GeoVax Highlights Peer-Reviewed Research Supporting Gedeptin's Potential to Enhance Cancer Immunotherapy Responses

GeoVax Labs, Inc. (Nasdaq: GOVX), a clinical-stage biotechnology company developing immunotherapies and vaccines for solid tumors and infectious diseases, today highlighted results from a newly published peer-reviewed research article in JCI Insight supporting the potential for intratumoral Gene Directed Enzyme Prodrug Therapy (GDEPT) to enhance immune checkpoint inhibitor responses across metastatic solid tumors.

The article, titled “Broadening Activity of Checkpoint Blockade Agents by Intratumoral Nucleoside Cleavage,” provides important scientific validation supporting the biologic rationale underlying GeoVax’s Gedeptin immuno-oncology platform and its planned clinical development strategy evaluating Gedeptin in combination with immune checkpoint inhibitors.

The investigators reported results from studies evaluating the ability of E. coli PNP/F-araA, the therapeutic concept underlying Gedeptin, to both kill treated tumors and enhance immune checkpoint inhibitor activity against both treated and untreated tumors. A triple-negative breast cancer (TNBC-EMT6) cell line, known to be resistant to conventional treatment approaches including radiation, immune checkpoint inhibitors, anti-TGF-β therapy, and other modalities, was utilized for these studies.

Results from in vitro investigations demonstrated that E. coli PNP/F-araA treatment initiated a signaling cascade previously associated with immune sensitization and enhanced responsiveness to immune checkpoint inhibitors. In complementary in vivo studies, tumors expressing E. coli PNP were implanted and grown in BALB/c mice harboring TNBC. Treatment with F-araAMP, a prodrug of F-araA, resulted in complete regression and cure of the PNP-expressing tumors in all treated animals.

To evaluate whether PNP/F-araA therapy could enhance immune checkpoint inhibitor activity in otherwise resistant tumors, investigators administered subcurative doses of F-araAMP followed by treatment with immune checkpoint inhibitors. Significant reductions in tumor burden were observed following combination treatment, with complete tumor regressions reported in treated animals.

Importantly, immune checkpoint blockade of non-PNP-expressing parental tumors was also enhanced when a contralateral PNP-expressing tumor was treated with F-araAMP and induced to regress. This anti-tumor effect on distant, untreated tumors was observed following a single cycle of PNP/F-araAMP therapy.

These findings suggest that localized treatment of lesions with Gedeptin may broaden the anti-tumor activity of immune checkpoint inhibitors beyond just the directly treated lesions. The observation that responses were enhanced in distant untreated tumors is of particular scientific interest given the limited effectiveness of checkpoint blockade in many treatment-resistant tumor settings and supports further investigation of this approach in combination immunotherapy strategies.

“These findings substantially expand the scientific relevance of Gedeptin beyond localized tumor control,” said David Dodd, Chairman and Chief Executive Officer of GeoVax. “The data suggest that localized Gedeptin treatment may function as a force multiplier for checkpoint inhibitors by activating systemic anti-tumor immunity, disrupting immunosuppressive tumor microenvironments, and potentially broadening immune checkpoint inhibitor responses beyond directly treated tumors.”

“We believe these findings position Gedeptin not simply as an intratumoral therapy, but as a broader immune-sensitization and tumor microenvironment engineering platform with potential applicability across multiple solid tumors where immune checkpoint therapy alone remains insufficient,” continued Mr. Dodd.

The publication also references prior clinical experience with PNP-based gene therapy approaches, supporting the translational relevance and clinical lineage of the underlying therapeutic mechanism.

About Gedeptin: Gedeptin is GeoVax’s proprietary gene-directed enzyme prodrug therapy (GDEPT) platform under development for the treatment of solid tumors. The therapy is designed for intratumoral administration and utilizes a non-replicating adenoviral vector encoding purine nucleoside phosphorylase (PNP). Following administration of fludarabine, the PNP enzyme converts the prodrug into a potent localized cytotoxic compound within the tumor microenvironment.

Key characteristics of Gedeptin include: localized activation of the prodrug fludarabine into the potent cytotoxic compound F-Ade; strong bystander killing effect capable of destroying neighboring tumor cells even when only a small fraction are directly transduced; tumor microenvironment remodeling and immune-sensitizing properties that may enhance responsiveness to checkpoint inhibitors; potential systemic immune activation supported by preclinical evidence of anti-tumor effects in distant untreated lesions; and favorable safety observations demonstrated across prior Phase 1 and Phase 1/2a clinical studies.

GeoVax is advancing development plans to evaluate Gedeptin in combination with checkpoint inhibitors, including pembrolizumab-based regimens, with the goal of amplifying anti-tumor immune activation and broadening the therapy’s applicability across multiple solid tumor settings.

For more information, visit www.geovax.com.