<PAGE>


      AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON AUGUST 24, 2000
                                                 REGISTRATION NO. 333-39118

================================================================================
                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549

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


                               AMENDMENT NO. 1 TO
                                    FORM S-3
                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933


                                   ----------

                         TRIANGLE PHARMACEUTICALS, INC.
             (Exact name of Registrant as Specified in Its Charter)

                Delaware                               56-1930728
    (State or Other Jurisdiction of                 (I.R.S. Employer
     Incorporation or Organization)                Identification No.)

                                   ----------

 4 University Place, 4611 University Drive, Durham, North Carolina, 27707 (919)
                                    493-5980
   (Address, Including Zip Code, And Telephone Number, Including Area Code, Of
                    Registrant's Principal Executive Offices)

                                   ----------

                              David W. Barry, M.D.
                      Chairman And Chief Executive Officer
                         TRIANGLE PHARMACEUTICALS, INC.

     4 University Place, 4611 University Drive, Durham, North Carolina 27707
                                 (919) 493-5980
 (Name, Address, Including Zip Code, and Telephone Number, Including Area Code,
                              of Agent For Service)

                                   ----------
                                   COPIES TO:
                            Luci Staller Altman, Esq.
                                 Lisa Tsou, Esq.
                         BROBECK, PHLEGER & HARRISON LLP
                            1633 Broadway, 47th Floor
                               New York, NY 10019
                                 (212) 581-1600
                                   ----------

   Approximate date of commencement of proposed sale to the public: From time to
time after the effective date of this registration statement.
   If only the securities being registered on this form are being offered
pursuant to dividend or interest reinvestment plans, please check the following
box: |_|
   If any of the securities being registered on this form are to be offered on a
delayed or continuous basis pursuant to Rule 415 under the Securities Act of
1933, other than securities offered only in connection with dividend or interest
reinvestment plans, check the following box: |X|
   If this form is filed to register additional securities for an offering
pursuant to Rule 462(b) under the Securities Act, check the following box and
list the Securities Act registration statement number of the earlier effective
registration statement for the same offering: |_|
   If this form is a post-effective amendment filed pursuant to Rule 462(c)
under the Securities Act, check the following box and list the Securities Act
registration statement number of the earlier effective registration statement
for the same offering: |_|
   If delivery of the prospectus is expected to be made pursuant to Rule 434,
please check the following box: |_|






<PAGE>

      THE REGISTRANT HEREBY AMENDS THIS REGISTRATION STATEMENT ON SUCH DATE OR
DATES AS MAY BE NECESSARY TO DELAY ITS EFFECTIVE DATE UNTIL THE REGISTRANT
SHALL FILE A FURTHER AMENDMENT WHICH SPECIFICALLY STATES THAT THIS REGISTRATION
STATEMENT SHALL THEREAFTER BECOME EFFECTIVE IN ACCORDANCE WITH SECTION 8(A) OF
THE SECURITIES ACT OF 1933, AS AMENDED, OR UNTIL THE REGISTRATION STATEMENT
SHALL BECOME EFFECTIVE ON SUCH DATE AS THE SEC, ACTING PURSUANT TO SAID SECTION
8(A), MAY DETERMINE.
================================================================================
<PAGE>


                 SUBJECT TO COMPLETION, DATED AUGUST 24, 2000


      The information in this prospectus is not complete and may be changed. The
selling stockholders may not sell the common stock covered by this prospectus
until the registration statement filed with the Securities and Exchange
Commission is effective. This prospectus is not an offer to sell the common
stock and it is not soliciting an offer to buy the common stock in any state
where the offer or sale is not permitted.

PRELIMINARY PROSPECTUS

                                 399,967 SHARES

                         TRIANGLE PHARMACEUTICALS, INC.
                                  COMMON STOCK

      This prospectus relates to the public offering, which is not being
underwritten, of 399,967 shares of our common stock by current stockholders
identified in this prospectus, all of which are currently issued and
outstanding. We issued the shares to the selling stockholders pursuant to an
agreement and plan of reorganization, dated June 30, 1997 and amended February
28, 1999 and March 24, 2000.

      The prices at which such stockholders may sell the shares will be
determined by the prevailing market price for the shares or in negotiated
transactions. We will not receive any of the proceeds from the sale of the
shares by the selling stockholders.


      Our common stock is traded on the Nasdaq National Market under the symbol
"VIRS." On August 22, 2000, the average of the high and low prices for the
common stock was $8.56 per share.


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

      THE COMMON STOCK OFFERED INVOLVES A HIGH DEGREE OF RISK. SEE "RISK
FACTORS" COMMENCING ON PAGE 3 FOR A DISCUSSION OF SOME IMPORTANT RISKS YOU
SHOULD CONSIDER BEFORE BUYING ANY SHARES OF COMMON STOCK.

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

      NEITHER THE SECURITIES AND EXCHANGE COMMISSION, SEC, NOR ANY STATE
SECURITIES COMMISSION HAS APPROVED OR DISAPPROVED THESE SECURITIES, OR PASSED
UPON THE ACCURACY OR ADEQUACY OF THIS PROSPECTUS. ANY REPRESENTATION TO THE
CONTRARY IS A CRIMINAL OFFENSE.

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



                 The date of this prospectus is August   , 2000

<PAGE>

                                TABLE OF CONTENTS
                                                                           Page
                                                                           ----

FORWARD-LOOKING STATEMENTS...................................................1
OUR BUSINESS.................................................................1
RISK FACTORS.................................................................1
WHERE YOU CAN FIND MORE INFORMATION.........................................13
INFORMATION INCORPORATED BY REFERENCE.......................................13
USE OF PROCEEDS.............................................................13
SELLING STOCKHOLDERS........................................................14
PLAN OF DISTRIBUTION........................................................16
LEGAL MATTERS...............................................................17
EXPERTS.....................................................................17
<PAGE>

                           FORWARD-LOOKING STATEMENTS

      IN ADDITION TO HISTORICAL INFORMATION, THIS PROSPECTUS MAY CONTAIN
FORWARD-LOOKING STATEMENTS. THESE STATEMENTS INVOLVE RISKS AND UNCERTAINTIES.
OUR ACTUAL RESULTS COULD DIFFER MATERIALLY FROM THOSE PROJECTED IN THE
FORWARD-LOOKING STATEMENTS. FACTORS THAT COULD CAUSE OR CONTRIBUTE TO SUCH
DIFFERENCES INCLUDE THOSE DISCUSSED IN THE SECTION ENTITLED "RISK FACTORS," AS
WELL AS THOSE DISCUSSED ELSEWHERE IN THIS PROSPECTUS OR IN DOCUMENTS
INCORPORATED BY REFERENCE HEREIN. WE UNDERTAKE NO OBLIGATION TO UPDATE THESE
FORWARD-LOOKING STATEMENTS.

                                  OUR BUSINESS

      We develop new drug candidates primarily in the antiviral area, with a
particular focus on therapies for HIV, including AIDS, and the hepatitis B
virus. We have an existing portfolio of five licensed drug candidates and
several drug candidates for which we have an option to acquire a license.
Members of our senior management, prior to joining Triangle, played instrumental
roles in developing several leading antiviral therapies. Our goal is to
capitalize on our management team's expertise, as well as on advances in
virology and immunology, to identify, develop and commercialize new drug
candidates that can be used alone or in combination to coactively treat serious
diseases.

      Triangle was incorporated in Delaware in July 1995. Our principal
executive offices are located at 4 University Place, 4611 University Drive,
Durham, North Carolina 27707, and our telephone number is (919) 493-5980.

                                  RISK FACTORS

IN ADDITION TO THE OTHER INFORMATION IN THIS PROSPECTUS, YOU SHOULD CAREFULLY
CONSIDER THE FOLLOWING RISKS AND UNCERTAINTIES BEFORE DECIDING TO PURCHASE
SHARES OF OUR COMMON STOCK. AN INVESTMENT IN OUR COMMON STOCK INVOLVES A HIGH
DEGREE OF RISK

ALL OF OUR PRODUCT CANDIDATES ARE IN DEVELOPMENT AND MAY NEVER BE SUCCESSFULLY
COMMERCIALIZED WHICH WOULD HAVE AN ADVERSE IMPACT ON YOUR INVESTMENT AND OUR
BUSINESS.

      Some of our drug candidates are at an early stage of development and all
of our drug candidates will require expensive and lengthy testing and regulatory
clearances. None of our drug candidates has been approved by regulatory
authorities. We do not expect any of our drug candidates to be commercially
available until at least the year 2002. There are many reasons that we may fail
in our efforts to develop our drug candidates, including that:

      o  our drug candidates will be ineffective, toxic or
         will not receive regulatory clearances,
      o  our drug candidates will be too expensive to manufacture or market or
         will not achieve broad market acceptance,
      o  third parties will hold proprietary rights that may preclude us from
         developing or marketing our drug candidates, or
      o  third parties will market equivalent or superior products.

      The success of our business depends upon our ability to successfully
develop and market our drug candidates.

WE HAVE INCURRED LOSSES SINCE INCEPTION AND MAY NEVER ACHIEVE PROFITABILITY.


      We formed Triangle in July 1995 and we have only a limited operating
history for you to review in evaluating our business. We have incurred losses
since our inception. At June 30, 2000, our accumulated deficit was $279.6
million. Our historical costs relate primarily to the acquisition and
development of our drug candidates and selling, general and administrative
costs. We have not generated any revenue from the sale of our drug


                                       1
<PAGE>

candidates to date, and do not expect to do so until at least the year 2002. In
addition, we expect annual losses to increase over the next several years as we
expand our drug development and commercialization efforts. To become profitable,
we must successfully develop and obtain regulatory approval for our drug
candidates and effectively manufacture, market and sell any products we develop.
We may never generate significant revenue or achieve profitable operations.

IF WE NEED ADDITIONAL FUNDS AND ARE UNABLE TO RAISE THEM, WE WOULD HAVE TO
CURTAIL OR CEASE OPERATIONS.

