Disarm Therapeutics to Begin Developing Therapy that Prevents Axonal Degeneration

Disarm Therapeutics has completed the first round of financing to develop a compound that prevents axonal degeneration in patients with multiple sclerosis (MS) and other neurodegenerative conditions.

The treatment approach is based on an earlier discovery at Washington University in St. Louis, showing that the enzyme SARM1 is a key driver of axon degeneration, a process that causes disability and progression in several diseases of the central, ocular, and peripheral nervous systems.

The discovery was published in the journal Neuron in March 2017. Researchers had earlier known that SARM1 was involved in the degeneration process, but thought that another, so-far unidentified enzyme was needed to perform key steps.

Titled “The SARM1 Toll/Interleukin-1 Receptor Domain Possesses Intrinsic NAD+ Cleavage Activity that Promotes Pathological Axonal Degeneration,” the report showed that SARM1 itself possessed this enzymatic ability, and hence was key in driving neuron death.

“In our recent Neuron publication, we demonstrated that SARM1 itself is the central driver of axonal degeneration,” Jeffrey Milbrandt and Aaron DiAntonio, both MDs and PhDs, co-founders of Disarm Therapeutics from Washington University, said in a press release.

“Importantly, we found that SARM1 possesses an intrinsic enzymatic activity that can be targeted by novel therapeutics,” they added.

SARM1 is involved in a type of axonal degeneration that occurs after injury. The process is a type of programmed self-destruction pathway that affects the axon of an injured cell.

Disarm licensed exclusive rights to SARM1 discoveries from Washington University.

The series A financing round was completed with $30 million, with Atlas Venture leading the investment. Atlas Venture was involved in founding the company with Milbrandt and DiAntonio. Lightstone Ventures and AbbVie Ventures also contributed to the first financing round.

The company is now working toward a therapy that can prevent the degeneration of axons — long neuronal processes that send signals to other neurons or muscles.

“Using our proprietary product engine, the Disarm team has discovered novel, potent SARM1 inhibitors,” said Rajesh Devraj, PhD, co-founder and CSO of Disarm. “We plan to translate these potential therapeutics to human proof-of-concept in a range of neurological diseases, supported by noninvasive biomarkers.”

To succeed, the company has gathered a scientific advisory board that includes prominent experts in the field.

“Solving the puzzle of axonal degeneration has challenged scientists and physicians for more than a century,” said Jason Rhodes, a partner at Atlas Venture and co-founder, chairman, and acting CEO of Disarm Therapeutics. “Now, for the first time, we have a therapeutic approach to directly prevent the loss of axons in patients with diseases including multiple sclerosis, amyotrophic lateral sclerosis, glaucoma, and peripheral neuropathies.”

The outcomes of the project are, however, far from clear. Another recent study, published in the Journal of Neuroinflammation at about the same time as the Neuron article, questioned the feasibility of preventing this type of axonal degeneration in slowing MS-related disability, based on experiments in mice.