.......................................................3

   3.1. Organization and Standing of the Company..................................................................3
   3.2. Capitalization............................................................................................3
   3.3. Validity of this Agreement................................................................................4
   3.4. Governmental Consent, Etc.................................................................................4
   3.5. Valid Issuance of Securities..............................................................................4
   3.6. Financial Statements......................................................................................5
   3.7. Accuracy and Completeness of Information..................................................................5
   3.8. Adverse Changes...........................................................................................5
   3.9. No Violation..............................................................................................6
   3.10. All Necessary Permits, Etc...............................................................................6
   3.11. Title to Properties......................................................................................6
   3.12. Securities Laws..........................................................................................6
   3.13. Relationship to the Regulated Holder.....................................................................6
   3.14. U.S. Activities..........................................................................................7

ARTICLE IV.  REPRESENTATIONS AND WARRANTIES OF THE INVESTORS......................................................7

   4.1. Authority of Investors, Validity of this Agreement........................................................7
   4.2. Investment Representations................................................................................7

ARTICLE V.  CONDITIONS TO INVESTORS' OBLIGATIONS..................................................................8

   5.1. Conditions to Closing.....................................................................................8

ARTICLE VI.  CONDITIONS TO THE COMPANY'S OBLIGATIONS.............................................................10

   6.1. Conditions to Closing....................................................................................10

ARTICLE VII.  COVENANTS OF THE COMPANY...........................................................................10

   7.1. Furnishing of Information................................................................................10
   7.2. Information with Respect to the Securities...............................................................11
   7.3. Shareholder Approval.....................................................................................11
   7.4. Investor's Rights........................................................................................11
   7.5. Filing for Amendment to Statuts..........................................................................11

                                                         (i)

<PAGE>

                                              Table of Contents
                                                 (continued)
                                                                                                                Page
                                                                                                                ----

   7.6. Election of Director.....................................................................................11
   7.7. Regulatory Matters Generally.............................................................................11
   7.8. Notification.............................................................................................12

ARTICLE VIII.  SURVIVAL AND INDEMNIFICATION......................................................................12

   8.1. Survival.................................................................................................12
   8.2. Indemnification..........................................................................................12

ARTICLE IX.  MISCELLANEOUS.......................................................................................13

   9.1. Notices..................................................................................................13
   9.2. Entire Agreement.........................................................................................14
   9.3. Amendments...............................................................................................14
   9.4. Assignment...............................................................................................15
   9.5. Benefit..................................................................................................15
   9.6. Governing Law............................................................................................15
   9.7. Severability.............................................................................................15
   9.8. Headings and Captions....................................................................................15
   9.9. No Waiver of Rights, Powers and Remedies.................................................................16
   9.10. Expenses................................................................................................16
   9.11. Brokers.................................................................................................16
   9.12. Confidentiality.........................................................................................16
   9.13. Counterparts............................................................................................17
   9.14. Further Assurances......................................................................................17
   9.15. Consent to Jurisdiction.................................................................................17
   9.16. Break-Up Fee............................................................................................17
</TABLE>

                                                         (ii)

<PAGE>

                                    EXHIBIT C

                            FLAMEL TECHNOLOGIES S.A.

                          REGISTRATION RIGHTS AGREEMENT

                  REGISTRATION  RIGHTS AGREEMENT,  dated as of April 5, 2000, by
and among Flamel  Technologies  S.A., a societe anonyme organized under the laws
of The Republic of France (the "Company") and BIOTECHNOLOGY  VALUE FUND, L.P., a
Delaware  limited  partnership,  BIOTECHNOLOGY  VALUE FUND II,  L.P., a Delaware
limited partnership, INVESTMENT 10 L.L.C., an Illinois limited liability company
(collectively,  the "BVF Investors"),  and ALTA BIOPHARMA  PARTNERS,  a Delaware
limited  partnership,  ALTA  EMBARCADERO  BIOPHARMA,  LLC, a California  limited
liability company, and FLAMEL CHASE PARTNERS (ALTABIO),  LLC, a Delaware limited
liability company (collectively,  "Alta"); and CHASE EUROPEAN EQUITY ASSOCIATES,
LLC, a Delaware limited  liability  company ("Chase" and,  together with the BVF
Investors and Alta, the "Investors").

                                 R E C I T A L S

                  WHEREAS,  the  Investors  have,  pursuant  to the terms of the
Securities Purchase  Agreement,  dated as of February 29, 2000, by and among the
Company  and the  Investors  (the  "Purchase  Agreement"),  agreed  to  purchase
ordinary shares,  nominal value 0.80 French francs per share ("Ordinary Shares")
and  bons  de   souscription  to  purchase   additional   Ordinary  Shares  (the
"Warrants"); and

                  WHEREAS,  the Company has agreed, as a condition  precedent to
the Investors' obligations under the Purchase Agreement,  to grant the Investors
certain registration rights; and

                  WHEREAS,  the Company and the  Investors  desire to define the
registration  rights of the Investors on the terms and subject to the conditions
herein set forth.

                  NOW, THEREFORE, in consideration of the foregoing premises and
for other good and valuable consideration, the parties hereby agree as follows:

                  1.       DEFINITIONS

                  As  used in this  Agreement,  the  following  terms  have  the
respective meaning set forth below:

<PAGE>


                  ADSs:  shall  mean  American  Depositary  Shares  representing
Ordinary Shares (the current ratio being one American  Depositary Share for each
deposited Ordinary Share) and represented by American Depositary Receipts of the
Company;

                  Commission:  shall mean the Securities and Exchange Commission
or any other federal agency at the time administering the Securities Act;

                  Exchange Act: shall mean the Securities  Exchange Act of 1934,
as amended;

                  Holder: shall mean any holder of Registrable Securities;

                  Initiating  Holder:  shall  mean  the BVF  Investors,  Alta or
Chase;

                  Person:  shall mean an  individual,  partnership,  joint-stock
company, corporation,  trust or unincorporated organization, and a government or
agency or political subdivision thereof;

                  register,  registered  and  registration:   shall  mean  to  a
registration  effected  by  preparing  and filing a  registration  statement  in
compliance with the Securities Act (and any  post-effective  amendments filed or
required to be filed) and the declaration or ordering of  effectiveness  of such
registration statement;

                  Registrable  Securities:  shall mean ADSs representing (A) the
Ordinary Shares issued pursuant to the Purchase  Agreement,  (B) Ordinary Shares
acquired by the  Investors  pursuant to the exercise of the Warrants and (C) any
capital  stock of the Company  issued as a dividend or other  distribution  with
respect  to, or in  exchange  for or in  replacement  of,  the  Ordinary  Shares
referred to in clause (A) or (B);

                  Registration Expenses: shall mean all expenses incurred by the
Company in  compliance  with Sections  2(a) and (b) hereof,  including,  without
limitation,  all  registration  and filing  fees,  printing  expenses,  fees and
disbursements  of counsel for the Company,  fees and expenses of one counsel for
all the Holders in an amount not to exceed  $15,000,  blue sky fees and expenses
and the  expense of any  special  audits  incident  to or  required  by any such
registration  (but  excluding  the  compensation  of  regular  employees  of the
Company, which shall be paid in any event by the Company);

                  Security,  Securities:  shall  have the  meaning  set forth in
Section 2(1) of the Securities Act;

                  Securities  Act:  shall mean the  Securities  Act of 1933,  as
amended; and

                  Selling  Expenses:  shall mean all underwriting  discounts and
selling  commissions  applicable to the sale of  Registrable  Securities and all
fees and  disbursements  of counsel for each of the Holders  other than fees and
expenses of one counsel for all the Holders in an amount not to exceed $15,000.

                                       2

<PAGE>

                  2.       REGISTRATION RIGHTS

                           (a)  Requested Registration.

                           (i) Request for  Registration.  If the Company  shall
         receive from an Initiating Holder who has not previously  exercised its
         right to call for a registration  under this Section  2(a)(i) a written
         request that the Company effect any registration with respect to all or
         a part of the Registrable Securities, the Company will:

                                    (A)  promptly  give  written  notice  of the
                  proposed  registration,  qualification  or  compliance  to all
                  other Holders; and

                                    (B) as soon as practicable, use its diligent
                  best efforts to effect such registration  (including,  without
                  limitation,   the   execution  of  an   undertaking   to  file
                  post-effective  amendments,  appropriate  qualification  under
                  applicable  blue  sky  or  other  state  securities  laws  and
                  appropriate  compliance  with  applicable  regulations  issued
                  under the Securities  Act) as may be so requested and as would
                  permit or facilitate the sale and  distribution of all or such
                  portion of such  Registrable  Securities  as are  specified in
                  such  request,  together  with  all  or  such  portion  of the
                  Registrable  Securities  of any Holder or  Holders  joining in
                  such request as are specified in a written request received by
                  the Company within ten (10) business days after written notice
                  from the  Company is given  under  Section  2(a)(i)(A)  above;
                  provided that the Company shall not be obligated to effect, or
                  take any action to effect,  any such registration  pursuant to
                  this Section 2(a):

                                            (x) In any  particular  jurisdiction
                     in which the Company would be required to execute a consent
                     (other  than a limited  consent)  to  service of process in
                     effecting such  registration,  qualification or compliance,
                     unless the  Company  is already  subject to service in such
                     jurisdiction   and  except  as  may  be   required  by  the
                     Securities   Act  or   applicable   rules  or   regulations
                     thereunder;

                                            (y) After the Company  has  effected
                     one  (1)  such  registration  requested  by each of the BVF
                     Investors,  Alta  and  Chase  (for a  total  of  three  (3)
                     registrations)  pursuant  to this  Section  2(a)  and  such
                     registrations  have been declared or ordered  effective and
                     the sales of such Registrable Securities shall have closed;
                     or

                                            (z) If the Company is in  possession
                     of  material  non-public   information  and  the  Board  of
                     Directors  of the  Company  determines  in good  faith that
                     disclosure  of such  information  would  not be in the best
                     interests  of the  Company and its  shareholders,  in which
                     case  the  filing  of such  registration  statement  may be
                     delayed until the earlier of the second  business day after
                     such  conditions  shall have  ceased to exist and the 120th
                     day after  receipt by the  Company of the  written  request
                     from  the  Initiating  Holders  under

                                       3

<PAGE>

                     this Section 2(a); provided,  however,  that the Initiating
                     Holders  shall be  advised  of any delay  arising  from the
                     operation of this clause (z) and may, without  prejudice to
                     their  other  rights,   withdraw   their  request  for  the
                     registration  of  Registrable  Securities in which case the
                     contemplated  registration shall not count for the purposes
                     of clause (y) above.