      Our drug development programs and potential commercialization of our drug
candidates require substantial capital expenditures, including expenses for
preclinical testing, chemical synthetic scale-up, manufacture of drug substance
for clinical trials, toxicology studies, clinical trials of drug candidates,
sales and marketing expenses, payments to our licensors and potential commercial
launch of our drug candidates. We expect our capital requirements to continue to
increase. Our future capital needs will depend on many factors, including:

      o  the progress and magnitude of our drug development programs,
      o  the scope and results of preclinical testing and clinical trials,
      o  the cost, timing and outcome of regulatory reviews,
      o  the costs under current and future license and option agreements for
         our drug candidates, including the costs of obtaining patent protection
         for our drug candidates,
      o  the costs of acquiring any additional drug candidates,
      o  the rate of technological advances,
      o  the commercial potential of our drug candidates,
      o  the magnitude of our administrative and legal expenses,
      o  the costs of establishing sales and marketing functions, and
      o  the costs of establishing third party arrangements for manufacturing.


      We have incurred negative cash flow from operations since we
incorporated Triangle and do not expect to generate positive cash flow from
our operations for at least the next several years. Although the strategic
alliance with Abbott Laboratories, the Abbott Alliance, provided us with
significant additional funding, we cannot assure you that such funding,
combined with other available sources of funds, will be sufficient to meet
our future needs. In addition, we cannot assure you that we will receive the
contingent future research funding payments under the Abbott Alliance.
Therefore, we may need additional future financings to fund our operations.
We may not be able to obtain adequate financing to fund our operations, and
any additional financing we obtain may be on terms that are not favorable to
us. In addition, any future financings could substantially dilute our
stockholders. If adequate funds are not available, we will be required to
delay, reduce or eliminate one or more of our drug development programs, to
enter into new collaborative arrangements or to modify the Abbott Alliance on
terms that are not favorable to us. These collaborative arrangements or
modifications could result in the transfer to third parties of rights that we
consider valuable. In addition, we often consider the acquisition of
technologies and drug candidates that would increase our capital requirements.


BECAUSE OUR PRODUCT CANDIDATES MAY NOT SUCCESSFULLY COMPLETE CLINICAL TRIALS
REQUIRED FOR COMMERCIALIZATION, OUR BUSINESS MAY NEVER ACHIEVE PROFITABILITY.


      To obtain regulatory approvals needed for the sale of our drug
candidates, we must demonstrate through preclinical testing and clinical
trials that each drug candidate is safe and effective. The clinical trial
process is complex and uncertain and the regulatory environment varies widely
from country to country. Positive results from preclinical testing and early
clinical trials do not ensure positive results in pivotal clinical trials.
Many companies in our industry have suffered significant setbacks in pivotal
clinical trials, even after promising results in earlier trials. Any of our
drug candidates may produce undesirable side effects in humans. These side
effects could cause us or regulatory authorities to interrupt, delay or halt
clinical trials of a drug candidate, as occurred with mozenavir dimesylate,
or could result in regulatory authorities refusing to approve the drug
candidate for any and all targeted indications. In April 2000, the Food and
Drug Administration, the FDA, issued a clinical hold on, and the Medicines
Control Council, the MCC, terminated, clinical study FTC-302 for our drug
candidate Coviracil(R), formerly known as FTC. Study FTC-302 was


                                      2



<PAGE>


being conducted under a U.S. Investigational New Drug Application, IND, at
sites in South Africa. The FDA indicated that study FTC-302 may not be
adequate to provide pivotal data in support of a New Drug Application, an
NDA. Discussions with the FDA and MCC on this issue are continuing. Due to
these circumstances, the planned submission of a U.S. NDA for Coviracil may
be significantly delayed. We, the FDA, or foreign regulatory authorities may
suspend or terminate clinical trials at any time if we or they believe the
trial participants face unacceptable health risks. Clinical trials may not
demonstrate that our drug candidates are safe or effective.


      Clinical trials are lengthy and expensive. They require adequate supplies
of drug substance and sufficient patient enrollment. Patient enrollment is a
function of many factors, including:

      o  the size of the patient population,
      o  the nature of the protocol,
      o  the proximity of patients to clinical sites, and
      o  the eligibility criteria for the clinical trial.

      Delays in patient enrollment can result in increased costs and longer
development times. Even if we successfully complete clinical trials, we may not
be able to file any required regulatory submissions in a timely manner and we
may not receive regulatory approval for the drug candidate.


      In addition, if the FDA or foreign regulatory authorities require
additional clinical trials, we could face increased costs and significant
development delays, as occurred with Coactinon(R) and which may occur with
Coviracil. Changes in regulatory policy or additional regulations adopted
during product development and regulatory review of information we submit
could also result in delays or rejections. The FDA has notified us that two
of our drug candidates, Coviracil and DAPD for the treatment of HIV, qualify
for designation as "fast track" products under provisions of the Food and
Drug Administration Modernization Act of 1997. The fast track provisions are
designed to expedite the review of new drugs intended to treat serious or
life-threatening conditions and essentially codified the criteria previously
established by the FDA for accelerated approval. These drug candidates may
not, however, continue to qualify for expedited review and our other drug
candidates may fail to qualify for fast track development or expedited
review. Even though some of our drug candidates have qualified for expedited
review, the FDA may not approve them at all or any sooner than other drug
candidates that do not qualify for expedited review.


IF WE OR OUR LICENSORS ARE NOT ABLE TO OBTAIN AND MAINTAIN ADEQUATE PATENT
PROTECTION FOR OUR PRODUCT CANDIDATES, WE MAY BE UNABLE TO COMMERCIALIZE OUR
PRODUCT CANDIDATES OR TO PREVENT OTHER COMPANIES FROM USING OUR TECHNOLOGY IN
COMPETITIVE PRODUCTS.

      Our success will depend on our ability and the ability of our licensors to
obtain and maintain patents and proprietary rights for our drug candidates and
to avoid infringing the proprietary rights of others, both in the United States
and in foreign countries. We have no patents in our own name and we have a small
number of patent applications of our own pending. One of our patent applications
is a joint application with co-inventors from another institution. We have,
however, licensed or we have an option to license patents, patent applications
and other proprietary rights from third parties for each of our drug candidates.
If we breach our licenses, we may lose rights to important technology and drug
candidates.

      Our patent position, like that of many pharmaceutical companies, is
uncertain and involves complex legal and factual questions for which important
legal principles are unresolved. We may not develop or obtain rights to products
or processes that are patentable. Even if we do obtain patents, they may not
adequately protect the technology we own or have in-licensed. In addition,
others may challenge, seek to invalidate, infringe or circumvent any patents we
own or in-license, and rights we receive under those patents may not provide
competitive advantages to us. Further, the manufacture, use or sale of our
products or processes may infringe the patent rights of others.

      Several pharmaceutical and biotechnology companies, universities and
research institutions have filed patent applications or received patents that
cover our technologies or technologies similar to ours. Others have filed patent
applications and received patents that conflict with patents or patent
applications we own or have in-licensed,

                                      3

<PAGE>

either by claiming the same methods or compounds or by claiming methods or
compounds that could dominate those owned by or licensed to us. In addition, we
may not be aware of all patents or patent applications that may impact our
ability to make, use or sell any of our drug candidates. For example, United
States patent applications are confidential while pending in the Patent and
Trademark Office, PTO, and patent applications filed in foreign countries are
often first published six months or more after filing. Any conflicts resulting
from third party patent applications and patents could significantly reduce the
coverage of our patents and limit our ability to obtain meaningful patent
protection. If other companies obtain patents with conflicting claims, we may be
required to obtain licenses to these patents or to develop or obtain alternative
technology. We may not be able to obtain any such license on acceptable terms or
at all. Any failure to obtain such licenses could delay or prevent us from
pursuing the development or commercialization of our drug candidates, which
would adversely affect our business.

      There are significant risks regarding the patent rights of two of our
in-licensed drug candidates. We may not be able to commercialize Coviracil or
DAPD due to patent rights held by third parties other than our licensors. Third
parties have filed numerous patent applications and have received numerous
issued patents in the United States and many foreign countries that relate to
these drug candidates and their use alone or coactively to treat HIV and
hepatitis B. As a result, our patent position regarding the use of Coviracil and
DAPD to treat HIV and/or hepatitis B is highly uncertain and involves numerous
complex legal and factual questions that are unknown or unresolved. If any of
these questions is resolved in a manner that is not favorable to us, we would
not have the right to commercialize Coviracil and/or DAPD in the absence of a
license from one or more third parties, which may not be available on acceptable
terms or at all. In addition, even if any of these questions is favorably
resolved, we may still attempt to obtain licenses from one or more third parties
to reduce or eliminate the risks relating to some or all of these matters. Such
licenses may not be available on acceptable terms or at all. Our inability to
commercialize either of these drug candidates could adversely affect our
business.

      COVIRACIL (EMTRICITABINE)

      Coviracil, a purified form of FTC, belongs to the same general class of
nucleosides as lamivudine, also known as 3TC. In the United States, the FDA has
approved 3TC for the treatment of hepatitis B and for use in combination with
zidovudine, also known as AZT, for the treatment of HIV. Regulatory authorities
have approved 3TC for the treatment of hepatitis B in several other countries
and for use in combination with other nucleoside analogues for the treatment of
HIV in a number of other countries. Glaxo Wellcome plc, Glaxo, currently sells
3TC for the treatment of HIV and hepatitis B under a license agreement with
BioChem Pharma Inc., BioChem Pharma. We obtained rights to Coviracil under a
license from Emory University, Emory. In 1990 and 1991, Emory filed in the
United States and thereafter in numerous foreign countries patent applications
with claims to compositions of matter and methods to treat HIV and hepatitis B
with Coviracil. In 1991, Yale University, Yale, filed in the United States
patent applications on FTC, including Coviracil and its use to treat hepatitis
B, and subsequently licensed its rights under those patent applications to
Emory. Our license arrangement with Emory includes all rights to Coviracil and
its uses claimed in the Yale patent applications.


