SCYNEXIS' SCY-635 Demonstrates Positive Antiviral Activity In Combination With Approved And Investigational Anti-HCV Agents

Main Category: Liver Disease / Hepatitis
Article Date: 04 Nov 2009 - 22:00 PST

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Drug discovery company SCYNEXIS, Inc. presented positive data from an in vitro study evaluating the antiviral activity of SCY-635 in combination with approved and investigational non-nucleoside polymerase inhibitors, nucleoside polymerase inhibitors, protease inhibitors, ribavirin and interferon alpha 2b. SCY-635 exhibited additive to synergistic antiviral activity when combined with each of the six compounds tested and all combinations exhibited greater-than-anticipated antiviral activity. SCY-635, a novel cyclophilin inhibitor, represents a new pharmacological class of inhibitors of hepatitis C virus (HCV) replication. The results were presented in a poster session at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston on November 3, 2009.

Dr. Yves Ribeill, President and Chief Executive Officer of SCYNEXIS, said: "SCY-635 has previously shown strong single-agent antiviral activity in a Phase 1b clinical study and has now also demonstrated promising antiviral activity when combined with a wide range of mechanistically diverse anti-HCV agents. These results provide a strong rationale for pursuing clinical evaluation of combination therapy with SCY-635. SCYNEXIS will initiate Phase 2 combination studies in the second quarter of 2010."

According to the study, SCY-635 demonstrated additive to synergistic activity when combined with interferon alpha and ribavirin, the current standards of care. SCY-635 also showed significant synergy when combined with nucleoside polymerase inhibitors and additive to synergistic activity when combined with non-nucleoside polymerase inhibitors. Additionally, the compound demonstrated additive to synergistic activity when combined with NS-3/4A protease inhibitors. No combination showed evidence of increased cell cytotoxicity. Importantly, evidence of hepatoprotection was observed in combination with the protease inhibitors, including telaprevir and boceprevir.

"There is a significant need for more effective treatments for HCV that work for a broader patient population and help overcome resistance issues," said Sam Hopkins, Chief Scientific Officer of SCYNEXIS. "SCY-635's novel cyclophilin inhibitor method-of-action, when used as part of a combination therapy regimen, may help overcome resistance and could also increase the percentage of patients that achieve a sustained virological response to therapy. If these positive results continue to be confirmed in further clinical studies, SCY-635 could play an important role in establishing a new standard of care for a wider spectrum of HCV patients."

In a prior Phase 1b 15-day monotherapy study, SCY-635 demonstrated highly clinically relevant single-agent activity in patients with genotype 1 HCV, with a 2.3 log10 reduction at day 15. All patients in the highest dose cohort experienced viral load reductions within 12-24 hours. SCY-635 was well tolerated, with no serious adverse events reported, no discontinuations and no dose-limiting toxicities.

About SCY-635 and SCYNEXIS' Cyclophilin Inhibitor Platform

SCY-635 represents a new class of therapeutic agents for the treatment of HCV infection. SCY-635 is the first candidate in a novel class of non-immunosuppressive cyclophilin inhibitors owned by SCYNEXIS. Cyclophilins are a family of enzymatic proteins that assist in the folding and transport of other proteins synthesized within a cell. Scientists at SCYNEXIS have synthesized derivatives of Cyclosporine A in which cyclophilin binding activity (which mediates anti-HCV activity) is separated from calcineurin binding activity (which mediates immunosuppression). A growing body of scientific evidence indicates that non-immunosuppressive analogs of Cyclosporine A may have applications in multiple therapeutic areas. Cyclophilins play a central role in the pathophysiology of chronic viral infection, neuro- and cardio- degenerative diseases. Cyclophilin inhibition therefore represents an attractive target for drug discovery and development.

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SCYNEXIS