                           The  registration  statement  filed  pursuant  to the
         request of the  Initiating  Holders may,  subject to the  provisions of
         Section  2(a)(ii) below,  include other securities of the Company which
         are held by Persons who, by virtue of agreements with the Company,  are
         entitled to include their securities in any such  registration  ("Other
         Stockholders").

                           The  registration  rights set forth in this Section 2
         may be assigned,  in whole or in part, to any transferee of Registrable
         Securities (who shall be bound by all obligations of this Agreement).

                           (ii)  Underwriting.  If the Initiating Holders intend
         to distribute the  Registrable  Securities  covered by their request by
         means of an underwriting, they shall so advise the Company as a part of
         their request made pursuant to Section 2(a).

                           If Other Stockholders  request to be included in such
         underwritten   offering,   the  Holders  shall  offer  to  include  the
         securities  of such  Other  Stockholders  in the  underwriting  and may
         condition  such offer on the acceptance by such Other  Stockholders  of
         the further applicable  provisions of this Section 2. The Holders whose
         shares are to be included in such  registration  and the Company  shall
         (together  with all Other  Stockholders  proposing to distribute  their
         securities  through  such  underwriting)  enter  into  an  underwriting
         agreement in customary form with the  representative of the underwriter
         or  underwriters  selected  for  such  underwriting  by the  Initiating
         Holders and reasonably  acceptable to the Company.  Notwithstanding any
         other provision of this Section 2(a), if the representative advises the
         Holders in writing that marketing  factors  require a limitation on the
         number of shares to be underwritten, the securities of the Company held
         by officers,  directors and Other  Stockholders  shall be excluded from
         such  registration  to the extent so required by such  limitation.  If,
         after  the  exclusion  of such  shares,  further  reductions  are still
         required,  the number of shares  included in the  registration  by each
         Holder  shall be reduced  on a pro rata  basis  (based on the number of
         shares held by such  Holder),  by such  minimum  number of shares as is
         necessary to comply with such request. No Registrable Securities or any
         other  securities  excluded  from the  underwriting  by  reason  of the
         underwriter's   marketing   limitation   shall  be   included  in  such
         registration.  If any Other Stockholder who has requested  inclusion in
         such  registration  as provided  above  disapproves of the terms of the
         underwriting,  such person may elect to withdraw  therefrom  by written
         notice to the Company,  the underwriter and the Initiating Holders. The
         securities so withdrawn shall also be withdrawn from  registration.  If
         the underwriter has not limited the number of Registrable Securities or
         other  securities  to be  underwritten,  the Company and  officers  and
         directors of the Company may include its or their securities for its or
         their own account in such registration if the  representative so

                                       4

<PAGE>

         agrees and if the number of Registrable Securities and other securities
         which  would  otherwise  have been  included in such  registration  and
         underwriting will not thereby be limited.

                           (b)  Company Registration.

                           (i) If the Company shall determine to register any of
         its equity  securities either for its own account or for the account of
         Other  Stockholders,  other  than a  registration  relating  solely  to
         employee  benefit  plans,  or  a  registration  relating  solely  to  a
         Commission Rule 145 transaction,  or a registration on any registration
         form  which  does  not  permit  secondary  sales  or does  not  include
         substantially  the same information as would be required to be included
         in  a   registration   statement   covering  the  sale  of  Registrable
         Securities, the Company will:

                                    (A)  promptly  give to each of the Holders a
              written  notice  thereof  (which  shall  include  a  list  of  the
              jurisdictions  in which the Company  intends to attempt to qualify
              such  securities  under  the  applicable  blue sky or other  state
              securities laws); and

                                    (B)  include in such  registration  (and any
              related  qualification  under blue sky laws or other  compliance),
              and in any  underwriting  involved  therein,  all the  Registrable
              Securities specified in a written request or requests, made by any
              Holder  within  fifteen  (15) days after  receipt  of the  written
              notice from the Company  described in clause (i) above,  except as
              set forth in Section  2(b)(ii)  below.  Such  written  request may
              specify all or a part of the Holders' Registrable Securities.

                  (ii)  Underwriting.  If the  registration of which the Company
         gives  notice  is  for  a  registered  public  offering   involving  an
         underwriting, the Company shall so advise each of the Holders as a part
         of the written  notice given  pursuant to Section  2(b)(i)(A).  In such
         event,  the right of each of the  Holders to  registration  pursuant to
         this Section 2(b) shall be conditioned upon such Holders' participation
         in such  underwriting  and the inclusion of such  Holders'  Registrable
         Securities  in the  underwriting  to the extent  provided  herein.  The
         Holders  whose  shares are to be  included in such  registration  shall
         (together  with the  Company  and the Other  Stockholders  distributing
         their securities through such underwriting)  enter into an underwriting
         agreement in customary form with the  representative of the underwriter
         or   underwriters   selected   for   underwriting   by   the   Company.
         Notwithstanding  any  other  provision  of this  Section  2(b),  if the
         representative  determines that marketing  factors require a limitation
         on the  number of shares to be  underwritten,  the  representative  may
         (subject to the  allocation  priority set forth below) limit the number
         of  Registrable  Securities  to be  included  in the  registration  and
         underwriting  to not less than twenty five percent  (25%) of the shares
         included therein (based on the number of shares).  The Company shall so
         advise  all  holders of  securities  requesting  registration,  and the
         number of shares of securities  that are entitled to be included in the
         registration  and  underwriting  shall be  allocated  in the  following
         manner:  The securities of the Company held by officers,  directors and
         Other  Stockholders of the

                                       5

<PAGE>

         Company (other than  Registrable  Securities and other than  securities
         held by holders who by  contractual  right  demanded such  registration
         ("Demanding  Holders"))  shall be excluded from such  registration  and
         underwriting  to the extent  required  by such  limitation,  and,  if a
         limitation  on the  number of shares is still  required,  the number of
         shares that may be included in the  registration  and  underwriting  by
         each of the Holders and Demanding  Holders  shall be reduced,  on a pro
         rata basis (based on the number of shares held by such Holder), by such
         minimum   number  of  shares  as  is  necessary  to  comply  with  such
         limitation.  If any of the  Holders or any  officer,  director or Other
         Stockholder  disapproves of the terms of any such underwriting,  he may
         elect to withdraw  therefrom  by written  notice to the Company and the
         underwriter. Any Registrable Securities or other securities excluded or
         withdrawn  from  such   underwriting   shall  be  withdrawn  from  such
         registration.

                           (c) Form  F-3.  Each of the BVF  Investors,  Alta and
Chase shall have the right to request one (1) registration (for a total of three
(3)  registrations)  on Form F-3 (such  requests  shall be in writing  and shall
state the number of shares of  Registrable  Securities to be disposed of and the
intended  method of disposition of shares by such holders),  subject only to the
following:

                           (i) The  Company  shall not be  required  to effect a
         registration  pursuant  to this  Section  2(c)  within  180 days of the
         effective date of the most recent registration pursuant to this Section
         2 in which  securities  held by the  requesting  Holder could have been
         included for sale or distribution.

                           (ii) The Company shall not be obligated to effect any
         registration   pursuant  to  this  Section   2(c)  in  any   particular
         jurisdiction  in which  the  Company  would be  required  to  execute a
         consent  (other  than a limited  consent)  to  service  of  process  in
         effecting such  registration,  qualification or compliance,  unless the
         Company is already subject to service in such  jurisdiction  and except
         as may be  required  by the  Securities  Act  or  applicable  rules  or
         regulations thereunder.

                           (iii) The Company  shall not be  obligated  to effect
         any  registration  pursuant to this  Section  2(c) if the Company is in
         possession  of  material  non-public   information  and  the  Board  of
         Directors of the Company  determines  in good faith that  disclosure of
         such information  would not be in the best interests of the Company and
         its  shareholders,  in  which  case  the  filing  of such  registration
         statement may be delayed  until the earlier of the second  business day
         after  such  conditions  shall  have  ceased to exist and the 120th day
         after receipt by the Company of the written request from the Initiating
         Holders under this Section 2(c);  provided,  however,  that the Holders
         shall be advised of any delay arising from the operation of this clause
         (iii) and may, without prejudice to their other rights,  withdraw their
         request for the  registration  of Registrable  Securities in which case
         the contemplated  registration shall not count for the purposes of this
         Section 2(c).

                                       6

<PAGE>

         The Company shall give written  notice to all Holders of the receipt of
a request for  registration  pursuant to this Section  2(c) and shall  provide a
reasonable  opportunity  for other Holders to participate  in the  registration,
provided that if the registration is for an underwritten  offering, the terms of
Section  2(a)(ii) shall apply to all  participants in such offering.  Subject to
the  foregoing,  the Company  will use its best  efforts to effect  promptly the
registration  of all shares of Registrable  Securities on Form F-3 to the extent
requested by the Holder or Holders thereof for purposes of disposition.