      HIV. Emory received a United States patent in 1993 covering a method to
treat HIV with Coviracil. Emory has also received United States and European
patents containing composition of matter claims that cover Coviracil. BioChem
Pharma filed a patent application in the United States in 1989 and received a
patent in 1991 covering a group of nucleosides in the same general class as
Coviracil, but which did not include Coviracil. BioChem Pharma filed foreign
patent applications in 1990, which expanded upon its 1989 United States
patent application to include FTC among a large class of nucleosides. The
foreign patent applications are pending in many countries and have issued in
a number of countries with claims directed to FTC that may cover Coviracil
and its use to treat HIV. In addition, BioChem Pharma filed a United States
patent application in 1991 specifically directed to Coviracil. BioChem Pharma
has received two patents in the United States based on this patent
application, one directed to Coviracil and the other directed to a method for
treating viral diseases with Coviracil. The PTO has determined that there are
conflicts between both BioChem Pharma patents and patent applications filed
by Emory because they have overlapping claims to the same technology. The PTO
is conducting two adversarial proceedings to determine whether BioChem Pharma
or Emory is entitled to the patent claims in dispute regarding BioChem
Pharma's two issued patents. Emory may not prevail in the adversarial
proceedings, and the proceedings may also delay the decision of the PTO
regarding Emory's patent application. BioChem Pharma also filed patent
applications in many foreign countries based upon


                                      4
<PAGE>

its 1991 United States patent application and has received patents in certain
countries. BioChem Pharma may have additional patent applications pending in the
United States.


      In the United States, the first to invent a technology is entitled to
patent protection on that technology. For patent applications filed prior to
January 1, 1996, United States patent law provides that a party who invented
a technology outside the United States is deemed to have invented the
technology on the earlier of the date it introduced the invention in the
United States or the date it filed its patent application. In a filing with
the Securities and Exchange Commission, the SEC, BioChem Pharma stated that
prior to January 1, 1996, it conducted substantially all of its research
activities outside the United States. BioChem Pharma also stated that it
considered this to be a disadvantage in obtaining United States patents based
on patent applications filed before January 1, 1996 as compared to companies
that mainly conducted research in the United States. We do not know whether
Emory or BioChem Pharma was the first to invent the technology claimed in
their respective United States patent applications or patents. We also do not
know whether BioChem Pharma invented the technology disclosed in its patent
applications in the United States or introduced that technology in the United
States before the date of its patent applications.


      In foreign countries, the first party to file a patent application on a
technology, not the first to invent the technology, is entitled to patent
protection on that technology. We believe that Emory filed patent applications
disclosing Coviracil as a useful anti-HIV agent in many foreign countries before
BioChem Pharma filed its foreign patent applications on that technology.
However, BioChem Pharma has received patents in several foreign countries. In
addition, BioChem Pharma has filed patent applications on Coviracil and its uses
in certain countries in which Emory did not file patent applications. Emory has
opposed or otherwise challenged patent claims on Coviracil granted to BioChem
Pharma in Australia and Europe. Emory may not initiate patent opposition
proceedings in any other countries or be successful in any foreign proceeding
attempting to prevent the issuance of, revoke or limit the scope of patents
issued to BioChem Pharma. BioChem Pharma has opposed patent claims on Coviracil
granted to Emory in Europe, Japan, Australia and South Korea. BioChem Pharma may
make additional challenges to Emory patents or patent applications, which Emory
may not succeed in defending. Our sales, if any, of Coviracil for the treatment
of HIV may be held to infringe United States and foreign patent rights of
BioChem Pharma. Under the patent laws of most countries, a product can be found
to infringe a third party patent either if the third party patent expressly
covers the product or method of treatment using the product, or if the third
party patent covers subject matter that is substantially equivalent in nature to
the product or method, even if the patent does not expressly cover the product
or method. If it is determined that the sale of Coviracil for the treatment of
HIV infringes a BioChem Pharma patent, we would not have the right to make, use
or sell Coviracil for the treatment of HIV in one or more countries in the
absence of a license from BioChem Pharma. We may be unable to obtain such a
license from BioChem Pharma on acceptable terms or at all.

      HEPATITIS B. Burroughs Wellcome Co, Burroughs Wellcome, filed patent
applications in March 1991 and May 1991 in Great Britain on a method to treat
hepatitis B with FTC and purified forms of FTC, that include Coviracil.
Burroughs Wellcome filed similar patent applications in other countries,
including the United States. Glaxo subsequently acquired Burroughs Wellcome's
rights under those patent applications. Those patent applications were filed in
foreign countries prior to the date Emory filed its patent application on the
use of Coviracil to treat hepatitis B. Burroughs Wellcome's foreign patent
applications, therefore, have priority over those filed by Emory. In July 1996,
Emory instituted litigation against Glaxo in the United States District Court to
obtain ownership of the patent applications filed by Burroughs Wellcome,
alleging that Burroughs Wellcome converted and misappropriated Emory's invention
and property and that an Emory employee is the inventor or a co-inventor of the
subject matter covered by the Burroughs Wellcome patent applications. In May
1999, Emory and Glaxo settled the litigation, and we became the exclusive
licensee of the United States and all foreign patent applications and patents
filed by Burroughs Wellcome on the use of Coviracil to treat hepatitis B. Under
the license and settlement agreements, Emory and we were also given access to
development and clinical data and drug substance held by Glaxo relating to
Coviracil.

      BioChem Pharma filed a patent application in May 1991 in Great Britain
also directed to a method to treat hepatitis B with FTC. BioChem Pharma filed
similar patent applications in other countries. In January 1996, BioChem Pharma
received a patent in the United States, which included a claim to treat
hepatitis B with Coviracil. The PTO has determined that there is a conflict
between the BioChem Pharma patent and patent applications filed

                                      5
<PAGE>

by Yale and Emory. The PTO is conducting an adversarial proceeding to determine
which party is entitled to the patent claims in dispute. Yale licensed all of
its rights relating to FTC, including Coviracil, and its uses claimed in this
patent application to Emory, which subsequently licensed these rights to us.
Neither Emory nor Yale may prevail in the adversarial proceeding, and the
proceeding may delay the decision of the PTO regarding Yale's and Emory's patent
applications. In addition, the PTO has recently added the U.S. patent
application filed by Burroughs Wellcome to this interference. Emory may not
pursue or succeed in any such proceedings. We will not be able to sell Coviracil
for the treatment of hepatitis B in the United States unless a United States
court or administrative body determines that the BioChem Pharma patent is
invalid or unless we obtain a license from BioChem Pharma. We may be unable to
obtain such a license on acceptable terms or at all. In July 1991, BioChem
Pharma received a United States patent on the use of 3TC to treat hepatitis B
and has corresponding patent applications pending or issued in foreign
countries. If it is determined that the use of Coviracil to treat hepatitis B is
not substantially different from the use of 3TC to treat hepatitis B, a court
could hold that the use of Coviracil to treat hepatitis B infringes these
BioChem Pharma 3TC patents.

      In addition, BioChem Pharma has filed in the United States and foreign
countries several patent applications on manufacturing methods relating to a
class of nucleosides that includes Coviracil, from which BioChem Pharma has
received several patents in the United States and many foreign countries. If we
use a manufacturing method that is covered by patents issued on any of these
applications, we will not be able to manufacture Coviracil without a license
from BioChem Pharma. We may not be able to obtain such a license on acceptable
terms or at all.

      DAPD


      We obtained our rights to DAPD under a license from Emory and the
University of Georgia Research Foundation, Inc., University of Georgia. Our
rights to DAPD include a number of issued United States patents that cover
composition of matter, a method for the synthesis of DAPD, methods for the
use of DAPD alone or in combination with certain other agents for the
treatment of hepatitis B, and a method to treat HIV with DAPD. We also have
rights to several foreign patents and patent applications that cover methods
for the use of DAPD alone or in combination with certain other anti-hepatitis
B agents for the treatment of hepatitis B. Additional foreign patent
applications are pending which contain claims for the use of DAPD to treat
HIV. Emory and the University of Georgia filed patent applications claiming
these inventions in the United States in 1990 and 1992. BioChem Pharma filed
a patent application in the United States in 1988 on a group of nucleosides
in the same general class as DAPD and their use to treat HIV, and has filed
corresponding patent applications in foreign countries. The PTO issued a
patent to BioChem Pharma in 1993 covering a class of nucleosides that
includes DAPD and its use to treat HIV. Corresponding patents have been
issued to BioChem Pharma in many foreign countries. Emory has filed an
opposition to patent claims granted to BioChem Pharma by the European Patent
Office based, in part, upon Emory's assertion that BioChem Pharma's patent
does not disclose how to make DAPD. In a patent opposition hearing held at
the European Patent Office on March 4, 1999, the Opposition Division ruled
that the BioChem Pharma European patent covering DAPD is valid. Emory has
appealed this decision to the European Patent Office Technical Board of
Appeal. If the Technical Board of Appeal affirms the decision of the
Opposition Division, or if Emory or Triangle do not pursue the appeal, we
would not be able to sell DAPD in Europe without a license from BioChem
Pharma, which may not be available on acceptable terms or at all. Patent
claims granted to Emory on a portion of the DAPD technology by the Australian
Patent Office have also been opposed by BioChem Pharma. We cannot assure you
that a court or administrative body would invalidate BioChem Pharma's patent
claims. Further, a sale of DAPD by us may infringe BioChem Pharma's patents.
If Emory, the University of Georgia and we do not challenge, or are not
successful in any challenge to, BioChem Pharma's issued patents, pending
patent applications, or patents that may issue from such applications, we
will not be able to manufacture, use or sell DAPD in the United States and
any foreign countries in which BioChem Pharma receives a patent without a
license from BioChem Pharma. We may not be able to obtain such a license from
BioChem Pharma on acceptable terms or at all.


      IMMUNOSTIMULATORY SEQUENCE PRODUCT CANDIDATES

      In March 2000, we entered into a licensing and collaborative agreement
with Dynavax Technologies


                                      6
<PAGE>

Corporation, Dynavax, to develop immunostimulatory polynucleotide sequence
product candidates for the prevention and/or treatment of serious viral
diseases, which became effective in April 2000. Immunostimulatory sequences are
polynucleotides which stimulate the immune system, and could potentially be used
in combination with our small molecule product candidates to increase the body's
ability to defend against viral infection. Immunostimulatory sequences can be
stabilized for use through internal linkages that do not occur in nature,
including phosphorothioate linkages.


