First-in-human trial of ALS therapy ASHA-624 expected in early 2025
Asha Therapeutics recently won grant from ALS Association to support effort
A newly awarded grant from the ALS Association will support Asha Therapeutics‘ work to advance ASHA-624, a small molecule being developed for amyotrophic lateral sclerosis (ALS), into a first-in-human clinical trial that’s expected to begin early next year.
The grant was through the Lawrence and Isabel Barnett Drug Development Program, which funds projects that seek to bridge the gap between discovering promising therapeutics in the lab and developing them through clinical testing and regulatory approval.
The award “represents an exceedingly competitive cornerstone of validation for therapeutic programs with the potential to reshape ALS treatment, and we are profoundly grateful and humbled by our selection as a grant recipient,” Bradlee Heckmann, PhD, Asha’s scientific co-founder, president, and chief scientific officer, said in a company press release.
ALS causes damage to motor neurons, the nerve cells that control voluntary movements, leading to muscle weakness and other symptoms. Some treatments can slow down symptom worsening, but none has reversed motor impairment.
What is ASHA-624?
ASHA-624 was designed using Asha’s PRISM platform to “glue” the SARM1 protein, a central regulator of nerve fiber degeneration, into an inactive state, which should prevent the damage that causes motor neurons to die in ALS.
In preclinical models of the disease, ASHA-624 restored motor function to levels similar to healthy controls, while it continued to worsen with a placebo. The data supported testing ASHA-624 as a disease-modifying therapy that might slow ALS progression or even reverse motor function loss.
“Based on our data’s demonstration of robust preclinical efficacy and safety, we are optimistic that ASHA-624 is a potential disease-modifying therapeutic for ALS,” Heckmann said.
Fixing SARM1 in its inactive form could also be an effective strategy for other neurodegenerative diseases, such as multiple sclerosis and Charcot-Marie-Tooth disease, which affects the nerves outside the brain and spinal cord, or peripheral nerves.
“SARM1 is a compelling therapeutic target for many central, peripheral, and ocular neurodegenerative diseases,” said Aaron DiAntonio, MD, PhD, from the Washington University School of Medicine in St. Louis, who will join Asha’s scientific advisory board. “I look forward to helping the team at Asha bring this therapy to patients in need.”
Jeffrey Milbrandt, MD, PhD, is the executive director of the McDonnell Genome Institute at Washington University who’s also been named to the company’s scientific advisory board. Both DiAntonio and Milbrandt were the first to report on the role of SARM1 in neurodegeneration.
“Asha’s novel intra-molecular glue approach for SARM1 inhibition represents a potentially highly selective and unique route for therapeutic intervention, said Milbrandt, who calls the ALS Association’s support to advance ASHA-624 toward clinical trials “a significant milestone for the program.”
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