GeoVax's GEO-CM04S1 Demonstrates Superior T-Cell Responses in CLL Patients, DSMB Ends Comparator Arm After mRNA Vaccine Failure

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 Research Letter in the British Journal of Haematology reports that GEO-CM04S1 met the study's primary immunologic endpoint, with 40% of recipients achieving the endpoint compared to 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.

The DSMB's decision to end the comparator arm and proceed exclusively with GEO-CM04S1 underscores the vaccine's clinical relevance for immunocompromised individuals. More than 40 million adults in the U.S. and 400 million globally have some degree of compromised immunity, many of whom fail to mount meaningful responses to currently authorized COVID-19 vaccines. GEO-CM04S1's superior performance in enhancing cellular immune response against SARS-CoV-2 in CLL patients, a population known for poor vaccine responsiveness, highlights its potential to fill this protection gap.

The Phase 2 study enrolled 31 CLL patients previously vaccinated with mRNA vaccines, with 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. Key findings published in the British Journal of Haematology show GEO-CM04S1 achieved approximately 10-fold higher nucleocapsid-specific CD4 T-cell activation compared to BNT162b2, with responses maintained through Day 180. The vaccine generated sustained N-IgG and demonstrated a correlation between N-specific antibodies and T-cell activation, while mRNA vaccination produced higher early RBD-IgG titers but limited cellular immunity.

GEO-CM04S1's dual-antigen design, targeting both spike and nucleocapsid proteins through an MVA-based platform, promotes robust, durable T-cell responses that appear less impacted by immune dysfunction and viral variation. This multi-antigen approach represents a significant advancement over single-antigen mRNA vaccines for immunocompromised populations. The findings reinforce the vaccine's value across multiple dimensions, addressing a critical unmet need for individuals who remain vulnerable and suboptimally protected from SARS-CoV-2 despite existing vaccination options.

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. David Dodd, Chairman & CEO, added that with more than 40 million immunocompromised Americans lacking durable protection from first-generation vaccines, GEO-CM04S1 represents a purpose-built solution for high-risk patients. The peer-reviewed publication strengthens the company's regulatory and partnering strategy as it advances toward potential commercialization in a market representing over $30 billion in annual commercial potential.