      There are a number of companies which have patent applications and issued
patents, both in the United States and in other countries, that cover
immunostimulatory sequences and their uses. Coley Pharmaceuticals, Inc.
has filed several patent applications in this area and has in addition
exclusively licensed a number of patent applications on this subject from the
University of Iowa and Isis Pharmaceuticals, Inc. A number of these patent
applications have been issued. A number of companies have also filed patent
applications and have or are expected to receive patents on certain
polynucleotides and methods for their use and manufacture. We could be prevented
from making, using or selling any immunostimulatory sequence that is covered by
a patent issued to a third party company, unless we obtain a license from that
company, which may not be available on reasonable terms or at all.

      With respect to any of our drug candidates, litigation, patent
opposition and adversarial proceedings, including the currently pending
proceedings, could result in substantial costs to us. We expect the costs of
the currently pending proceedings to increase significantly during the next
several years. We anticipate that additional litigation and/or proceedings
will be necessary or may be initiated to enforce any patents we own or
in-license, or to determine the scope, validity and enforceability of other
parties' proprietary rights and the priority of an invention. Any of these
activities could result in substantial costs and/or delays to us. The outcome
of any of these proceedings may significantly affect our drug candidates and
technology. United States patents carry a presumption of validity and
generally can be invalidated only through clear and convincing evidence. As
indicated above, the PTO is conducting three adversarial proceedings in
connection with the emtricitabine technology. We cannot assure you that a
court or administrative body would hold our in-licensed patents valid or
would find an alleged infringer to be infringing. Further, the license and
option agreements with Emory, the University of Georgia, The Regents of the
University of California, The DuPont Pharmaceuticals Company, Mitsubishi
Chemical Corporation, and Dynavax provide that each of these licensors is
primarily responsible for any patent prosecution activities, such as
litigation, patent conflict proceeding, patent opposition or other actions,
for the technology licensed to us. These agreements also provide that in
general we are required to reimburse these licensors for the costs they incur
in performing these activities. Similarly, Yale and the University of
Georgia, the licensors of clevudine to Bukwang Pharm. Ind. Co., Ltd., are
primarily responsible for patent prosecution activities with respect to
clevudine at our expense. As a result, we generally do not have the ability
to institute or determine the conduct of any such patent proceedings unless
our licensors elect not to institute or to abandon such proceedings. If our
licensors elect to institute and prosecute patent proceedings, our rights
will depend in part upon the manner in which these licensors conduct the
proceedings. In any proceedings they elect to initiate and maintain, these
licensors may not vigorously pursue or defend or may decide to settle such
proceedings on terms that are unfavorable to us. An adverse outcome of these
proceedings could subject us to significant liabilities to third parties,
require disputed rights to be licensed from third parties or require us to
cease using such technology, any of which could adversely affect our
business. Moreover, the mere uncertainty resulting from the initiation and
continuation of any technology related litigation or adversarial proceeding
could adversely affect our business pending resolution of the disputed
matters.

      We also rely on unpatented trade secrets and know-how to maintain our
competitive position, which we seek to protect, in part, by confidentiality
agreements with employees, consultants and others. These parties may breach
or terminate these agreements, and we may not have adequate remedies for any
breach. Our trade secrets may also be independently discovered by
competitors. We rely on certain technologies to which we do not have
exclusive rights or which may not be patentable or proprietary and thus may
be available to competitors. We have filed applications for, but have not
obtained, trademark registrations for various marks in the United States and
other jurisdictions. We have received U.S. trademark registrations for our
corporate name and logo, Coactinon(R) and Coviracil(R). We have also received
registrations in the European Union for the mark Coactinon(R) and our
corporate logo. Our pending application in the European Union for the mark
CoviracilTM has been opposed by Orsem, based upon registrations for the mark
Coversyl in various countries, and Les Laboratories Serveir, based on a
French registration for the mark Coversyl. We do not believe that the marks
Coviracil and Coversyl are confusingly similar, but, in the event


                                      7
<PAGE>

they are found to be confusingly similar, we may need to adopt a different
product name for emtricitabine in the applicable jurisdictions. Several other
companies use trade names that are similar to our name for their businesses. If
we are unable to obtain any licenses that may be necessary for the use of our
corporate name, we may be required to change our name. Our management personnel
were previously employed by other pharmaceutical companies. The prior employers
of these individuals may allege violations of trade secrets and other similar
claims relating to their drug development activities for us.

WE ARE SUBJECT TO EXTENSIVE GOVERNMENT REGULATION AND MAY FAIL TO RECEIVE
REGULATORY APPROVAL WHICH COULD PREVENT OR DELAY THE COMMERCIALIZATION OF OUR
PRODUCTS.


      In addition to preclinical testing, clinical trials and other approval
procedures for human pharmaceutical products, we are subject to numerous
other regulations covering the development of pharmaceutical products. These
regulations include, for example, domestic and international regulations
relating to the manufacturing, safety, labeling, storage, record keeping,
reporting, marketing and promotion of pharmaceutical products. We are also
regulated with respect to laboratory practices, safe working conditions and
the use and disposal of hazardous substances, including radioactive compounds
and infectious disease agents used in connection with our development work.
The requirements vary widely from country to country. We expect the process
of obtaining these approvals and complying with appropriate government
regulations to be time consuming and expensive. Even if our drug candidates
receive regulatory approval, we may still face difficulties in marketing and
manufacturing those drug candidates. Further, any approval may require
postmarketing studies or other conditions. The approval of any of our drug
candidates may limit the indicated uses of the drug candidate. A marketed
product, its manufacturer and the manufacturer's facilities are subject to
continual review and periodic inspections. The discovery of previously
unknown problems with a product, manufacturer or facility may result in
restrictions on the product or manufacturer, including withdrawal of the
product from the market. The failure to comply with applicable regulatory
requirements can, among other things, result in:


      o  fines,
      o  suspended regulatory approvals,
      o  refusal to approve pending applications,
      o  refusal to permit exports from the United States,
      o  product recalls,
      o  seizure of products,
      o  injunctions,
      o  operating restrictions, and
      o  criminal prosecutions.

      In addition, adverse clinical results by others could negatively impact
the development and approval of our drug candidates. Some of our drug candidates
are intended for use as coactive therapy with one or more other drugs, and
adverse safety, effectiveness or regulatory developments in connection with such
other drugs will also have an adverse effect on our business.

INTENSE COMPETITION MAY RENDER OUR DRUG CANDIDATES NONCOMPETITIVE OR OBSOLETE.

      We are engaged in segments of the drug industry that are highly
competitive and rapidly changing. Any of our current drug candidates that we
successfully develop will compete with numerous existing therapies. In addition,
many companies are pursuing novel drugs that target the same diseases we are
targeting. We believe that a significant number of drugs are currently under
development and will become available in the future for the treatment of HIV and
hepatitis B. We anticipate that we will face intense and increasing competition
as new products enter the market and advanced technologies become available. Our
competitors' products may be more effective, or more effectively marketed and
sold, than any of our products. Competitive products may render our products
obsolete or noncompetitive before we can recover the expenses of developing and
commercializing our drug candidates. Furthermore, the development of a cure or
new treatment methods for the diseases we are targeting could render our drug
candidates noncompetitive, obsolete or uneconomical. Many of our competitors:

                                      8

<PAGE>

      o  have significantly greater financial, technical and human resources
         than we have and may be better equipped to develop, manufacture and
         market products,
      o  have extensive experience in preclinical testing and clinical trials,
         obtaining regulatory approvals and manufacturing and marketing
         pharmaceutical products, and
      o  have products that have been approved or are in late stage development
         and operate large, well-funded research and development programs.

      Smaller companies may also prove to be significant competitors,
particularly through collaborative arrangements with large pharmaceutical and
biotechnology companies. Academic institutions, governmental agencies and other
public and private research organizations are also becoming increasingly aware
of the commercial value of their inventions and are more actively seeking to
commercialize the technology they have developed.

      If we successfully develop and obtain approval for our drug candidates, we
will face competition based on the safety and effectiveness of our products, the
timing and scope of regulatory approvals, the availability of supply, marketing
and sales capability, reimbursement coverage, price, patent position and other
factors. Our competitors may develop or commercialize more effective or more
affordable products, or obtain more effective patent protection, than we do.
Accordingly, our competitors may commercialize products more rapidly or
effectively than we do, which could hurt our competitive position.

BECAUSE WE FACE RISKS RELATED TO OUR LICENSE AND OPTION AGREEMENTS, WE COULD
LOSE OUR RIGHTS TO OUR DRUG CANDIDATES.

      We have in-licensed or obtained an option to in-license our drug
candidates under agreements with our licensors. These agreements permit our
licensors to terminate the agreements under certain circumstances, such as our
failure to achieve certain development milestones or the occurrence of an
uncured material breach by us. The termination of any of these agreements could
result in the loss of our rights to a drug candidate. Upon termination of most
of our license agreements, we are required to return the licensed technology to
our licensors. In addition, most of these agreements provide that our licensors
are primarily responsible for any patent prosecution activities, such as
litigation, patent conflict, patent opposition or other actions, for the
technology licensed to us. These agreements also provide that in general we are
required to reimburse our licensors for the costs they incur in performing these
activities. We believe that these costs as well as other costs under our license
and option agreements will be substantial and may increase significantly during
the next several years. Our inability or failure to pay any of these costs with
respect to any drug candidate could result in the termination of the license or
option agreement for the drug candidate.

BECAUSE WE MAY BE UNABLE TO SUCCESSFULLY MANUFACTURE OUR DRUG CANDIDATES, OUR
BUSINESS MAY NEVER ACHIEVE PROFITABILITY.

