Asha Therapeutics has secured a grant from the ALS Association's Barnett Drug Development Program to propel ASHA-624, an innovative brain-penetrant intra-molecular glue inhibitor targeting SARM1, towards clinical trials for Amyotrophic Lateral Sclerosis (ALS). This funding aims to support the development of ASHA-624 as a potential disease-modifying therapy for ALS, a progressive neurodegenerative disorder affecting motor neurons in the spinal cord and brain. The company also announced the appointment of key SARM1 experts to its Scientific Advisory Board, including the founders of Disarm Therapeutics, Drs. Jeffrey Milbrandt and Aaron DiAntonio, alongside Dr. Jeffrey Rothstein.
ASHA-624: A Novel Approach to ALS Treatment
ASHA-624 was developed using Asha's proprietary PRISM™ drug design technology. It works by selectively "gluing" SARM1, the central regulator of axon degeneration, into an inactive state, thereby preventing the loss of nerve cell projections (axons). In preclinical models of ALS, ASHA-624 demonstrated robust neuroprotection and restored motor function, suggesting its potential to modify the course of the disease.
ALS, also known as Lou Gehrig's disease, affects approximately 30,000 people in the United States, with about 5,000 new cases diagnosed each year. The disease leads to the progressive loss of muscle control, impaired motor function, and eventually affects the muscles required for speaking, eating, and breathing. Currently, there is no cure for ALS, and treatments primarily focus on managing symptoms and improving quality of life.
Expert Insight and Scientific Validation
The addition of Drs. Jeffrey Milbrandt and Aaron DiAntonio, pioneers in SARM1 biology and therapeutic development, to Asha's Scientific Advisory Board further strengthens the company's position. Dr. Milbrandt and Dr. DiAntonio were the first to characterize the function of SARM1 in axonal degeneration and founded Disarm Therapeutics, which was acquired by Eli Lilly in 2020.
"SARM1 is a compelling therapeutic target for many central, peripheral, and ocular neurodegenerative diseases. Asha Therapeutics has developed a completely novel approach for inhibiting SARM1, and I look forward to helping the team at Asha bring this therapy to patients in need," noted Dr. Aaron DiAntonio, M.D., Ph.D.
Dr. Jeffrey Milbrandt, M.D., Ph.D. added, "Asha’s novel intra-molecular glue approach for SARM1 inhibition represents a potentially highly selective and unique route for therapeutic intervention in diseases including ALS and other peripheral neuropathies. Furthermore, the support from the ALS Association to advance ASHA-624 towards clinical trials is a significant milestone for the program. I am excited to work with the Asha team to develop new SARM1 therapeutics."
Clinical Development and Future Directions
ASHA-624 is a first-in-class compound designed to inhibit SARM1 with hyper selectivity. Preclinical studies have demonstrated a robust safety profile and efficacy in models of ALS, with treated groups showing reversed motor impairment and dysfunction to levels similar to healthy controls. Asha Therapeutics anticipates initiating clinical trials for ASHA-624 in early 2025.
"The Barnett Drug Development grant from the ALS Association represents an exceedingly competitive cornerstone of validation for therapeutic programs with the potential to reshape ALS treatment," commented Dr. Bradlee Heckmann, Ph.D., Asha’s Scientific Co-founder, President & Chief Scientific Officer.
