– Potent, uncompetitive inhibitors of the pro-degenerative NADase SARM1 reported
– Molecular basis of product-assisted inhibition of NAD hydrolases like SARM1 and CD38 that have been implicated in neurological diseases elucidated
– Research supports Nura Bio’s goal of entering First-in-Human trials with oral, brain-penetrant SARM1 inhibitors in early 2023
South San Francisco, Calif., September 13, 2022 (BUSINESS WIRE) – Nura Bio Inc., a biopharma company based in South San Francisco, focused on the discovery and development of disease-modifying neuroprotective drugs, today announced the publication of research elucidating the molecular details of a conserved, NAD-dependent inhibitory mechanism that results in highly potent small molecule inhibitors of NAD hydrolases like SARM1 and CD38. The publication also discloses several highly potent small molecule inhibitors of SARM1. The study, titled “Uncompetitive, adduct forming SARM1 inhibitors are neuroprotective in preclinical models of nerve injury and disease”, by Bratkowski et al., was published online in Neuron and will appear in the November issue of the journal.
“Deploying high-resolution structures and sophisticated mechanistic models, our scientific team at Nura Bio has validated a conserved, NAD-dependent mechanism of inhibition of NAD hydrolases like SARM1 and CD38 as a viable therapeutic strategy for neuroprotection,” said Shilpa Sambashivan, PhD, lead author and Chief Scientific Officer at Nura Bio. “ We show that these inhibitors achieve potent inhibition of hydrolase activity by forming a conjugate with a product of the hydrolysis reaction resulting in inhibitors that confer significant structural and functional protection in preclinical models of neurological injury and disease.”
Since its conception in 2018, Nura Bio has been steadily growing a differentiated, small molecule pipeline focused on targets implicated in driving axon degeneration and neuroinflammation in neurological diseases. Nura Bio’s lead program, the SARM1 inhibitor program is currently in IND-enabling studies with the goal of entering First-in-Human trials in early 2023.
“The scientific advances published in Neuron reflect Nura Bio’s commitment to prosecuting novel mechanisms and complex biology to drive our drug discovery programs,” said Tim Kutzkey PhD, Founding Chairman, Nura Bio and Managing Partner at the Column Group. “We believe that oral, brain-penetrant SARM1 inhibitors have broad therapeutic potential in slowing or preventing axon degeneration and associated functional loss across multiple neurological diseases including ALS, MS, CIPN and TBI.”
About Nura Bio
At Nura Bio we envision a world where the diagnosis of a neurological disorder comes with the hope of a cure. Expanding on recent breakthroughs in crucial neurodegenerative pathways, we are positioned to deliver transformative neuroprotective therapies to prevent and protect against neuronal loss and related neuroimmune dysregulation. The company’s research and development strategy is currently centered on two approaches: prevention of neuronal loss to preserve neurological function; and restoring the function of the neuron-glia axis to improve the nervous system’s immune surveillance capacity in response to neurological injury. The company’s discovery engine and emerging multi-target pipeline spans these approaches and is well positioned to address a broad range of neurological diseases. Nura Bio’s lead program is the SARM1 inhibitor program. SARM1 has recently emerged as an axon-intrinsic metabolic sensor that is a pivotal driver of axonal degeneration and neuronal integrity. Axon degeneration is an early event in several neurological disorders, and halting it early has tremendous potential in the treatment of central, peripheral, and ocular neurological diseases.
For more information, visit www.nurabio.com.