Development of polymeric synthetic biomaterial IP-001 to potentiate asystemic immunotherapy of hepatocellular carcinoma via thermal ablation

Abstract: Immunophotonics is a biotech company developing a synthetic biopolymer, IP-001, to potentiate a systemic immunotherapy via microwave (MWA) thermal tumor ablation for treatment of Hepatocellular carcinoma (HCC). The goal of this SBIR Fast Track is to complete preclinical safety and efficacy testing to support an investigational new drug (IND) application based on the feedback from a meeting with the FDA. Significance: HCC is the fourth most common cause of cancer-related death worldwide, with 42,030 new cases in the U.S. in 2019. This rise is partly due to an increase in hepatitis-induced cirrhosis and non-alcoholic steatohepatitis (NASH) associated with obesity and diabetes. Currently, hepatic transplant and surgical resection provide the best opportunity for long term remission, but less than 20% of patients are eligible. Non- surgical candidates with regional disease only have a 10.8% five-year survival rate. Thermal liver ablative therapies like MWA are a standard of care alternative to surgeries for BCLC stage 0, A and a subset of stage B HCC patients. However, ablation targets only local tumors, and systemic tumoricidal effects on micro-metastasis are rare, leading to recurrence rate of around 70% after two years. Better therapies for HCC are needed. Product: IP-001 is intended for intratumoral injection immediately after thermal ablation (MWA). It acts by 1) localizing tumor antigens liberated by ablation and prolonging their availability to the immune system and 2) activating immune cells such as antigen-presenting cells. This results in a stronger systemic T cell response that can reduce local recurrence, eliminate metastases, and elicit long-term memory. Investigator-driven trials in advanced breast cancer show a favorable toxicity profile and early signs of systemic efficacy, with some complete responders achieving long-term remission. The company has received clinical trial application (CTA) approval in Switzerland to begin a Phase 1/2 clinical trial in melanoma and soft tissue sarcoma. Impact: In HCC patients who receive MWA ablation, IP-001 aims to lower recurrence by 50% in stage 0, A & B patients and prolong progression-free survival by 50% and overall survival in stage B & C patients with regional disease. IP-001 could revolutionize the field of interventional oncology by transforming it into a means of early immunotherapy that is broadly applicable to other solid cancers without disruption to the standard of care. Approach and Specific Aims: In the Phase I, Immunophotonics will generate feasibility data of MWA+ IP-001 in orthotopic rat HCC model H-4-II-E (in collaboration with Dr. Rob Martin at the University of Louisville) to 1) establish efficacy and generate data demonstrating heightened systemic immune stimulation against cancer, 2) explore potential synergism with systemic immunotherapy, i.e. checkpoint inhibitor anti-PD-1 in mouse HCC model Hepa1-6. In the Phase II segment, Immunophotonics will further determine 1) maximum tolerated dose of IP-001 for liver injection, 2) impacts of common comorbidity NASH/cirrhosis on treatment efficacy, and 3) will develop CMC methods for scaling up and analysis of the drug product.