<PAGE>

                                                                   Exhibit 10.45

          Confidential Materials omitted and filed separately with the
         Securities and Exchange Commission. Asterisks denote omissions.

                                LICENSE AGREEMENT

      AGREEMENT, dated January 1, 1995, between THE TRUSTEES OF COLUMBIA
UNIVERSITY IN THE CITY OF NEW YORK, a New York corporation ("Columbia"), and
ONTOGENY, INC., a Massachusetts corporation ("Ontogeny").

      1. Definitions.

            a. "Affiliate" shall mean any corporation or other business entity
which directly or indirectly controls, is controlled by, or is under common
control with Ontogeny. Control means ownership or other beneficial interest in
50% or more of the voting stock or other voting interest of a corporation or
other business entity.

            b. "Licensed Patents" shall mean (i) the patent application United
States Serial No. 108/202,040 entitled "DNA Encoding A Vertebrate Homolog of
Hedgehog, Vhh-1, Expressed By the Notochord and Uses Thereof" filed February 25,
1994 and any corresponding foreign patent application or related foreign
document, including any division, continuation, continuation-in-part,
substitute, renewal, reissue, extension, confirmation, reexamination or
registration thereof and any patent issuing thereon including any substitute,
renewal, reissue, extension, confirmation, reexamination or registration
thereof; and (ii) any United States patent application or foreign patent
application or related foreign document, including any division, continuation,
continuation-in-part, substitute, renewal, reissue, extension, confirmation,
reexamination or registration thereof and any patent issuing thereon including
any substitute, renewal, reissue, extension, confirmation, reexamination or
registration thereof which is owned or controlled, in whole or in part, by
Columbia.

            c. "Licensed Products" shall mean any product, which includes the
protein, its fragments, covalent derivatives or antibodies to the protein, the
manufacture, use, sale, rental or lease of which is covered by a claim of an
issued patent included in the Licensed Patents which has neither expired nor
been declared invalid by a court from which no appeal has or can be taken.


                                       1
<PAGE>

            d. "Licensed Research Information" shall mean proprietary
information and materials (including any chemical compound or substances,
biological cell, or component thereof, whether derived from biological material
or synthesized) substantially relating to the invention covered by a Licensed
Patent but not covered by a claim of such Licensed Patent that is furnished to
Ontogeny and (i) was developed at Columbia under the direction of Dr. Jessell
prior to the effective date of this Agreement; or (ii) arises from, and is
developed by Dr. Jessell in the course of their research activities at Columbia.
Licensed Research Information shall be set forth as Appendix A, as amended from
time to time by agreement of the parties.

            e. "Milestone Products" shall mean any therapeutic product that is
not a Licensed Product and that (a) is an agonist or antagonist to a protein
covered by the Licensed Patents or to any fragments, covalent derivatives or
antibodies of such protein, or (b) incorporates a material part of, or could not
have been developed without the use, of Licensed Research Information.

            f. "Net Sales" shall mean all fees or other payments invoiced by
Ontogeny or an Affiliate for the use, sale, rental or lease of Licensed
Products, less returns and customary trade discounts actually taken, outbound
freight, value added, sales or use taxes and custom duties. In the case of sale,
rental, lease or use of Licensed Products by an Affiliate, Net Sales shall be
based upon the Net Sales of the Affiliate. In the case of a sale of Licensed
Products by Ontogeny to a sublicensee for resale by the sublicensee, Net Sales
shall be based solely on the Net Sales of the sublicensee and shall not include
the sale by Ontogeny to the sublicensee.

            g. "Sublicensees" shall mean third parties to whom Ontogeny has
granted sublicenses pursuant to this Agreement.

      2. License Grant.

            a. Columbia grants to Ontogeny, upon and subject to all the terms
and conditions of this Agreement.

