Cocrystal Pharma announced that its investigational broad-spectrum influenza PB2 inhibitor CC-42344 exhibits remarkable antiviral activity against the highly pathogenic H5N1 avian influenza A strain (A/Texas/37/2024), demonstrating approximately 1,000-fold greater potency than the current standard of care, Tamiflu.
Exceptional Antiviral Potency Against H5N1
The virology study revealed that CC-42344 achieved an EC50 of 0.003 µM against the H5N1 avian influenza virus, compared to Tamiflu's EC50 of 2.69 µM. This dramatic difference in potency positions CC-42344 as a potentially transformative treatment option for both pandemic and seasonal influenza infections.
The study specifically utilized the highly pathogenic H5N1 avian strain (influenza A/Texas/37/2024) and employed Tamiflu as a reference inhibitor to establish comparative efficacy. The results further confirmed previous structural and in vitro data demonstrating CC-42344's binding to the PB2 protein of the 2024 H5N1 avian influenza virus.
Mechanism of Action and Development Status
CC-42344 functions as a novel inhibitor that binds to a highly conserved active site of the PB2 protein, effectively disrupting the viral replication process. This mechanism of action represents a departure from existing influenza treatments and targets a critical component of viral reproduction.
The compound is currently in development as an oral treatment for pandemic avian and seasonal influenza A infections. Initial clinical data have shown a favorable safety and tolerability profile, with Phase 1 study results supporting further clinical evaluation for both pandemic and seasonal flu applications.
Addressing Critical Public Health Concerns
The timing of these results is particularly significant given the ongoing spread of H5N1 in U.S. dairy cattle since March 2024. The highly pathogenic avian H5N1 influenza virus was first confirmed in a dairy cow in Texas on March 25, 2024, and has continued to spread widely, causing several human cases.
There is growing concern that the H5N1 virus could adapt for human-to-human transmission, potentially resulting in an influenza pandemic. The Centers for Disease Control and Prevention has documented the first instance of likely mammal-to-human spread of this virus in April 2024, and reported the first human case without known occupational exposure to infected animals in September 2024.
Market Opportunity and Unmet Medical Need
According to company executives, influenza represents a major global health concern that may become increasingly challenging to treat as highly pathogenic avian viruses emerge and develop resistance to approved antivirals. In the United States, approximately 8% of the population contracts influenza each season, with the disease responsible for an estimated $11.2 billion in direct and indirect costs annually.
CDC analysis of blood samples from the 2021-2022 and 2022-2023 flu seasons revealed extremely low to no population immunity to clade 2.3.4.4b A (H5N1) viruses in the U.S. Notably, antibody levels remained low regardless of seasonal flu vaccination status, indicating that current seasonal flu vaccines do not provide protection against avian flu H5N1 viruses.
Leadership Perspective
"We are excited to share these H5N1 results that further validate our structure-based drug discovery platform technology and strengthen our position in developing treatments for influenza infection," said Sam Lee, PhD, President and co-CEO of Cocrystal Pharma. "These important antiviral data along with the favorable safety profile observed in a Phase 1 study support further clinical evaluation of CC-42344 for pandemic and seasonal flu."
James Martin, CFO and co-CEO of Cocrystal Pharma, emphasized the commercial potential: "We are developing a therapeutic candidate with the potential to address the multibillion-dollar influenza market."
Company Background
Cocrystal Pharma is a clinical-stage biotechnology company focused on discovering and developing novel antiviral therapeutics targeting the replication process of influenza viruses, coronaviruses (including SARS-CoV-2), noroviruses, and hepatitis C viruses. The company employs structure-based technologies and Nobel Prize-winning expertise to create first- and best-in-class antiviral drugs.
