GeoVax Labs, Inc. announced the publication of interim Phase 2 clinical data showing its next-generation COVID-19 vaccine, GEO-CM04S1, generated significantly stronger and more durable SARS-CoV-2-specific T-cell responses than BNT162b2 in patients with chronic lymphocytic leukemia. The findings, published in the British Journal of Haematology, reveal that 40% of GEO-CM04S1 recipients met the study's primary immunologic endpoint compared to just 14.3% for the mRNA vaccine.
Following interim analysis, the trial's Data and Safety Monitoring Board ruled to discontinue the randomized, double-blind comparator arm after the mRNA vaccine failed to meet the predefined primary immunogenicity endpoint. Enrollment is now proceeding exclusively in a single-arm cohort receiving GEO-CM04S1, as previously described in GeoVax's clinical update at the European Hematology Association 2025 Conference. This decision underscores the vaccine's clinical relevance for immunocompromised individuals who generally respond suboptimally to vaccines designed to induce humoral responses.
The Phase 2 study involved CLL patients previously vaccinated with mRNA vaccines, with 31 enrolled and 27 evaluable for primary analysis. The primary endpoint measured a greater than or equal to 3-fold rise in antigen-specific IFN-y-secreting T cells at Day 56. GEO-CM04S1 demonstrated higher Spike-specific IFN-y responses at Days 28, 56, and 84, along with approximately 10-fold higher Nucleocapsid-specific CD4 T-cell activation compared to BNT162b2, with responses maintained through Day 180. No Grade greater than or equal to 3 adverse events were reported.
Kelly T. McKee, MD, MPH, Chief Medical Officer, stated that these results demonstrate GEO-CM04S1's ability to address the immune limitations of CLL patients by inducing strong, durable T-cell responses to both spike and nucleocapsid proteins of SARS-CoV-2. The vaccine's dual-antigen design stimulates immune responses that appear to be more durable and variant-resilient than single-antigen mRNA approaches, representing a purpose-built solution for high-risk patients.
The medical and commercial significance of these findings is substantial, with more than 40 million adults in the U.S. and 400 million globally having some degree of compromised immunity. Many of these individuals fail to mount meaningful responses to currently authorized COVID-19 vaccines, creating a critical unmet need that GEO-CM04S1 is specifically designed to address through its MVA-based platform. These segments represent a $30B+ annual potential commercial market, strengthening GeoVax's regulatory and partnering strategy as the company advances toward potential commercialization.
GEO-CM04S1 is being evaluated in multiple Phase 2 trials, including as a primary vaccine for immunocompromised individuals and as a booster vaccination for CLL patients. The vaccine has generated robust immune responses in difficult-to-vaccinate populations including CAR-T and stem-cell transplant recipients, who typically fail to respond well to first-generation vaccines. For more information about the current status of clinical trials and other updates, visit the company's website at https://www.geovax.com.