                           (d)  Expenses  of   Registration.   All  Registration
Expenses  incurred  in  connection  with  any  registration,   qualification  or
compliance  pursuant to this  Section 2 shall be borne by the  Company,  and all
Selling  Expenses  shall be borne by the Holders of the securities so registered
pro rata on the basis of the number of their shares so registered.

                           (e)  Registration  Procedures.  In the  case  of each
registration  effected  by the Company  pursuant to this  Section 2, the Company
will keep the Holders, as applicable, advised in writing as to the initiation of
each registration and as to the completion thereof. At its expense,  the Company
will:

                           (i) keep such registration  effective for a period of
         two hundred  seventy  (270) days or until the Holders,  as  applicable,
         have sold all the Registrable Securities included in such registration,
         whichever first occurs; provided, however, that (A) such 270-day period
         shall be extended for a period of time equal to the period during which
         the  Holders,  as  applicable,  refrain  from  selling  any  securities
         included in such  registration in accordance with provisions in Section
         2(i) hereof;  and (B) in the case of any  registration  of  Registrable
         Securities on Form F-3 which are intended to be offered on a continuous
         or delayed basis,  such 270-day period shall be extended until all such
         Registrable  Securities  are  sold,  provided  that  Rule  415,  or any
         successor  rule under the  Securities  Act,  permits an  offering  on a
         continuous or delayed basis, and provided further that applicable rules
         under  the   Securities   Act  governing  the   obligation  to  file  a
         post-effective  amendment  permit,  in lieu of filing a  post-effective
         amendment  which (y) includes any prospectus  required by Section 10(a)
         of the Securities  Act or (z) reflects  facts or events  representing a
         material  or  fundamental  change in the  information  set forth in the
         registration  statement,  the incorporation by reference of information
         required  to be  included  in (y)  and (z)  above  to be  contained  in
         periodic  reports filed pursuant to Section 12 or 15(d) of the Exchange
         Act in the registration statement;

                           (ii)  furnish such number of  prospectuses  and other
         documents incident thereto as each of the Holders, as applicable,  from
         time to time may reasonably request;

                           (iii)  promptly  notify  each  Holder of  Registrable
         Securities  covered by such  registration at any time when a prospectus
         relating  thereto is required to be delivered  under the Securities Act
         of the  happening  of any  event as a result  of which  the  prospectus
         included in such registration statement, as then in effect, includes an
         untrue  statement of a material  fact or omits to state a material fact
         required  to be stated  therein  or  necessary  to make the  statements
         therein not misleading in the light of the circumstances then existing;

                                       7

<PAGE>

                           (iv)  furnish,  on the  date  that  such  Registrable
         Securities  are  delivered  to  the  underwriters  for  sale,  if  such
         securities are being sold through  underwriters  or, if such securities
         are  not  being  sold  through  underwriters,  on  the  date  that  the
         registration   statement  with  respect  to  such  securities   becomes
         effective,  (1) an  opinion,  dated  as of such  date,  of the  counsel
         representing the Company for the purposes of such registration, in form
         and  substance  as  is  customarily   given  to   underwriters   in  an
         underwritten public offering and reasonably  satisfactory to a majority
         in  interest  of  the  Holders   participating  in  such  registration,
         addressed to the underwriters, if any, and to the Holders participating
         in such registration and (2) a letter,  dated as of such date, from the
         independent  certified public  accountants of the Company,  in form and
         substance  as is  customarily  given by  independent  certified  public
         accountants to  underwriters  in an  underwritten  public  offering and
         reasonably  satisfactory  to a  majority  in  interest  of the  Holders
         participating in such registration,  addressed to the underwriters,  if
         any,  and if  permitted  by  applicable  accounting  standards,  to the
         Holders participating in such registration; and

                           (v) assist the  Holders  in the  deposit of  Ordinary
         Shares with the  depositary  and the  issuance  of American  Depositary
         Receipt representing the ADSs equivalent to such Ordinary Shares.

                           (f)  Indemnification.

                           (i) The Company will  indemnify  each of the Holders,
         as applicable,  each of its officers,  directors and partners, and each
         person   controlling  each  of  the  Holders,   with  respect  to  each
         registration  which has been  effected  pursuant to this Section 2, and
         each   underwriter,   if  any,  and  each  person  who  controls   such
         underwriter,  against all claims,  losses,  damages and liabilities (or
         actions  in  respect  thereof)  arising  out of or based on any  untrue
         statement (or alleged untrue statement) of a material fact contained in
         any  prospectus,  offering  circular or other  document  (including any
         related registration  statement,  notification or the like) incident to
         any such  registration,  qualification  or compliance,  or based on any
         omission  (or  alleged  omission)  to state  therein  a  material  fact
         required  to be stated  therein  or  necessary  to make the  statements
         therein  not  misleading,  or  any  violation  by  the  Company  of the
         Securities Act or the Exchange Act or any rule or regulation thereunder
         applicable  to the Company and relating to action or inaction  required
         of the Company in connection with any such registration,  qualification
         or  compliance,  and will  reimburse  each of the Holders,  each of its
         officers,  directors and partners,  and each person controlling each of
         the  Holders,  each such  underwriter  and each person who controls any
         such  underwriter,  for any  legal and any  other  expenses  reasonably
         incurred in connection with investigating and defending any such claim,
         loss, damage,  liability or action,  provided that the Company will not
         be liable in any such case to the  extent  that any such  claim,  loss,
         damage,  liability  or expense  arises out of or is based on any untrue
         statement or omission based upon written  information  furnished to the
         Company by the Holders or underwriter and stated to be specifically for
         use therein.

                                       8

<PAGE>

                           (ii)  Each  of  the  Holders  will,  if   Registrable
         Securities  held by it are included in the  securities as to which such
         registration,  qualification or compliance is being effected, indemnify
         the Company,  each of its directors and officers and each  underwriter,
         if any,  of the  Company's  securities  covered by such a  registration
         statement,  each person who controls  the Company or such  underwriter,
         each  Other  Stockholder  and each of their  officers,  directors,  and
         partners,  and each person  controlling such Other Stockholder  against
         all  claims,  losses,  damages and  liabilities  (or actions in respect
         thereof)  arising out of or based on any untrue  statement  (or alleged
         untrue statement) of a material fact contained in any such registration
         statement, prospectus, offering circular or other document made by such
         Holder,  or any  omission  (or  alleged  omission)  to state  therein a
         material  fact  required to be stated  therein or necessary to make the
         statements by such Holder  therein not  misleading,  and will reimburse
         the Company and such Other Stockholders, directors, officers, partners,
         persons,  underwriters  or control  persons  for any legal or any other
         expenses  reasonably  incurred  in  connection  with  investigating  or
         defending any such claim,  loss,  damage,  liability or action, in each
         case to the extent, but only to the extent,  that such untrue statement
         (or alleged untrue statement) or omission (or alleged omission) is made
         in such registration statement,  prospectus, offering circular or other
         document in reliance  upon and in conformity  with written  information
         furnished  to the Company by such Holder and stated to be  specifically
         for use therein; provided, however, that the obligations of each of the
         Holders  hereunder  shall  be  limited  to an  amount  equal to the net
         proceeds to such Holder of securities sold as contemplated herein.

                           (iii) Each party  entitled to  indemnification  under
         this Section 2(f) (the  "Indemnified  Party")  shall give notice to the
         party required to provide  indemnification  (the "Indemnifying  Party")
         promptly after such Indemnified Party has actual knowledge of any claim
         as to which indemnity may be sought,  and shall permit the Indemnifying
         Party  to  assume  the  defense  of any such  claim  or any  litigation
         resulting therefrom;  provided that counsel for the Indemnifying Party,
         who shall conduct the defense of such claim or any litigation resulting
         therefrom,  shall be approved by the Indemnified  Party (whose approval
         shall not  unreasonably  be  withheld)  and the  Indemnified  Party may
         participate  in  such  defense  at such  party's  expense  (unless  the
         Indemnified  Party shall have reasonably  concluded that there may be a
         conflict of interest between the Indemnifying Party and the Indemnified
         Party in such  action,  in which case the fees and  expenses of counsel
         shall  be at the  expense  of the  Indemnifying  Party),  and  provided
         further  that the  failure of any  Indemnified  Party to give notice as
         provided  herein  shall  not  relieve  the  Indemnifying  Party  of its
         obligations  under  this  Section 2 unless  the  Indemnifying  Party is
         materially prejudiced thereby. No Indemnifying Party, in the defense of
         any such claim or  litigation  shall,  except  with the consent of each
         Indemnified  Party,  consent to entry of any judgment or enter into any
         settlement which does not include as an unconditional  term thereof the
         giving by the  claimant or  plaintiff  to such  Indemnified  Party of a
         release from all liability in respect to such claim or litigation. Each
         Indemnified  Party shall furnish such  information  regarding itself or
         the claim in question as an Indemnifying  Party may reasonably  request
         in writing and as shall be

                                       9

<PAGE>

         reasonably  required in  connection  with the defense of such claim and
         litigation resulting therefrom.

