Mitochondrial proteins

SBT-589 showed mitochondrial protection across models of Friedreich's ataxia SBT-589 displayed cardioprotective effects in aggressive mouse model of FA cardiomyopathy Ongoing studies are expected to build on these insights as SBT-589 progresses through developmental stage-gates NEEDHAM, Mass., March 19, 2024 /PRNewswire/ -- Stealth BioTherapeutics Inc. (the "Company" or "Stealth"), 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-589 data demonstrating cardioprotective effects across pre-clinical models of Friedreich's ataxia (FA). The data were presented at the Wellcome Trust Conference on Mitochondrial Medicine – Therapeutic Development, held March 18-20, 2024, in Cambridge, England. FA is a chronic disease of metabolic disruption that is typically diagnosed in childhood or adolescence, is inexorably progressive and usually results in premature death from cardiomyopathy or heart failure. There are no approved therapies for the progressive cardiomyopathy, which is linked to severe mitochondrial dysfunction, and is the leading cause of early death in this devastating disease. SBT-589 is a promising novel molecule that acts on mitochondrial pathways essential for cellular health and energy production that are impaired in FA cardiomyopathy. To evaluate the potential of SBT-589 in FA, a series of studies were conducted in FA patient-derived cells, isolated heart mitochondria, and an aggressive mouse model of FA cardiomyopathy. SBT-589 improved bioenergetics in FA patient-derived cells and mitochondria. In an FA mouse model with prominent cardiac hypertrophy and aggressive mortality, mice treated with once-daily SBT-589 displayed significantly reduced cardiac hypertrophy and a delay in the onset of mortality compared to vehicle-treated mice. "Mitochondrial dysfunction is a central contributor to pathology in Friedreich's ataxia, a disease in which heart failure and sudden cardiac events are among the leading causes of mortality," said David A. Brown, Senior Vice President, Discovery. "Mitigating heart disease in FA is central to Stealth's ongoing efforts to improve the lives of individuals with FA. The new findings presented today support continued development of SBT-589 as a potentially disease-modifying therapy to address the unmet need in cardiomyopathy associated with Friedreich's ataxia." The data were presented by Dr. Laura E. Kropp, Senior Manager of Discovery Biology at Stealth, and recipient of the Keith Michael Andrus Cardiac Award from the Friedreich's Ataxia Research Alliance. About Friedreich's Ataxia Friedreich's ataxia is a rare genetic disease affecting an estimated 1 in 50,000 individuals in the United States. The disease is caused by a defect in the frataxin gene resulting in a relative deficiency of frataxin, leading to mitochondrial iron accumulation and oxidative stress. More than 90% of patients with Friedreich's ataxia experience progressive cardiomyopathy which usually becomes fatal by early adulthood and is the leading cause of early mortality. About Stealth BioTherapeutics Stealth BioTherapeutics is a clinical-stage biotechnology company focused on the discovery, development, and commercialization of novel therapies for age-related and rare genetic diseases involving mitochondrial dysfunction. The Company is initiating Phase 3 clinical trials of elamipretide, its lead investigational product candidate, in dry age-related macular degeneration. Elamipretide is also being tested in a fully enrolled Phase 3 clinical trial in primary mitochondrial myopathy, a rare skeletal myopathic disease caused by nuclear DNA mutations, and is the subject of a New Drug Application for Barth syndrome, an ultra-rare cardioskeletal disease. The Company is evaluating its second-generation clinical-stage candidate, SBT-272, for ophthalmic and neurological disease indications. The Company has a deep pipeline of novel mitochondria-targeted compounds under evaluation as therapeutic product candidates. Several of these lead compounds, including SBT-589, have progressed through pre-clinical development stage-gates and toward IND-enabling studies. Investor Contact Kendall Investor Relations Adam Bero, Ph.D. [email protected] [email protected] Media Contact Anna Stallman Communications Anna Stallman [email protected] SOURCE Stealth BioTherapeutics Inc.

