SCYNEXIS' SCY-635 Demonstrates Impressive Barrier to Resistance in HCV Treatment
--Candidate requires virus to develop multiple mutations to establish resistance--
--Results presented in an oral presentation at EASL--
RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--Apr 15, 2010 - Drug discovery company SCYNEXIS, Inc. today presented data supporting an impressive resistance profile for SCY-635—a novel, oral cyclophilin inhibitor being studied for the treatment of hepatitis C virus (HCV) infection. In the study, SCYNEXIS demonstrated that the hepatitis C virus required multiple mutations across two separate proteins in order to establish resistance to SCY-635. The majority of HCV drugs on the market and in development require only one targeted viral mutation to establish resistance. The results were presented in an oral session entitled, “Resistance Selection Following 15 Days of Monotherapy with SCY-635 a Non-immunosuppressive Cyclophilin Inhibitor with Potent Anti-HCV Activity,” at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria.
“These latest findings greatly strengthen the promise of SCY-635 as an important new drug candidate for the treatment of HCV,” said Sam Hopkins, PhD, Chief Scientific Officer of SCYNEXIS. “Over the year, we have established that single-agent treatment with SCY-635 yields a clinically meaningful reduction in viral load while exhibiting a very favorable safety profile. We have shown that SCY-635 exhibits additive to synergistic antiviral activity when combined with both approved and leading investigational agents and now we have demonstrated that SCY-635 appears to present the hepatitis C virus with a much a higher barrier to resistance than current therapies in development.”
Previous Phase 1b studies demonstrated that single-agent SCY-635 was associated with a clinically meaningful decline in plasma viremia (group mean maximum decrease of 2.3 log10) and that the mean maximal decline was observed on the last day of the study, day 15, suggesting a high barrier to the development of viral resistance. For the resistance studies presented at EASL, SCYNEXIS conducted an in-depth analysis of samples of plasma virus from individuals who participated in the Phase 1b study to assess the extent to which prolonged SCY-635 monotherapy treatment is associated with markers of drug resistance.
Participants had either received placebo (n=3) or 900 milligrams daily of SCY-635 (n=6). Samples were obtained at three time points during the study—day 1 (immediately before treatment), day 15 (the final day of treatment) and day 22 (follow-up seven days after completing treatment). HCV-specific RNA was extracted from patient plasma and RT-PCR was performed using specific primers to amplify the NS5A and NS5B genetic regions, which encode key viral replication proteins. Both strands of the resulting PCR products were sequenced and sequences obtained on days 15 and 22 were compared against day 1 sequence data to assess for the emergence of resistance mutations. No treatment-associated mutations in NS5A were detected in any samples. Two subjects experienced treatment-associated mutations in NS5B, but neither patient showed evidence of virologic break-through during treatment. These data are consistent with previous in vitro studies which also indicate that multiple mutations in NS5A and NS5B are required to confer high level resistance to SCY-635.
“There is a significant need for more effective treatments for HCV that work for a broader patient population and help overcome resistance issues,” said Yves J. Ribeill, PhD, President and Chief Executive Officer of SCYNEXIS. “We become more confident every day that SCY-635 could play an important role in establishing a new standard of care for a wider spectrum of HCV patients and look forward to continuing studies to this end. SCYNEXIS will initiate a Phase 2a study of SCY-635 in treatment naïve genotype 1 HCV patients in combination with the standard of care in the second quarter of 2010 and we anticipate top-line results from this study by year-end.”
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.
SCYNEXIS is a premier drug discovery and development company delivering effective and innovative drug pipeline solutions to pharmaceutical and global health partners. Our record of success is demonstrated by the delivery of 11 pre-clinical and clinical drug candidates over the last 5 years. The Company, which is located in Research Triangle Park, North Carolina, is developing a proprietary internal pipeline based on cyclophilin inhibitors, a class of drugs that hold significant potential for the treatment of a broad range of diseases. Please visit our website at www.scynexis.com.
Contact: Media Contact:
MacDougall Biomedical Communications
Sarah Cavanaugh, 781-235-3060
Terry Marquardt, 919-544-8603
Posted: April 2010