Cocrystal Pharma, Inc. (Nasdaq: COCP) is extending enrollment in its Phase 2a human challenge study of CC-42344, an investigational oral influenza PB2 inhibitor, after unexpectedly low influenza infection rates were observed among study participants challenged with the H3N2 viral strain. The randomized, double-blind, placebo-controlled trial is being conducted at a single site in the United Kingdom to assess the safety, tolerability, pharmacokinetics, antiviral activity, and clinical measurements of CC-42344.
The decision to extend the trial comes despite the drug demonstrating a favorable safety and tolerability profile, with no serious adverse events or drug-related discontinuations reported to date. However, the low infectivity rate of the challenge influenza strain has hindered antiviral data analysis, making it difficult to determine clinical endpoints for evaluating the antiviral molecule.
Addressing Low Infectivity Rates
Sam Lee, Ph.D., Cocrystal’s President and co-CEO, expressed disappointment with the low infectivity rate but remained optimistic about CC-42344's potential. "While CC-42344 showed a favorable safety and tolerability profile, we’re disappointed by the low infectivity rate of the challenge influenza strain used in this study," Lee stated. "The establishment of robust influenza infection in healthy, uninfected study subjects is critical to determine clinical endpoints for evaluating antiviral molecules. The low infectivity obtained in this study hindered antiviral data analysis."
To address this issue, Cocrystal Pharma is collaborating with its clinical research organization to prepare a protocol amendment for approval by the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA). The goal is to extend enrollment in the study and ensure the necessary infection rates among enrolled subjects.
About CC-42344
CC-42344 represents a novel class of antiviral treatment designed to block a crucial step in the viral replication and transcription of pandemic and seasonal influenza A viruses. Discovered using Cocrystal’s proprietary structure-based drug discovery platform technology, CC-42344 has shown excellent in vitro antiviral activity against various influenza A strains, including those resistant to existing treatments like Tamiflu® and Xofluza®.
In June 2024, Cocrystal reported in vitro studies demonstrating that CC-42344 inhibited the activity of the PB2 protein in the new highly pathogenic avian influenza A (H5N1) PB2 protein recently identified in humans. The company initiated the Phase 2a human challenge study in December 2024, following authorization from the MHRA, building on favorable safety and tolerability results from a Phase 1 study in healthy subjects conducted in Australia in late 2022.
Influenza A: A Significant Global Health Threat
Influenza remains a major global health threat, with approximately 1 billion cases of seasonal influenza occurring worldwide each year, resulting in 3-5 million severe illnesses and up to 650,000 deaths. In the U.S. alone, about 8% of the population contracts influenza each season, contributing to an estimated $11.2 billion in direct and indirect costs annually.
The emergence of highly pathogenic avian influenza viruses and increasing resistance to approved influenza antivirals underscore the urgent need for new, effective treatment options. Cocrystal Pharma aims to address this unmet need with CC-42344, leveraging its unique mechanism of action and high barrier to resistance development.
Structure-Based Drug Discovery
Cocrystal’s structure-based platform technology plays a pivotal role in the discovery and development of novel antiviral agents. By providing a three-dimensional structure of inhibitor complexes at near-atomic resolution, the platform enables rapid turnaround of structural information and facilitates the identification of novel binding sites. This approach aims to develop best-in-class antiviral therapies with fast onset of action, shortened treatment times, and effectiveness against all viral subtypes, while also minimizing the risk of viral resistance.
