<PAGE>

               FIRST AMENDMENT TO RESTATED INVESTORS' RIGHTS AGREEMENT



         This First Amendment to Restated Investors' Rights Agreement (the
"Amendment") is made as of this 6th day of June, 1997, by and among Triangle
Pharmaceuticals, Inc., a Delaware corporation (the "Company"), the investors
executing this Amendment on the signature pages hereto under the heading "The
Investors," and the investors executing this Amendment on the signature pages
hereto under the heading "The New Investors" (the "Soros Funds"), and amends
certain portions of the Restated Investors' Rights Agreement dated June 11, 1996
(the "Agreement"), among the Company and the individuals and entities listed on
SCHEDULE A to the Agreement (the "Existing Investors").  Capitalized terms not
otherwise defined herein will have the meanings given to them in the Agreement.

                                       RECITALS

         WHEREAS, the Company desires to sell and issue to the Soros Funds, and
the Soros Funds desire to purchase from the Company, 2,000,000 shares of the
Company's Common Stock (the "Shares") pursuant to the Common Stock Purchase
Agreement dated of even date herewith (the "Stock Purchase Agreement"), the form
of which is attached hereto as EXHIBIT A.

         WHEREAS, the Existing Investors desire for the Soros Funds to purchase
the Shares and, as a condition thereof and to induce such investment, the
Existing Investors are willing to enter into this Amendment to permit the Soros
Funds to become parties to certain sections of the Agreement, as amended by this
Amendment (the "Amended Agreement").

         WHEREAS, the Existing Investors are holders of a sufficient number of
Registrable Securities to effectively amend the Agreement.

         NOW, THEREFORE, for good and valuable consideration, the receipt and
adequacy of which are hereby acknowledged, the parties hereto agree as follows:

         1.   AMENDMENTS TO AGREEMENT.  The Agreement is hereby amended as
follows:

              1.1  SECTION 1.1(f).  Section 1.1(f) is hereby amended and
restated in its entirety to read as follows:

              "(f) The term "Registrable Securities" means (i) the Common Stock
    issuable or issued upon conversion of the Series A Preferred Stock, (ii)
    the Common Stock issuable or issued upon conversion of the Series B
    Preferred Stock, (iii) the 2,000,000 shares of Common Stock purchased by
    the Soros Funds on June 6, 1997 (the "Soros Shares"), and

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    (iv) any Common Stock of the Company issued as (or issuable upon the
    conversion or exercise of any warrant, right or other security which is
    issued as) a dividend or other distribution with respect to, or in exchange
    for or in replacement of the shares referenced in (i), (ii) or (iii) above;
    excluding in all cases, however, any Registrable Securities sold by a
    person or entity in a transaction in which its rights under this Section 1
    are not assigned; and PROVIDED, HOWEVER, that notwithstanding anything
    herein to the contrary, the Soros Shares and any shares of Common Stock
    referenced in (iv) above that are issued in respect of any Soros Shares
    shall not be "Registrable Securities" for purposes of Sections 1.2, 1.6,
    1.11, 1.12 or 1.14."

              1.2  SECTION 1.1(g).  Section 1.1(g) is hereby amended and
restated in its entirety to read as follows:

              "(g) The number of shares of "Registrable Securities then
    outstanding" means the number of shares of Common Stock outstanding which
    are, and the number of shares of Common Stock issuable pursuant to then
    exercisable or convertible securities which are, Registrable Securities for
    purposes of the Section of this Agreement pursuant to which such
    calculation is made."

              1.3  SECTION 1.1(i).  A new section 1.1(i) is hereby added to the
Agreement as follows:

              "(i) The term "Soros Funds" shall mean the entities that acquired
    the Soros Shares pursuant to a certain Common Stock Purchase Agreement
    dated as of June 6, 1997."

              1.4  SECTION 3.7.  Section 3.7 is hereby amended and restated in
its entirety to read as follows:

              "3.7 AMENDMENTS AND WAIVERS.  Any term of this Agreement may be
    amended and the observance of any term of this Agreement may be waived
    (either generally or in a particular instance and either retroactively or
    prospectively), only with the written consent of the Company and the
    holders of a majority of the Registrable Securities then outstanding for
    purposes of the Section of the Agreement to which the amendment or waiver
    relates.  Any amendment or waiver effected in accordance with this
    paragraph shall be binding upon each holder of any Registrable Securities
    then outstanding, each future holder of all such Registrable Securities,
    and the Company."