            (i) a worldwide exclusive license under the Licensed Patents to
manufacture, use, sell, rent or lease Licensed Products for the term provided
under Section 14 hereof;


                                       2
<PAGE>

            (ii) a worldwide exclusive license to any Licensed Research
Information until such time as it is published or otherwise publicly distributed
and thereafter a non-exclusive license thereto. Columbia shall notify Ontogeny a
sufficient period of time prior to any publication of the licensed Research
Information so that Ontogeny can, if it deems appropriate, request Columbia to
file a patent application with respect to such Licensed Research Information.

            b. Columbia grants to Ontogeny the right to sublicense third
parties, provided that the terms and provisions of this Agreement are met where
applicable, that the Sublicense includes a provision that it is subject to the
terms of this Agreement, and that Ontogeny obtains Columbia's approval of any
proposed sublicensee prior to execution, which approval shall not be
unreasonably withheld by Columbia. Ontogeny may from time to time provide to
Columbia a written notice describing one or more potential sublicensees, and
Columbia shall be deemed to have approved for the purposes of this Subsection
2(b) each such sublicensee except to the extent that Columbia notifies Ontogeny,
within 30 days after its receipt of such notice, that it does not approve of any
specific sublicensee or sublicensees. Any notice provided by Ontogeny hereunder
must refer to this Subsection 2(b) and to the 30-day period referred to herein.

            c. To the extent any invention covered by a Licensed Patent, or any
Licensed Research Information arises from foundation or federally funded
research, as specified by Columbia in Appendix B, all rights granted by Columbia
to Ontogeny under this Section 2 and under this Agreement are subject to the
requirements 35 U.S.C. ss.ss. 200 et seq. and implementing regulations. To the
extent required by applicable government regulations, Ontogeny agrees that any
Licensed Products embodying any invention arising from federally funded research
or produced through the use of any such invention that are used, sold, rented or
leased by the Ontogeny, an Affiliate or a Sublicensee in the United States will
be manufactured substantially in the United States.

      3. Royalties and Payments.

            a. In consideration of the license granted under Section 2(a) of
this Agreement, Ontogeny shall pay to Columbia:


                                       3
<PAGE>

          Confidential Materials omitted and filed separately with the
         Securities and Exchange Commission. Asterisks denote omissions.

            (i) a license fee of [**] upon execution of the Agreement and an
additional [**] on the one-year anniversary of signing this Agreement.

            (ii) a royalty of [**] of Net Sales of Licensed Products made by
Ontogeny or an Affiliate or a sublicensee anywhere in the world.

            (iii) at the earlier of the marketing of the Licensed Product or
[**], a minimum annual royalty payment of [**]. [**] of such amount will be
credited against earned royalties. This minimum payment shall be required for
[**]; and

            (iv) the patent expense incurred to date by Columbia and all
reasonable future patent expenses related to Licensed Patents incurred by
Columbia.

            b. If Ontogeny, its Affiliates or Sublicenses, in order to make,
use, sell or otherwise exploit the Licensed Products in any jurisdiction,
reasonably determines that it must make royalty payments ("Third Party
Payments") to one or more independent third parties to obtain a license or
similar right to make, use, sell or otherwise exploit the Licensed Products,
excluding royalties payable to Harvard University, Ontogeny may reduce the
royalty due to Columbia by one-third of such Third Party Payments, but in no
event shall any such payment due to Columbia be reduced by more than [**] as a
result of such reduction.

            c. With respect to Milestone Products, Ontogeny shall pay to
Columbia the amounts set forth below at the following milestones:

                    Phase 2 clinical
                    completion                      $[**]

                    NDA Filing                      $[**]

                    Product Sales Initiation        $[**]

      4. Reports and Payments.

            a. Following market introduction of the first Licensed Product, on
or before the last business day of February, May, August and November of each
year of this Agreement, Ontogeny shall


                                       4
<PAGE>

submit to Columbia a written report with respect to the preceding calendar
quarter (the "Payment Report") stating:

            (i) Net Sales made by Ontogeny and any Affiliate during such quarter
for Licensed Products;

            (ii) Amounts accruing to Ontogeny from its Sublicensees during such
quarter;

            (iii) Net Sales made by Sublicensees during such quarter; and

            (iv) A calculation under Section 3 of the amounts due to Columbia,
making reference to each subsection. Simultaneously with the submission of each
Payment Report, Ontogeny shall make payments to Columbia of the amounts due for
the calendar quarter covered by the Payment Report.

            b. Ontogeny shall maintain at its principal office usual books of
account and records showing its actions under this Agreement. Upon reasonable
notice, such books and records shall be open to inspection and copying, during
usual business hours, by an independent certified public accountant to whom
Ontogeny has no reasonable objection, for two years after the calendar quarter
to which they pertain, for purposes of verifying the accuracy of the amounts
paid by Ontogeny under this Agreement.

