Gedeptin® Development Programs
The mechanism of action for Gedeptin is applicable to a broad range of needle-accessible tumors (see “Gedeptin Technology Overview”). While GeoVax is initially focusing on development of Gedeptin for head and neck cancers, following the success of this unique therapy in this indication other tumor types will be addressed similarly. Such tumors may include soft tissue sarcoma, glioma, and cancers of the cervix, breast, and prostate among others, which represent a significant and unmet medical need.
Treatment of Head and Neck Cancers
Head and neck cancer accounts for approximately 4.5% of all cancers in the United States. Head and neck cancer is the 7th most common cancer worldwide and is increasing. Overall, this cancer is more common in men, African Americans, and individuals over the age of 45. The American Cancer Society estimates that there will be approximately 70,000 new head and neck cancer cases and 15,000 deaths in the US in 2023, and the World Health Organization estimates 400,000 deaths annually worldwide from head and neck cancer. Primary therapies include surgery, radiotherapy, and chemotherapy. Tumor recurrence develops in approximately one-third of patients and the prognosis for patients with recurrent or metastatic cancer is poor, with five-year survival rates ranging from 25% to 40%. Consequently, there has been considerable interest in investigating new therapies for this disease.
Head and neck cancer was selected as the first commercial target for Gedeptin, to take advantage of the obvious accessibility of certain forms (oral and pharyngeal being examples) and the significant number of cases diagnosed annually which will provide a large patient base from which to recruit trial participants.
Completed Phase 1 Clinical Trial: Based on promising anti-tumor activity observed in preclinical models, a Phase 1 clinical trial (PNP-001) in end-stage HNSCC was conducted, with directed intratumoral administration of Gedeptin. The Phase 1 trial included 12 patients and demonstrated excellent safety and efficacy. The pronounced effect on tumor volume after a single treatment cycle suggests that repeat administration of the therapy can be very effective in the treatment of local advanced head and neck cancer and other malignancies.
Completed Phase 1/2 Clinical Trial: A Phase 1/2 trial (PNP-002), evaluating the safety and efficacy of repeat cycles of Gedeptin therapy in patients with recurrent head and neck squamous cell carcinoma (HNSCC), with tumor(s) accessible for injection and no curable treatment options recently completed enrollment at the Stanford University Cancer Institute, the Emory University Winship Cancer Institute, and the Thomas Jefferson University Sidney Kimmel Cancer Center. The trial design involved repeat administration using Gedeptin followed by systemic fludarabine (prodrug). This initial Phase 1/2 clinical study was funded by the FDA pursuant to its Orphan Products Clinical Trials Grants Program.
During 2024, we convened a special clinical advisory board to conduct a comprehensive review of the PNP-002 trial results, together with the previously completed Phase 1 trial (PNP-001). This review concluded that Gedeptin demonstrated an acceptable safety and efficacy profile to support continued development.
Planned Phase 2 Clinical Trial: ICIs have become a cornerstone of treatment across multiple solid tumor indications; however, a substantial proportion of patients fail to achieve durable responses. GeoVax believes that Gedeptin’s localized tumor-debulking and immune-sensitizing mechanism may complement checkpoint inhibition by increasing antigen release and immune recognition within the tumor microenvironment.
We have initiated activities in support of a Phase 2 clinical study, evaluating Gedeptin therapy in combination with an approved ICI as first-line treatment of patients with squamous cell head and neck cancer eligible for curative surgery. The trial is designed to assess major pathological response (MPR) as well as associated immunologic and biomarker outcomes following two pre-surgical cycles of therapy, and event-free survival over a one-year period. Gedeptin’s tumor-targeting and immune-sensitizing mechanism may help overcome the limitations of checkpoint monotherapy by enhancing immune activation within the tumor microenvironment. Necessary planning activities are underway, including protocol development, manufacturing and CRO selection, with the trial anticipated to begin in the second half of 2027.
Orphan Drug Status: The FDA has granted orphan drug status to Gedeptin, for the intratumoral treatment of anatomically accessible oral and pharyngeal cancers, including cancers of the lip, tongue, gum, floor of the mouth, salivary gland, and other oral cavities. The orphan drug designation is awarded to drugs designed to treat a rare disease or condition that affects fewer than 200,000 people in the U.S., and it is applied specifically to novel therapeutics that represents a major improvement. Orphan drug status provides regulatory incentives, reduced fees, and a more rapid review by the FDA, and stipulates that competing therapies can be blocked from the market for up to seven years. Additionally, this status qualifies the drug sponsor for various development incentives, including tax credits for qualified clinical testing.