Topical treatment for burn pain by blocking cutaneous pain receptors.

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.

Grant Number: 1R43GM150295-01A1
NIH Institute/Center: NIH
Principal Investigator: Kumaril Bhargava