Disarm Therapeutics, Inc.

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

Lilly will work with QurAlis to identify and develop additional therapies targeting UNC13A Eli Lilly is splicing another asset onto its neurodegenerative disease pipeline, paying QurAlis $45 million for rights to a preclinical treatment for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The deal gives Lilly global rights to QRL-204, a splice-switching antisense oligonucleotide (ASO) designed to restore UNC13A function. Researchers linked a variant in UNC13A to ALS and FTD years ago, but it took longer to find a causal link between the gene and diseases. A 2022 paper showed how UNC13A variants exacerbate reduced function of TDP-43, the RNA-binding protein implicated in many ALS and FTD cases.  QurAlis designed QRL-204 to modulate UNC13A splicing and restore normal synaptic activities in ALS and FTD. Having shared preclinical evidence that it is on to something in March, the biotech has persuaded Lilly to pay $45 million upfront and up to $577 million in milestones to add the ASO to its pipeline.  “Genetic precision medicines like QRL-204 that target specific causal components of disease pathology hold great promise for delivering meaningful advances against a range of neurodegenerative diseases like ALS and FTD,” Andrew Adams, Ph.D., senior vice president, neurodegeneration research at Lilly, said in a statement. While hustling QRL-204 toward the clinic, Lilly will work with QurAlis to identify and develop additional therapies targeting UNC13A. The partners will use a QurAlis platform designed to create splice-switching ASOs with improved potency and increased therapeutic index. UNC13A is implicated in roughly two-thirds of ALS cases and one-third of FTD cases, numbers that have caught the attention of a small band of biotechs. AcuraStem has an ASO against UNC13A in development for ALS and FTD. Maze Therapeutics also discovered an UNC13A ASO but has handed the rights to a new biotech that is yet to exit stealth, according to its pipeline. While Lilly is a new challenger for the UNC13A niche, it is a familiar presence in the broader ALS and FTD spaces. The drugmaker expanded in ALS through its $135 million takeover of Disarm Therapeutics in 2020 and a smaller partnership with Verge Genomics the following year. Lilly added a FTD prospect to its pipeline when it bought Prevail Therapeutics for $880 million and has a stake in Arkuda Therapeutics.