Immunophotonics is a biotech company developing a synthetic biopolymer, IP-001, to potentiate asystemic immunotherapy via microwave (MWA) thermal tumor ablation for treatment of Hepatocellularcarcinoma (HCC). The goal of this SBIR Fast Track is to complete preclinical safety and efficacy testing tosupport 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 newcases in the U.S. in 2019. This rise is partly due to an increase in hepatitis-induced cirrhosis and non-alcoholicsteatohepatitis (NASH) associated with obesity and diabetes. Currently, hepatic transplant and surgicalresection 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 ablativetherapies like MWA are a standard of care alternative to surgeries for BCLC stage 0, A and a subset of stage BHCC patients. However, ablation targets only local tumors, and systemic tumoricidal effects on micro-metastasisare 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 responsethat can reduce local recurrence, eliminate metastases, and elicit long-term memory. Investigator-driven trialsin advanced breast cancer show a favorable toxicity profile and early signs of systemic efficacy, with somecomplete 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 & Bpatients and prolong progression-free survival by 50% and overall survival in stage B & C patients with regionaldisease. IP-001 could revolutionize the field of interventional oncology by transforming it into a means of earlyimmunotherapy 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-001in 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 HCCmodel Hepa1-6. In the Phase II segment, Immunophotonics will further determine 1) maximum tolerated doseof 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.
Public Health Relevance Statement: PROJECT NARRATIVE Immunophotonics proposes this IND-enabling research project for the development of a polymeric synthetic biomaterial, IP-001, to potentiate a systemic immunotherapy via microwave thermal tumor ablation for treatment of hepatocellular carcinoma. IP-001 aims to reduce recurrence post ablation and prolong overall survival in patients by eliciting immune control over systemic micro-metastases. It revolutionizes the field of interventional radiology by transforming it into a means of early immunotherapy that can be applied broadly to other solid cancers without disruption to the standard of care.
Project Terms: Interferon Type II ; Gamma interferon ; IFN-Gamma ; IFN-g ; IFN-γ ; IFNG ; IFNγ ; Immune Interferon ; Interferon Gamma ; Interferon-gamma ; lFN-Gamma ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Liver ; hepatic body system ; hepatic organ system ; Alcoholic Liver Cirrhosis ; Alcoholic Cirrhosis ; Alcoholic Hepatic Cirrhosis ; Portal Cirrhosis ; liver transplantation ; Hepatic Transplantation ; Liver Grafting ; Liver Transplant ; melanoma ; Malignant Melanoma ; Methods ; Methodology ; microwave electromagnetic radiation ; Microwave Electromagnetic ; Microwaves ; microwave radiation ; Mus ; Mice ; Mice Mammals ; Murine ; Neoplasm Metastasis ; Metastasis ; Metastasize ; Metastatic Lesion ; Metastatic Mass ; Metastatic Neoplasm ; Metastatic Tumor ; Secondary Neoplasm ; Secondary Tumor ; cancer metastasis ; tumor cell metastasis ; neutrophil ; Blood Neutrophil ; Blood Polymorphonuclear Neutrophil ; Marrow Neutrophil ; Neutrophilic Granulocyte ; Neutrophilic Leukocyte ; Polymorphonuclear Cell ; Polymorphonuclear Leukocytes ; Polymorphonuclear Neutrophils ; Obesity ; adiposity ; corpulence ; Patients ; Polymers ; Interventional radiology ; Rattus ; Common Rat Strains ; Rat ; Rats Mammals ; Recurrence ; Recurrent ; Research Personnel ; Investigators ; Researchers ; Safety ; Survival Rate ; Switzerland ; Time ; Tumor Antigens ; Tumor-Associated Antigen ; cancer antigens ; tumor-specific antigen ; United States ; Universities ; Liver Dysfunction ; Normal Range ; Normal Values ; Metastatic Neoplasm to the Lung ; Metastasis to the Lung ; Metastatic Tumor to the Lung ; lung metastasis ; metastasize to the lung ; pulmonary metastasis ; Investigational New Drug Application ; analytical method ; base ; Solid ; Clinical ; Phase ; Lesion ; Serum ; Blood Serum ; liver function ; CD8-Positive T-Lymphocytes ; CD8 Cell ; CD8 T cells ; CD8 lymphocyte ; CD8+ T cell ; CD8+ T-Lymphocyte ; CD8-Positive Lymphocytes ; T8 Cells ; T8 Lymphocytes ; Progression-Free Survivals ; chemical property ; Research Project Grants ; R-Series Research Projects ; R01 