Data Enhances Understanding of ContraVir’s Complementary Anti-HBV Compounds Tenofovir Exalidex (TXL™) and CRV431
The data were presented today in separate poster presentations at
“The two EASL posters support ContraVir’s strategy of combining two drug candidates with distinct and complementary modes of action, an approach that may halt or slow the progression of chronic hepatitis B virus,” said
TXL™, a potent prodrug of the successful antiviral agent tenofovir, works by lowering infectious viral HBV DNA in the liver and blood. CRV431, a cyclophilin inhibitor, complements the activity of TXL™ by reducing levels of the hepatitis B surface antigen (HBsAg), a viral protein that is a marker of HBV infectivity and disease progression. CRV431 also impedes the binding of HBx, another key HBV protein, to cyclophilin A, an important cellular protein; together, HBx and HBsAg are considered essential to hepatitis B viral replication, disease progression, and pathogenesis of liver disease, including fibrosis and liver cancer. The inhibitory effect of CRV431 on the binding of these proteins as seen in in vitro testing potentially provides the environment for the patient’s immune system to disable the HBV virus and its products.
As part of today’s “HBV/HDV Experimental” EASL poster tour, Dr. Foster provided an overview of a poster entitled, “The cyclophilin inhibitor CRV431 prevents both cyclophilin A-HBx complex formation and HBV replication.” The poster demonstrated that CRV431 appears to exert an anti-HBV effect by interfering with the binding interaction between HBx and cyclophilin A, thereby reducing HBV replication.
In the other poster presentation, “CRV431 and CMX157: Anti-HBV combination effects in vitro between a cyclophilin inhibitor and a nucleotide prodrug,” Dr. Foster and colleagues reported that TXL™ and CRV431 synergistically suppress HBV DNA. Overall, the results suggest that combining TXL™ and CRV431 can be a viable therapeutic drug strategy, and that the two agents’ complementary actions may reasonably extend to drugs with other modes of activity.
“The synergistic effects of TXL™ and CRV431 may bring us closer to a ‘functional cure’ of HBV, whereby the virus remains suppressed following completion of drug therapy,” commented Dr. Foster. “Our combination approach may therefore facilitate progress toward the goal of eradicating HBV, potentially relieving patients of the worry of the long-term consequences of infection.”
ContraVir is a biopharmaceutical company focused on the development and commercialization of targeted antiviral therapies with a specific focus on developing a potentially curative therapy for hepatitis B virus (HBV). The Company is developing two novel anti-HBV compounds with complementary mechanisms of action. One compound, TXL™ is an analog of the antiviral drug Viread® (tenofovir disoproxil fumerate), and is currently in Phase 2a of development. TXL™ has demonstrated the potential for low, once-daily dosing and a low systemic exposure, thereby potentially reducing renal and bone side effects. CRV431, the other anti-HBV compound, is a next-generation cyclophilin inhibitor with a unique structure that increases its potency and selective index against HBV. ContraVir is also developing Valnivudine, an orally available nucleoside analogue prodrug; Valnivudine is currently in Phase 3 for the treatment of herpes zoster. In addition to direct antiviral activity, Phase 2 data suggest that Valnivudine has the potential to reduce the incidence of debilitating shingles-associated pain known as post-herpetic neuralgia (PHN). For more information visit www.contravir.com.
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