Rare Daily Staff

Stealth BioTherapeutics said it is initiating a first-in-human phase 1 trial evaluating its second-generation pipeline compound, SBT-272, in healthy subjects. 

SBT-272 is a novel peptidomimetic being developed for the treatment of neurodegenerative diseases involving mitochondrial dysfunction. The experimental therapy has been shown to increase adenosine triphosphate (ATP) production and decrease levels of reactive oxygen species (ROS) in dysfunctional mitochondria in preclinical studies.

Treatment with SBT-272 was associated with a dose-dependent delay in the onset of neurological disease, a reduction in systemic markers of neurodegeneration and prolonged lifespan in a mouse model of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease characterized by motor neuron deterioration and muscle atrophy.

SBT-272 demonstrates higher mitochondrial uptake, greater concentrations in the brain, and improved oral bioavailability relative to elamipretide, Stealth’s first-in-class lead compound. 

Shares of Stealth tumbled at the end of the year when elamipretide failed in a late-stage study in primary mitochondrial myopathy. The news was followed with a restructuring plan that included the layoff of 42 employees or about 60 percent of the staff, as well as the departure of the company’s chief scientific officer Mark Bamberger. Bamberger is serving as a consultant to the company through the end of 2020.

The phase 1 trial is a double-blind, placebo-controlled, single-ascending dose study enrolling up to 40 healthy subjects across multiple cohorts. SBT-272 is being administered orally in the study.  As a primary objective, the study will evaluate safety and tolerability of SBT-272. Secondary objectives include an analysis of the pharmacokinetic profile and appropriate dose range.

“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 (ALS),” said Reenie McCarthy, CEO of Stealth. “Importantly, our preclinical work identified a responsive biomarker, which may help inform our ongoing preclinical studies in ALS and multiple system atrophy (MSA), as well as future development efforts in other neurodegenerative diseases in which mitochondrial dysfunction has been implicated.”

Photo: Reenie McCarthy, CEO of Stealth BioTherapeutics

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