              1.5  SCHEDULE A.  SCHEDULE A to the Agreement is hereby amended
and restated in its entirety with SCHEDULE A attached to this Amendment.


                                         -2-

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    2.   CONSENT AND WAIVER.  Each Existing Investor, on behalf of itself and
all of the other Existing Investors under the Agreement, hereby (a) consents to
(i) adding the Soros Funds as parties to the Amended Agreement, (ii) granting
the registration rights to the Soros Funds as set forth in the Amended Agreement
and (iii) granting the registration rights to the Soros Funds as set forth in
the Stock Purchase Agreement, and (b) waives any rights the Existing Investors
may have under the Agreement or otherwise to cause the Company to register any
of the Investors' Registrable Securities as part of the registration of the
resale of the Soros Shares in accordance with the provisions of the Stock
Purchase Agreement.

    3.   EFFECT OF AMENDMENT; CONFLICTS.  Except as specifically amended by
this Amendment, the Agreement shall continue in full force and effect.  In the
event of any conflict between the terms of the Agreement and the terms of this
Amendment, the terms of this Amendment shall govern and control.

    4.   COUNTERPARTS.  This Amendment may be executed in any number of
counterparts, each of which will be deemed an original, and all of which
together shall constitute one instrument.






                  [REMAINDER OF THIS PAGE INTENTIONALLY LEFT BLANK]


                                         -3-


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    IN WITNESS WHEREOF, this Amendment is hereby executed as of the date first
above written.

                             THE COMPANY:

                                                       , a Delaware corporation
                             --------------------------


                             By:
                                ------------------------------------------

                             Its:
                                 -----------------------------------------


                             THE NEW INVESTORS:


                             ---------------------------------------------
                                       (INVESTOR NAME)


                             By:
                                ------------------------------------------

                             Its:
                                 -----------------------------------------


                             THE INVESTORS:


                             ---------------------------------------------
                                       (INVESTOR NAME)


                             By:
                                ------------------------------------------

                             Its:
                                 -----------------------------------------





                        [SIGNATURE PAGE TO FIRST AMENDMENT TO
                        RESTATED INVESTORS' RIGHTS AGREEMENT]

<PAGE>

                                      SCHEDULE A

                                SCHEDULE OF INVESTORS

Dr. David Barry
Dr. Dennis Carson
Chung K. Chu
John R. Cook
Dr. M. Nixon Ellis
Forward Ventures II, L.P.
Forward Ventures Vanguard Fund
Dr. Phillip Furman
Dr. Karl Y. and Margaretha Hostetler,
  Trustees of The Hostetler Family Trust
  UTD March 18, 1992
Carolyn Jenkins
James Klein
Dr. Sandra Lehrman
Dennis Liotta
Alexander B. McFadden deceased,
  Mellon Bank N.A., Alexander Cushing
  & George McFadden U/W
Carol McFadden
George McFadden
George & Lesley Taylor McFadden
  Trustees, U/A DTD 9/22/71 F/B/O
  Elizabeth Cutting McFadden Trust
GS Triangle Holdings
John H. McFadden
Whilelmina Joseph McFadden 1995 Trust Dtd.
  Nov. 6th, 1995, between George McFadden as
  Donor and David R. Hamilton as Trustee
McFadden Brothers
Chris A. Rallis
Dr. Douglas and Eva Richman,
  Co-Trustees of the Richman
  Family Trust dated June 2, 1983
Raymond Schinazi
Schroder Venture Managers Limited
Jeff Sollender
Soros Funds (as defined above)
Lesley Taylor
UMB as Trustee for Brobeck, Phleger & Harrison
  Retirement Savings Trust FBO John A. Denniston
Venrock Associates
Venrock Associates II, L.P.
The Wellcome Trust Limited as trustee of
  The Wellcome Trust


                                     SCHEDULE A-1

<PAGE>

                                      EXHIBIT A

                       FORM OF COMMON STOCK PURCHASE AGREEMENT




                                     EXHIBIT A-1