                           (iv)  If the  indemnification  provided  for in  this
         Section  2(f)  is  held  by a court  of  competent  jurisdiction  to be
         unavailable  to  an  Indemnified   Party  with  respect  to  any  loss,
         liability,  claim,  damage or  expense  referred  to  herein,  then the
         Indemnifying  Party, in lieu of  indemnifying  such  Indemnified  Party
         hereunder,  shall  contribute  to the  amount  paid or  payable by such
         Indemnified Party as a result of such loss, liability, claim, damage or
         expense in such  proportion as is  appropriate  to reflect the relative
         fault of the Indemnifying  Party on the one hand and of the Indemnified
         Party on the other in connection with the statements or omissions which
         resulted in such loss, liability,  claim, damage or expense, as well as
         any other relevant equitable considerations.  The relative fault of the
         Indemnifying  Party and of the Indemnified Party shall be determined by
         reference  to,  among  other  things,  whether  the untrue (or  alleged
         untrue)  statement  of a  material  fact or the  omission  (or  alleged
         omission) to state a material fact relates to  information  supplied by
         the  Indemnifying  Party or by the  Indemnified  Party and the parties'
         relative  intent,  knowledge,  access to information and opportunity to
         correct or prevent such statement or omission.

                           (v) Notwithstanding the foregoing, to the extent that
         the provisions on  indemnification  and  contribution  contained in the
         underwriting agreement entered into in connection with any underwritten
         public offering contemplated by this Agreement are in conflict with the
         foregoing  provisions,  the provisions in such  underwriting  agreement
         shall be controlling.

                           (vi) The foregoing indemnity agreement of the Company
         and Holders is subject to the condition that, insofar as they relate to
         any loss, claim,  liability or damage made in a preliminary  prospectus
         but  eliminated or remedied in the amended  prospectus on file with the
         Commission at the time the  registration  statement in question becomes
         effective or the amended prospectus filed with the Commission  pursuant
         to Commission Rule 424(b) (the "Final  Prospectus"),  such indemnity or
         contribution   agreement   shall  not  inure  to  the  benefit  of  any
         underwriter  or Holder if a copy of the Final  Prospectus was furnished
         to the  underwriter  and was not furnished to the person  asserting the
         loss, liability, claim or damage at or prior to the time such action is
         required by the Securities Act.

                           (g)  Information by the Holders.

                           (i) Each of the Holders holding  securities  included
         in any  registration  shall  furnish to the  Company  such  information
         regarding such Holder and the  distribution  proposed by such Holder as
         the  Company  may  reasonably  request  in  writing  and  as  shall  be
         reasonably required in connection with any registration,  qualification
         or compliance referred to in this Section 2.

                                       10

<PAGE>

                           (ii) In the event that,  either  immediately prior to
         or subsequent to the effectiveness of any registration  statement,  any
         Holder shall distribute  Registrable  Securities to its partners,  such
         Holder  shall so advise the  Company and provide  such  information  as
         shall  be  necessary  to  permit  an  amendment  to  such  registration
         statement  to provide  information  with respect to such  partners,  as
         selling   securityholders.   Promptly   following   receipt   of   such
         information,  the Company shall file an  appropriate  amendment to such
         registration  statement  reflecting the  information  so provided.  Any
         incremental  expense to the Company resulting from such amendment shall
         be borne by such Holder.

                           (h)  Rule 144 Reporting.

                  With a view to making  available the benefits of certain rules
and  regulations  of the  Commission  which may  permit  the sale of  restricted
securities to the public without registration, the Company agrees to:

                           (i) make and keep  public  information  available  as
         those terms are understood and defined in Rule 144 under the Securities
         Act ("Rule 144");

                           (ii) use its best efforts to file with the Commission
         in a timely  manner all  reports  and other  documents  required of the
         Company under the Securities Act and the Exchange Act at any time after
         it has become subject to such reporting requirements; and

                           (iii)  so long as the  Holder  owns  any  Registrable
         Securities,  furnish to the Holder upon request, a written statement by
         the Company as to its  compliance  with the reporting  requirements  of
         Rule 144 (at any time from and after  ninety  (90) days  following  the
         effective date of the first registration statement filed by the Company
         for an offering of its  securities to the general  public),  and of the
         Securities  Act and the  Exchange  Act (at any time after it has become
         subject  to such  reporting  requirements),  a copy of the most  recent
         annual or quarterly  report of the Company,  and such other reports and
         documents  so filed as the Holder may  reasonably  request in  availing
         itself of any rule or regulation of the Commission  allowing the Holder
         to sell any such securities without registration.

                           (i)  Holdback  Agreement.   If  any  registration  of
Registrable  Securities  shall  be in  connection  with an  underwritten  public
offering,  each Holder of Registrable Securities agrees not to effect any public
sale or  distribution,  including  any  sale  pursuant  to Rule  144  under  the
Securities  Act, of any equity  securities  of the  Company,  or of any security
convertible  into or  exchangeable or exercisable for any equity security of the
Company (in each case, other than as part of such underwritten public offering),
within  seven (7) days before or such  period not to exceed  ninety (90) days as
the  underwriting  agreement  may require (or such lesser period as the managing
underwriters may permit) after the effective date of such  registration  (except
as part of such  registration),  provided  that all  other  stockholders  of the
Company having registration rights, the Company and each officer and director of
the Company shall have agreed to a similar holdback restriction.

                  3.  MISCELLANEOUS

                                       11

<PAGE>

                           (a) Directly or  Indirectly.  Where any  provision in
this Agreement refers to action to be taken by any Person,  or which such Person
is prohibited  from taking,  such  provision  shall be  applicable  whether such
action is taken directly or indirectly by such Person.

                           (b) Governing Law. This  Agreement  shall be governed
by and construed in accordance with the laws of the State of New York.

                           (c) Section  Headings.  The  headings of the sections
and  subsections of this Agreement are inserted for  convenience  only and shall
not be deemed to constitute a part thereof.

                           (d)  Notices.

                           (i) All communications  under this Agreement shall be
         in writing and shall be  delivered  by hand or  facsimile  or mailed by
         overnight courier or by registered or certified mail, postage prepaid:

                                    (A)   if   to   the   Company,   to   Flamel
                  Technologies  S.A.,  Parc  Club du Moulin a Vent,  33,  avenue
                  Docteur   Georges  Levy,   69693  Venisseux   Cedex,   France,
                  Attention:     Chief     Executive     Officer     (facsimile:
                  (011-33-4-72-78-3446), or at such other address as it may have
                  furnished in writing to the Holders;

                                    (B) if to the  Holders,  at the  address  or
                  facsimile number listed on Schedule I hereto, or at such other
                  address or  facsimile  number as may have been  furnished  the
                  Company in writing.

                           (iii) Any notice so  addressed  shall be deemed to be
         given: if delivered by hand or facsimile, on the date of such delivery;
         if mailed by courier,  on the first  business day following the date of
         such mailing;  and if mailed by  registered  or certified  mail, on the
         third business day after the date of such mailing.

                           (e) Reproduction of Documents. This Agreement and all
documents relating thereto, including, without limitation, any consents, waivers
and  modifications  which may  hereafter  be executed may be  reproduced  by the
Holders  by  any  photographic,  photostatic,  microfilm,  microcard,  miniature
photographic  or other similar  process and the Holders may destroy any original
document so  reproduced.  The parties  hereto agree and stipulate  that any such
reproduction  shall be  admissible  in  evidence as the  original  itself in any
judicial  or  administrative  proceeding  (whether  or not  the  original  is in
existence  and whether or not such  reproduction  was made by the Holders in the
regular  course of  business)  and that any  enlargement,  facsimile  or further
reproduction of such reproduction shall likewise be admissible in evidence.

                           (f)  Successors  and Assigns.  This  Agreement  shall
inure to the benefit of and be binding upon the  successors  and assigns of each
of the parties.

                                       12

<PAGE>


                           (g) Entire  Agreement;  Amendment  and  Waiver.  This
Agreement  constitutes  the  entire  understanding  of the  parties  hereto  and
supersedes  all prior  understanding  among such parties.  This Agreement may be
amended,  and the observance of any term of this  Agreement may be waived,  with
(and only with) the written  consent of the  Company  and each of the  Investors
holding then outstanding Registrable Securities Holders.

                           (h) Severability. In the event that any part or parts
of this  Agreement  shall  be held  illegal  or  unenforceable  by any  court or
administrative  body of competent  jurisdiction,  such  determination  shall not
affect the  remaining  provisions of this  Agreement  which shall remain in full
force and effect.

                           (i)  Counterparts.  This Agreement may be executed in
one or more  counterparts,  each of which shall be deemed an original and all of
which together shall be considered one and the same agreement.

                      [THIS SPACE INTENTIONALLY LEFT BLANK]

                                       13

<PAGE>


                  IN  WITNESS  WHEREOF,   the  undersigned  have  executed  this
Agreement as of the date first set forth above.


                       FLAMEL TECHNOLOGIES S.A.


                       By:
                           --------------------------------------
                           Gerard Soula
                           Chief Executive Officer

                       INVESTORS:

                       BIOTECHNOLOGY VALUE FUND, L.P.

                       By:   BVF PARTNERS L.P., its General Partner

                             By: BVF, INC., its General Partner

                                        By:
                                                 -------------------------------
                                                 Mark N. Lampert
                                                 President

                       BIOTECHNOLOGY VALUE FUND II, L.P.

                       By:   BVF PARTNERS L.P., its General Partner

                             By: BVF, INC., its General Partner

                                        By:
                                                 -------------------------------
                                                 Mark N. Lampert
                                                 President

                       INVESTMENT 10 L.L.C.