      We do not have any internal manufacturing capacity and we rely on third
party manufacturers for the manufacture of all of our clinical trial material.
We plan to expand our existing relationships or to establish relationships with
additional third party manufacturers for products that we successfully develop.
The terms of the Abbott Alliance provide that Abbott Laboratories, Abbott, will
manufacture all or a portion of our product requirements for those products that
are or become covered by the Abbott Alliance. We may be unable to maintain our
relationship with Abbott or to establish or maintain relationships with other
third party manufacturers on acceptable terms, and third party manufacturers may
be unable to manufacture products in commercial quantities on a cost effective
basis. Our dependence upon third parties for the manufacture of our products may
adversely affect our profit margins and our ability to develop and commercialize
products on a timely and competitive basis. Further, third party manufacturers
may encounter manufacturing or quality control problems in connection with the
manufacture of our products and may be unable to maintain the necessary
governmental licenses and approvals to continue manufacturing our products.

WE MAY BE UNABLE TO SUCCESSFULLY MARKET, SELL OR DISTRIBUTE OUR DRUG CANDIDATES.

                                      9
<PAGE>

      In the United States, we currently intend to market the drug candidates
covered by the Abbott Alliance in collaboration with Abbott and to market other
drug candidates that we successfully develop, that do not become part of the
Abbott Alliance, through a direct sales force. Outside of the United States, we
expect Abbott to market drug candidates covered by the Abbott Alliance and, for
any other drug candidates that we successfully develop that do not become part
of the Abbott Alliance, we intend to market and sell through arrangements or
collaborations with third parties. In addition, we expect Abbott to handle the
distribution and sale of drug candidates covered by the Abbott Alliance both
inside and outside the United States. With respect to the United States, our
ability to market the drug candidates that we successfully develop will be
contingent upon recruitment, training and deployment of a sales and marketing
force as well as the performance of Abbott under the Abbott Alliance. We may be
unable to establish marketing or sales capabilities or to maintain arrangements
or enter into new arrangements with third parties to perform those activities on
favorable terms. In addition, any such third parties may have significant
control or influence over important aspects of the commercialization of our drug
candidates, including market identification, marketing methods, pricing,
composition of sales force and promotional activities. We also may have limited
control over the amount and timing of resources that a third party may devote to
our drug candidates. Our business may never achieve profitability if we fail to
establish or maintain a sales force and marketing, sales and distribution
capabilities.

BECAUSE WE DEPEND ON THIRD PARTIES FOR THE DEVELOPMENT AND ACQUISITION OF DRUG
CANDIDATES, WE MAY NOT BE ABLE TO SUCCESSFULLY ACQUIRE ADDITIONAL DRUG
CANDIDATES OR COMMERCIALIZE OR DEVELOP OUR CURRENT DRUG CANDIDATES.


      We have engaged and intend to continue to engage third party contract
research organizations and other third parties to help us develop our drug
candidates. Although we have designed the clinical trials for our drug
candidates, the contract research organizations have conducted many of the
clinical trials. As a result, many important aspects of our drug development
programs have been and will continue to be outside of our direct control. In
addition, the contract research organizations may not perform all of their
obligations under arrangements with us. If the contract research
organizations do not perform clinical trials in a satisfactory manner or
breach their obligations to us, the development and commercialization of any
drug candidate may be delayed or precluded. We do not currently intend to
engage in drug discovery. Our strategy for obtaining additional drug
candidates is to utilize the relationships of our management team and
scientific consultants to identify drug candidates for in-licensing from
companies, universities, research institutions and other organizations. We
may not succeed in acquiring additional drug candidates on acceptable terms
or at all.


BECAUSE WE MAY NOT BE ABLE TO ATTRACT AND RETAIN KEY PERSONNEL AND ADVISORS, WE
MAY NOT SUCCESSFULLY DEVELOP OUR PRODUCTS OR ACHIEVE OUR OTHER BUSINESS
OBJECTIVES.

      We are highly dependent on our senior management and scientific staff,
including Dr. David Barry, our Chairman and Chief Executive Officer. We have
entered into employment agreements with each vice president of Triangle. Dr.
Barry's employment agreement contains certain non-competition provisions. In
addition, the employment agreements for each of the vice presidents provide for
certain severance payments which are contingent upon each vice president's
refraining from competition with Triangle. The loss of the services of any
member of our senior management or scientific staff may significantly delay or
prevent the achievement of product development and other business objectives.
Our ability to attract and retain qualified personnel, consultants and advisors
is critical to our success. In order to pursue our drug development programs and
marketing plans, we will need to hire additional qualified scientific and
management personnel. Competition for qualified individuals is intense and we
face competition from numerous pharmaceutical and biotechnology companies,
universities and other research institutions. We may be unable to attract and
retain these individuals, and our failure to do so would have an adverse effect
on our business.

HEALTH CARE REFORM MEASURES AND THIRD PARTY REIMBURSEMENT PRACTICES ARE
UNCERTAIN AND MAY ADVERSELY IMPACT THE COMMERCIALIZATION OF OUR PRODUCTS.

      The efforts of governments and third party payors to contain or reduce the
cost of health care will continue to affect the business and financial condition
of drug companies. A number of legislative and regulatory proposals

                                      10

<PAGE>

to change the health care system have been proposed in recent years. In
addition, an increasing emphasis on managed care in the United States has and
will continue to increase pressure on drug pricing. While we cannot predict
whether legislative or regulatory proposals will be adopted or what effect those
proposals or managed care efforts may have on our business, the announcement
and/or adoption of such proposals or efforts could have an adverse effect on our
profit margins and financial condition. Sales of prescription drugs depend
significantly on the availability of reimbursement to the consumer from third
party payors, such as government and private insurance plans. These third party
payors frequently require that drug companies give them predetermined discounts
from list prices, and they are increasingly challenging the prices charged for
medical products and services. Present coactive treatment regimens for the
treatment of HIV are expensive; published reports indicate the cost per patient
per year can exceed $13,000, and may increase as new combinations are developed.
These costs have resulted in limitations in the reimbursement available from
third party payors for the treatment of HIV infection, and we expect that
reimbursement pressures will continue in the future. If we succeed in bringing
one or more products to the market, these products may not be considered cost
effective and reimbursement to the consumer may not be available or sufficient
to allow us to sell our products on a competitive basis.

IF OUR DRUG CANDIDATES DO NOT ACHIEVE MARKET ACCEPTANCE, OUR BUSINESS MAY NEVER
ACHIEVE PROFITABILITY.

      Our success will depend on the market acceptance of any products we
develop. The degree of market acceptance will depend upon a number of factors,
including the receipt and scope of regulatory approvals, the establishment and
demonstration in the medical community of the safety and effectiveness of our
products and their potential advantages over existing treatment methods, and
reimbursement policies of government and third party payors. Physicians,
patients, payors or the medical community in general may not accept or utilize
any product that we may develop.

WE MAY NOT HAVE ADEQUATE INSURANCE PROTECTION AGAINST PRODUCT LIABILITY.

      Our business exposes us to potential product liability risks that are
inherent in the testing of drug candidates and the manufacturing and marketing
of drug products and we may face product liability claims in the future. We
currently have only limited product liability insurance. We may be unable to
maintain our existing insurance and/or obtain additional insurance in the future
at a reasonable cost or in sufficient amounts to protect against potential
losses. A successful product liability claim or series of claims brought against
us could require us to pay substantial amounts that would decrease our
profitability, if any.

WE MAY INCUR SUBSTANTIAL COSTS RELATED TO OUR USE OF HAZARDOUS MATERIALS.

      We use hazardous materials, chemicals, viruses and various radioactive
compounds in our drug development programs. Although we believe that our
handling and disposing of these materials comply with state and federal
regulations, the risk of accidental contamination or injury still exists. In the
event of such an accident, we could be held liable for any damages or fines that
result and any such liability could exceed our resources.

OUR CONTROLLING STOCKHOLDERS MAY MAKE DECISIONS WHICH YOU DO NOT CONSIDER TO BE
IN YOUR BEST INTEREST.


      As of June 30, 2000, our directors, executive officers and their
affiliates, excluding Abbott, owned approximately 12.5% of our outstanding
common stock and Abbott owned approximately 17.3% of our outstanding common
stock. Pursuant to the terms of the Abbott Alliance, Abbott has the right to
purchase additional amounts of our common stock up to a maximum aggregate
percentage of 21% of our outstanding common stock and has certain rights to
purchase shares directly from us in order to maintain its existing level of
ownership, also known as antidilution protection. One Abbott designee serves as
a member of our Board of Directors. As a result, our controlling stockholders
are able to significantly influence all matters requiring stockholder approval,
including the election of directors and the approval of significant corporate
transactions. This concentration of ownership could also delay or prevent a
change in control of Triangle that may be favored by other stockholders.


THE MARKET PRICE OF OUR STOCK MAY BE ADVERSELY AFFECTED BY MARKET VOLATILITY.

                                      11

<PAGE>

      The market price of our common stock is likely to be volatile and could
fluctuate widely in response to many factors, including:

      o  announcements of the results of clinical trials by
         us or our competitors,
      o  developments with respect to patents or proprietary
         rights,
      o  announcements of technological innovations by us or
         our competitors,
      o  announcements of new products or new contracts by us
         or our competitors,
      o  actual or anticipated variations in our operating results due to the
         level of development expenses and other factors,
      o  changes in financial estimates by securities analysts and whether our
         earnings meet or exceed such estimates,
      o  conditions and trends in the pharmaceutical and
         other industries,
      o  new accounting standards,
      o  general economic, political and market conditions
         and other factors, and
      o  the occurrence of any of the risks described in
         these "Risk Factors."

      In the past, following periods of volatility in the market price of the
securities of companies in our industry, securities class action litigation has
often been instituted against those companies. If we face such litigation in the
future, it would result in substantial costs and a diversion of management
attention and resources, which would negatively impact our business.


      In addition, if our stockholders sell a substantial number of shares of
our common stock in the public market, the market price of our common stock
could be reduced. As of June 30, 2000, there were 38,293,849 shares of common
stock outstanding, of which approximately 24,500,000 were immediately
eligible for resale in the public market without restriction. Holders of
approximately 6,850,000 shares have rights to cause us to register them for
sale to the public. We have filed registration statements to register the
sale of approximately 3,550,000 of these shares. On June 12, 2000, we filed a
registration statement on Form S-3 with the SEC for sale in the public market
substantially all of the 400,000 shares issued to former stockholders of Avid
Corporation, Avid, in March 2000. In addition, Abbott will have the right on
or after June 30, 2002 to cause us to register for resale in the public
market the 6,571,428 shares of common stock purchased at the closing of the
Abbott Alliance. Any such sales may make it more difficult for us to raise
needed capital through an offering of our equity or convertible debt
securities and may reduce the market price of our common stock.