      5. Use for Research Purposes of Licenses Granted. Columbia reserves the
right to use the Licensed Patents and Licensed Research Information for research
purposes and to permit other entities or individuals to use same for research
purposes. Columbia shall obtain from all such entities or individuals an
agreement in writing not to use the Licensed Patents or Licensed Research
Information for commercial purposes and shall inform Ontogeny of the identity of
such entities or individuals.

      6. Reasonable Commercial Efforts.

            a. Ontogeny shall use its reasonable commercial efforts to develop
and market Licensed Products for commercial sale and distribution throughout the
world, and shall provide Columbia with annual reports on its research and
development efforts.

            b. If Ontogeny fails to devote reasonable commercial efforts toward
the development or commercialization of a Licensed Product, Columbia may convert
the license granted hereunder to a non-exclusive license or terminate the
license granted hereunder and all rights will be


                                       5
<PAGE>

returned to Columbia. If Columbia elects to terminate the license or convert the
license to a non-exclusive license, Columbia shall provide written notice to
Ontogeny of its decision and Ontogeny shall have 90 days to cure its lack of
reasonable commercial efforts to Columbia's reasonable satisfaction.

      7. Infringement.

            a. Columbia will protect its Licensed Patents from infringement and
prosecute infringers at its own expense when in its sole judgment such action
may be reasonably necessary, proper and justified.

            b. If Ontogeny shall have supplied Columbia with written evidence
demonstrating to Columbia's satisfaction prima facie infringement of a claim of
a Licensed Patent by a third party selling products in competition with Ontogeny
or any of its Affiliates or Sublicensees, Ontogeny may by notice request
Columbia to take steps to protect the Licensed Patent. Unless Columbia shall
within three months of the receipt of such notice either (i) cause such
infringement to terminate or (ii) initiate legal proceedings against the
infringer, Ontogeny, may upon notice to Columbia initiate legal proceedings
against the infringer at Ontogeny's expense. In such event Ontogeny may deduct
from payments due hereunder to Columbia reasonable costs and legal fees incurred
to conduct such proceedings, but in no event shall any such payments be reduced
by more than 50 percent of the amount otherwise due to Columbia hereunder. Any
recovery by Ontogeny in such proceedings shall first be used to reimburse
Ontogeny for reasonable costs and legal fees incurred to conduct such
proceedings and next to pay any amounts withheld from Columbia by Ontogeny under
this Section 7 during the pendency of the proceedings. The balance shall be
divided 90% to Ontogeny and 10% to Columbia.

            c. In the event one party shall initiate or carry on legal
proceedings to enforce any Licensed Patent against an alleged infringer, the
other party shall use its best efforts to fully cooperate with and shall supply
all assistance reasonably requested by the party initiating or carrying on such
proceedings. The party which institutes any proceeding to protect or enforce a
Licensed Patent shall have sole control of that proceeding and shall bear the
reasonable expenses incurred by said other party in providing such assistance
and cooperation as is requested pursuant to this paragraph.


                                       6
<PAGE>

      8. Warranty; Representations. Nothing in this Agreement shall be construed
as a warranty or representation by either party as to the validity of any
Licensed Patent. Nothing in this Agreement shall be construed as a warranty or
representation by either party that anything made, used, sold or otherwise
disposed of under any license granted under this Agreement is or will be free
from infringement of domestic or foreign patents of other parties.

            Columbia Represents that it has the sole and full authority to grant
to Ontogeny the license to the Licensed Patents granted hereunder.

      9. Prohibition Against Use of Name. Ontogeny will not use the name,
insignia or symbols of Columbia, its faculties or departments, or any variation
or combination thereof, or the name of any trustee, faculty member, other
employee or student of Columbia for any purpose whatsoever without Columbia's
prior written consent, provided that Ontogeny may state that it is a licensee of
Columbia and that Dr. Jessell is a member of its Scientific Advisory Board.