                       By:   BVF PARTNERS, L.P., its Investment Advisor

                             By: BVF, INC., its General Partner

                                        By:
                                                 -------------------------------
                                                 Mark N. Lampert
                                                 President

                                       14

<PAGE>


                       ALTA BIOPHARMA PARTNERS LP

                       By: Alta BioPharma Management LLC

                                        By:
                                             -----------------------------------
                                             Name:
                                             Title:

                       ALTA EMBARCADERO BIOPHARMA, LLC

                                        By:
                                             -----------------------------------
                                             Name:
                                             Title:

                       FLAMEL CHASE PARTNERS (ALTA BIO), LLC

                       By: Alta/Chase BioPharma Management, LLC

                                        By:
                                             -----------------------------------
                                             Name:
                                             Title:

                       CHASE EUROPEAN EQUITY ASSOCIATES, LLC

                       By: Chase Capital Partners, its Manager

                                        By:
                                             -----------------------------------
                                             Name:
                                             Title:

                                       15

<PAGE>


                                   SCHEDULE I

Name and Address
of Investor

BIOTECHNOLOGY VALUE FUND, L.P.
c/o BVF Partners, L.P.
One Sansome Street, 39th Floor
San Francisco, CA 94104

BIOTECHNOLOGY VALUE FUND II, L.P.
c/o BVF Partners, L.P.
One Sansome Street, 39th Floor
San Francisco, CA 94104

INVESTMENT 10 L.L.C.
c/o BVF Partners, L.P.
One Sansome Street, 39th Floor
San Francisco, CA 94104

ALTA BIOPHARMA PARTNERS LP
One Embarcadero Center
Suite 4050
San Francisco, CA 94111

ALTA EMBARCADERO BIOPHARMA, LLC
One Embarcadero Center
Suite 4050
San Francisco, CA 94111

FLAMEL CHASE PARTNERS (ALTA BIO), LLC
One Embarcadero Center
Suite 4050
San Francisco, CA 94111

CHASE EUROPEAN EQUITY ASSOCIATES, LLC
380 Madison Avenue
12th Floor
New York, NY 10017-2951


<PAGE>


                                    Exhibit D


                                   NO EXHIBIT


<PAGE>


                                   EXHIBIT E

FREE TRANSLATION FROM FRENCH


- --------------------------------------------------------------------------------
                              FLAMEL TECHNOLOGIES
   A French Corporation (Societe Anonyme) with Share Capital of FRF10,351,352
                               Registered Office:
                               ------------------
                           Parc Club du Moulin a Vent
                       33, Avenue du Docteur Georges Levy
                            69693 VENISSIEUX (Rhone)

               Lyon Trade and Company Registry No. B 379 001 530

- --------------------------------------------------------------------------------


                                  CERTIFICATE


I, Patrick PERRIN, Chief Financial Officer hereby certify that _________________

Is  registered  in the register of BSA  (Registre des BSA) of the Company as the
owner of  ___________________________  Class A BSA  issued by the  Extraordinary
General Meeting of shareholders of March 23, 2000.

Each of those BSA  entitles its owner to  subscribe  for one  Ordinary  Share of
FLAMEL TECHNOLOGIES at the price of FF 39.10.

All  the  conditions  of the  exercise  of the  BSA are  defined  in the  fourth
resolution of the minutes of the  Extraordinary  General Meeting of shareholders
of March 23, 2000.


At:

On:


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FREE TRANSLATION FROM FRENCH


I.   FEATURES OF THE STOCK WARRANTS

     1.  Issue price of the BSAs - Payment

         The BSAs are issued today at a price of FRF 0.01 per warrant to be paid
         up in full in cash at the time of subscription.

     2.  Date of allotment of and subscription for the BSAs

         Subscriptions  for the BSAa shall be  accepted  starting  at the end of
         this Shareholders'  Meeting,  and the subscription  period shall end on
         March 30, 2000,  provided however that the  subscription  period may be
         closed in advance.

         BSAs shall be subscribed for by signing the  application  form provided
         to the subscriber by the Company,  and by payment to the Company of the
         subscription price of the BSAs.

     3.  Form of BSAs

         The BSAs are being issued in registered  form only.  Ownership  thereof
         shall be evidenced by registration in the specific BSA register kept by
         the Company,  once the  beneficiaries  have  subscribed for the BSAs in
         accordance with the provisions of paragraph 2 above.

     4.  Transfer of BSAs

         The assignment,  contribution or transmission of the BSAs in any manner
         whatever shall not be subject to any  restrictions  whatever,  with the
         exception of any French and/or  foreign legal  restrictions  (including
         pursuant to applicable U.S. securities regulations).

     5.  Terms governing the exercise of BSAs

         a) The BSAs may be exercised by the  beneficiaries for a period of five
         years from the date of the Shareholders' Meeting.

         b) Each BSA shall  entitle  the  holder  thereof to  subscribe  for one
         Ordinary  share of the  Company,  provided  however  that no more  than
         1,799,000   Ordinary  shares  of  the  Company  may  be  subscribed  by
         exercising the BSAs (subject to any adjustments, notably in the case of
         fractional shares).

         c) The subscription price for the Ordinary Shares of the Company issued
         through  the  exercise  of  the  BSAs,  which  is to  be  paid  by  the
         beneficiaries, shall be paid in full at the time of subscription.

         d) If a  beneficiary  decides to exercise  some or all of its BSAs,  it
         shall so  notify  the  Company  by  certified  letter,  return  receipt
         requested within the time period specified in (a) above, accompanied by
         a subscription form for new Ordinary Shares and the subscription  price
         for  those  shares  calculated  in  accordance  with the  terms of this
         article.

     6.  Dividends earned by the Ordinary Shares of the Company acquired through
         the exercise of the BSAs

         The Ordinary Shares of the Company  subscribed for through the exercise
         of the BSAs  shall  earn  dividends  as of the date on which  they were
         subscribed.

     7.  Transfer of Ordinary  Shares of the Company  subscribed for through the
         exercise of BSAs

         The assignment, contribution  or transmission in any manner whatever of
         the Ordinary Shares of the Company  subscribed for through the exercise
         of the BSAs shall not be subject to any restrictions  whatsoever,  with
         the  exeception  of  any  French  and/or  foreign  legal   restrictions
         (including those pursuant to applicable U.S. securities regulations).

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FREE TRANSLATION FROM FRENCH


II.  MEASURES TO PROTECT THE RIGHTS OF WARRANT  HOLDERS IN THE CASE OF FINANCIAL
     TRANSACTIONS SUBSEQUENT TO THE ALLOTMENT OF WARRANTS

     1.  New financial transactions

         a)  In view of the terms and  conditions  governing  the  allotment and
             exercise of the stock  warrants set out below,  the legal  measures
             referred to in articles 194-5, paragraph 2 and 3 of the Act of July
             24, 1966  designed to protect the rights of stock  warrant  holders
             shall have no effect as regards such warrants as they have not been
             subject to a Warrant Exercise Confirmation.

         b)  Beginning on the date on which the stock warrants have been subject
             to a  Warrants  Exercise  Confirmation  and  for so  long  as  said
             warrants  exist,  there  shall be no  capitalization  of  reserves,
             profits, or share premiums nor any cash distribution of reserves or
             distribution  in the form of  securities  unless  the rights of the
             holder of said warrants are protected as follows:

               o   in the event of a capital increase through the capitalization
                   of reserves,  profits, or share premiums, the Special Meeting
                   of  Shareholders  which carries out said  increase  shall pay
                   into a frozen reserve  account such amount as may be required
                   either to increase the par value of those shares which may be
                   subscribed  for by the  holder  of the stock  warrants  or to
                   allot free shares to the holder of the stock  warrants on the
                   same terms and conditions, except with respect to the vesting
                   of the rights associated with the shares, in a quantity equal
                   to what it would have  received if it had been a  shareholder
                   at the time of the principal allotment.

               o   in the event of the  distribution  of premiums or reserves in
                   the form of cash or securities,  the Meeting of  Shareholders
                   which  makes said  distribution  shall pay said amount into a
                   frozen reserve account and retain such securities, if any, as
                   are  necessary  to remit to the warrant  holder the amount or
                   the  securities - which may have a different  dividend date -
                   that he would have received if he had been a  shareholder  at
                   the time of the distribution and had participated therein.

                   (i)   Distribution   of   equity   securities   or   compound
                         securities held in a portfolio.

                         In the event that the  company  whose  securities  were
                         distributed  then  engages in a  transaction  involving
                         stock  rights or  allocation  rights  set aside for its
                         shareholders, the issuing company may, in the interests
                         of the warrant  holder,  exercise the right attached to
                         such  securities it has retained. In that case it shall
                         offer the  securities so obtained to the warrant holder
                         as soon as they are  exercised  and the warrant  holder
                         shall be required to repay it any sums that may be paid
                         to subscribe for them.

                         In the event that the number of securities to which the
                         warrant holder is entitled includes  fractional shares,
                         this  fraction  shall  give  rise  to  a  cash  payment
                         calculated on the basis of the most recent market price
                         of said security  prior to the warrant  exercise  date.
                         The price  used shall be that on the  regulated  French
                         exchange on which said security is listed,  if any, and
                         shall be determined in accordance  with the  provisions
                         of article 1843-4 of the Civil Code in all other cases.
                         The rights  associated  with the shares  obtained  as a
                         result of the  transactions  described above shall pass
                         at that time.

                   (ii)  Distribution of bonds held in a portfolio

                         In the  case of the  distribution  of  bonds  held in a
                         portfolio,  said bonds  shall be  distributed  together
                         with  all  bonds   which   have  not   matured  by  the
                         subscription date.

                         In  the  event  that  the  distribution  of  securities
                         involved  bonds and that said bonds were redeemed prior
                         to the stock warrant  exercise  date, the rights of the
                         holder of the  warrants  shall be  satisfied  when said
                         warrants are  exercised  by a cash  payment  calculated
                         proportionate   to  the   redemption   price   of  said
                         securities.


