Disarm Therapeutics, Inc.

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 . Forward-Looking Statements The matters discussed in this release that are not historical facts are “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and we intend that such forward-looking statements be subject to the safe harbor created thereby. Forward-looking statements include, but are not limited to, statements containing the words “believes,” “anticipates,” “intends,” “estimates,” “plans,” “expects,” “projects” and words of similar import. Readers are cautioned not to place undue reliance on these forward-looking statements, which are based on the information available to management at this time and which speak only as of the date of this release. The Company undertakes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. These forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements of the Company or its industry to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. While the Company believes the information contained herein is reliable, the Company makes no representations or warranties regarding the accuracy or completeness of this information.

A promising new approach that could slow, stop or prevent nerves from dying may get its first test in patients next year. Nura Bio, a startup based in South San Francisco, has developed an oral small molecule inhibitor of the enzyme SARM1, which neuroscientists believe is involved in many neurological conditions such as ALS. On Tuesday, the startup said it recently finished testing its drug, NB-4746, in healthy volunteers. The company also announced that it raised $68 million in an extension of its Series A financing, bringing its total funding to $141 million since launching in 2020 . The new funds are expected to help Nura begin a Phase 1b/2 trial in patients in 2025. Shilpa Sambashivan, who was previously the company’s chief scientific officer and has now been promoted to CEO, told Endpoints News that she believes the drug “has very broad therapeutic potential.” Her team is still deciding which disease to test the drug in first. Eli Lilly is also developing a SARM1 inhibitor , which it got from its acquisition of Disarm Therapeutics in 2020 for $135 million upfront and up to $1.225 billion in milestone payments. Lilly is testing the drug’s safety in a large Phase 1 study of healthy volunteers that’s expected to wrap up in June 2025. But the pharma company also hasn’t said which disease it will test the drug in first. Picking the right test case for the drug will be key. The neurodegenerative disease space is littered with compounds that looked promising in preclinical studies but have failed to meaningfully stall disease in humans. Sambashivan said that Nura has tested its drug in models of ALS, multiple sclerosis and traumatic brain injury. She also envisions a role for the drug in treating eye diseases like glaucoma and preventing peripheral neuropathies caused by chemotherapy. To get a read on how well the drug is working, Nura will look at levels of a protein called neurofilament light, which is shed as neurons die, she added. Nura Bio, which has fewer than 20 employees, was partly based on research from Marc Freeman, a scientist at Oregon Health & Science University who discovered genetic mutations in SARM1 that protected against axon degeneration. Scientists initially suspected the protein was part of the immune system, but soon realized it was an enzyme that breaks down a molecule called NAD, which is important for the proper functioning of many other enzymes. Much of the work at Nura has focused on unraveling the inner workings of the enzyme to create a drug that can inhibit it. Yet in many ways, the enzyme still remains a mystery. It doesn’t chew up the ends of neurons itself, and how exactly its role in breaking down NAD leads to axon degeneration is unknown. “We don’t completely understand the connection,” Sambashivan said. What is clear is that the enzyme is shut down in healthy people, she added. “It’s very tightly regulated. There are checks and balances that keep it turned off. Because when it turns on, it’s catastrophic in the degenerative loss that it drives.” Nura’s new funding round was led by The Column Group, the startup’s founding investor. Prior investors Samsara BioCapital and Euclidean Capital and newcomer Sanofi Ventures chipped in, too. “We’ve been very fortunate to have our investors stay with us,” Sambashivan said. “The science hasn’t been easy, and sometimes, as you know, you can’t expedite the science by throwing a whole lot of money or resources at it.”