ANTITAKEOVER PROVISIONS IN OUR CHARTER DOCUMENTS AND DELAWARE LAW COULD DELAY,
DEFER OR PREVENT A TENDER OFFER OR TAKEOVER ATTEMPT THAT YOU CONSIDER TO BE IN
YOUR BEST INTEREST.

      We have adopted a number of provisions that could have antitakeover
effects. On January 29, 1999, our Board of Directors, the Board, adopted a
preferred stock purchase rights plan, commonly referred to as a "poison pill."
The rights plan is intended to deter an attempt to acquire Triangle in a manner
or on terms not approved by the Board. Thus, the rights plan will not prevent an
acquisition of Triangle which is approved by the Board. Our charter authorizes
the Board to issue shares of undesignated preferred stock without stockholder
approval on terms as the Board may determine. Moreover, the issuance of
preferred stock may make it more difficult for a third party to acquire, or may
discourage a third party from acquiring, voting control of Triangle. Our bylaws
divide the Board into three classes of directors with each class serving a three
year term. These and other provisions of our charter and our bylaws, as well as
certain provisions of Delaware law, could delay or impede the removal of
incumbent directors and could make more difficult a merger, tender offer or
proxy contest involving Triangle, even if the events could be beneficial to our
stockholders. These provisions could also limit the price that investors might
be willing to pay for our common stock.

WE HAVE NOT DECLARED OR PAID ANY DIVIDENDS ON OUR COMMON STOCK.

      We have never declared or paid any cash dividends on our common stock, and
we currently do not intend to pay any cash dividends on our common stock in the
foreseeable future. We intend to retain our earnings, if any, for the operation
of our business.

                                      12

<PAGE>

                       WHERE YOU CAN FIND MORE INFORMATION

      We file reports, proxy statements and other information with the SEC. You
may read and copy any document we file at the SEC's public reference rooms in
Washington, D.C., New York, New York and Chicago, Illinois. Please call the SEC
at 1-800-SEC-0330 for further information on the public reference rooms. Our SEC
filings are also available to the public on the SEC's website at
http://www.sec.gov.

                      INFORMATION INCORPORATED BY REFERENCE

      The SEC allows us to "incorporate by reference" the information we file
with them, which means that we can disclose important information to you by
referring you to those documents. The information incorporated by reference is
considered to be part of this prospectus, and later information filed with the
SEC will update and supersede this information. We incorporate by reference the
documents listed below and any future filings we make with the SEC under Section
13(a), 13(c), 14, or 15(d) of the Securities Exchange Act of 1934 until our
offering is completed.

      1. Our Annual Report on Form 10-K for the fiscal year ended December 31,
         1999 (file no. 000-21589), including certain information in our
         Definitive Proxy Statement in connection with our 2000 Annual Meeting
         of Stockholders;

      2. Our Quarterly Report on Form 10-Q for the quarterly period ended March
         31, 2000 (file no. 000-21589);


      3. Our Quarterly Report on Form 10-Q for the quarterly period ended
         June 30, 2000 (file no. 000-21589);

      4. The description of our common stock contained in our Registration
         Statements on Form 8-A filed October 18, 1996, February 10, 1999, and
         June 18, 1999 (file no. 000-21589); and

      5. The description of our Preferred Stock Purchase Rights, contained in
         our Registration Statement on Form 8-A filed February 10, 1999, as
         amended on Form 8-A/A filed June 18, 1999 (file no. 000-21589),
         including any amendments or reports filed for the purpose of updating
         such descriptions.


      The reports and other documents that we file after the date of this
prospectus will update and supersede the information in this prospectus.

      You may request a copy of these filings, at no cost, by writing or
telephoning us at:

                        Triangle Pharmaceuticals, Inc.
                        4 University Place
                        4611 University Drive
                        Durham, North Carolina, 27707
                        (919) 493-5980
                        Attn:  General Counsel.

      YOU SHOULD RELY ONLY ON THE INFORMATION PROVIDED OR INCORPORATED BY
REFERENCE IN THIS PROSPECTUS. WE HAVE NOT AUTHORIZED ANYONE TO PROVIDE YOU WITH
DIFFERENT INFORMATION. THE SELLING STOCKHOLDERS ARE NOT AUTHORIZED TO MAKE AN
OFFER OF THESE SECURITIES IN ANY STATE WHERE THE OFFER IS NOT PERMITTED. YOU
SHOULD NOT ASSUME THAT THE INFORMATION IN THIS PROSPECTUS IS ACCURATE AS OF ANY
DATE OTHER THAN THE DATE ON THE FRONT OF THE DOCUMENT.

      We have received U.S. trademark registrations for our corporate name and
logo, Coactinon(R) and Coviracil(R). This prospectus also includes names and
trademarks of other companies.

                                 USE OF PROCEEDS

                                      13

<PAGE>

      We will not receive any of the proceeds from the sale of the shares by the
selling stockholders.

                              SELLING STOCKHOLDERS

      We are registering all 399,967 shares of common stock covered by this
prospectus on behalf of the selling stockholders named in the table below. We
issued all of the shares to the selling stockholders pursuant to an amendment
dated March 24, 2000 to the agreement and plan of reorganization, dated June 30,
1997, executed in connection with the merger of a wholly-owned subsidiary of
Triangle with and into Avid. We have registered the shares of common stock to
permit the selling stockholders and their pledgees, donees, transferees or other
successors-in-interest that receive their shares from a selling stockholder as a
gift, partnership distribution or other non-sale related transfer after the date
of this prospectus to resell the shares when they deem appropriate.


      We have agreed to prepare and file such amendments and supplements to the
Registration Statement as may be necessary to keep this Registration Statement
effective for 90 calendar days following its declaration of effectiveness and
we may continue to do so afterwards.


      The following table sets forth the name of each of the selling
stockholders, the number of shares owned by each of the selling stockholders,
the number of shares that may be offered under this prospectus, and the number
of shares of our common stock owned by each of the selling stockholders after
this offering is completed. None of the selling stockholders has had a material
relationship with us within the past three years other than as a result of the
ownership of the shares or other securities of Triangle. The number of shares in
the column "Number of Shares Being Offered" represent all of the shares that
each selling stockholder may offer under this prospectus. We do not know how
long the selling stockholders will hold the shares before selling them or if
they will sell them and we currently have no agreements, arrangements or
understandings with any of the selling stockholders regarding the sale of any of
the shares. The shares offered by this prospectus may be offered from time to
time by the selling stockholders named below.


      Unless otherwise indicated, each person has sole investment and voting
power with respect to the shares listed in the table, subject to community
property laws, where applicable. For purposes of this table, a person or group
of persons is deemed to have "beneficial ownership" of any shares which such
person has the right to acquire within 60 days. Percentage ownership is based on
38,293,849 shares of common stock of Triangle outstanding on June 30, 2000. For
purposes of computing the percentage of outstanding shares held by each person
or group of persons named below, any security which such person or group of
persons has the right to acquire within 60 days is deemed to be outstanding for
the purpose of computing the percentage ownership for such person or persons,
but is not deemed to be outstanding for the purpose of computing the percentage
ownership for other persons. This registration statement shall also cover any
additional shares of common stock which become issuable in connection with the
shares registered for sale hereby as a result of any stock dividend, stock
split, recapitalization or other similar transaction effected without the
receipt of consideration which results in an increaase in the number of
Triangle's outstanding shares of common stock.


<TABLE>
<CAPTION>
                                                      NUMBER        SHARES
                                         SHARES         OF       BENEFICIALLY
                                   BENEFICIALLY OWNED SHARES         OWNED
                                   PRIOR TO OFFERING   BEING    AFTER OFFERING
                                   NUMBER             OFFERED
   NAME OF SELLING STOCKHOLDER        (1)    PERCENT    (2)     NUMBER  PERCENT
<S>                               <C>        <C>     <C>      <C>       <C>
Forrest H. Anthony...............     136       *         60       76      *
BancBoston Ventures, Inc......... 118,021       *     57,222   60,176      *
Ralph G. Berglund................     169       *         74       95      *
Caroline DellaPenna..............       8       *          4        4      *
Sharon A. Manco..................     266       *        116      150      *
Louis R. Marlack.................      88       *         39       49      *
MDS Health Ventures Inc..........  81,475       *     37,931   43,544      *
Oxford Bioscience Partners LP....  94,468       *     44,883   49,294      *
Oxford Bioscience Partners
  (Bermuda) LP...................  27,418       *     13,052   14,274      *

