<PAGE>


                                             ***TEXT OMITTED AND FILE SEPARATELY
                                                CONFIDENTIAL TREATMENT REQUESTED
                                            UNDER 17 C.F.R. SS.SS. 200.80(B)(4),
                                                            200.83 AND 240.24B-2


                           SECOND AMENDMENT AGREEMENT
                           --------------------------

         This Second Amendment Agreement ("Amendment No.2") effective as of the
last date on the signature page hereof, by and between Corvas International,
Inc. ("Corvas") and Schering Corporation and Schering-Plough Ltd. (collectively
"Schering") amends and supplements that certain Collaboration and License
Agreement among Corvas and Schering effective December 14, 1994, as amended by:
the Letter of Understanding signed on December 17, 1996; the Letter of
Agreement, dated December 15, 1998, extending the term of the Factor Xa Research
Program; and the Amendment Agreement dated February 18, 1999 (collectively, the
"Agreement").

         The parties hereby agree to further amend the Agreement as follows:

         Except as expressly defined herein, all capitalized terms shall have
the meanings set forth in the Agreement, as amended.

1. The parties acknowledge that during the term of the Agreement, Schering shall
have the right, in its sole discretion, to screen Program Thrombin Inhibitors
and/or Program Factor Xa Inhibitors against any of Schering's biological targets
to determine whether such compounds have activity other than as a Thrombin
Inhibitor or Factor Xa Inhibitor (hereinafter an "Alternative Activity").

2. In the event that a Program Thrombin Inhibitor and/or Program Factor Xa
Inhibitor is determined by Schering to have Alternative Activity (hereinafter an
"Active Compound"), Schering shall have the right, in its sole discretion, to
initiate a research program based upon such Active Compounds. The research
program may include medicinal chemistry and/or biological research to modify an
Active Compound and/or create Derivative Compounds (as defined in Paragraph 3 of
this Amendment No. 2) for pre-clinical, clinical and/or commercial development.
Any such research program undertaken by Schering pursuant to this Amendment No.2
will be outside the scope of the Factor Xa Research Program.

3. The term "Derivative Compound" shall mean a compound derived by or on behalf
of Schering from an Active Compound, and having Alternative Activity against the
same biological target as such Active Compound. For purposes of this Amendment
No. 2, a compound shall be deemed to have been "derived" from an Active Compound
if it is: (i) a chemical modification made to an Active Compound; (ii) otherwise
derived from a chemical synthesis program based on an Active Compound; (iii)
based on proprietary structure-function data obtained from Active Compounds; or
(iv) developed through the material use of Know-How owned by Corvas.

4. Subject to the terms and conditions set forth in Paragraphs 5, 6, 7 and 8 of
this Amendment No.2, Active Compounds and Derivative Compounds shall be deemed
to be Licensed Compounds under the Agreement.



                                       1.
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5. Notwithstanding anything in the Agreement to the contrary, Schering shall
have [...***...] payment obligations to Corvas under Sections 2.5, 2.6, 2.7,
2.8, 2.9, 2.10, 2.11 or 2.12 of the Agreement with respect to Active Compounds
and/or Derivative Compounds discovered and developed by Schering for an
Alternative Activity and not as a Thrombin Inhibitor or Factor Xa Inhibitor. In
addition, the Earned Royalty payable by Schering (under Article III of the
Agreement) on Net Sales of Licensed Products and Licensed Combinations
containing an Active Compound or Derivative Compound, discovered and developed
by Schering for an Alternative Activity and not as a Thrombin Inhibitor or
Factor Xa Inhibitor, as the only ingredient which is a Licensed Compound shall
be fixed at the rate of:

       (i)    [...***...] percent of Net Sales for Licensed Products in
              countries in the Territory where the Active Compound or Derivative
              Compound contained in the Licensed Product is specifically
              disclosed and claimed in any of the Patent Rights; or

       (ii)   [...***...] percent of Net Sales for Licensed Products not subject
              to Paragraph 5(i), above; or

       (iii)  for Licensed Combinations at the corresponding rate determined in
              accordance Section 1.7B of the Agreement and Paragraph 5(i) or
              5(ii) of this Amendment No.2, as appropriate.