Neurodegenerative disorders progress in a variety of ways, but one characteristic many of them share is the breakdown of axons, a cable-like fiber that extends from a neuron and transmits electrical signals. While scientists have long known about axon degeneration, they haven’t had tools to stop it. Nura Bio’s lead drug candidate blocks a novel target associated with this damage to axons and the startup now has $68 million to proceed to a Phase 2 test. The new financing announced Tuesday was led by founding investor The Column Group. Along with the new capital, South San Francisco-based Nura Bio announced the appointment of Shilpa Sambashivan as CEO and a member of the company’s board of directors. The initial target of Nura Bio’s research is SARM1, an enzyme that is involved in axonal degeneration. SARM1 is not activated in healthy people and if it has a role in states of health, scientists have not found it, Sambashivan said. But once activated, the enzyme leads to axonal degeneration. That activation can be sparked by a chemical injury, such as chemotherapy, or a physical one, such as traumatic brain injury. presented by Health IT Accelerating Claim Processing: Strategies to Shorten the Life of a Claim These strategies and practices can significantly shorten the life cycle of claims, leading to quicker resolutions and improved financial outcomes. By Greenway Health “We all know that axon degeneration is important,” said Sambashivan, who was part of Nura Bio’s founding team and previously served as the startup’s chief scientific officer. “We thought of it as a passive process. This is not a passive process. There is actually a mechanism in axons that is sensitive to changes in the environment.” Nura Bio aims to stop axon degeneration with a brain-penetrating drug that inhibits SARM1. The company’s lead program, NB-4746, recently completed Phase 1 testing in healthy volunteers. Sambashivan said results showed the twice-daily pill was well tolerated with no adverse effects. Scientists confirmed that the drug penetrated into the brain by measuring for it in cerebrospinal fluid. However, Sambashivan said the Phase 1 test was unable to show whether NB-4746 engaged SARM1 in the healthy volunteers because the enzyme is activated only in states of disease. Showing the drug’s effect on the target enzyme will come with the next stage of clinical testing. The Phase 1b/2 test is expected to begin in 2025 in a yet-to-be-determined neurological indication. Sambashivan said one key measure of this study will be to measure levels of neurofilament light (NfL) proteins, a type of protein released into the blood by damaged neurons. These proteins are a biological indicator for neurological disease and they are an indirect way to measure SARM1, Sambashivan said. There’s precedent for using NfL levels as a surrogate clinical trial endpoint. The reduction of blood levels of this protein was the basis for the 2023 accelerated FDA approval of Biogen’s Qalsody, a treatment for amyotrophic lateral sclerosis (ALS) driven by a certain genetic mutation. Sambashivan acknowledged ALS is one potential indication for Nura Bio’s NB-4746. Others include multiple sclerosis and chemotherapy-induced peripheral neuropathy. In 2022, the company published research in the journal Neuron showing SARM1 inhibitors were neuroprotective in preclinical models of nerve injury and neuropathy. Reduction of NfL levels was a key measure of this research. While Nura Bio believes its lead program has potential applications in a wide range of neurological disorders, Sambashivan said the company is still determining which indication to choose first to demonstrate proof of biology. presented by Health Tech The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani Nura Bio’s approach is based on the SARM1 research of scientific founders Marc Freeman of Oregon Health & Science University and Steven McKnight of University of Texas Southwestern Medical Center. The startup’s drugs (additional pipeline details and drug targets remain undisclosed) were all discovered within the company, Sambashivan said. Nura Bio’s SARM1 efforts face potential competition from Eli Lilly. In 2020, the pharmaceutical giant acquired Disarm Therapeutics, a startup that was in preclinical development with SARM1 inhibitors. The M&A deal came three years after the startup emerged from stealth with science based on the SARM1 research of its Washington University academic co-founders. Lilly’s pipeline currently lists a SARM1 inhibitor in Phase 1 development as a potential treatment for neurodegeneration. Asked what differentiates Nura Bio’s approach from Disarm’s, Sambashivan said all Nura Bio knows about the Disarm research is what is in the public domain, which is not much. She added that her company does not have additional insight to offer at this time. Nura Bio’s new financing adds to a $73 million Series A financing announced in 2020, extending the round’s total to $141 million. Sanofi Ventures joined the latest round as a new investor. Other participants include earlier investors Samsara Bio Capital and Euclidean Capital. Sambashivan said the new capital is enough to get Nura Bio’s lead program to the end of the proof-of-biology clinical trial. Even though Nura Bio just closed the additional financing, the startup is already preparing for the next round. “Once you get to the clinical stage and you’re moving more molecules into the clinic, you’re always raising,” Sambashivan said. Photo by Nura Bio