<PAGE>

FREE TRANSLATION FROM FRENCH


         c)  Solely with  respect to such stock  warrants as have  already  been
             subject to a Warrants  Exercise  Confirmation,  the  provisions  of
             article 194-6,  paragraph 2 of the Act of July 24, 1966 shall apply
             to any capital increase set aside for the shareholders.

         d)  Beginning  on the date on which the stock  warrants  will have been
             subject to Warrants  Exercise  Confirmation and for so long as said
             warrants exist,  the Company shall be prohibited from redeeming its
             capital  stock  or  reducing  it by  way  of  redemption,  or  from
             modifying the distribution of its profits.

     2.  Dissolution of the Company by merger or demerger - reduction of capital

         a)  In the event that the Company is merged into an existing company or
             participants  in a merger  involving the creation of a new company,
             or in the  event of a  demerger  or  spin-off  involving  a capital
             contribution to newly formed or existing  companies,  the rights of
             the warrant  holder shall be extended to the stock of the acquiring
             company or of the new company or companies  which it may  subscribe
             for in  place  of the  stock  of the  Company  by  exercising  said
             warrants on the terms and conditions set out below.

             The number of shares  which it shall be entitled to  subscribe  for
             shall be  calculated  by  correcting  the  number  of shares of the
             Company which is issuing the shares to which the warrant holder was
             entitled by the exchange  ratio of the shares of the latter company
             to the shares of the  acquiring  company,  or of the new company or
             companies;  those  companies  shall be substituted  for the issuing
             company for purposes of the above provisions, which are intended to
             protect the rights, if any, of the stock warrant holder in the case
             of financial  transactions  or transactions  involving  securities,
             and,  as a general  matter,  to ensure that the rights of the stock
             warrant  holder are  respected in  accordance  with the  applicable
             statutory, regulatory and contractual conditions.

         b)  In the event of a reduction  of capital due to losses,  through the
             reduction  of either  the par value of the  shares or the number of
             shares,  the  rights  of the stock  warrant  holder  which  opts to
             exercise said  warrants  shall be reduced  accordingly,  as if said
             warrant  holder had been a shareholder  since the date on which the
             stock, warrants were issued.

<PAGE>

FREE TRANSLATION FROM FRENCH


- --------------------------------------------------------------------------------

                              FLAMEL TECHNOLOGIES
   A French Corporation (Societe Anonyme) with Share Capital of FRF10,351,352
                               Registered Office:
                               ------------------
                           Parc Club du Moulin a Vent
                       33, Avenue du Docteur Georges Levy
                            69693 VENISSIEUX (Rhone)

               Lyon Trade and Company Registry No. B 379 001 530

- --------------------------------------------------------------------------------


                                   CERTIFICATE


I,   Patrick   PERRIN,    Chief   Financial    Officer   hereby   certify   that
______________________________________________.

Is  registered  in the register of BSA  (Registre des BSA) of the Company as the
owner  of  ____________________________________   Class  B  BSA  issued  by  the
Extraordinary General Meeting of shareholders of March 23, 2000.

Each of those BSA  entitles its owner to  subscribe  for one  Ordinary  Share of
FLAMEL TECHNOLOGIES at the price of FF 39.10.

All  the  conditions  of the  exercise  of the  BSA  are  defined  in the  fifth
resolution of the minutes of the  Extraordinary  General Meeting of shareholders
of March 23, 2000.

At:


On:

<PAGE>

FREE TRANSLATION FROM FRENCH


I.   FEATURES OF THE STOCK WARRANTS

     1.  Issue price of the BSAs - Payment

         The BSAs are issued today at a price of FRF 0.01 per warrant to be paid
         up in full in cash at the time of subscription.

     2.  Date of allotment of and subscription for the BSAs

         Subscriptions  for the BSAa shall be  accepted  starting  at the end of
         this Shareholders'  Meeting,  and the subscription  period shall end on
         March 30, 2000,  provided however that the  subscription  period may be
         closed in advance.

         BSAs shall be subscribed for by signing the  application  form provided
         to the subscriber by the Company,  and by payment to the Company of the
         subscription price of the BSAs.

     3.  Form of BSAs

         The BSAs are being issued in registered  form only.  Ownership  thereof
         shall be evidenced by registration in the specific BSA register kept by
         the Company,  once the  beneficiaries  have  subscribed for the BSAs in
         accordance with the provisions of paragraph 2 above.

     4.  Transfer of BSAs

         The assignment,  contribution or transmission of the BSAs in any manner
         whatever shall not be subject to any  restrictions  whatever,  with the
         exception of any French and/or  foreign legal  restrictions  (including
         pursuant to applicable U.S. securities regulations).

     5.  Terms governing the exercise of BSAs

         a) The BSAs may be exercised by the  beneficiaries for a period of five
         years from the date of the Shareholders' Meeting.

         b) Each BSA shall  entitle  the  holder  thereof to  subscribe  for one
         Ordinary  Share of the  Company,  provided  however  that no more  that
         1,927,500   Ordinary  shares  of  the  Company  may  be  subscribed  by
         exercising the BSAs (subject to any adjustments, notably in the case of
         fractional shares).

         c) The subscription price for the Ordinary Shares of the Company issued
         through  the  exercise  of  the  BSAs,  which  is to  be  paid  by  the
         beneficiaries, shall be paid in full at the time of subscription.

         d) The right for the  beneficiaries  to  exercise  some or all of their
         BSAs will be subject to the following:

         o  One  tranche,   representing  the  right  to
         exercise   one-third   of  the  BSA,   will  be
         exercisable  only if during the period  between
         February 29, 2000,  and the earlier of December
         31, 2000 or the date of exericse, there did not
         exist 8 or more days on which the closing price
         of Flamel ADSs, as reported on NASDAQ, was less
         than $6.00;

         o  One  tranche,   representing  the  right  to
         exercise   one-third   of  the  BSA,   will  be
         exercisable  only if during the period  between
         February 29, 2000,  and the earlier of December
         31, 2000 or the date of exercise, there did not
         exist 8 or more days on which the closing price
         of Flamel ADSs, as reported on NASDAQ, was less
         than $4.51; and

         o  One  tranche,   representing  the  right  to
         exercise   one-third   of  the  BSA,   will  be
         exercisable  only if during the period  between
         February 29, 2000, and the

<PAGE>

FREE TRANSLATION FROM FRENCH


         earlier  of  December  31,  2000 or the date of
         exercise, there did not exist 8 or more days on
         which  the  closing  price of Flamel  ADSs,  as
         reported on NASDAQ, was less than $3.00.

         e) If a  beneficiary  decides to exercise  some or all of its BSAs,  it
         shall so  notify  the  Company  by  certified  letter,  return  receipt
         requested within the time period specified in (a) above, accompanies by
         a subcription form for new Ordinary Shares and the  subscription  price
         for  those  shares  calculated  in  accordance  with the  terms of this
         article.

     6.  Dividends earned by the Ordinary Shares of the Company acquired through
         the exercise of the BSAs

         The Ordinary Shares of the Company  subscribed for through the exercise
         of the BSAs  shall  earn  dividends  as of the date on which  they were
         subscribed.

     7.  Transfer of Ordinary  Shares of the Company  subscribed for through the
         exercise of BSAs

         The assignment, contribution  or transmission in any manner whatever of
         the Ordinary Shares of the Company  subscribed for through the exercise
         of the BSAs shall not be subject to any restrictions  whatsoever,  with
         the  exeception  of  any  French  and/or  foreign  legal   restrictions
         (including those pursuant to applicable U.S. securities regulations).

II.  MEASURES TO PROTECT THE RIGHTS OF WARRANT  HOLDERS IN THE CASE OF FINANCIAL
     TRANSACTIONS SUBSEQUENT TO THE ALLOTMENT OF WARRANTS

     1.  New financial transactions

         a)  In view of the terms and  conditions  governing  the  allotment and
             exercise of the stock  warrants set out below,  the legal  measures
             referred to in articles 194-5, paragraph 2 and 3 of the Act of July
             24, 1966  designed to protect the rights of stock  warrant  holders
             shall have no effect as regards such warrants as they have not been
             subject to a Warrant Exercise Confirmation.

         b)  Beginning on the date on which the stock warrants have been subject
             to a  Warrants  Exercise  Confirmation  and  for so  long  as  said
             warrants  exist,  there  shall be no  capitalization  of  reserves,
             profits, or share premiums nor any cash distribution of reserves or
             distribution  in the form of  securities  unless  the rights of the
             holder of said warrants are protected as follows:

                o  in the event of a capital increase through the capitalization
                   of reserves,  profits, or share premiums, the Special Meeting
                   of  Shareholders  which carries out said  increase  shall pay
                   into a frozen reserve  account such amount as may be required
                   either to increase the par value of those shares which may be
                   subscribed  for by the  holder  of the stock  warrants  or to
                   allot free shares to the holder of the stock  warrants on the
                   same terms and conditions, except with respect to the vesting
                   of the rights associated with the shares, in a quantity equal
                   to what it would have  received if it had been a  shareholder
                   at the time of the principal allotment.

                o  in the event of the  distribution  of premiums or reserves in
                   the form of cash or securities,  the Meeting of  Shareholders
                   which  makes said  distribution  shall pay said amount into a
                   frozen reserve account and retain such securities, if any, as
                   are  necessary  to remit to the warrant  holder the amount or
                   the  securities - which may have a different  dividend date -
                   that he would have received if he had been a  shareholder  at
                   the time of the distribution and had participated therein.

                   (i)   Distribution   of   equity   securities   or   compound
                         securities held in a portfolio.

