SBT-272 improved neuronal health, superior to other approved and investigational agents
Phase 1 study to evaluate safety and tolerability of SBT-272 in healthy volunteers is underway
BOSTON, June 8, 2022 — Stealth BioTherapeutics Corp (NASDAQ: MITO), a clinical-stage biotechnology company focused on the discovery, development, and commercialization of novel therapies for diseases involving mitochondrial dysfunction, announced today the presentation of new SBT-272 preclinical data demonstrating functional improvement in upper motor neurons with TDP-43 pathology, which plays a significant role in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The data were presented at the Keystone Neurodegeneration Symposium in Keystone, CO held June 5-9, 2022. A Phase 1 study to evaluate the safety and tolerability of SBT-272 in healthy volunteers is underway.
SBT-272 significantly improved mitochondrial structural integrity and motility in TDP-43 mutant (A315T)-expressing upper motor neurons. These enhancements in mitochondrial health were associated with improved axon outgrowth, a key indicator of improved neuronal health. The effect of SBT-272 on axon outgrowth was superior to edaravone (approved for the treatment of ALS) and AMX0035 (NDA under FDA review). Chronic in vivo administration of SBT-272 reduced upper motor neuron degeneration and neuroinflammation in the motor cortex of the prp‐hTDP‐43A315T‐UeGFP mouse model of ALS. Together, these data support further investigation of SBT-272 as a potential treatment for ALS with TDP-43 pathology.
“Upper motor neuron degeneration is an early event in ALS, which is characterized by degeneration of both the upper motor neurons in the brain and the lower motor neurons in the spinal cord,” said Hande Ozdinler, PhD, Associate Professor of Neurology, Feinberg School of Medicine, Northwestern University. “Therefore, to build effective treatment strategies for ALS, it is necessary for therapeutics to demonstrate efficacy on upper motor neuron health and function. The new findings presented today further strengthen the importance of improving mitochondrial health with respect to TDP-43 pathology in ALS and lay a strong foundation for the clinical development of SBT-272 for ALS patients.”
“ALS is a devastating progressive neuromuscular disease with a significant unmet medical need,” said Reenie McCarthy, Chief Executive Officer of Stealth BioTherapeutics. “We designed SBT-272 to target mitochondrial dysfunction in the brain, which is known to precede and contribute to several neurodegenerative diseases, including ALS. We are encouraged that Dr. Ozdinler’s team has elucidated these signals of neuronal protection, and we look forward to working with the ALS community to progress the clinical development of SBT-272.”
SBT-272 is a novel small molecule that targets the cardiolipin-rich inner mitochondrial membrane which is crucial for normal mitochondrial structure and function. Preclinical SBT-272 data have demonstrated mitochondria-protective and neuroprotective effects in models of ALS, FTD, alpha-synucleinopathy, a rare form of dementia that is similar to Parkinson’s disease, Huntington’s disease and ischemic stroke. We have also observed SBT-272-mediated improvements in functional assessments, lifespan, inflammation, and reduction of protein aggregates across certain nonclinical models. A Phase 1 study evaluating subcutaneous SBT-272 in healthy volunteers is ongoing. We aim to develop SBT-272 for ALS and other neurological diseases of mitochondrial dysfunction.
About Stealth BioTherapeutics
We are a clinical-stage biotechnology company focused on the discovery, development, and commercialization of novel therapies for diseases involving mitochondrial dysfunction. Mitochondria, found in nearly every cell in the body, are the body’s main source of energy production and are critical for normal organ function. Dysfunctional mitochondria characterize a number of rare genetic diseases and are involved in many common age-related diseases, typically involving organ systems with high energy demands such as the eye, the neuromuscular system, the heart and the brain. We believe our lead product candidate, elamipretide, has the potential to treat ophthalmic diseases entailing mitochondrial dysfunction, such as dry AMD, rare neuromuscular disorders, such as primary mitochondrial myopathy and Duchenne muscular dystrophy, and rare cardiomyopathies, such as Barth syndrome. We are evaluating our second-generation clinical-stage candidate, SBT-272, for rare neurological disease indications, such as amyotrophic lateral sclerosis and frontotemporal lobar dementia, following promising preclinical data. We have optimized our discovery platform to identify novel mitochondria-targeted compounds which may be nominated as therapeutic product candidates or utilized as mitochondria-targeted vectors to deliver other compounds to mitochondria.