      10. Compliance with Governmental Obligations.

            a. Notwithstanding any provisions in this Agreement, Columbia
disclaims any obligations or liabilities to government authorities arising under
the license provisions of this Agreement if Ontogeny is charged in a
governmental action for not complying with or fails to comply with governmental
regulations in the course of taking effective steps to bring any Licensed
Product to a point of practical application.

            b. Ontogeny shall comply upon reasonable notice from Columbia with
all governmental requests directed to either Columbia or Ontogeny and provide
all information and assistance necessary to comply with the governmental
requests.

            c. Ontogeny shall insure that research, development, and marketing
under this Agreement will comply with all government regulations in force and
effect including, but not limited to, Federal, state and municipal legislation.


                                       7
<PAGE>

      11. Indemnity and Insurance.

            a. Ontogeny will indemnify, defend and hold Columbia harmless
against any and all actions, suits, claims, demands, prosecutions, liabilities,
costs and expenses (including reasonable attorneys' fees) based on or arising
out of the development, manufacture, packaging, use, sale, rental or lease of
Licensed Products, even if altered for use for a purpose not intended, or use of
Licensed Patents or Licensed Research Information by Ontogeny, its Affiliates,
its Sublicensees or its (or their) customers and any representation made or
warranty given by Ontogeny, its Affiliates or Sublicensees with respect to
Licensed Products.

            b. Ontogeny shall maintain, during the term of this Agreement,
comprehensive general liability insurance, including products liability
insurance, with reputable and financially secure insurance carriers acceptable
to Columbia to cover the activities of Ontogeny, its Affiliates and its
Sublicensees, for minimum limits of $2,000,000 combined single limit for bodily
injury and property damage per occurrence and in the aggregate. Such insurance
shall include Columbia, its trustees, directors, officers, employees, and agents
as additional insureds. Ontogeny shall furnish a certificate of insurance
evidencing such coverage, with thirty days' written notice to Columbia of
cancellation or material change.

            The Ontogeny insurance shall be primary coverage; any insurance
Columbia may purchase shall be excess and noncontributory. Such insurance shall
be written to cover claims incurred, discovered, manifested, or made during or
after the expiration of this Agreement.

            Ontogeny shall at all times comply with all statutory workers'
compensation and employers' liability requirements covering its employees with
respect to activities performed under this Agreement.

      12. Marketing.

            a. Prior to the issuance of patents, Ontogeny will mark Licensed
Products made, sold, or otherwise disposed of by it under the license granted in
this Agreement with the words "Patent Pending", and following the issuance of
one or more patents, with the numbers of such patents.


                                       8
<PAGE>

            b. Columbia's counsel will directly notify Ontogeny and provide
copies of any official communications from the United States and foreign patent
offices relating to said prosecution. Columbia's counsel shall also provide
Ontogeny with advance copies of all relevant communications to the various
patent offices, so that Ontogeny may be informed and apprised for the continuing
prosecution of patent applications in Licensed Patents. Ontogeny shall have
reasonable opportunities to participate in decision making on all key decisions
affecting filing, prosecution and maintenance of patents and patent applications
in Licensed Patents including, without limitation, the right to approve or
disapprove the abandonment of any patent or claims thereof and Columbia will use
reasonable efforts to incorporate Ontogeny's reasonable suggestions regarding
said prosecution. Columbia shall use all reasonable efforts to amend any patent
application to include claims reasonably requested by Ontogeny to protect
Licensed Products.

            c. Columbia and Ontogeny agree to cooperate fully in the
preparation, filing, prosecution and maintenance of Licensed Patents and of all
patents and patent applications licensed to Columbia hereunder, executing all
papers and instruments or requiring members of Columbia or Ontogeny execute such
papers and instruments so as to enable Columbia to apply for, to prosecute and
to maintain patent applications and patents in Columbia's name in any country.

            d. If Ontogeny elects no longer to pay the expenses of a patent
application or patent included within Licensed Patents, Ontogeny shall notify
Columbia not less than sixty (60) days prior to such action, such date being at
least thirty (30) days prior to any pending action or expenditure.

      13. Breach and Cure.

            a. In addition to applicable legal standards, Ontogeny, shall be
considered to be in material breach of this Agreement for (i) failure to pay
fully and promptly amounts due pursuant to Section 3 and payable pursuant to
Section 4; or (ii) failure to comply with governmental requests directed to
Columbia or Ontogeny pursuant to Section 10(b).


