Stealth BioTherapeutics announced the initiation of a first-in-human Phase 1 trial evaluating its second generation pipeline compound, SBT-272, in healthy subjects.
"We are excited to advance our second generation of mitochondrial therapeutics into the clinic," said Reenie McCarthy, Chief Executive Officer of Stealth. "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). 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."
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.
Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special offers
from American Pharmaceutical Review – all delivered right to your inbox! Sign up now!
SBT-272 is a novel peptidomimetic being developed for the treatment of neurodegenerative diseases involving mitochondrial dysfunction. SBT-272 has been shown to increase adenosine triphosphate (ATP) production and decrease levels of reactive oxygen species (ROS) in dysfunctional mitochondria in preclinical studies. 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. 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. The compound is currently being evaluated in another ALS preclinical model, as well as in a preclinical model indicative of activity in multiple system atrophy (MSA), a neurological disorder leading to parkinsonism, cerebellar ataxia, dysautonomia and other motor and non-motor symptoms. Mitochondrial dysfunction is believed to contribute to the progression of ALS and MSA, as well as other neurodegenerative diseases including Parkinson's, Huntington's and Alzheimer's.