Gigamune, Inc.

In Vivo Gene Delivery to Regulatory T Cells to Drastically Reduce the Cost of Regulatory T Cell Therapy - Project Summary Project Title: in Vivo Gene Delivery to Regulatory T Cells to Drastically Reduce the Cost of Regulatory T Cell Therapy Organization: Gigamune Inc. Pi: David Johnson, PH.D. Over 9,000 Patients Will Receive Liver Transplants This Year, and About 75% of Those Patients Will Survive at Least 5 Years. Long Term Immune Suppression Is Required for Nearly All Patients, But Most Immune Suppressants (e.g., Corticosteroids) Are Systemic Rather Than Targeted. Immune Suppressants Lead to Long-term Toxicities Such as Malignancy (5% Incidence), Lymphoproliferative Disorder (3% Incidence), and Infections. About 50% of Patients Never Tolerate the Transplant to the Point Where Immune Suppressants Can Be Removed. Adoptive Cell Therapies Wherein Chimeric Antigen Receptors (CARS) or T Cell Receptors (TCRS) Are Engineered Into Autologous T Cells Ex Vivo Have Shown Strong Clinical Efficacy and Safety. Regulatory T Cells Engineered With Cars (“car Tregs”) Are a Relatively New Concept Wherein Cars Are Used to Direct Antigen-specific Immune Suppression. Car-tregs Are Under Preclinical and Clinical Investigation for Indications Such as Transplant and Autoimmunity, With the Goal of Inducing Long-term Tolerance Without Toxicities. However, the Cost of Manufacturing Cell Therapies Is Hundreds of Thousands of Dollars Per Patient, Driving Total Per-patient Costs to Up to $1 Million Per Patient. Recent Pioneering Work Used Lipid Nanoparticles (LNPS) and Lentivirus (LVS) to Deliver Cars to T Cells in Vivo, Eliminating the Need for Manufacture of Engineered Cells Ex Vivo. Gigamune Has Developed a Novel Next- Generation Lentivirus Platform (gigalentitm) for in Vivo Delivery of Cars and TCRS Specifically to T Cells in Vivo. the Specific Aim of This Phase I Sbir Project Is to Use in Vitro Models to Assess the Translational Potential of Chimeric Antigen Receptor Gene Delivery to Regulatory T Cells for Liver Transplant Tolerance, at Drastically Reduced Cost Compared to Conventional Cell Therapy.