Late-stage development and de-risking of a novel monoclonal antibody immunotherapy for EGFR-positive solid cancers

Abstract The primary objective of this project is to develop therapeutic IgA to uniquely harness the tumor cytolytic potential of neutrophils to target EGFR-mutant non-small cell lung cancer (NSCLC), thereby enabling these patients to live better, longer lives. Toward this goal, TigaTx is developing TIGA-001, a first-in-class, IgA-based monoclonal antibody treatment for advanced/metastatic EGFR-positive NSCLC, with plans to initiate a first-in-human clinical trial. TigaTx has generated a robust data package around the TIGA-001 molecule, leading to its selection as our first development candidate. TIGA-001 has demonstrated excellent in vitro potency and in vivo efficacy, and is well tolerated in non-human primates with favorable safety and pharmacokinetic profiles. TIGA-001 utilizes our patented, structure-driven protein engineering to overcome the known manufacturing liabilities of natural IgA, enabling us to be the first to transform IgA into a clinically-relevant platform technology. In this project, we will progress our TIGA-001 candidate into CMC activities, in vitro pharmacology, and biomarker identification and assay development to support filing of an Investigational New Drug application with the FDA. Supported CMC activities will consist of vector generation through master cell bank establishment. Supported pharmacology studies will focus on in vitro safety assessment and studies to support GLP toxicology species selection. Biomarker assays developed from these studies will be incorporated into our first-in-human clinical trial to evaluate dose-PD response relationships, enable patient selection/enrichment, and otherwise inform clinical strategy. Because therapeutic IgA is a platform technology with potential to target a wide variety of tumor- associated antigens, demonstrating clinical proof of concept with our TIGA-001 program would not only benefit patients with EGFR-expressing tumors, but would also open the door to using this approach against other targets in a wide range of additional clinical settings.