SCYNEXIS Presents In Vitro Toxicity Study Suggesting that SCY-635 is Unique in the Cyclophilin Inhibitor Class
--Results presented in poster presentation at EASL--
RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--Apr 16, 2010 - Drug discovery company SCYNEXIS, Inc. today presented results from two separate studies of SCY-635—a novel, oral cyclophilin inhibitor being studied for the treatment of hepatitis C virus (HCV) infection—at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria. The first presentation outlined results from an in vitro study demonstrating that, unlike other cyclophilin inhibitors, SCY-635 is not associated with an increased risk of hyperbilirubinemia in 15-day clinical studies. These data suggest that SCY-635 may be uniquely positioned in the cyclophilin inhibitor class. The second presentation outlined the effects of SCY-635 in in vitro studies on collagen production and fibrosis and suggests that SCY-635 may have an anti-fibrotic effect independent of demonstrated anti-HCV activity. SCY-635 will enter Phase 2 studies in HCV in the second half of 2010.
“The results of our bilirubin transport studies demonstrate a potentially important differentiation among candidates within the cyclophilin class of drugs and further position SCY-635 as the leading cyclophilin inhibitor in development for the treatment of HCV,” said Yves Ribeill, PhD, Chief Executive Officer of SCYNEXIS. “Treatment-associated, potentially toxic elevations in total bilirubin had been reported in the literature following acute exposure of adults with chronic HCV infection to some cyclophilin inhibitor analogs. Importantly, this effect had not been observed in clinical studies of SCY-635 to date in patients with HCV. Based on the results of the study presented today, we believe that SCY-635 is a very weak inhibitor of the major drug transporter, MRP2, a conjugated bilirubin transporter, and, as a result, treatment with SCY-635 does not appear to interfere with the normal processing and transport of bilirubin in the liver or bloodstream. Additional clinical studies are planned to confirm this finding over a longer time period.”
In the poster presentation entitled, “In vitro Models for Assessing the Relative Risk of Hyperbilirubinemia Associated with Cyclophilin Inhibitor Therapy,” SCYNEXIS examined the qualitative relationship between drug-mediated inhibition of multidrug resistance protein 2 (MRP2) and treatment-associated hyperbilirubinemia in a rodent hepatocyte model. Data indicated that treatment with SCY-635, which is a weak inhibitor of MRP2, resulted in fewer indications of hyperbilirubinemia—including lower accumulation into hepatocytes, greater efflux into bile canaliculi and reduced inhibition of hepatic efflux transporters than the cyclosporin-based cyclophilin inhibitors NIM811 and Debio-025. The study suggests that hyperbilirubinemia liver toxicity is not a class effect, but may be the result of drug-mediated MRP2 inhibition.
SCYNEXIS also presented a second poster entitled “The Effects of SCY-635, a Non-immunosuppressive Cyclosporin Analog, on Stellate Cell Proliferation, Collagen Synthesis, TIMP-1 and Collagenase Production.” These data demonstrate a number of anti-fibrogenic properties for SCY-635 in isolated human and rat liver cells and suggest that the observed effect is mediated through the TGF-beta signaling pathway. Patients with HCV often develop fibrosis, or collagen generated scar tissue, on the liver and this early-stage study suggests that SCY-635 may have an anti-fibrotic effect independent of its demonstrated anti-HCV activity. The findings will continue to be explored in Phase 2 studies of SCY-635, which are expected to initiate in the second quarter of 2010.
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.
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MacDougall Biomedical Communications
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Terry Marquardt, 919-544-8603
Posted: April 2010