                                       9
<PAGE>

            b. Either party shall have the right to cure its material breach.
The cure shall be effected within a reasonable period of time but in no event
later than thirty days after notice of any other breach given by the
non-breaching party.

      14. Term of Agreement.

            a. This Agreement shall be effective as of the date first set forth
above and shall continue in full force and effect until its expiration or
termination in accordance with this Section 14.

            b. Unless terminated earlier under any provision of this Agreement,
the term of the exclusive license granted under the Licensed Patents shall
extend until the expiration of the last to expire of the Licensed Patents or
fifteen years from the effective date hereof.

            c. The license granted under this Agreement may be terminated by
Columbia (i) upon thirty days' written notice to Ontogeny if Columbia elects to
terminate in accordance with Section 6(b), (ii) upon sixty days' written notice
to Ontogeny for Ontogeny's material breach of the Agreement and Ontogeny's
failure to cure such material breach in accordance with Section 13(b), or (iii)
should Ontogeny commit any act of bankruptcy, become insolvent, file a petition
under any bankruptcy or insolvency act or have any such petition filed against
it.

            d. After the payment by Ontogeny to Columbia of the total $100,000
license fee, this Agreement may be terminated by Ontogeny upon 60 days written
notice to Columbia.

            e. Upon any termination of this Agreement pursuant to Section 14(c)
(i) or (ii) or Section 14(d), all sublicenses granted by Ontogeny under it shall
be assigned to Columbia.

      15. Notices. Any notice required or permitted to be given under this
Agreement shall be sufficient if sent by certified mail (return receipt
requested), postage prepaid, if to Columbia, to:

                                             Columbia Innovation Enterprise
                                             363 Engineering Terrace
                                             Columbia University
                                             New York, New York 10027

                    copy to:                 General Counsel
                                             Columbia University
                                             110 Low Memorial Library
                                             New York, New York  10027


                                       10
<PAGE>

                    if to Ontogeny, to:      William W. Helman
                                             Ontogeny, Inc.
                                             One Kendall Square
                                             Building 600
                                             Cambridge, MA  02139

                    copy to:                 Mark G. Borden, Esq.
                                             Hale and Dorr LLP
                                             60 State Street
                                             Boston, MA  02109

or to such other address as a party may specify by notice hereunder.

      16. Assignment. This Agreement may not be assigned without the written
consent of the other party.

      17. Governing Law. This Agreement shall be governed by New York law
applicable to agreements made and to be performed in New York.


                                       11
<PAGE>

      IN WITNESS THEREOF, Columbia and have caused this Agreement to be executed
by their duly authorized representatives as of the day and year first written
above.


                                          THE TRUSTEES OF COLUMBIA
                                          UNIVERSITY IN THE CITY OF NEW YORK

                                          By    /s/
                                            ------------------------------------


                                          ONTOGENY INC.

                                          By    /s/
                                            ------------------------------------


                                       12
<PAGE>

Columbia/Ontogeny Hedgehog Agreement

                                   APPENDIX A

                         LICENSED RESEARCH INFORMATION

1.    Sequence of vhh-1 in rat, zebrafish (Roelink et al., 1994).

2.    Expertise on floorplate, motor neuron and forebrain neuron induction
      assays (see Roelink et al., 1994, Ericson et al., 1995).

3.    Expertise on expression of functional forms of vhh-1 in mammalian cell
      lines (Roelink et al., 1994; Ericson et al., 1995).

4.    Information contained in the February 24, 1995 PCT of the
      continuation-in-part of United States Patent Application Serial No.
      08/202,040 filed February 25,1994.


                                       13
<PAGE>

Columbia/Ontogeny Hedgehog Agreement

                                   APPENDIX B

           Foundations And Federal Agencies That Provided Funding For
                Licensed Patent And Licensed Research Information

T. M. Jessell
      Howard Hughes Medical Institute

J. Dodd
      N. I. H. Grant NS-30532

T. Edlund
      Swedish Medical Research Council

M. Placzek
      Medical Research Council, U.K.


                                       14
<PAGE>

CIE Columbia Innovation Enterprise

                                          July 19, 1995

Mr. William W. Helman
Greylock Management Corporation
One Federal Street, 26th Floor
Boston, Massachusetts 02110-2065

      Re:   Ontogeny/Hedgehog Agreement

Dear Mr. Helman:

      Reference is made to the License Agreement between The Trustees of
Columbia University in the City of New York (the "University") and Ontogeny,
Inc. ("Ontogeny"), dated as of January 1, 1995 (the "License Agreement").

