GeoVax's GEO-CM04S1 Vaccine Shows Superior T-Cell Response in CLL Patients, DSMB Ends Comparator Arm

GeoVax Labs, Inc. announced the publication of interim Phase 2 clinical data for its next-generation COVID-19 vaccine, GEO-CM04S1, 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, generating significantly stronger and more durable SARS-CoV-2-specific T-cell responses than BNT162b2 in patients with CLL, a population known for poor vaccine responsiveness.

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.

GEO-CM04S1's superior performance in enhancing cellular immune response against SARS-CoV-2 in individuals with CLL underscores its potential to fill a protection gap for profoundly immunocompromised patients. 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 is specifically designed to address this gap through its dual-antigen, MVA-based platform, which promotes robust, durable T-cell responses that are less impacted by immune dysfunction and viral variation.

The Phase 2 study enrolled 31 CLL patients previously vaccinated with mRNA vaccines, with 27 evaluable for primary analysis. The primary endpoint was a greater than or equal to 3-fold rise in antigen-specific IFN-y-secreting T cells at Day 56. No Grade greater than or equal to 3 adverse events were reported.

Key findings published in the British Journal of Haematology show that 40% of GEO-CM04S1 recipients met the primary endpoint versus 14.3% for BNT162b2. GEO-CM04S1 achieved higher Spike-specific IFN-y responses at Days 28, 56, and 84, and demonstrated durable activation of Nucleocapsid-specific T cells with approximately 10-fold higher N-specific CD4 T-cell activation versus BNT162b2, with responses maintained through Day 180. The vaccine generated broader immune engagement despite CLL-associated humoral defects, producing sustained N-IgG and a correlation between N-specific antibodies and T-cell activation.

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. 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 findings published in the British Journal of Haematology, combined with the DSMB's action, reinforce the value of GEO-CM04S1's differentiated profile. Immunocompromised individuals remain vulnerable and suboptimally protected from SARS-CoV-2, representing a critical unmet need. GEO-CM04S1's dual-antigen design stimulates immune responses that appear more durable and variant-resilient than single-antigen mRNA approaches. These segments represent a $30B+ annual potential commercial market.

GEO-CM04S1 is a dual-antigen MVA-vectored COVID-19 vaccine being evaluated in multiple Phase 2 trials, including a primary vaccination for immunocompromised individuals and 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. For more information about the current status of clinical trials and other updates, visit https://www.geovax.com.