Cocrystal Pharma has announced that its investigational drug candidate CDI-988 demonstrates potent activity against emerging GII.17 norovirus variants, which have recently overtaken GII.4 as the dominant strain causing significant outbreaks across the United States and Europe in 2024-2025.
The company's proprietary structure-based platform technology enabled researchers to obtain high-resolution crystal structures of the GII.17 protease, confirming that CDI-988 binds to a highly conserved region with excellent potency comparable to its activity against previously dominant GII.4 variants.
"Norovirus is the most common cause of acute gastroenteritis worldwide, yet there are no approved antiviral treatments or vaccines available to combat it," said Sam Lee, Ph.D., Cocrystal's President and co-CEO. "Norovirus antiviral and vaccine development has been extremely challenging due to high diversity among variants that include 10 genogroups and 49 genotypes."
Global Burden of Norovirus
Norovirus represents a significant global health challenge, with an estimated 685 million cases and approximately 50,000 child deaths attributed to the virus annually worldwide. The economic impact is substantial, with societal costs estimated at $60 billion per year.
James Martin, Cocrystal's CFO and co-CEO, emphasized the urgency of their work: "We are addressing the urgent need for norovirus and other emerging viral outbreaks through our platform technology that facilitates the rapid, efficient development of potentially highly effective and safe direct-acting antivirals."
Novel Mechanism of Action
CDI-988 is a protease inhibitor specifically designed as a broad-spectrum antiviral inhibitor targeting a highly conserved region in the active site of 3CL viral proteases. This novel mechanism of action allows the compound to demonstrate activity against both noroviruses and coronaviruses.
The company has already completed a single-center, randomized, double-blind Phase 1 study in healthy adults evaluating safety, tolerability, and pharmacokinetics of orally administered CDI-988 compared with placebo. The study included a food-effect cohort to understand how the drug behaves under different consumption conditions.
Proprietary Technology Platform
Cocrystal's development approach leverages its proprietary structural biology capabilities, combined with expertise in enzymology and medicinal chemistry. The platform provides three-dimensional structures of inhibitor complexes at near-atomic resolution, offering immediate insights to guide structure-activity relationships.
This technology helps identify novel binding sites and allows for rapid turnaround of structural information through highly automated X-ray data processing and refinement. The goal is to develop best-in-class antiviral therapies with fast onset of action, shortened treatment time, favorable safety profiles, and effectiveness against all viral subtypes with a high barrier to resistance.
Clinical Development Plans
Following the successful Phase 1 results, Cocrystal plans to initiate a human norovirus challenge study in 2025 in the United States. This study will evaluate CDI-988 as a potential prevention and treatment option for norovirus infection, potentially positioning it as a first-in-class oral antiviral for this indication.
Dr. Lee highlighted the significance of their recent findings: "We are gratified to have determined the first crystal structure of GII.17 protease and demonstrated broad-spectrum antiviral activity of CDI-988 against newly circulating major norovirus GII.17 variants. Based on a novel mechanism of action and superior broad-spectrum antiviral activity, CDI-988 is a compelling candidate for advancement as a first-in-class oral antiviral to be used for both prevention and treatment of norovirus infection."
About Cocrystal Pharma
Cocrystal Pharma is a clinical-stage biotechnology company discovering and developing novel antiviral therapeutics that target the replication process of noroviruses, influenza viruses, coronaviruses (including SARS-CoV-2), and hepatitis C viruses. The company employs unique structure-based technologies and Nobel Prize-winning expertise to create first- and best-in-class antiviral drugs.
The company's approach to antiviral development addresses a critical gap in the treatment landscape. While norovirus is often perceived as causing only mild, self-limiting gastroenteritis, its impact on vulnerable populations such as young children, the elderly, and immunocompromised individuals can be severe and sometimes fatal. The lack of approved treatments or preventive vaccines has left healthcare providers with limited options beyond supportive care.
If successful in clinical development, CDI-988 could represent a significant advancement in the management of norovirus outbreaks, particularly in healthcare facilities, cruise ships, schools, and other settings where rapid spread can occur.
