US-based genomic medicine company Sangamo Therapeutics has received the US Food and Drug Administration (FDA) investigational new drug (IND) approval for its ST-503 programme.
ST-503 is an investigational epigenetic regulator intended for the treatment of intractable pain due to idiopathic small fibre neuropathy (iSFN), a type of peripheral neuropathy.
It works by leveraging an adeno-associated virus (AAV) vector carrying an engineered zinc finger repressor (ZFR) to specifically target the human gene, SCN9A.
SCN9A encodes the Nav1.7 sodium channel, which plays a key role in pain signalling.
Neuropathic pain is a chronic pain condition caused by damage or dysfunction in the nervous system, including nerves, the spinal cord, or the brain.
ST-503 is not intended for sporadic or acute pain, but for chronic, intractable pain that completely dominates and often destroys the lives of patients over many years.
Sangamo chief development officer Nathalie Dubois-Stringfellow said: “The FDA’s clearance of the IND application to evaluate ST-503 in idiopathic small fibre neuropathy represents an important milestone for Sangamo on our journey to becoming a neurology genomic medicine company.
“We strongly believe in the power of our zinc finger technology to address neurological conditions and are excited about our plans to advance this program into the clinic next year, to bring hope to patients suffering from debilitating, intractable pain, for which there are insufficient current treatment options.”
Sangamo said that developing small molecules that specifically target Nav1.7 is challenging due to the high structural similarities between different sodium channels.
Its ST-503 is designed to directly target the SCN9A gene and has been shown to selectively reduce the expression of Nav1.7 sodium channels in sensory neurons in animal models.
Also, a single intrathecal administration of ST-503 has resulted in a significant reduction in pain hypersensitivity, said the genomic medicine company.
In preclinical research, ST-503 was well tolerated in nonhuman primates, with substantial Nav1.7 reduction and no off-target effects, showing promise in chronic neuropathic pain.
Sangamo will conduct a Phase 1/2 study to assess the safety, tolerability, and preliminary efficacy of ST-503 in addressing iSFN, with plans to initiate patient enrolment in mid-2025.
Earlier this year, Sangamo signed a licensing agreement, worth up to $1.95bn, with Roche’s subsidiary Genentech, to develop genomic therapies for neurodegenerative diseases.