      The University and Ontogeny wish to execute this letter agreement (the
"Amendment") to amend the License Agreement to add the Howard Hughes Medical
Institute as an indemnitee under the indemnity granted by Ontogeny pursuant to
Paragraph 11 of the License Agreement.

      NOW, THEREFORE, for good and valuable consideration, receipt of which is
hereby acknowledged, and intending to be legally bound hereby, the University
and Ontogeny agree as follows:

      Subparagraph a. of Paragraph 11 of the License Agreement is hereby deleted
and the following substituted in its place:

            a. Ontogeny will indemnify, defend and hold the University and the
            Howard Hughes Medical Institute harmless against any and all
            actions, suits, claims, demands, prosecutions, liabilities, costs
            and expenses (including reasonable attorneys' fees) based on or
            arising out of the development, manufacture, packaging, use, sale,
            rental or lease of Licensed Products, even if altered for use for a
            purpose not intended, or use of Licensed Patents or Licensed
            Research Information by Ontogeny, its Affiliates, its Sublicensees
            or its (or their) customers and any representation made or warranty
            given by Ontogeny, its Affiliates or sublicensees with respect to
            Licensed Products.

      Except as expressly provided above, the License Agreement shall remain in
full force and effect, and, except as amended by this Amendment, the License
Agreement is ratified and confirmed in all respects.


                                       15
<PAGE>

      If the foregoing accurately reflects our understanding, please execute
this Amendment in the space indicated below, whereupon this Amendment will
become a legally binding agreement between us, to be effective as of the date
first above written.

                                          Very truly yours,

                                          THE TRUSTEES OF COLUMBIA UNIVERSITY


                                          By  /s/  Jack M. Granowitz
                                            ------------------------------------
                                                Jack M. Granowitz
                                                Director,
                                                Columbia University

ACCEPTED AND AGREED:
ONTOGENY, INC.


By  /s/
-------------------------------


                                       16
<PAGE>

          Confidential Materials omitted and filed separately with the
         Securities and Exchange Commission. Asterisks denote omissions.

                      AMENDMENT NO. 2 TO LICENSE AGREEMENT

      This AMENDMENT No. 2 is made as of this 30th day of August, 1996, by and
between THE TRUSTEES OF COLUMBIA University in the City of New York, a New York
Corporation ("Columbia"), and ONTOGENY, INC., a Delaware corporation
("Ontogeny").

      WHEREAS, Columbia and Ontogeny are parties to a License Agreement, dated
as of January 1, 1995 (the "License Agreement"); and

      WHEREAS Columbia and Ontogeny wish to amend the License Agreement as
hereafter provided.

      NOW, THEREFORE, in consideration of the mutual covenants of Columbia and
Ontogeny and further good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, Columbia and Ontogeny, intending
to be legally bound, hereby agree as follows:

1.    The definition of "Net Sales" contained in Section 1 of the License
      Agreement is hereby amended to read in full as follows:

            "f. 'Net Sales' shall mean all fees or other payments invoiced by
            Ontogeny or an Affiliate for the use, sale, rental or lease of
            Licensed Products, less returns and customary trade discounts
            actually taken, outbound freight, value added, sales or use taxes
            and custom duties. In the case of sale, rental, lease or use of
            Licensed Products by an Affiliate, Net Sales shall be based upon the
            Net Sales of the Affiliate.

