Biocryst Pharmaceuticals begins HIV trial in humans with oral formulation of BCX-34.

BIRMINGHAM, Ala.--(BW HealthWire)--April 30, 1997--

Preclinical Studies Support Novel Immunomodulatory

Therapeutic Approach

BioCryst Pharmaceuticals (Nasdaq: BCRX) today announced the initiation of a Phase I feasibility study using an oral formulation of its lead drug, BCX-34, for the treatment of HIV in combination with standard antiretroviral therapy. BCX-34 is a small-molecule drug that modulates the proliferation of T-cells. Based on preclinical studies, scientists at the University of Alabama at Birmingham (UAB) and BioCryst theorize that BCX-34 may reduce HIV load in the bloodstream by inhibiting the replication of infected T-cells. The study, which is being conducted under Michael S. Saag, M.D. at UAB, is designed to obtain safety, pharmacology and biological data.

"Plasma HIV load increases through the proliferation of infected T-cells, which replicate at a faster rate than healthy T-cells," said George M. Shaw, M.D., Ph.D., Professor of Medicine and Microbiology, and Deputy Director, Center for AIDS Research at UAB, who conducted the preclinical research using BCX-34 against HIV. "As BCX-34 acts selectively on replicating T-cells, and not on resting T-cells, it may preferentially target rapidly multiplying infected T-cells in vivo to help reduce viral load in HIV patients. Our in vitro research in peripheral blood cells infected with HIV showed that BCX-34 significantly inhibited viral replication."

Clinical research has shown that viral load in the bloodstream correlates with disease stage, can predict subsequent clinical outcome, and acts as a direct indicator of the effect of antiretroviral treatments. While potent combination antiviral drug therapy has led to significant clinical improvements in patients with late stage disease, it is not clear that these same effects can be achieved in earlier-stage patients where the benefit to risk ratio of combination antiretroviral therapy may be less. In addition, there is growing recognition that replication of infected T-cells plays an important role in sustaining HIV-1 production in vivo at all stages of disease, raising the possibility that inhibition of T-cell activation can potentially complement antiretroviral therapy. Still another potential advantage gained by inhibiting T-cell activation and HIV replication may come from a delay in the emergence of drug-resistant virus, an outcome that limits the effectiveness of all currently approved antiretroviral therapies. Thus, BCX-34 could potentiate the effectiveness of all currently available antiretroviral drugs and drug combinations.

"Unlike anti-viral therapies targeting HIV, BCX-34 acts against the virus' T-cell host and consequently should not be affected by drug resistance resulting from viral mutation," said George A. Omura, M.D., Vice President, Clinical Development and Medical Director at BioCryst. "Ongoing open label studies with oral BCX-34 in other indications have shown the drug to be safe and to have reversible immunosuppressant properties. We therefore believe it presents a safe and potentially effective approach to reducing viral load in HIV-infected patients.

"This particular trial will evaluate BCX-34 in patients with early stage disease in which a reversible change in T-cell counts should not compromise the patient's immune system, and where combination immunomodulatory and antiviral therapy may have the greatest clinical impact. Patients will be closely monitored through the treatment regimen to ensure that their T-cell counts remain stable," he added.

Cohorts of seven HIV-infected patients with CD4 T-cell counts greater than 400 cells/mm3 will be enrolled in the Phase I study. Five patients will be dosed with oral BCX-34 and two will receive placebo. Patients in the initial drug cohort will receive a daily dose totaling 20mg (10mg per dose twice daily) for 14 consecutive days, followed by a two week observation period, with an increasing dose to 40mg in a subsequent course. Over the course of the trial, subsequent cohorts will receive a higher dose level, until the maximum tolerated dose is established. Patients will also be treated with other antiretroviral drugs AZT and 3TC. BCX-34 therapy will be discontinued in any patient whose overall CD4 T-cell count decreases more than 25 percent from baseline.

"It is our hope that this feasibility study will duplicate the proof of principle obtained in preclinical studies and will support the clinical utility of oral BCX-34 as an anti-HIV therapy," said J. Claude Bennett, M.D., President and Chief Operating Officer of BioCryst. "HIV represents the third disease target for our oral BCX-34 clinical program targeting aberrant T-cell proliferation and autoimmune diseases. We are currently preparing IND applications for additional indications and may begin other clinical trials later this year."

BioCryst's lead drug, BCX-34, is in clinical trials with both topical and oral formulations. The Company is currently conducting two multi-center Phase III clinical trials with topical BCX-34 for the treatment of cutaneous T-cell lymphoma (CTCL) and psoriasis, and two Phase I/II clinical trials with an oral formulation of BCX-34 to treat T-cell cancers and psoriasis. These diseases and other disorders, including rheumatoid arthritis and transplant rejection, are associated with the proliferation of T-cells.

Founded in 1986, BioCryst Pharmaceuticals, Inc. designs and develops novel small-molecule pharmaceuticals using structure-based drug design, an approach to drug discovery that integrates advanced biology, biophysics and medicinal chemistry. The Company is developing drug treatments for immunological and viral diseases. In addition to its T-cell inhibition program, the Company is advancing two preclinical programs to develop drugs to inhibit the influenza neuraminidase enzyme associated with flu infection, and activation of the complement signaling pathway implicated in a number of immunological and cardiovascular diseases.

This press release contains projections or other forward-looking statements regarding future events or the future financial performance of the Company. These statements are only predictions and the actual events or results may differ materially. Please refer to the documents BioCryst files from time to time with the Securities and Exchange Commission, specifically BioCryst's most recent Form 10-K and Form 10-Q. These documents contain and identify important factors that could cause the actual results to differ materially from those contained in the projections or forward-looking statements.

CONTACT: BioCryst Pharmaceuticals, Inc.

John L. Higgins

Vice President, Corporate Development

205/444-4600

or

Burns McClellan, Inc.

James W. Heins (Media)

Jonathan M. Nugent (Investors)

212/505-1919