BLUE BELL, Pa.--( BUSINESS WIRE )-- Mitochon Pharmaceuticals today announced that it was awarded approval from EMA to begin enrollment for a Phase I/IIa biomarker study in Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Huntington’s Disease (HD) and Alzheimer’s Disease (AD) participants. Mitochon’s MP101, a once-daily, oral brain penetrant mitochondrial stimulator, that improves central nervous system survival and function will be used in this 14-day pilot study. The aim of the study is to show safety in the target patient populations and demonstrate meaningful changes in disease specific biomarkers. Successful completion of this study will provide the basis for long term Phase IIb clinical studies in ALS, Secondary & Primary Progressive MS, HD, and AD patients, leading to the first mitochondrial specific therapy for these truly insidious diseases. “We are delighted for the opportunity to explore this provocative idea that most, if not all neurodegenerative diseases are rooted in mitochondrial dysfunction. We predict that chronic treatment with this unique platform, at micro-doses, will resolve mitochondrial issues and change important disease specific biomarkers in all four indications similarly,” said Dr. John G. Geisler, Ph.D., co-founder and CSO of Mitochon. MP101 and MP201 are mitochondrial targeted, once-a-day, oral therapies that have been shown to shield cells from damage caused by a host of degenerative processes (genetic and non-genetic, auto-immune and injury). In preclinical studies, these compounds have exhibited striking protective and functional benefits in disease models. Benefits include: brain volume sparing in Huntington’s disease; axonal protection from demyelination in Multiple Sclerosis, protection of neuromuscular junction in ALS, blocking the loss of short-term memory in Alzheimer’s, and protecting brain cells from traumatic brain injury (TBI) such as severe concussions. About Mitochon Pharmaceuticals Mitochon was founded in 2015 with the mission to develop treatments for insidious diseases through the modulation of mitochondrial physiology, with applications to neurodegeneration, neuromuscular, and neuro-trauma. Mitochon’s lead programs, MP101 and MP201, specifically harnesses the power of the mitochondria to provide broad neural protection (MOA: https://www.mitochonpharma.com/mechanism-of-action/ ). These compounds elicit mild increases in energy expenditure that result in strengthening cellular survival – similar to the positive effects seen with fasting and exercise. These compounds also induce an important neurotrophin, Brain Derived Neurotrophic Factor (BDNF), involved in cognition, growth and repair. Additional Information: www.mitochonpharma.com

You can still be celebrated, even if you're buried in mud. A new study shows that innumerable other bacteria flock around cable bacteria in the oxygen-free seabed in something that looks like a dance. They apparently use the cable bacteria as an electrical lifeline for oxygen. Video recordings show that the dance stops abruptly if you cut the cable bacteria in half. You can still be celebrated, even if you're buried in mud. A new study shows that innumerable other bacteria flock around cable bacteria in the oxygen-free seabed in something that looks like a dance. They apparently use the cable bacteria as an electrical lifeline for oxygen. Video recordings show that the dance stops abruptly if you cut the cable bacteria in half. The party-poopers cutting the cable bacteria are researchers from the Center for Electromicrobiology (CEM) at Aarhus University. The centre's work focuses on unravelling the mysteries of how cable bacteria work. Cable bacteria are centimeter long, wire-shaped bacteria equipped with internal wiring that transports electrons between oxygen-rich and oxygen-free "dead" zones in the muddy seabed. The first person to stop the dance was PhD student Jesper Jensen Bjerg. Many years ago, he was sitting in a laboratory at the University of Vienna, struggling to follow the transport of electrons in cable bacteria by measuring the differences in the amount of electrons present in the bacteria's cytochrome proteins. (The protein is important for the energy metabolism of cells.) "As I became more and more impatient, I suddenly discovered something unexpected in the microscope: Hundreds of different bacteria flocked around the part of a cable bacteria that was in an oxygen-free environment. It looked like they were dancing and having a great time," says Jesper Jensen Bjerg, who is now a postdoc at CEM. He later discovered that the party stopped when he cut the cable bacteria with a laser. Years of effort His discoveries led to years of effort by the researchers at CEM to explain the phenomenon. And they have now published their preliminary results in the journal Nature Communications. The interesting thing is not the party culture of bacteria, but what happens chemically/physically between the cable bacteria and their tiny neighbours, and what each of them get out of the interaction. "The smaller bacteria are all aerobic, i.e. they need oxygen, and they obviously benefit greatly by transferring electrons to the cable bacteria and thereby getting an electrical connection to oxygen. But we don't yet know how the electrons are actually transferred to the cable bacteria. And we don't know how this affects the cable bacteria. Does it benefit or harm them? Or doesn't it matter to them at all?" says Professor Andreas Schramm, deputy director of CEM. Lots of questions ahead However, the research group has shown that the small bacteria are metabolically active and that the cytochromes in their cells are more oxidized (in other words, release electrons) when they are close to a cable bacteria. This means that the small bacteria are carrying out extracellular electron transfer (EET). But the discovery of the party in the mud raises more questions than it has so far answered. The researchers themselves list the questions in their scientific article: