New Antiviral in Phase 2a Trial May Target H5N1 in Humans Exposed to Infected Cows

Cocrystal Pharma, Inc. (Nasdaq: COCP), based in Bothell, Washington, has announced promising in vitro results for its investigational antiviral drug, CC-42344. This novel, broad-spectrum antiviral has shown efficacy in inhibiting the activity of the PB2 protein of the highly pathogenic avian influenza A (H5N1) virus, recently identified in infected dairy cattle. The company is currently conducting a Phase 2a clinical trial to assess the safety, tolerability, and antiviral benefits of orally administered CC-42344 in subjects infected with influenza A, with expected topline results in the latter half of 2024.

CC-42344 represents a new class of antiviral medications designed to disrupt critical stages of the influenza A virus's replication and transcription processes. Using a proprietary structure-based platform, Cocrystal has developed a high-resolution crystal structure of the avian influenza A H5N1 PB2 protein, confirming that CC-42344 binds effectively to a highly conserved region of the PB2 protein. The in vitro data suggest that CC-42344's activity against avian H5N1 is consistent with its efficacy against other pandemic and seasonal influenza A strains.

"The validation of our broad-spectrum antiviral approach is crucial, especially in light of the absence of FDA-approved vaccines against this virus in humans," stated Sam Lee, PhD, President and co-CEO of Cocrystal. Lee noted that these findings support earlier preclinical data showing CC-42344’s potent activity against various influenza A strains, including those with emerging mutations. CC-42344 has demonstrated a high barrier to resistance owing to its unique mechanism of action as an inhibitor compound.

The Centers for Disease Control and Prevention (CDC) recently reported outbreaks of avian flu in the U.S., including the first human cases resulting from exposure to infected dairy cows. James Martin, CFO and co-CEO of Cocrystal, expressed concern over these developments, citing significant outbreaks in more than 100 dairy herds across 12 states. The CDC also reported additional human cases of avian influenza infection from dairy cow exposure in early June.

The World Health Organization (WHO) has recorded 889 cases of avian influenza A H5N1 and 463 deaths across 23 countries from 2003 to April 2024. The CDC reported the first case of highly pathogenic avian influenza A H5N1 in a Texas farmworker in April 2024, with subsequent cases in Michigan farmworkers. Studies analyzing blood samples from various age groups across the U.S. during recent flu seasons indicated extremely low or no population immunity to the H5N1 virus, whether or not individuals received a seasonal flu vaccination.

Cocrystal's determination of the high-resolution crystal structure of the avian influenza A (H5N1) PB2 protein revealed new mutations outside the PB2 active site. Subsequent studies confirmed that CC-42344 binds to this active site, showing high potency against the avian H5N1 PB2 protein in preliminary in vitro assays.

CC-42344 has advanced to Phase 2a trials following favorable safety and tolerability results from a Phase 1 study with healthy volunteers in Australia. The drug has demonstrated excellent antiviral activity against both pandemic and seasonal influenza A strains, including those resistant to existing treatments like Tamiflu® and Xofluza®. Cocrystal's proprietary structure-based drug discovery platform technology was instrumental in developing CC-42344, which binds to a crucial PB2 site in the influenza polymerase complex, essential for viral replication.

Cocrystal Pharma, Inc., a clinical-stage biotechnology firm, leverages unique structure-based technologies to develop antiviral drugs targeting the replication processes of various viruses, including influenza, coronaviruses, noroviruses, and hepatitis C. The company continues to innovate in the antiviral therapeutic landscape, aiming to deliver first- and best-in-class treatments.