ONCOLOGY
Expanding to the Clinic and More Cancer Therapies and Indications
With the acquisition of Gedeptin®, GeoVax expanded the company’s presence in oncology into clinical-stage development. The company is developing and advancing products utilizing two platforms with each offering potential advantages beyond the current limitations of conventional cancer treatment.
Work is progressing with using an MVA virus vector introducing tumor-associated antigens (TAA) designed to provoke the immune system to attack the tumor. TAA are proteins, glycoproteins, glycolipids, or carbohydrates expressed on the surface of tumor cells that the immune system may use to identify a malignant cell from a healthy, normal cell. It is well known that many cancers have ways to turn off or hide from the body's ability to find and identify important TAAs.
Furthermore, the anticipated synergy between Gedeptin and MVA vaccines targeting solid tumors presents additional opportunities for novel cancer therapies. For example, the MVA platform can be used to stimulate the immune system and Gedeptin can be used to achieve direct tumor cell oncolysis (i.e., the destruction of cancer cells). Both agents can potentially be combined with checkpoint inhibitors to reverse immune tolerance and drive long-lasting therapeutic responses.
The convenience, safety, and low toxicity of cancer vaccines emerging from these approaches have the potential to make them invaluable tools to be included in future immunotherapy approaches for treating various cancers.
GV-MVA-VLP™ and Gedeptin Development Programs
We believe our MVA vector platform is well-suited for the development of therapeutic cancer vaccines based on the expression of tumor-associated antigens such as MUC1, Cyclin B1 or others. Preclinical data thus far have been encouraging and we plan to further expand upon our efforts in this important area.
The mechanism of action for Gedeptin is applicable to a broad range of needle-accessible tumors. While GeoVax is initially focusing on accelerating the development of Gedeptin for advanced head and neck squamous cell carcinoma (HNSCC). Following the success of this unique therapy in HNSCC, other tumor types will be addressed similarly. Such tumors include soft tissue sarcoma, glioma, and cancers of the cervix, breast, and prostate among others, which represent a significant and unmet medical need.
MVA-VLP and Solid Tumor Cancers
Initial results with MVA-VLP-MUC1 candidates have been encouraging. We are using our MVA-VLP vaccine platform to express abnormal, aberrantly glycosylated forms of the cell surface-associated Mucin 1 (MUC1) protein that is associated with a wide range of cancers, including breast, colon, ovarian, prostate, pancreatic, and lung. The company has recently presented results from two preclinical programs. In a therapeutic evaluation, MVA-VLP-MUC1 in combination with anti-PD-1 resulted in a 57% reduction in tumor growth compared to untreated controls. In a preventive (“tumor recurrence”) model vaccination with MVA-VLP-MUC1 resulted in 100% prevention of tumor growth vs 100% tumor growth in the untreated cohort.
Gedeptin Development Programs
A phase 1/2 clinical trial investigating Gedeptin at Stanford University, Emory University and Thomas Jefferson University recently closed to additional patient enrollment. The trial design involved repeat administration using Gedeptin followed by systemic fludarabine, to gain additional information prior to expansion towards a larger patient trial. Previously, data from a Phase 1 program showed a pronounced effect on tumor volume after a single treatment cycle with the novel immunotherapy. The FDA provided funding for the Phase 1/2 clinical trial under its orphan products clinical trial grants program.
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 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.
Ongoing Phase 1/2 Clinical Trial: A Phase 1/2 trial (NCT03754933), 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). Expansion towards a larger, Phase 2 patient trial is anticipated. The FDA has granted Gedeptin orphan drug status for the intra-tumoral treatment of anatomically accessible oral and pharyngeal cancers, including cancers of the lip, tongue, gum, floor of mouth, salivary gland and other oral cavities. Also, this initial Phase 1/2 clinical study was funded by the FDA pursuant to its Orphan Products Clinical Trials Grants Program.
Following a formal review of the results of the Phase 1/2 Gedeptin study, discussions are anticipated with the FDA related to an expanded Phase 2 program with the focus on achieving an expedited registration pathway for use among the critically needed area of advanced head and neck cancer.
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.
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