The foregoing notwithstanding, [...***...] royalties shall be due with respect
to sales of Licensed Products or Licensed Combinations containing a Licensed
Compound which is conceived more than [...***...] years after the term of the
Factor Xa Research Program

6. Schering shall notify Corvas in writing:

       (i)    of any and all Active Compounds that are identified; and

       (ii)   upon filing of a New Drug Application for a Licensed Product or
              Licensed Combination containing an Active Compound and/or
              Derivative Compound for any Alternative Activity.

Schering will have no other reporting obligations under the Agreement or this
Amendment No.2 with respect to its research and development activities relating
to Active Compounds and/or Derivative Compounds. Schering shall provide Corvas
with written notice of the First Commercial Sale of each Licensed Compound
and/or Licensed Combination containing an Active Compound or Derivative Compound
for which royalties are payable hereunder.

7. Schering will be solely responsible for all decisions relating to the
selection, development and commercialization of Active Compounds and/or
Derivative Compounds for any Alternative Activity. Schering shall use diligent
efforts to develop and commercialize itself or through its Affiliate(s) or
sublicensee(s) Licensed Products and/or Licensed Combinations containing an
Active Compound or Derivative Compound discovered and developed by Schering for
an Alternative Activity and not as a Thrombin Inhibitor or Factor Xa Inhibitor.
Diligence efforts shall be comparable to those efforts Schering makes with
respect to its own pharmaceutical products of comparable market potential and
status. The diligence obligations set forth in Sections 4.6 and 4.7 of the
Agreement shall not apply to the development and commercialization of such
Active Compounds and Derivative Compounds.

--------
* CONFIDENTIAL TREATMENT REQUESTED


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8. Schering's diligence obligations under Paragraph 7 of this Amendment No.2 are
expressly conditioned upon the continuing absence of any adverse condition or
event which warrants a delay in commercialization of a Licensed Product and/or
Licensed Combination, including, but not limited to, an adverse condition or
event relating to the safety or efficacy of a Licensed Product or Licensed
Combination, unfavorable labeling, pricing or pricing reimbursement approvals,
or lack of regulatory approval, and the obligation of Schering to develop or
market any such Licensed Product or Licensed Combination shall be delayed or
suspended so long as in Schering's reasonable opinion any such condition or
event exists.

9. Notwithstanding the terms of Article VI of the Agreement, Schering shall be
responsible, at Schering's expense for the filing, prosecution, maintenance and
defense of any patent applications or patents relating to Derivative Compounds
and/or the use of any ActiveCompounds and/or Derivative Compounds for an
Alternative Activity.

         Except as expressly amended and supplemented hereby, all other terms of
the Agreement and the Extension Agreement shall remain in full force and effect.

         IN WITNESS WHEREOF, the parties hereto have caused this Amendment
Agreement to be executed in duplicate by their duly authorized representatives.

CORVAS INTERNATIONAL, INC.                     SCHERING CORPORATION


BY:      /s/ RANDALL E. WOODS                  BY:      /s/ DAVID POORVIN
   ----------------------------------             ------------------------------
NAME:    Randall E. Woods                      NAME:    David Poorvin
     --------------------------------               ----------------------------
TITLE:   President & CEO                       TITLE:   Vice President
      -------------------------------                ---------------------------
DATE:    June 29, 1999                         DATE:    6/25/99
     ---------------------------------              ----------------------------


                                               SCHERING-PLOUGH LTD.

                                               BY:      /s/ DAVID POORVIN
                                                  ------------------------------
                                               NAME:    David Poorvin
                                                    ----------------------------
                                               TITLE:   Prokurist
                                                     ---------------------------
                                               DATE:    6/25/99
                                                    ----------------------------


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