                                      14

<PAGE>

George Raymond/Mary Ellen Raymond
  JTWROS.........................      39       *         18       21      *
Harold A. Shaub..................     278       *        122      156      *
Harold A. Shaub/Eileen B. Schaub,
  Trustees.......................      54       *         24       30      *
ARCH Development.................   3,607       *      1,787    1,820      *
Bruce Bailey.....................   5,793       *      2,869    2,894      *
Baruch Blumberg..................     541       *        268      273      *
Eugene Garfield..................  31,129       *     15,415   15,620      *
Gerlach and Co. (Saabro).........   7,216       *      3,574    3,642      *
Gerlach and Co. (Dumont).........   7,216       *      3,574    3,642      *
Gerlach and Co. (Saabro).........   2,188       *      1,084    1,104      *
GIMV.............................  64,950       *     32,166   32,784      *
Health Care and Bio. Ven. Fund
  (MDS)..........................  13,279       *      6,577    6,702      *
Barry Katz.......................     721       *        358      363      *
Mason Marlin Ltd.................   2,159       *      1,070    1,080      *
Dr. J. A. Milliken...............   1,082       *        536      546      *
MYCOsearch Inc...................   1,803       *        894      909      *
Industriforsikring AS (Norsk
  Hydro).........................  36,083       *     17,870   18,213      *
Oxford Bioscience Partners
  (Adjunct) LP...................  18,852       *      9,335    9,437      *
PSA International SA.............  18,040       *      8,935    9,105      *
Barry Roberts/Joanne Roberts.....     360       *        179      181      *
Rorer Trusts, Elizabeth Rorer,
  Trustee........................   3,607       *      1,787    1,820      *
Altamira Management Ltd. As Agent
  for A/C 40.....................  30,815       *     15,252   15,563      *
Altamira Management Ltd. As Agent
  for A/C 124....................  15,407       *      7,626    7,626      *
Altamira Management Ltd. As Agent
  for A/C 360....................  15,407       *      7,626    7,626      *
Bailey and Company, Inc..........   5,227       *      2,588    2,588      *
Banque Indo Suez.................     463       *        230      230      *
Banque Leu.......................   3,078       *      1,524    1,524      *
Credit Suisse....................   7,093       *      3,517    3,519      *
Carlo Gillet.....................   3,018       *      1,494    1,494      *
N.V. Biotech Fonds Vlaanderen....  61,623       *     30,500   30,500      *
The Health Care and Biotechnology
  Venture Fund...................  11,461       *      5,673    5,673      *
MDS Health Ventures International
  Limited........................  34,754       *     17,202   17,202      *
Montaine Fund NV.................   3,080       *      1,525    1,525      *
Industriforsikring A.S...........  32,351       *     16,012   16,012      *
Oxcal Venture Fund...............   6,161       *      3,050    3,050      *
Purling Holdings Limited.........   7,733       *      3,829    3,849      *
Marc Rebagliati..................   3,018       *      1,494    1,494      *

                                      15
<PAGE>

C. S. Rennie.....................   2,156       *      1,068    1,068      *
Sam Bailey.......................   5,227       *      2,588    2,588      *
S. B. S..........................   5,820       *      2,884    2,884      *
Terivian Enterprises Inc.........  19,949       *      9,874    9,874      *
Willcocks Investments Limited....   5,227       *      2,588    2,588      *
                                  -------------------------------------------
      TOTAL                       820,114     2.1%   399,967  420,147    1.1%
</TABLE>

----------
*     Represents beneficial ownership of less than one percent.
(1)   Includes shares held in escrow for the benefit of the selling stockholders
      pursuant to the agreement and plan of reorganization, dated June 30, 1997,
      as amended.
(2)   This registration statement also shall cover any additional shares of
      common stock which become issuable in connection with the shares
      registered for sale hereby by reason of any stock dividend, stock split,
      recapitalization or other similar transaction effected without the receipt
      of consideration which results in an increase in the number of our
      outstanding shares of common stock.

                              PLAN OF DISTRIBUTION

      The selling stockholders may sell the shares from time to time. The
selling stockholders will act independently of us in making decisions regarding
the timing, manner and size of each sale. The sales may be made on one or more
exchanges or in the over-the-counter market or otherwise, at prices and at terms
then prevailing or at prices related to the then current market price, or in
negotiated transactions. The selling stockholders may effect such transactions
by selling the shares to or through broker-dealers. The shares may be sold by
one or more of, or a combination of, the following:

      o     a block trade in which the broker-dealer will attempt to sell the
            shares as agent but may position and resell a portion of the block
            as principal to facilitate the transaction,
      o     purchases by a broker-dealer as principal and resale by such
            broker-dealer for its account under this prospectus,
      o     an exchange distribution in accordance with the rules of such
            exchange,
      o     ordinary brokerage transactions and transactions in which the broker
            solicits purchasers, and
      o     in privately negotiated transactions.

      To the extent required, this prospectus may be amended or supplemented
from time to time to describe a specific plan of distribution. In effecting
sales, broker-dealers engaged by the selling stockholders may arrange for other
broker-dealers to participate in the resales.

      The selling stockholders may enter into hedging transactions with
broker-dealers in connection with distributions of the shares or otherwise. In
these transactions, broker-dealers may engage in short sales of the shares in
the course of hedging the positions they assume with selling stockholders. The
selling stockholders also may sell shares short and redeliver the shares to
close out such short positions. The selling stockholders may enter into option
or other transactions with broker-dealers which require the delivery to the
broker-dealer of the shares. The broker-dealer may then resell or otherwise
transfer such shares under this prospectus. The selling stockholders also may
loan or pledge the shares to a broker-dealer. The broker-dealer may sell the
shares so loaned, or upon a default the broker-dealer may sell the pledged
shares under this prospectus.

      Broker-dealers or agents may receive compensation in the form of
commissions, discounts or concessions from selling stockholders. Broker-dealers
or agents may also receive compensation from the purchasers of the shares for
whom they act as agents or to whom they sell as principals, or both.
Compensation as to a particular broker-dealer might be in excess of customary
commissions and will be in amounts to be negotiated in connection with the sale.
Broker-dealers or agents and any other participating broker-dealers or the
selling stockholders may be deemed to be "underwriters" within the meaning of
Section 2(11) of the Securities Act of 1933, the Securities Act, in connection
with sales of the shares. Accordingly, any such commission, discount or
concession received by them and any profit on the resale of the shares purchased
by them may be deemed to be underwriting discounts or commissions under the
Securities Act. Because selling stockholders may be deemed to be "underwriters"
within the

                                      16
<PAGE>

meaning of Section 2(11) of the Securities Act, the selling stockholders will be
subject to the prospectus delivery requirements of the Securities Act. In
addition, any securities covered by this prospectus which qualify for sale
pursuant to Rule 144 promulgated under the Securities Act may be sold under Rule
144 rather than under this prospectus. There is no underwriter or coordinating
broker acting in connection with the proposed sale of shares by the selling
stockholders.

      The shares will be sold only through registered or licensed brokers or
dealers if required under applicable state securities laws. In addition, in
certain states the shares may not be sold unless they have been registered or
qualified for sale in the applicable state or an exemption from the registration
or qualification requirement is available and is complied with.

      Under applicable rules and regulations under the Exchange Act, any person
engaged in the distribution of the shares may not simultaneously engage in
market making activities with respect to our common stock for a period of two
business days prior to the commencement of such distribution. In addition, each
selling stockholder will be subject to applicable provisions of the Exchange Act
and the associated rules and regulations under the Exchange Act, including
Regulation M, which provisions may limit the timing of purchases and sales of
shares of our common stock by the selling stockholders. We will make copies of
this prospectus available to the selling stockholders and have informed them of
the need to deliver copies of this prospectus to purchasers at or prior to the
time of any sale of the shares.

      We will file a supplement to this prospectus, if required, to comply with
Rule 424(b) under the Securities Act upon being notified by a selling
stockholder that any material arrangements have been entered into with a
broker-dealer for the sale of shares through a block trade, special offering,
exchange distribution or secondary distribution or a purchase by a broker or
dealer. Such supplement will disclose:

      o     the name of each such selling stockholder and of the participating
            broker-dealer(s),
      o     the number of shares involved,
      o     the price at which such shares were sold,
      o     the commissions paid or discounts or concessions allowed to such
            broker-dealer(s), where applicable,
      o     that such broker-dealer(s) did not conduct any investigation to
            verify the information set out or incorporated by reference in this
            prospectus, and
      o     other facts material to the transaction.

      In addition, upon being notified by a selling stockholder that a donee or
pledgee intends to sell more than 500 shares, we will file a supplement to this
prospectus.

      We will bear all costs, expenses and fees in connection with the
registration of the shares. The selling stockholders will bear all commissions
and discounts, if any, attributable to the sales of the shares. The selling
stockholders may agree to indemnify any broker-dealer or agent that participates
in transactions involving sales of the shares against certain liabilities,
including liabilities arising under the Securities Act. The selling stockholders
have agreed to indemnify certain persons against certain liabilities in
connection with the offering of the shares, including liabilities arising under
the Securities Act.

                                  LEGAL MATTERS

      For purposes of this offering, Brobeck, Phleger & Harrison LLP, New York,
New York, is giving its opinion as to the validity of the shares.

                                     EXPERTS

      The financial statements incorporated in this prospectus by reference to
the Annual Report on Form 10-K of Triangle for the year ended December 31, 1999,
have been incorporated in reliance on the report of PricewaterhouseCoopers LLP,
independent accountants, given on the authority of that firm as experts in
auditing and accounting.

                                      17
<PAGE>

WE HAVE NOT AUTHORIZED ANY PERSON TO
MAKE A STATEMENT THAT DIFFERS FROM WHAT
IS IN THIS PROSPECTUS. IF ANY PERSON
DOES MAKE A STATEMENT THAT DIFFERS FROM
WHAT IS IN THIS PROSPECTUS, YOU SHOULD
NOT RELY ON IT. THIS PROSPECTUS IS NOT               399,967 Shares
AN OFFER TO SELL, NOR IS IT AN OFFER TO
BUY, THESE SECURITIES IN ANY STATE IN
WHICH THE OFFER OR SALE IS NOT
PERMITTED. THE INFORMATION IN THIS
PROSPECTUS IS COMPLETE AND ACCURATE AS
OF ITS DATE, BUT THE INFORMATION MAY
CHANGE AFTER THAT DATE.

                                                        TRIANGLE
                                                  PHARMACEUTICALS, INC.

                                                      COMMON STOCK

                                              -----------------------------
                                                       PROSPECTUS
                                              -----------------------------


                                                     AUGUST __, 2000


<PAGE>

                                     PART II
                     INFORMATION NOT REQUIRED IN PROSPECTUS

ITEM 14.  OTHER EXPENSES OF ISSUANCE AND DISTRIBUTION.

      The following table sets forth all expenses payable by the Registrant in
connection with the sale of the common stock being registered. All the amounts
shown are estimates, except for the registration fee.

<TABLE>
<S>                                                 <C>
      Registration Fee......................        $     720
      Printing and engraving expenses.......           15,000
      Legal fees and expenses...............           10,000
      Accounting fees and expenses..........            3,000
      Transfer Agent and Registrar Fees.....            1,000
      Miscellaneous Expenses................            1,000

            TOTAL...........................        $  30,720
                                                    ---------
</TABLE>

ITEM 15.  INDEMNIFICATION OF OFFICERS AND DIRECTORS.

