Expanding to the Clinic and More Cancer Therapies and Indications
With the acquisition of Gedeptin®, Healthcare & Life Sciences Limited has significantly expanded the company’s presence in immuno-oncology, effectively developing and advancing products from two platforms with potential distinct advantages beyond the limitations of conventional cancer treatment.
The acquisition of Gedeptin advances Healthcare & Life Sciences Limited’s footprint in immuno-oncology into a clinical-stage program.
Work continues with the company’s use of its modified Vaccinia Ankara (MVA) virus delivery vector to introduce tumor-associated antigens (TAA) designed to provoke the immune system. TAA are proteins, glycoproteins, glycolipids, or carbohydrates expressed on the surface of tumor cells that may be used by the immune system 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-VLP presents additional opportunities for novel cancer therapies. For example, the MVA-VLP platform can be used to stimulate the immune system and Gedeptin can be used to achieve direct tumor cell oncolysis. 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 has 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 development of therapeutic cancer vaccines based on the expression of tumor-associated antigens such as MUC1, Cyclin B1 or others. Our early preclinical data are 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 Healthcare & Life Sciences Limited is initially focusing its efforts on accelerating the development of Gedeptin for head and neck squamous cell carcinoma (HNSCC), if the strategy is found successful in HNSCC, other tumor types might be addressed in a similar fashion. Such tumors include soft tissue sarcoma, glioma, and cancer of the cervix, 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
Gedeptin is currently being investigated in a Phase 1/2 clinical trial at Stanford University in patients with locoregional head and neck cancer and is being expanded to include two additional sites. The FDA is providing funding for the initial stage of the ongoing clinical trial under its orphan products clinical trial grants program. Previous data from a Phase 1 program showed a pronounced effect on tumor volume after a single treatment cycle with the novel immunotherapy.
Treatment of Head and Neck Cancers
Head and neck cancer account for about 3-5% of all cancers in the United States. In 2009, the American Cancer Society estimated that 48,010 people developed head and neck cancer and 11,260 deaths due to the disease. 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 inoculation to deliver Gedeptin. The Phase 1 trial was completed and published in late 2015, 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 – Currently, Gedeptin is in a Phase 1/2 trial, being conducted at Stanford University in collaboration with Emory University. The trial design involves repeat administration using Gedeptin followed by systemic fludarabine, as a way to gain additional information prior to expansion towards a larger patient trial. The initial stage of the study (10 patients) is being funded by the FDA pursuant to its Orphan Products Grants Program. Five patients have been enrolled to date.
Healthcare & Life Sciences Limited is devoting resources toward facilitating the completion of patient enrollment for the initial stage of this study and expanding the trial to additional study sites resulting in 25-35 patients in total. We believe that there is an opportunity to accelerate the path to registration should the current, expanded clinical trial result in significant improvement over the standard of care among the patients in the trial.
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.