Potential Oral Treatment for Cell Energy in ALS to Enter Phase 1 Trial, Stealth Bio Announces

Stealth BioTherapeutics announced the initiation of a Phase 1 trial to assess the safety and tolerability of its investigational oral treatment, SBT-272, in healthy volunteers.

SBT-272 is being developed to treat neurodegenerative diseases marked by problems in the workings of mitochondria (a cell’s powerhouse), including amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and multiple system atrophy (MSA).

In ALS, evidence suggests a link between mitochondria unable to produce the energy needed by cells and the death of motor nerve cells. SBT-272, Stealth’s second generation pipeline product, is designed to improve mitochondrial function by targeting a specific lipid (a type of fat), called cardiolipin, found in the inner membrane of these cellular structures.

The compound has been shown to increase cellular energy production and to decrease oxidative stress — an imbalance between the production of harmful free radicals and the ability of cells to detoxify, resulting in cellular damage — in mitochondria.

Preclinical work in a mouse model of ALS showed treated male animals had a dose-dependent delay in the onset of neurological symptoms, and lived longer than untreated mice.

This mouse study also found a potential biomarker of response to SBT-272 — blood levels of neurofilament light chain (NfL) significantly dropped after treatment with an effective dose. NfL is a proposed blood biomarker of nerve cell damage for ALS and multiple sclerosis.

“We are excited to advance our second generation of mitochondrial therapeutics into the clinic,” Reenie McCarthy, JD, chief executive officer of Stealth, said in a press release.

Researchers plan to recruit up to 40 healthy individuals for this double-blind, placebo-controlled, and single-ascending dose trial. Those enrolled will be divided among multiple study cohorts (arms), and given varying doses of oral SBT-272.

The study’s primary goal is to evaluate the therapy’s safety and tolerability. Scientists will also assess SBT-272’s pharmacokinetic profile — how the medicine is absorbed, distributed, metabolized, and eliminated — and determine the most appropriate dose range for a future Phase 2 trial.

“We designed this product candidate for neurodegenerative diseases, aiming to improve potency and blood-brain barrier penetration, and we’re encouraged by early signals of its efficacy in a preclinical study in amyotrophic lateral sclerosis,”  McCarthy said.

“Importantly, our preclinical work identified a responsive biomarker, which may help inform our ongoing preclinical studies in ALS … as well as future development efforts in other neurodegenerative diseases in which mitochondrial dysfunction has been implicated,” he added.