      Section 145 of the Delaware General Corporation Law permits
indemnification of officers and directors of Triangle under certain conditions
and subject to certain limitations. Section 145 of the Delaware General
Corporation Law also provides that a corporation has the power to purchase and
maintain insurance on behalf of its officers and directors against any liability
asserted against such person and incurred by him or her in such capacity, or
arising out of his or her status as such, whether or not the corporation would
have the power to indemnify him or her against such liability under the
provisions of Section 145 of the Delaware General Corporation Law.

      Article VII, Section (i) of the Restated Bylaws of Triangle provides that
Triangle shall indemnify its directors and executive officers to the fullest
extent not prohibited by the Delaware General Corporation Law. The rights to
indemnity thereunder continue as to a person who has ceased to be a director,
officer, employee or agent and inure to the benefit of the heirs, executors and
administrators of the person. In addition, expenses incurred by a director or
officer in defending any civil, criminal, administrative or investigative
action, suit or proceeding by reason of the fact that he or she is or was a
director or officer of Triangle (or was serving at Triangle's request as a
director or officer of another corporation) shall be paid by Triangle in advance
of the final disposition of such action, suit or proceeding upon receipt of an
undertaking by or on behalf of such director or officer to repay such amount if
it shall ultimately be determined that he or she is not entitled to be
indemnified by Triangle as authorized by the relevant section of the Delaware
General Corporation Law.

      As permitted by Section 102(b)(7) of the Delaware General Corporation Law,
Article 5, Section (a) of Triangle's Second Restated Certificate of
Incorporation provides that a director of Triangle shall not be personally
liable for monetary damages for breach of fiduciary duty as a director, except
for liability (i) for any breach of the director's duty of loyalty to Triangle
or its stockholders, (ii) for acts or omissions not in good faith or acts or
omissions that involve intentional misconduct or a knowing violation of law,
(iii) under Section 174 of the Delaware General Corporation Law or (iv) for any
transaction from which the director derived any improper personal benefit.

      Triangle has entered into indemnification agreements with its directors
and executive officers. Generally, the indemnification agreements attempt to
provide the maximum protection permitted by Delaware law as it may be amended
from time to time. Under such additional indemnification provisions, however, an
individual will not receive indemnification for judgments, settlements or
expenses if he or she is found liable to Triangle (except to the extent the
court determines he or she is fairly and reasonably entitled to indemnity for
expenses), for settlements not approved by Triangle or for settlements and
expenses if the settlement is not approved by the court. The indemnification
agreements provide for Triangle to advance to the individual any and all
reasonable expenses (including legal fees and expenses) incurred in
investigating or defending any such action, suit or proceeding. In order to
receive an advance of expenses, the individual must submit to Triangle copies of
invoices presented to him or her for such expenses. Also, the individual must
repay such advances upon a final judicial decision that he or she

                                      II-1

<PAGE>

is not entitled to indemnification.

      The Registrant has an insurance policy covering the directors and officers
of the Registrant with respect to certain liabilities, including liabilities
arising under the Securities Act or otherwise.

ITEM 16.  EXHIBITS AND FINANCIAL STATEMENT SCHEDULES.

      (A)  EXHIBITS.


      EXHIBIT NO.     DESCRIPTION
      -----------     -----------
      +4.1            Instruments defining the rights of stockholders.
                      Reference is made to the Registration Statement on
                      Form  8-A, filed October 18, 1996 (file no.
                      000-21589), and the Registration Statement on Form
                      8-A, filed February 10, 1999 (file no. 000-21589), as
                      amended on June 18, 1999 (file no. 000-21589).
      +5.1            Opinion of Brobeck, Phleger & Harrison LLP
       23.1           Consent of PricewaterhouseCoopers LLP, Independent
                      Accountants
      +23.2           Consent of Brobeck, Phleger & Harrison LLP.  Reference
                      is made to Exhibit 5.1.
      +24.1           Power of Attorney. Reference is made to page II-4.


      +Previously filed.


ITEM 17.  UNDERTAKINGS.

      The undersigned Registrant hereby undertakes:

      (1) To file, during any period in which offers or sales are being made,
a post-effective amendment to this registration statement to include any
material information with respect to the plan of distribution not previously
disclosed in the registration statement or any material change to such
information in the registration statement;

      (2) That, for the purpose of determining any liability under the
Securities Act, each such post-effective amendment shall be deemed to be a new
registration statement relating to the securities offered therein, and the
offering of such securities at that time shall be deemed to be the initial bona
fide offering thereof;

      (3) To remove from registration by means of a post-effective amendment
any of the securities being registered which remain unsold at the termination of
the offering.

      (4) If the registrant is a foreign private issuer, to file a
post-effective amendment to the registration statement to include any financial
statements required by Rule 3-19 of Regulation S-X at the state of any delayed
offering or throughout a continuous offering. Financial statements and
information otherwise required by Section 10(a)(3) of the Securities Act need
not be furnished, provided, that the registrant includes in the prospectus, by
means of a post-effective amendment, financial statements required pursuant to
this paragraph (a)(4) and other information necessary to ensure that all other
information in the prospectus is at least as current as the date of those
financial statements. Notwithstanding the foregoing, with respect to
registration statements on Form F-3, a post-effective amendment need not be
filed to include financial statements and information required by Section
10(a)(3) of the Securities Act or Rule 3-19 of this chapter if such financial
statements and information are contained in periodic reports filed with or
furnished to the Commission by the registrant pursuant to section 13 or section
15(d) of the Securities Exchange Act of 1934 that are incorporated by reference
in the Form F-3.


                                      II-2

<PAGE>

      The undersigned Registrant hereby undertakes that, for purposes of
determining any liability under the Securities Act, each filing of the
Registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
Securities Exchange Act of 1934 (and, where applicable, each filing of an
employee benefit plan's annual report pursuant to Section 15(d) of the
Securities Exchange Act of 1934) that is incorporated by reference in the
Registration Statement shall be deemed to be a new registration statement
relating to the securities offered therein, and the offering of such securities
at that time shall be deemed to be the initial bona fide offering thereof.

      The undersigned Registrant hereby undertakes to deliver or cause to be
delivered with the Prospectus, to each person to whom the Prospectus is sent or
given, the latest annual report to security holders that is incorporated by
reference in the Prospectus and furnished pursuant to and meeting the
requirements of Rule 14a-3 or Rule 14c-3 under the Securities Exchange Act of
1934; and, where interim financial information required to be presented by
Article 3 of Regulation S-X are not set forth in the Prospectus, to deliver, or
cause to be delivered to each person to whom the Prospectus is sent or given,
the latest quarterly report that is specifically incorporated by reference in
the Prospectus to provide such interim financial information.

      Insofar as indemnification for liabilities arising under the Securities
Act may be permitted to directors, officers and controlling persons of Triangle
pursuant to the foregoing provisions, Delaware Corporation law, the Underwriting
Agreement or otherwise, the Registrant has been advised that in the opinion of
the Securities and Exchange Commission such indemnification is against public
policy as expressed in the Securities Act and is, therefor, unenforceable. In
the event that a claim for indemnification against such liabilities (other than
the payment by the Registrant of expenses incurred or paid by a director,
officer, or controlling person of the Registrant in the successful defense of
any action, suit, or proceeding) is asserted by such director, officer, or
controlling person in connection with the securities being registered hereunder,
the Registrant will, unless in the opinion of its counsel the question has been
settled by controlling precedent, submit to a court of appropriate jurisdiction
the question of whether such indemnification by it is against public policy as
expressed in the Securities Act and will be governed by the final adjudication
of such issue.

                                      II-3

<PAGE>

                                   SIGNATURES


      Pursuant to the requirements of the Securities Act, the Registrant
certifies that it has reasonable grounds to believe that it meets all of the
requirements for filing on Form S-3 and has duly caused this Registration
Statement to be signed on its behalf by the undersigned, thereunto duly
authorized, in the City of Durham, State of North Carolina, on the 24th day
of August, 2000.


                                    TRIANGLE PHARMACEUTICALS, INC.


                                    By:   /s/ DAVID W. BARRY
                                          ------------------------------------
                                          David W. Barry
                                          Chairman and Chief Executive Officer





      Pursuant to the requirements of the Securities Act, this Registration
Statement has been signed by the following persons in this capacities and on the
dates indicated:

         Signature                        Title
         ---------                        -----


    /s/ David W. Barry        Chairman of the Board and Chief    August 24, 2000
---------------------------    Executive Officer (Principal
      David W. Barry                Executive Officer)


    /s/ Chris A. Rallis        Director, President and Chief     August 24, 2000
---------------------------          Operating Officer
      Chris A. Rallis


  /s/ Robert F. Amundsen, Jr. Executive Vice President and       August 24, 2000
----------------------------- Chief Financial Officer (Principal
    Robert F. Amundsen, Jr.    Financial and Accounting Officer)


             *                           Director                August 24, 2000
---------------------------
     Anthony B. Evnin


             *                           Director                August 24, 2000
---------------------------
    Standish M. Fleming


             *                           Director                August 24, 2000
---------------------------
    Dennis B. Gillings


             *                           Director                August 24, 2000
---------------------------
     Arthur J. Higgins


             *                           Director                August 24, 2000
---------------------------
    Henry G. Grabowski


             *                           Director                August 24, 2000
---------------------------
      George McFadden


*By: /s/ Chris A. Rallis
---------------------------
    Chris A. Rallis
    Attorney-in-Fact



                                      II-4

<PAGE>

                                  EXHIBIT INDEX


EXHIBIT NO.     DESCRIPTION
-----------     -----------
+4.1            Instruments defining the rights of stockholders.
                Reference is made to the Registration Statement on
                Form  8-A, filed October 18, 1996 (file no.
                000-21589), and the Registration Statement on Form
                8-A, filed February 10, 1999 (file no. 000-21589), as
                amended on June 18, 1999 (file no. 000-21589).
+5.1            Opinion of Brobeck, Phleger & Harrison LLP.
 23.1           Consent of PricewaterhouseCoopers LLP, Independent
                Accountants.
+23.2           Consent of Brobeck, Phleger & Harrison LLP.  Reference
                is made to Exhibit 5.1.
+24.1           Power of Attorney. Reference is made to page II-4.


+Previously filed.