ABSTRACT Multi-PIs: Yin, A (HAWA Therapeutics) and Yin, H (UGA) Muscle strain injury (also called pulled muscle or eccentric contraction-induced muscle injury) is a common health problem affecting everyone in daily life. A mildly strained muscle may recover completely within one to two weeks; whereas moderate-to-severe muscle strains usually result in a prolonged and incomplete recovery with persistent pain, myofiber atrophy, and fibrotic scar formation in the injured muscles. Although muscle strains are common, our current knowledge of the healing process and therapeutic approaches are very limited and ineffective. Our promising preliminary data demonstrate that a small-molecule inhibitor of hypoxia-inducible factor 2 alpha (HIF2A) can significantly improve the muscle regeneration and functional recovery after moderate/severe muscle strains in animal models. These data support therapeutic applications of HIF2A inhibitor for treating moderate-to-severe muscle strains. The ultimate goal of HAWA Therapeutics is to commercialize topical and muscle injection formulations of HIF2A inhibitors for treating muscle strains. The objectives of the proposed Phase I STTR study are to: 1) test the feasibility and efficacy of HIF2A inhibitor PT2385, and 2) determine the effectiveness and toxicity of PT2385 in vitro and in vivo. The successful accomplishment of this proposed study will pave the way for pre- and clinical trials of HIF2A inhibitor treatments in large animals and human patients. If this product is proved to be efficacious and safe, the commercialization of the product will benefit millions of people in the future.