                         In the event that the  company  whose  securities  were
                         distributed  then  engages in a  transaction  involving
                         stock  rights or  allocation  rights  set aside for its
                         shareholders, the

<PAGE>

FREE TRANSLATION FROM FRENCH


                         issuing  company  may, in the  interests of the warrant
                         holder,  exercise the right attached to such securities
                         it has  retained.  In  the  case  it  shall  offer  the
                         securities so obtained to the warrant holder as soon as
                         they are  exercised  and the  warrant  holder  shall be
                         required  to  repay  it any  sums  that  may be paid to
                         subscribe for them.

                         In the event that the number of securities to which the
                         warrant holder is entitled includes  fractional shares,
                         this  fraction  shall  give  rise  to  a  cash  payment
                         calculated on the basis of the more recent market price
                         of said security  prior to the warrant  exercise  date.
                         The price  used shall be that on the  regulated  French
                         exchange on which said security is listed,  if any, and
                         shall be determined in accordance  with the  provisions
                         of article 1843-4 of the Civil Code in all other cases.
                         The rights  associated  with the shares  obtained  as a
                         result of the  transactions  described above shall pass
                         at that time.

                   (ii)  Distribution of bonds held in a portfolio

                         In the  case of the  distribution  of  bonds  held in a
                         portfolio,  said bonds  shall be  distributed  together
                         with  all  bonds   which   have  not   matured  by  the
                         subscription date.

                         In  the  event  that  the  distribution  of  securities
                         involved  bonds and that said bonds were redeemed prior
                         to the stock warrant  exercise  date, the rights of the
                         holder of the  warrants  shall be  satisfied  when said
                         exercised by a cash payment calculated proportionate to
                         the redemption price of said securities.

         c)  Solely with  respect to such stock  warrants as have  already  been
             subject to a Warrants  Exercise  Confirmation,  the  provisions  of
             article 194-6,  paragraph 2 of the Act of July 24, 1966 shall apply
             to any capital increase set aside for the shareholders.

         d)  Beginning  on the date on which the stock  warrants  will have been
             subject to Warrants  Exercise  Confirmation and for so long as said
             warrants exist,  the Company shall be prohibited from redeeming its
             capital  stock  or  reducing  it by  way  of  redemption,  or  from
             modifying the distribution of its profits.

     2.  Dissolution of the Company by merger or demerger - reduction of capital

         a)  In the event that the Company is merged into an existing company or
             participants  in a merger  involving the creation of a new company,
             or in the  event of a  demerger  or  spin-off  involving  a capital
             contribution to newly formed or existing  companies,  the rights of
             the warrant  holder shall be extended to the stock of the acquiring
             company or of the new company or companies  which it may  subscribe
             for in  place  of the  stock  of the  Company  by  exercising  said
             warrants on the terms and conditions set out below.

             The number of shares  which it shall be entitled to  subscribe  for
             shall be  calculated  by  correcting  the  number  of shares of the
             Company which is issuing the shares to which the warrant holder was
             entitled by the exchange  ratio of the shares of the latter company
             to the shares of the  acquiring  company,  or of the new company or
             companies;  those  companies  shall be substituted  for the issuing
             company for purposes of the above provisions, which are intended to
             protect the rights, if any, of the stock warrant holder in the case
             of financial  transactions  or transactions  involving  securities,
             and,  as a general  matter,  to ensure that the rights of the stock
             warrant  holder are  respected in  accordance  with the  applicable
             statutory, regulatory and contractual conditions.

         b)  In the event of a reduction  of capital due to losses,  through the
             reduction  of either  the par value of the  shares or the number of
             shares,  the  rights  of the stock  warrant  holder  which  opts to
             exercise said  warrants  shall be reduced  accordingly,  as if said
             warrant  holder had been a shareholder  since the date on which the
             stock warrants were issued.

<PAGE>

FREE TRANSLATION FROM FRENCH


- --------------------------------------------------------------------------------

                              FLAMEL TECHNOLOGIES
   A French Corporation (Societe Anonyme) with Share Capital of FRF10,351,352
                               Registered Office:
                               ------------------
                           Parc Club du Moulin a Vent
                       33, Avenue du Docteur Georges Levy
                            69693 VENISSIEUX (Rhone)

               Lyon Trade and Company Registry No. B 379 001 530

- --------------------------------------------------------------------------------


                                   CERTIFICATE


I,   Patrick   PERRIN,    Chief   Financial    Officer   hereby   certify   that
______________________________________________.

Is  registered  in the register of BSA  (Registre des BSA) of the Company as the
owner  of  ____________________________________   Class  C  BSA  issued  by  the
Extraordinary General Meeting of shareholders of March 23, 2000.

Each of those BSA  entitles its owner to  subscribe  for one  Ordinary  Share of
FLAMEL TECHNOLOGIES at the price of FF 0.80.

All  the  conditions  of the  exercise  of the  BSA  are  defined  in the  sixth
resolution of the minutes of the  Extraordinary  General Meeting of shareholders
of March 23, 2000.

At:


On:

<PAGE>

FREE TRANSLATION FROM FRENCH


     FEATURES OF THE STOCK WARRANTS

     1.  Issue price of the BSAs - Payment

         The BSAs are  issued  today at a price of FRF 0.01 per  warrant,  to be
         paid up in full in cash at the time of subscription.

     2.  Date of allotment of and subscription for the BSAs

         Subscriptions  for the BSAs shall be  accepted  starting  at the end of
         this Shareholders'  Meeting,  and the subscription  period shall end on
         March 30, 2000,  provided however that the  subscription  period may be
         closed in advance.

         BSAs shall be subscribed for by signing the  application  form provided
         to the subscriber by the Company,  and by payment to the Company of the
         subscription price of the BSAs.

     3.  Form of BSAs

         The BSAs are being issued in registered  form only.  Ownership  thereof
         shall be evidenced by registration in the specific BSA register kept by
         the Company,  once the  beneficiaries  have  subscribed for the BSAs in
         accordance with the provisions of paragraph 2 above.

     4.  Transfer of BSAs

         The assignment,  contribution or transmission of the BSAs in any manner
         whatever shall not be  subject to any  restriction  whatever, with that
         exception of any French and/or  foreign legal  restrictions  (including
         pursuant to applicable U.S. securities regulations).

     5.  Terms governing the exercise of BSAs

         a) The BSAs may be exercised by the  beneficiaries for a period of five
         years from the date of the Shareholders' Meeting.

         b) Each BSA shall  entitle  the  holder  thereof to  subscribe  for one
         Ordinary  Share of the  Company,  provided  however  that no more  than
         1,927,500   Ordinary  shares  of  the  Company  may  be  subscribed  by
         exercising the BSAs (subject to any adjustments, notably in the case of
         fractional shares).

         c) The subscription price for the Ordinary Shares of the Company issued
         through  the  exercise  of  the  BSAs,  which  is to  be  paid  by  the
         beneficiaries, shall be paid in full at the time of subscription.

         d) The right for the  beneficiaries  to  exercise  some or all of their
         BSAs will be the following:

         o If at any time  during  the  period  between  February  29,  2000 and
         December  31,  2000,  there are 8 dates on which the  closing  price of
         Flamel ADSs, as reported on NASDAQ,  is less than $6.00, then the right
         to exercise one-third of the BSA shall become effective as of beginning
         of the day immediately following such 8 day.

         o If at any time  during  the  period  between  February  29,  2000 and
         December  31,  2000,  there are 8 dates on which the  closing  price of
         Flamel ADSs, as reported on NASDAQ,  is less than $4.51, then the right
         to exercise an additional  one-third of the BSA shall become  effective
         as of beginning of the day immediately following such 8 day.

         o If at any  time  during  the  period  between  February  29, 2000 and
         December  31,  2000,  there are 8 dates on which the  closing  price of
         Flamel ADSs, as


<PAGE>

FREE TRANSLATION FROM FRENCH


         reported on NASDAQ,  is less than $3.00, then the right to exercise the
         entire  BSA  shall  become   effective  as  of  beginning  of  the  day
         immediately following such 8 day.

         e) If a  beneficiary  decides to exercise  some or all of its BSAs,  it
         shall so  notify  the  Company  by  certified  letter,  return  receipt
         requested within the time period specified in (a) above, accompanied by
         a subscription form for new Ordinary Shares and the subscription  price
         for  those  shares  calculated  in  accordance  with the  terms of this
         article.

    6.   Dividends earned by the Ordinary Shares of the Company acquired through
         the exercise of the BSAs.

         The Ordinary Shares of the Company  subscribed for through the exercise
         of the BSAs  shall  earn  dividends  as of the date on which  they were
         subscribed.

    7.   Transfer of Ordinary  Shares of the Company  subscribed for through the
         exercise of BSAs

         The assignment,  contribution or transmission in any manner whatever of
         the Ordinary Shares of the Company  subscribed for through the exercise
         of the BSAs shall not be subject to any restrictions  whatsoever,  with
         the  exception  of  any  French  and/or   foreign  legal   restrictions
         (including those pursuant to applicable U.S. securities regulations).

