Nura Bio Secures $68M for Brain-Penetrating Drug to Protect Axons

Neurodegenerative disorders often share a common trait: the degeneration of axons. Axons are crucial fibers that extend from neurons to transmit electrical signals. While the breakdown of these axons has been understood for some time, effective tools to halt this process have been elusive. Nura Bio, a biotechnology startup based in South San Francisco, is pioneering a novel approach to stop axonal degeneration with their lead drug candidate, which targets this specific issue. With a fresh infusion of $68 million in funding, the company is poised to advance its research to Phase 2 clinical trials.

The latest round of financing, led by founding investor The Column Group, also marks a significant leadership change with Shilpa Sambashivan stepping in as the new CEO and joining the board of directors. Nura Bio's primary research target is the enzyme SARM1, which plays a critical role in axonal degeneration. In healthy individuals, SARM1 remains inactive, and its precise role in normal physiological conditions remains undiscovered. However, when activated, SARM1 triggers the breakdown of axons, a process that can be initiated by chemical injuries like chemotherapy or physical injuries such as traumatic brain injury.

Sambashivan, who was part of the founding team and previously served as the startup’s chief scientific officer, emphasized that axonal degeneration is not merely a passive process. "We all know that axon degeneration is important," she said. "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 combat this degeneration with NB-4746, a brain-penetrating drug that inhibits SARM1. The company recently completed Phase 1 trials of this drug in healthy volunteers, which demonstrated that the twice-daily pill was well tolerated without adverse effects. The presence of the drug in the brain was confirmed through measurements in cerebrospinal fluid. However, since SARM1 is activated only in disease states, the Phase 1 trial could not verify whether NB-4746 effectively engaged the enzyme. This crucial measure will be assessed in the upcoming Phase 1b/2 trial.

Scheduled to begin in 2025, the Phase 1b/2 trial will focus on an unspecified neurological condition. One key metric will be the levels of neurofilament light (NfL) proteins in the blood, which are released by damaged neurons and serve as biological markers for neurological diseases. These proteins provide an indirect method to gauge SARM1 activity. The reduction of NfL levels has precedent as a surrogate clinical trial endpoint, exemplified by the FDA’s accelerated approval of Biogen’s Qalsody for ALS in 2023.

ALS is one of several potential conditions that Nura Bio is considering for NB-4746, along with multiple sclerosis and chemotherapy-induced peripheral neuropathy. In 2022, the company published research in the journal Neuron showing that SARM1 inhibitors had neuroprotective effects in preclinical models of nerve injury and neuropathy, with NfL levels being a significant measure. Although Nura Bio sees broad applications for its lead program in various neurological disorders, they are still determining the initial indication to demonstrate proof of biology.

Nura Bio’s approach is built on the foundational SARM1 research by scientific founders Marc Freeman of Oregon Health & Science University and Steven McKnight of the University of Texas Southwestern Medical Center. All drugs in Nura Bio’s pipeline were discovered internally, with details on additional targets remaining undisclosed.

Despite potential competition from pharmaceutical giant Eli Lilly, which acquired Disarm Therapeutics for its SARM1 inhibitors in 2020, Nura Bio is focused on advancing its unique approach. The new financing, which adds to a $73 million Series A round from 2020, brings their total funding to $141 million. With new investor Sanofi Ventures and existing investors such as Samsara Bio Capital and Euclidean Capital participating, Nura Bio now has sufficient capital to progress its lead candidate through proof-of-biology clinical trials. Sambashivan noted that even with the recent funding, the company is preparing for future financing rounds as it moves more molecules into clinical trials.