CINCINNATI--(BUSINESS WIRE)--Asha Therapeutics (Asha), a life sciences company pioneering breakthrough therapeutics for neurological disease, announced today the company has been awarded a grant from the ALS Association through its Lawrence and Isabel Barnett Drug Development Program for the advancement of ASHA-624, a novel brain-penetrant intra-molecular glue inhibitor of SARM1. The grant will support the continued development of ASHA-624 towards first-in-human clinical trials as a potential disease-modifying therapeutic for Amyotrophic Lateral Sclerosis (ALS).
ASHA-624 was designed using Asha’s proprietary PRISM™ drug design technology, which creates new medicines to restore normal biology and provide functional cures for difficult to treat diseases with high unmet medical need. ASHA-624 prevents the loss of nerve cell projections (axons) by selectively “gluing” the central regulator of axon degeneration, SARM1 into an inactive state, a mechanism of action which represents an industry first. In a preclinical model of ALS, treatment with ASHA-624 safely provided robust neuroprotection and restored motor function.
ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder that affects nerve cells (neurons) in the spinal cord and brain. Loss of motor neurons in ALS patients leads to debilitating loss of muscle control and impaired motor function. ALS ultimately affects the regulation and control of muscles which are required for speaking, eating, and breathing. ALS is fatal, with no available cure.
Additionally, Asha announced SARM1 and axon degeneration experts Dr. Jeffrey Milbrandt, M.D., Ph.D. and Dr. Aaron DiAntonio, M.D., Ph.D. will join the company’s Scientific Advisory Board. Dr. Milbrandt and Dr. DiAntonio were the first to characterize the function of SARM1 in axonal degeneration and are the founders of Disarm Therapeutics, acquired by Eli Lilly and Company (NYSE: LLY) in late 2020. Dr. Milbrandt is the Executive Director of McDonnell Genome Institute (MGI), James S. McDonnell Professor of Genetics, and Professor of Pathology & Immunology, Medicine, and Neurology at Washington University School of Medicine in St. Louis. Dr. DiAntonio is the Alan A. and Edith L. Wolff Professor of Developmental Biology at Washington University School of Medicine in St. Louis. Dr. Jeffrey Rothstein, M.D., Ph.D. has also joined Asha’s Scientific Advisory Board. Dr. Rothstein is the John W. Griffin Director for the Brain Science Institute (BSi), as well as a Professor of Neurology and Neuroscience, and the Founding Director of the Robert Packard Center for ALS Research at Johns Hopkins University School of Medicine. Dr. Rothstein has been Professor of Neurology and Neuroscience at Johns Hopkins for over 25 years.
“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."
“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, and we are profoundly grateful and humbled by our selection as a grant recipient. This award, along with the addition of Dr. Milbrandt and Dr. DiAntonio, pioneers in SARM1 biology and therapeutic development targeting SARM1, and the addition of clinical expertise in ALS brought by Dr. Rothstein, strongly positions Asha to rapidly advance ASHA-624 to clinic. 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," commented Dr. Bradlee Heckmann, Ph.D., Asha’s Scientific Co-founder, President & Chief Scientific Officer.
About ASHA-624: ASHA-624 is a first-in-class, novel intra-molecular glue compound that exploits the normal biology of SARM1, a key protein that promotes axonal degeneration and neurodegeneration by selectively “gluing” activated SARM1 into an inactive conformation, leading to robust neuroprotection through the prevention of axon and neuron loss. In ALS, the activation of SARM1 leads to axonal loss, neurodegeneration, and ultimately motor dysfunction. ASHA-624 was designed to inhibit SARM1 with hyper selectivity, and in preclinical studies has demonstrated a robust safety profile as a functional cure in models of ALS. ASHA-624 therapeutic intervention in preclinical models of ALS reversed motor impairment and dysfunction to levels similar to healthy controls, while placebo treated groups exhibited continual and exacerbated decline in motor function. In addition to ALS, ASHA-624 has potential indications in Chemotherapy-Induced Peripheral Neuropathy (CIPN), Multiple Sclerosis (MS), Spinal Cord Injury and TBI, Glaucoma, and rare disorders including Charcot-Marie Tooth (CMT) and Autosomal Dominant Optic Atrophy (ADOA).
About Asha Therapeutics: Asha Therapeutics (www.ashatherapeutics.com) is a life sciences company at the forefront of a new era of precision drug design, leveraging the power of its proprietary PRISM™ technology to custom design de novo compounds to create disease modifying and curative therapeutics for diseases with high unmet medical need.
Asha's lead therapeutic programs, ASHA-624 and ASHA-091 with indications in Amyotrophic Lateral Sclerosis, Parkinson's Disease and Alzheimer’s Disease, are anticipated to enter clinical trials in early 2025.
About the ALS Association: The ALS Association is the largest philanthropic funder of ALS research in the world. The Association funds global research collaborations, assists people with ALS and their families through its nationwide network of care and certified clinical care centers, and advocates for better public policies for people with ALS. The ALS Association is working to make ALS a livable disease while urgently searching for new treatments and a cure. For more information about the ALS Association, visit our website at als.org. For more information about the Lawrence and Isabel Barnett Drug Development Program, visit als.org/BarnettProgram.
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