II. MEASURES TO PROTECT THE RIGHTS OF WARRANT HOLDERS IN THE CASE OF FINANCIAL
    TRANSACTIONS SUBSEQUENT TO THE ALLOTMENT OF WARRANTS

    1.   New financial transactions

         a)  In view of the terms and  conditions  governing  the  allotment and
             exercise of the stock  warrants set out below,  the legal  measures
             referred to in  articles  194.5,  paragraphs  2 and 3 of the Act of
             July 24,  1966  designed  to protect  the  rights of stock  warrant
             holders  shall have no effect as regards such warrants as they have
             not been subject to a Warrants Exercise Confirmation.

         b)  Beginning on the date on which the stock warrants have been subject
             to a  Warrants  Exercise  Confirmation  and  for so  long  as  said
             warrants  exist,  there  shall be no  capitalization  of  reserves,
             profits, or share premiums nor any cash distribution of reserves or
             distribution  in the form of  securities  unless  the rights of the
             holder of said warrants are protected as follows:

                o  in the event of a capital increase through the capitalization
                   of reserves,  profits, or share premiums, the Special Meeting
                   of  Shareholders  which carries out said  increase  shall pay
                   into a frozen reserve  account such amount as may be required
                   either to increase the par value of those shares which may be
                   subscribed  for by the  holder  of the stock  warrants  or to
                   allot free shares to the holder of the stock  warrants on the
                   same terms and conditions, except with respect to the vesting
                   of the rights associated with the shares, in a quantity equal
                   to what it would have  received if it had been a  shareholder
                   at the time of the principal allotment.

                o  in the event of the  distribution  of premiums or reserves in
                   the form of cash or securities,  the Meeting of  Shareholders
                   which  makes said  distribution  shall pay said amount into a
                   frozen reserve account and retain such securities, if any, as
                   are  necessary  to remit to the warrant  holder the amount or
                   the   securities--which   may  have  a   different   dividend
                   date--that   he  would  have   received  if  he  had  been  a
                   shareholder  at  the  time  of  the   distribution   and  had
                   participated therein.

                   (i)   Distribution   of   equity   securities   or   compound
                         securities held in a portfolio.

                         In the event that the  company  whose  securities  were
                         distributed  then  engages in a  transaction  involving
                         stock  rights or  allocation  rights  set aside for its
                         stockholders, the issuing company man, in the interests
                         of the warrant  holder,  exercise the right attached


<PAGE>

FREE TRANSLATION FROM FRENCH


                         to such  securities  it has  retained.  In that case it
                         shall offer the  securities  so obtained to the warrant
                         holder as soon as they are  exercised  and the  warrant
                         holder  shall be required to repay it any sums that may
                         be paid to  subscribe  for them.  In the event that the
                         number of  securities  to which the  warrant  holder is
                         entitled  includes  fractional  shares,  this  fraction
                         shall  give rise to a cash  payment  calculated  on the
                         basis of the most recent  market price of said security
                         prior to the  warrant  exercise  date.  The price  used
                         shall be that on the regulated French exchange on which
                         said   security  is  listed,   if  any,  and  shall  be
                         determined in accordance with the provisions of article
                         1843-4 of the Civil Code in all other cases. The rights
                         accosicated with the shares obtained as a result of the
                         transactions described above shall pass at that time.

                   (ii)  Distribution of bonds held in a portfolio.

                         In the  case of the  distribution  of  bonds  held in a
                         portfolio,  said bonds  shall be  distributed  together
                         with  all  bonds   which   have  not   matured  by  the
                         subscription date.

                         In  the  event  that  the  distribution  of  securities
                         involved  bonds and that said bonds were redeemed prior
                         to the stock warrant  exercise  date, the rights of the
                         holder of the  warrants  shall be  satisfied  when said
                         warrants are  exercised  by a cash  payment  calculated
                         proportionate   to  the   redemption   price   of  said
                         securities.

         c)  Solely with  respect to such stock  warrants as have  already  been
             subject to a Warrants  Exercise  Confirmation,  the  provisions  of
             article 194-6,  paragraph 2 of the Act of July 24, 1966 shall apply
             to any capital increase set aside for the stockholders.

         d)  Beginning  on the date on which the stock  warrants  will have been
             subject to Warrants  Exercise  Confirmation and for so long as said
             warrants exist,  the Company shall be prohibited from redeeming its
             capital  stock  or  reducing  it by  way  of  redemption,  or  from
             modifying the distribution of its profits.

    2.   Dissolution of the Company by merger or demerger--reduction of capital

         a)  In the event that the Company is merged into an existing company or
             participates  in a merger  involving the creation of a new company,
             or in the  event of a  demerger  or  spin-off  involving  a capital
             contribution to newly formed or existing  companies,  the rights of
             the warrant  holder shall be extended to the stock of the acquiring
             company or of the new company or companies  which it may  subscribe
             for in  place  of the  stock  of the  Company  by  exercising  said
             warrants on the terms and conditions set out below.

             The number of shares  which it shall be entitled to  subscribe  for
             shall be  calculated  by  correcting  the  number  of shares of the
             Company which is issuing the shares to which the warrant holder was
             entitled by the exchange  ratio of the shares of the latter company
             to the shares of the  acquiring  company,  or of the new company or
             companies;  those  companies  shall be substituted  for the issuing
             company for purposes of the above provisions, which are intended to
             protect the rights, if any, of the stock warrant holder in the case
             of financial  transactions  or transactions  involving  securities,
             and,  as a general  matter,  to ensure that the rights of the stock
             warrant  holder are  respected in  accordance  with the  applicable
             statutory, regulatory and contractual conditions.

         b)  In the event of a reduction  of capital due to losses,  through the
             reduction  of either  the par value of the  shares or the number of
             shares,  the  rights  of the stock  warrant  holder  which  opts to
             exercise said  warrants  shall be reduced  accordingly,  as if said
             warrant  holder had been a sharehodler  since the date on which the
             stock warrants were issued.


<PAGE>

                                    EXHIBIT F

          Flamel Technologies Announces $12.8 Million Private Placement




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Lyon, France,  March 1, 2000 -- Flamel  Technologies  (Nasdaq:  FLMLY) announced
today that it has entered  into an  agreement  for a private  placement of $12.8
million of its securities. Investors participating in this financing include the
venture capital funds and affiliates of Biotechnology Value Fund, Alta BioPharma
Partners and Chase Capital Partners. Upon the close of this financing,  which is
anticipated at the end of March, the company will have cash and cash equivalents
of about $16 million.

Pursuant to the agreement  Flamel will sell units at the French Franc equivalent
to $4.00 per unit  consisting of one ordinary  share,  0.56 of a Class A Warrant
and  0.60  of a  combination  of  Class B or C  Warrants.  The  Warrants  have a
five-year term. In total, 3,212,500 additional ordinary shares will initially be
issued,  together  with  Warrants  covering an aggregate  of 3,726,500  ordinary
shares.  Following the completion of this  transaction,  the company will have a
total of 16,151,715 shares outstanding, excluding the exercise of Warrants.

Flamel  expects to use the proceeds from the private  placement to fund research
and  development  activities  including  clinical  trials,  and for  general and
administrative expenses, capital expenditures and working capital.

The Class A Warrants will be exercisable at the French franc equivalent of $6.00
per  share.  The  Class B  Warrants  will be  exercisable  at the  French  franc
equivalent  of $6.00 per share and the Class C Warrants will be  exercisable  at
the French franc equivalent of $0.12 per share. The Class B and Class C Warrants
are structured  into three  tranches,  such that the investors will  effectively
have the right to purchase some  combination of the Class B and Class C Warrants
depending on the trading price for the company's  ADSs on Nasdaq for the balance
of the year 2000.  If the closing  price of its ADSs on Nasdaq falls below $6.00
for more than eight trading days,  then the proportion of Class C Warrants which
are  exercisable  will increase and the proportion of the Class B Warrants which
are exercisable will correspondingly  decrease.  The relative percentage of each
(33%,  66% or 100%) that will be  exercisable  will be  determined  at specified
benchmark prices below $6.00. If the ADSs do not trade below $6.00 for more than
eight days prior to the end of the year,  then all of the Class B Warrants  will
be  exercisable,  and  none  of  the  Class  C  Warrants  will  be  exercisable.
Conversely, if the ADSs trade below $3.00 for more than 8 days, all of the Class
C  Warrants  will be  exercisable  and  none of the  Class  B  Warrants  will be
exercisable.

Under  French  law,  the  transaction  is subject  to  shareholder  approval.  A
shareholder's  meeting  has been  scheduled  for  March  23,  and all  materials
conforming to French law  requirements  will be distributed to holders of Flamel
ADSs in the next several days.

"We are pleased  that this  transaction  will  solidify  our cash  position  and
provide Flamel with the financial  resources  which we believe will permit us to
continue our research and development program through the next two years.


<PAGE>


We also believe that the additional capital will permit us to accelerate some of
our other programs,  such as the  development of our long-acting  protein," said
Dr. Gerard Soula, President and CEO of Flamel.

Flamel  Technologies S.A. is principally  engaged in the development of advanced
polymer  technologies  for  unique  medicinal  applications.  To meet  important
medical  needs and  develop  commercially  valuable  products,  the  company  is
building  on its  primary  technology  platforms: the Medusa(R) system  for  the
controlled  peritoneal  delivery of proteins and peptides,  and the Micropump(R)
system for the controlled delivery of certain oral drugs.



Agsome(TM),  Basulin(TM) and ColCys(TM) are  trademarks,  and  Micropump(R)  and
Medusa(R) are registered trademarks of Flamel Technologies.

This  document  contains  a number of  matters,  particularly  as related to the
status of various research  projects and technology  platforms,  that constitute
forward-looking   statements  within  the  meaning  of  the  Private  Securities
Litigation  Reform Act of 1995.  The  presentation  reflects the current view of
management   with  respect  to  future  events  and  is  subject  to  risks  and
uncertainties  that could cause actual  results to differ materially  from those
contemplated in such forward-looking statements.  These risks include risks that
products in the  development  stage may not  achieve  scientific  objectives  or
milestones or meet stringent regulatory  requirements,  uncertainties  regarding
market acceptance of products in development, the impact of competitive products
and pricing, and the risks associated with  Flamel's reliance on outside parties
and key strategic  alliances.  These and other risks are described more fully in
Flamel's Annual Report on the Securities and Exchange  Commission Form 20-F for
the year ended December 31, 1998.


Copyright(C) 1999 Flamel Technologies, S.A. All rights reserved.  (Updated March
2000).



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