PR Newswire; Wednesday July 1, 8:31 am EST

"We continue to be encouraged by the data generated from our anti-HIV drug candidates," said David W. Barry, M.D., Chairman and CEO of Triangle Pharmaceuticals. "We believe that the depth and breadth of our portfolio comprising two nucleoside reverse transcriptase (RT) inhibitors (FTC and DAPD), a non-nucleoside RT inhibitor (MKC-442), and a protease inhibitor of a new chemical class (DMP-450) will provide us with a wide degree of flexibility in addressing the future therapeutic needs of patients infected with this dreadful virus," he added.

At today's satellite symposium, Dr. Barry summarized progress on the Company's most advanced compound, MKC-442. Previous studies have shown a dose of 750 mg twice a day of MKC-442 suppresses the amount of HIV in the blood (viral load) by an average of 96% (1.4 log(10)) when given as monotherapy. "We have recently initiated clinical trials utilizing coactive therapy with MKC-442 to treat both newly diagnosed patients as well as those who have had incomplete or only temporary response to prior therapy," said Dr. Barry. "Two ongoing studies in drug-naive patients involve combinations of MKC-442 with either d4T and 3TC, or d4T and ddI. A third ongoing study in anti-retroviral- experienced patients includes the addition of nelfinavir with nucleosides as well as MKC-442. Triangle plans to initiate additional studies in 1998 to assess combinations with other agents, including non-nucleoside RT inhibitors. Studies with a pediatric liquid formulation of MKC-442 are also expected to begin later in the year."

Triangle also reported progress on one of its nucleoside RT inhibitor drug candidates, FTC, including data from the Phase I/II monotherapy study in infected patients. Dr. Barry stated that he was particularly pleased that data from all 41 patients confirmed FTC's potent activity and safety which was previously reported from a limited number of patients in the same study.

In the monotherapy FTC study, doses ranging from 25 mg twice a day to 200 mg twice a day were given for two weeks. (A brief duration of monotherapy exposure was selected to limit the development of resistance.) The drug was well tolerated and, at each dose regimen containing 200 mg or more per day, a 98% (1.75 log(10)) or greater viral suppression was observed. A single, once- a-day, 200 mg dose reduced the viral load by an average of 99% (1.92 log(10)).

"Such potent activity with once-a-day therapy is impressive and raises the possibility of more convenient dosing regimens that can facilitate patient adherence," said Dr. Barry. "Coactive studies with a variety of combinations of other anti-HIV drugs are scheduled to begin in the next few months and monotherapy studies in hepatitis B virus (HBV) have recently been initiated," he added.

Data were also presented on the in vitro anti-HIV and anti-hepatitis B virus activity of Triangle's drug candidate DAPD, a nucleoside analogue RT inhibitor which has a dioxolane structure not found in other anti-HIV or HBV RT inhibitors. In vitro studies with DAPD have shown a resistance pattern different from most other nucleosides. DAPD is activated by the cellular enzyme adenosine deaminase to be a potent and selective inhibitor of both HIV and HBV reverse transcriptase. It is synergistic in vitro against HIV with a wide range of nucleosides, non-nucleosides and protease inhibitors. DAPD is also synergistic with FTC and L-FMAU against HBV in vitro, and has shown good activity in the woodchuck model of hepatitis B. The Company plans to complete chronic toxicology studies this fall, with clinical studies initiated shortly thereafter.

During the symposium, Dr. Barry also updated Triangle's progress on DMP- 450, a protease inhibitor of a novel chemical class that differs from all marketed protease inhibitors. It is a symmetrical cyclic urea and thus has a straightforward synthesis and high solubility. Long-term toxicology studies have been completed and the drug has been well tolerated in Phase I human studies. Pharmacokinetic analysis indicates a twice daily dosing regimen is likely, and the Company expects that Phase II studies in combination with a variety of other anti-HIV agents will begin this year.

Dr. Barry also provided an update on the Company's potent anti-HBV compound, L-FMAU. Studies in the woodchuck model have shown that when L-FMAU was given at a dose of 10 mg/kg for 12 weeks, the virus did not return in the majority of animals for prolonged periods of time after the cessation of dosing. Molecular evidence of viral infection in the liver could no longer be detected between 4 and 12 weeks after treatment and remained undetectable for the entire 36-week post treatment observation period. Acute toxicology studies have shown a benign profile and long-term toxicology studies are scheduled to begin in the near future.

Triangle Pharmaceuticals, Inc., based in Durham, N.C., is engaged in the development of new drug candidates primarily in the antiviral area, with a particular focus on therapies for the human immunodeficiency virus, including AIDS, and hepatitis B virus. Prior to their employment with the Company, members of the Company's management team played instrumental roles in the identification, clinical development and commercialization of several leading antiviral therapies. Dr. Barry is also Chairman of the Inter-Company Collaboration for AIDS Drug Development. For more information about Triangle, visit the Triangle Pharmaceuticals' website at: http://www.tripharm.com.

Statements in this press release may constitute forward-looking statements and are subject to numerous risks and uncertainties, including the failure to successfully complete pivotal clinical trials, the Company's future capital needs, the inability to commercialize FTC and DAPD due to patent rights held by third parties, the Company's ability to obtain additional funding, patent protection and required regulatory approvals for its drug candidates, the development of competitive products by others, the costs of coactive therapy and the extent to which coactive therapy achieves market acceptance, the Company's success in identifying new drug candidates, acquiring rights to the candidates on favorable terms and developing any candidates to which the Company acquires any rights, and these and other risks detailed from time to time in the Company's filings with the SEC. The actual results may differ materially from those contained in this press release. The Company disclaims any obligations to update these statements in this press release.

SOURCE: Triangle Pharmaceuticals, Inc.

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