2.    Section 3.a. of the License Agreement is hereby amended to read in full as
      follows:

            "a. In consideration of the license granted under Section 2 (a)
            of this Agreement, Ontogeny shall pay to Columbia:

            (i) a license fee of [**] upon execution of the License Agreement
            and an additional [**] on the one year anniversary of the signing
            the License Agreement. Columbia hereby acknowledges receipt of both
            [**] payments; and

            (ii) a royalty of [**] of Net Sales of Licensed Products made by
            Ontogeny or an Affiliate anywhere in the world; and

            (iii) if Ontogeny grants a sublicense under the License Agreement to
            a sublicensee (other than an Affiliate), Ontogeny shall pay to
            Columbia [**] of any royalties, fees or other amounts received by
            Ontogeny or its Affiliates as a result of the sublicensee's
            development or sale of Licensed Products, excluding (x) amounts paid
            in partial or fall consideration of equity of Ontogeny or its
            Affiliates, (y) amounts paid to fund research and development
            activities conducted by Ontogeny or its Affiliates, and (z)
            non-monetary considerations, including, without limitation patent
            expenses, equity securities, licenses, technical assistance,
            marketing cooperation, intellectual property rights, noncompetition
            covenants and the like; and


                                       17
<PAGE>

          Confidential Materials omitted and filed separately with the
         Securities and Exchange Commission. Asterisks denote omissions.

            (iv) beginning at the earlier of the first commercial marketing of
            any Licensed Product or [**], a minimum annual royalty payment of
            [**]. [**] of such amount will be credited against earned
            royalties. This minimum payment shall be required for [**] years;
            and

            (v) the patent expense incurred to date by Columbia and all
            reasonable future patent expenses related to Licensed Patents
            incurred by Columbia.

3.    Section 3.b. of the License Agreement is hereby amended to read in full as
      follows:

            "If Ontogeny or its Affiliates, in order to make, use, sell or
            otherwise exploit the Licensed Products in any jurisdiction,
            reasonably determines that it must make royalty payments ("Third
            Party Payments") to one or more independent third parties to obtain
            a license or similar right to make, use, sell or otherwise exploit
            the Licensed Product, excluding royalties payable to Harvard
            University, Ontogeny may reduce the royalty due to Columbia by
            one-third of such Third Party Payments, but in no event shall any
            such payment due to Columbia be reduced by more than [**] as a
            result of such reduction."

4.    Section 3.c. of the License Agreement is hereby amended to read in full as
      follows:

            "With respect to Milestone Products, Ontogeny shall pay to Columbia
            the following payments and shall not pay the amounts specified in
            Section 3.a.(iii). Such amounts are set forth below at the following
            milestones:

            Phase 2 clinical completion      $[**]
            NDA Filing                       $[**]
            Product Sales Initiation         $[**]


                                       18
<PAGE>

          Confidential Materials omitted and filed separately with the
         Securities and Exchange Commission. Asterisks denote omissions.

5.    The "Notice to Ontogeny" in Section 15 of the License Agreement is hereby
      amended to read in full as follows:

            if to Ontogeny, to:          Chief Executive Officer
                                         Ontogeny, Inc.
                                         45 Moulton Street
                                         Cambridge, MA  02138-1118

            copy to:                     Mark G. Borden, Esq.
                                         Hale and Dorr LLP
                                         60 State Street
                                         Boston, MA  02109

6.    The "Notice to Columbia" in Section 15 of the License Agreement is hereby
      amended to read in full as follows:

            if to Columbia, to:          Columbia Innovation Enterprise
                                         500 West 120th Street
                                         Columbia University
                                         New York, NY  10027

            copy to:                     General Counsel
                                         Columbia University
                                         110 Lowell Memorial Library
                                         New York, NY  10027

7.    If the terms of this Amendment are agreed to and executed by Columbia
      Innovation Enterprise on or before August 31, 1996, Ontogeny shall pay
      Columbia [**].

8.    Except as expressly amended by this Amendment No. 2, the License Agreement
      shall remain in full force and effect as the same was in effect
      immediately prior to the effectiveness of this Amendment No. 2.

9.    This Amendment No. 2 shall be governed by, and construed on the same basis
      as the License Agreement, as set forth therein.


                                       19
<PAGE>

      IN WITNESS WHEREOF, each of the parties hereto has fully executed this
Amendment No. 2 all as of the day and year first above written.

                              THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF
                              NEW YORK

                              By  /s/  Jack M. Granowitz
                                 -----------------------------------------------
                                    Jack M. Granowitz
                                    Director,


                              ONTOGENY, INC.

                              By  /s/  Thomas D. Ingolia
                                 -----------------------------------------------
                                    Thomas D. Ingolia, Ph.D
                                    Senior Vice President


                                       20