SPECIFIC AIMS Unmet Need: Burns have comprised 5-20% of military casualties sustained in post-World War II conflicts. Burn symptoms vary depending on the severity or degree of the burn, but all burns are painful. There are no treatments for burn pain available that acts on specific pain receptors on the skin and can be applied topically. Our goal is to develop one. Innovation: The Transient Receptor Potential Vanilloid 1 (TRPV1) channel is a polymodal protein with functions linked to the generation of pain. Cutaneous TRPV1 receptor activation in sensory neurons induces pain and occurs through several mechanisms including thermal injury. Blockage of the TRPV1 receptor through direct cutaneous application of a topical small molecule antagonist may significantly ameliorate burn pain as this receptor has been shown in many animal models to be an important gating mechanism in pain and in the inflammatory cascade. Serentrix’s lead molecule, SER114, a TRPV1 receptor antagonist, has been successfully tested in Phase 1 clinical trials for neuropathic pain. As TRPV1 has been shown to be a key receptor involved in the mediation of pain and inflammation in the skin, our goal is to develop the compound as a novel topically applied small molecule TRPV1 antagonist for the treatment of cutaneous burn pain. As our compound selectively binds to the receptor, developing a topical formulation would further reduce the chances of adverse effects and provide a dosage form that can be used for local delivery for topical burns. This makes SER114 a highly innovative drug candidate ideal for treatment of burn pain by targeting pain receptors present on the skin. Research Strategy: As TRPV1 has been shown to be a key receptor involved in the mediation of cutaneous pain, our goal is to develop our compound as a novel topically applied TRPV1 antagonist for the treatment of cutaneous burn pain.