CC-31244

Program Discovery Preclinical Phase 1 Phase 2 Phase 3
Hepatitis C CC-31244 - University of MD
(Pan-genotypic NS5B NNI)
Discovery Phase complete
Preclinical Phase complete
Phase 1 Phase complete
Phase 2 Phase in progress
Phase 3 Phase not started
Hepatitis C CC-31244 - Hong Kong
(Pan-genotypic NS5B NNI)
Discovery Phase complete
Preclinical Phase complete
Phase 1 Phase complete
Phase 2 Phase in progress
Phase 3 Phase not started

CC-31244, a non-nucleoside polymerase inhibitor, is a potential best-in-class pan-genotypic inhibitor of NS5B polymerase for the treatment of hepatitis C infection. It has the potential to be an important component in an all-oral ultra-short duration HCV combination therapy.

CC-31244 is currently being evaluated in a Phase 2a clinical study. The Phase 2a open-label study is designed to evaluate the safety, tolerability and preliminary efficacy of CC-31244 with an approved HCV drug. Dr. Joel Chua, Institute of Human Virology, University of Maryland Baltimore, is the Principal Investigator of the study. Enrolled subjects will self-administer orally 400 mg of CC-31244 and a fixed dose combination of sofosbuvir and velpatasvir for 14 days. After 14 days the subjects will continue the treatment for another 4 weeks on the fixed dose combination of sofosbuvir and velpatasvir. Subjects will be followed up until 24 weeks after the last dose of sofosbuvir and velpatasvir to determine if they have achieved sustained virologic response (SVR). Primary and secondary efficacy endpoints are SVR at 12 weeks post-treatment (SVR12) and at 24 weeks post-treatment (SVR24), respectively.

The Company has also entered into a Clinical Trial Agreement for an investigator-initiated study of CC-31244 with the Humanity & Health Research Centre, Hong Kong, PR China. Under the Clinical Trial Agreement, the Phase 2a study of CC-31244 for the treatment of HepC will be sponsored and conducted by the Humanity & Health Research Centre, Hong Kong under the guidance of Dr. George Lau, MBBS (HKU), M.D. (HKU), FRCP (Edin, Lond), FHKAM (Med), FHKCP, FAASLD, Chairman of Humanity and Health Medical Centre, Hong Kong. As part of the agreement, Cocrystal will provide CC-31244, its lead product in development for HepC. Cocrystal's CC-31244 is an investigational, oral, potent, broad-spectrum replication inhibitor called a non-nucleoside inhibitor (NNI). It has a high barrier to drug resistance designed and developed using the Company's proprietary structure-based drug discovery technology. It is active against HCV genotypes 1-6 with no significant cytotoxicity in multiple cell types at high concentrations.

The Company previously reported positive data from the Phase 1a/1b trial of CC-31244 for the treatment of chronic hepatitis C infection. The Phase 1a/1b study was a randomized, placebo-controlled, double-blind trial designed to evaluate single and multiple ascending doses of CC-31244 for safety/tolerability, pharmacokinetics, and antiviral activity in hepatitis C infected patients. In Phase 1a, 30 healthy volunteers received single doses (20-400 mg) of CC-31244, and 12 healthy volunteers received repeated doses of CC-31244 (either 200 or 400 mg) for 7 days. In Phase 1b, 15 patients with hepatitis C genotype 1 infection received CC-31244 for 7 days (6, 400 mg daily; 6, 600 mg daily; 3, 200 mg twice daily).

As reported, there were no dose-limiting adverse events, study discontinuations due to adverse events, or serious adverse events. Viral load data showed that CC-31244 administered once daily (400 mg or 600 mg) or twice daily (200 mg) for 7 days had a substantial and durable antiviral effect, with an average hepatitis C RNA viral load decline from baseline of 1000-fold by Day 4. Interestingly, the mean viral load at 6 days after the last dose persisted in the range of 100-fold below baseline. Hepatitis C genotype 1b cell-based replicon assays using combinations of CC-31244 with other classes of hepatitis C drugs showed additive and synergistic effects of CC-31244, providing important information for ultra-short duration therapy cocktail regimens.


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