Phase 1 trial of ABA-101 for progressive MS gets FDA OK

Abata Therapeutics is expected to launch a Phase 1 clinical trial by the end of the year to test ABA-101, its experimental therapy for progressive multiple sclerosis (MS), after getting a green light from the U.S. Food and Drug Administration (FDA).

The FDA approved Abata’s investigational new drug (IND) application for ABA-101 in progressive MS, a patient population with few therapeutic options. ABA-101 works by modifying a type of immune cell known as regulatory T-cells, or Tregs.

That decision cleared the way for this first-in-human trial, which will test the treatment candidate in patients with progressive MS.

“Receiving IND clearance for ABA-101 validates our unique approach of leveraging the natural role of Tregs in the immune system to treat autoimmune diseases where current treatments are either insufficient or non-existent,” Richard M. Ransohoff, MD, co-founder and adviser of Abata, said in a company press release.

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ABA-101 works by modifying Treg immune cells

ABA-101 is being developed for progressive MS patients who have imaging evidence of ongoing inflammatory tissue injury and are HLA-DRB1*15:01 positive — meaning they have a genetic variation that affects their immune system’s ability to recognize its own body’s cells. This patient population, according to Abata, is believed to right now be about 45,000 people in the U.S.

The therapy aims to harness the unique biology of T-cells, a type of immune cells. These cells have a specialized receptor on their surface that recognizes very specific molecular targets.

While receptor binding for most T-cells leads to increased inflammation, for a subset of T-cells known as Tregs, receptor binding leads to the secretion of molecules that instead decrease inflammation. Tregs are known to reduce excessive immune responses in autoimmune diseases, such as MS.

During ABA-101 treatment, Tregs are collected from individual patients and modified to have a receptor that recognizes damaged myelin, the fatty coating that covers and protects nerve fibers. Myelin damage is a hallmark of MS.

When reintroduced into patients, these modified Tregs will selectively move through the body, looking specifically for damaged myelin in the central nervous system, or CNS, comprised of the brain, spinal cord, and optic nerves. Once they identify a lesion with damaged myelin, these Tregs get activated, and an anti-inflammatory immune response is initiated. This reduction in inflammation potentially blocks the buildup of disease-promoting pro-inflammatory immune cells that degrade myelin, and possibly even promote myelin repair.

“In preclinical studies, ABA-101 was shown to be safe and demonstrated tissue-specific trafficking, persistence, and robust suppression of inflammation, supporting its potential therapeutic effect.

Because these cells are modified to target the CNS, Abata believes it is unlikely that they will globally reduce immune functioning — a common negative side effect of several available treatments for autoimmune diseases — and therefore offer a strong safety profile.

“Across the MS treatment landscape, there are no effective therapies that address the CNS-compartmentalized inflammation driving progressive multiple sclerosis. ABA-101 is uniquely positioned to ameliorate this progressive pathology [disease mechanisms] as well as promote repair and clinical improvement,” Ransohoff said.

Abata also hopes ABA-101 will be “durable,” suggesting the treatment approach, based on tissue-specific Tregs, has the potential for a single dose to last for years or even a lifetime.

Samantha Singer, president and CEO of Abata, called ABA-101 “a significant advancement in the field as one of the first tissue-targeted Treg cell therapies for autoimmune disease,” and said the company is looking forward to testing it in the upcoming Phase 1 trial.

“In preclinical studies, ABA-101 was shown to be safe and demonstrated tissue-specific trafficking, persistence, and robust suppression of inflammation, supporting its potential therapeutic effect,” Singer said.