Mechanism ; R01 Program ; Research Grants ; Research Projects ; Oncology ; Oncology Cancer ; Collaborations ; longterm memory ; long term memory ; Frequencies ; Immunes ; Immune ; Contralateral ; Hepatic Neoplasm Secondary ; Hepatic metastasis ; Liver secondaries ; Liver secondary cancer ; Metastatic Tumor to the Liver ; Metastatic malignant neoplasm to liver ; liver metastases ; malignant liver neoplasm, specified as secondary ; metastasis in the liver ; metastasis to the liver ; metastasize to the liver ; metastatic cancer to liver ; metastatic liver ; metastatic liver neoplasm ; secondary liver malignancy ; secondary malignant liver neoplasm ; Metastatic Neoplasm to the Liver ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; Remission ; Disease remission ; Ablation ; meetings ; physical property ; animal data ; tumor growth ; synergism ; Toxicities ; Toxic effect ; thermal ablation ; thermal tumor ablation ; Thermal Ablation Therapy ; Immunomodulation ; immune modulation ; immune regulation ; immunologic reactivity control ; immunomodulatory ; immunoregulatory ; immunoregulation ; novel ; Reporting ; Abscission ; Extirpation ; Removal ; Surgical Removal ; resection ; Excision ; Maximal Tolerated Dose ; Maximally Tolerated Dose ; Maximum Tolerated Dose ; Genetic analyses ; genetic analysis ; Modeling ; response ; Intervention Strategies ; interventional strategy ; Intervention ; Dose ; Data ; MICMET ; Micromets ; Micrometastasis ; pre-clinical testing ; Preclinical Testing ; Regional Disease ; Cancer Etiology ; Cancer Cause ; research clinical testing ; Clinical Evaluation ; Clinical Testing ; clinical test ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Tumor Immunity ; anti-tumor immunity ; antitumor immunity ; cancer immunity ; Validation ; Monitor ; Development ; developmental ; Cirrhosis ; cirrhotic ; Treatment Efficacy ; intervention efficacy ; therapeutic efficacy ; therapy efficacy ; Outcome ; scale up ; Implant ; mouse model ; murine model ; tumor ; nonalcoholic steatohepatitis ; NASH ; non-alcohol induced steatohepatitis ; non-alcoholic steato-hepatitis ; non-alcoholic steatohepatitis ; nonalcoholic steato-hepatitis ; standard of care ; Biological Markers ; bio-markers ; biologic marker ; biomarker ; preclinical safety ; pre-clinical safety ; safety testing ; efficacy testing ; T cell response ; microwave ablation ; predictive marker ; predictive biomarkers ; predictive molecular biomarker ; Breast Cancer Patient ; Breast Tumor Patient ; Soft tissue sarcoma ; Immune checkpoint inhibitor ; Checkpoint inhibitor ; immune check point inhibitor ; PD-1 inhibitors ; PD1 inhibitors ; anti programmed cell death protein 1 inhibitor ; anti-PD-1 inhibitors ; anti-PD1 inhibitors ; Injections ; anti-PD-1 ; aPD-1 ; aPD1 ; anti programmed cell death 1 ; anti-PD1 ; anti-programmed cell death protein 1 ; antiPD-1 ; antiPD1 ; αPD-1 ; αPD1 ; advanced breast cancer ; advanced stage breast cancer ; Phase I/II Clinical Trial ; Phase 1/2 Clinical Trial ; Aftercare ; After Care ; After-Treatment ; post treatment ; Antigen-Presenting Cells ; accessory cell ; Antigens ; immunogen ; Biocompatible Materials ; Biomaterials ; biological material ; Biopolymers ; Biotechnology ; Biotech ; Blood ; Blood Reticuloendothelial System ; Blood Chemical Analysis ; Blood Chemical Analyses ; blood chemistry ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Cells ; Cell Body ; Chemistry ; Clinical Trials ; comorbidity ; co-morbid ; co-morbidity ; Cessation of life ; Death ; Dendritic Cells ; Veiled Cells ; Diabetes Mellitus ; diabetes ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Investigational Drugs ; Investigational New Drugs ; Feedback ; Goals ; Grant ; Growth ; Generalized Growth ; Tissue Growth ; ontogeny ; Health ; Hepatitis ; Primary carcinoma of the liver cells ; Hepatocarcinoma ; Hepatocellular Carcinoma ; Hepatocellular cancer ; Hepatoma ; Liver Cells Carcinoma ; liver carcinoma ; Immune system ; allergic/immunologic body system ; allergic/immunologic organ system ; Immunity ; Immunization ; Immunologic Sensitization ; Immunologic Stimulation ; Immunological Sensitization ; Immunological Stimulation ; Immunostimulation ; Immunotherapy ; Immune mediated therapy ; Immunologically Directed Therapy ; immune therapeutic approach ; immune therapeutic interventions ; immune therapeutic regimens ; immune therapeutic strategy ; immune therapy ; immune-based therapies ; immune-based treatments ; immuno therapy ;
