Neurodegeneration is a common, yet unaddressed feature for a broad range of neurological diseases that can affect many of your body’s activities, such as balance, movement, talking, breathing, and heart function. However, currently, no treatment exists as attempts to develop neuroprotective treatments for neurodegenerative disorders have not succeeded in the clinic.

The pharmaceutical giant Eli Lilly and Company recently announced a definitive agreement to acquire Disarm Therapeutics, a privately-held biotechnology company creating a new class of disease-modifying therapeutics for patients with axonal degeneration. Degeneration of the axon, the long cable where electrical impulses from the neuron travel away to be received by other neurons, has been recognized as a predominant driver of disability and disease progression in central nervous system diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis, and Parkinson’s disease, as well as peripheral nervous system disorders such as chemotherapy-induced, diabetic, and inherited neuropathies, and ocular disorders, such as glaucoma.

Disarm’s scientific founders, Dr. Jeffrey Milbrandt and Dr. Aaron DiAntonio of Washington University School of Medicine in St Louis, discovered that the SARM1 protein is a central mediator of axonal degeneration in response to injury and stress, making it a unique therapeutic target with the potential to treat a range of neurodegenerative diseases. Mechanistically, SARM1 contains enzymatic activity that depletes the key cellular metabolite nicotinamide adenine dinucleotide (NAD+).

A decrease in the levels of NAD+ is an early indication of disease-associated and age-related neurodegeneration, and the balance between axon survival and self-destruction is intimately tied to the metabolism of NAD+. SARM1 initiates a local destruction program involving a rapid breakdown of NAD+ after injury. A reduction of cellular concentrations of this molecule by SARM1 eventually leads to an energetic catastrophe and cell death. So, blocking SARM1’s NAD+ depletion activity is critical to prevent axonal degeneration and is being pursued as an alternative or synergistic therapeutic strategy for the treatment of neurologic disorders.

Disarm is advancing SARM1 inhibitors that are designed to directly block NAD+ depleting activity and prevent the loss of axons in preclinical development, with the goal of delivering breakthrough treatments to patients with peripheral neuropathy and other neurological diseases. By inhibiting the SARM1 protein’s ability to deplete NAD+ in response to injury or stress, these therapeutics may prevent the loss of axons in chronic and acute diseases of the central, ocular, and peripheral nervous systems. For a broad range of neurological diseases, the therapeutic goal is to prevent further degeneration of axons, stabilize disease, and allow for functional recovery of the nervous system.

Under the terms of the agreement, Lilly will acquire Disarm for an upfront payment of $135.0 million. Disarm equity holders may be eligible for up to $1.225 billion in additional future payments for potential development, regulatory and commercial milestones should Lilly successfully develop and commercialize new medicines resulting from the acquisition.

“Lilly continues to seek medicines to treat the debilitating pain and loss of function associated with nerve damage,” said Mark Mintun, M.D., vice president of pain and neurodegeneration research at Lilly in a press release. “The scientific team at Disarm discovered an important and highly promising approach to combat axonal degeneration. We will move quickly to develop their SARM1 inhibitors into potential medicines for peripheral neuropathy and neurological diseases, such as ALS and multiple sclerosis.”

“Disarm’s innovative approach to treating axonal degeneration holds tremendous promise for addressing a wide spectrum of neurological diseases, and we have made significant strides toward enabling potentially transformative therapies,” said Alvin Shih, M.D., Chief Executive Officer of Disarm in a press release. “Lilly is ideally suited to advance this exciting new approach to treating axonal degeneration, and we look forward to seeing patients benefit from the work that Disarm initiated.”

Disarm was founded by Atlas Venture, Drs. Milbrandt and DiAntonio of Washington University School of Medicine in St. Louis, and Atlas Entrepreneurs-in-Residence Dr. Rajesh Devraj and Dr. Raul Krauss. Lightstone Ventures and AbbVie Ventures co-invested with Atlas to support the foundational work at Disarm.