FDA Clears Sangamo's IND for ST-503 to Treat Idiopathic Small Fiber Neuropathy

Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a company specializing in genomic medicine, has announced that the U.S. Food and Drug Administration (FDA) has approved the investigational new drug (IND) application for its ST-503 program. This program focuses on an investigational epigenetic regulator intended to treat severe pain caused by idiopathic small fiber neuropathy (iSFN), a chronic type of neuropathic pain.

Neuropathic pain arises from a variety of conditions affecting the central or peripheral nervous systems, including surgical trauma, spinal cord injuries, nerve compression, neurological diseases, infections, and metabolic or hereditary conditions. ST-503 is designed to manage chronic, unyielding pain rather than sporadic or acute pain, offering relief to patients who suffer for extended periods. The Phase 1/2 trial will evaluate the safety and effectiveness of ST-503 for iSFN, a form of peripheral neuropathy that causes severe symptoms such as burning, prickling, stabbing, or "lightning-like" pain. It is estimated that at least 43,000 people in the U.S. have iSFN, while nearly 40 million Americans are affected by peripheral neuropathies. Currently, treatment options include antidepressants, anticonvulsants, opioids, and topical therapies, but there are no lasting or curative treatments available for iSFN, creating a significant unmet medical need for these patients.

Dr. Nathalie Dubois-Stringfellow, Chief Development Officer at Sangamo, emphasized the importance of the FDA's IND approval for ST-503, marking a significant step for Sangamo in its mission to become a leader in neurology genomic medicine. She expressed confidence in the company's zinc finger technology to address neurological conditions and highlighted plans to progress this program into clinical trials next year, aiming to bring new hope to patients suffering from severe, intractable pain that current treatments cannot adequately address.

A considerable amount of research indicates that sodium channels are central to the pathophysiology of neuropathic pain. ST-503 employs an adeno-associated virus (AAV) vector that carries an engineered zinc finger repressor (ZFR) specifically targeting the human gene SCN9A. This gene encodes the Nav1.7 sodium channel, which plays a crucial role in pain signaling. Developing small molecule drugs that target Nav1.7 is challenging due to the structural similarities among various sodium channels, which complicates achieving selectivity and avoiding unwanted effects. By directly targeting the SCN9A gene, ST-503 has been shown to selectively reduce Nav1.7 channel expression in sensory neurons in animal studies, significantly decreasing pain hypersensitivity after a single intrathecal administration of ST-503. Sangamo's preclinical studies have demonstrated that ST-503 is well tolerated in nonhuman primates, with significant Nav1.7 reduction and no off-target effects, underscoring its potential as a therapy for chronic neuropathic pain, irrespective of the underlying cause.

Sangamo is preparing to initiate a Phase 1/2 clinical study to evaluate the safety, tolerability, and preliminary efficacy of a single dose of ST-503, administered intrathecally to patients experiencing intractable pain due to iSFN. The company plans to begin enrolling patients in mid-2025. If successful, Sangamo aims to expand the development of ST-503 to include other patient populations suffering from different types of chronic neuropathic pain.

Sangamo Therapeutics is committed to developing genomic medicines that can transform the lives of patients and families affected by severe neurological diseases with limited or no treatment options. The company believes that its zinc finger epigenetic regulators hold promise for addressing debilitating neurological disorders, and its capsid discovery platform can enhance delivery beyond current intrathecal delivery methods, including to the central nervous system. Sangamo's pipeline features multiple programs, some of which are in partnership or open to partnership and investment opportunities.