Mitocliondrial permeability transition pore

Barth Syndrome is an Ultra-rare, Progressive, Life-Shortening, Cardioskeletal Disease that Affects Approximately 150 Individuals in the United States If Approved, Elamipretide Would Become the First Approved Therapy for Barth Syndrome NEEDHAM, Mass., May 7, 2024 /PRNewswire/ -- Stealth BioTherapeutics, a clinical-stage biotechnology company focused on the discovery, development and commercialization of novel therapies for diseases involving mitochondrial dysfunction, today announced that the U.S. Food and Drug Administration ("FDA") has now determined that its New Drug Application ("NDA") for elamipretide for the treatment of Barth syndrome is entitled to a Priority Review designation. Per FDA policy, the user fee goal date of January 29, 2025 is unchanged. The FDA grants Priority Review to applications for therapies that have the potential to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. Barth syndrome is an ultra-rare cardioskeletal disease which results in frequent pediatric deaths and imposes a significant disease burden on all affected individuals. There are no other therapies approved or known to be in clinical development for this disease. The FDA's decision to grant Priority Review designation follows its March 29, 2024 filing decision in which the FDA assigned a standard review designation. Elamipretide has previously received Orphan Drug, Fast Track and Rare Pediatric Designations for elamipretide for the treatment of Barth syndrome. "We are pleased that the FDA has recognized the serious nature of Barth syndrome, the urgency of the unmet medical need, and the potential for elamipretide, if approved, to significantly improve treatment of this devastating disease," said Reenie McCarthy, Chief Executive Officer. "We welcome our continued constructive engagement with the Agency as we complete the review process and plan for an anticipated advisory committee meeting later this year." If approved, this would be the first marketing authorization for elamipretide, a first-in-class mitochondrial targeted therapeutic. Elamipretide is also in development for primary mitochondrial myopathy, with pivotal data from the fully-enrolled Phase 3 NuPOWER trial expected in late 2024, and dry age-related macular degeneration, with pivotal Phase 3 clinical trials initiating this quarter. About Barth Syndrome Barth syndrome is an ultra-rare genetic condition characterized by cardiac abnormalities leading to exercise intolerance, muscle weakness, debilitating fatigue, heart failure, recurrent infections, and delayed growth. The disease is associated with reduced life expectancy, with 85% of early deaths occurring by age 5. Barth syndrome occurs almost exclusively in males and is estimated to affect one in 1,000,000 males worldwide or around 150 individuals in the United States. There are currently no FDA- or EMA-approved therapies for patients with Barth syndrome. Elamipretide has Orphan Drug, Fast Track and Rare Pediatric Designation from the FDA and Orphan Drug Designation from the EMA for the treatment of Barth syndrome. About Stealth BioTherapeutics Stealth BioTherapeutics is 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 heart, the eye, and the brain. The Company believes its lead product candidate, elamipretide, has the potential to treat rare diseases including Barth syndrome and primary mitochondrial myopathy and common age-related diseases including dry age-related macular degeneration. The Company is also evaluating a topical ophthalmic formulation of its second-generation clinical-stage candidate, SBT-272, for dry age-related macular degeneration. The Company has a deep pipeline of novel compounds under evaluation for rare neurological and cardiac disease indications following promising preclinical data. Media Contact Anna Stallmann Communications Anna Stallmann [email protected] Investor Relations Contact Austin Murtagh Stern Investor Relations [email protected] SOURCE Stealth BioTherapeutics Inc.

Barth Syndrome is an Ultra-rare, Progressive, Life-Shortening, Cardioskeletal Disease that Affects Approximately 150 Individuals in the United States If Approved, Elamipretide Would Become the First Approved Therapy for Barth Syndrome NEEDHAM, Mass., April 8, 2024 /PRNewswire/ -- Stealth BioTherapeutics, a clinical-stage biotechnology company focused on the discovery, development and commercialization of novel therapies for diseases involving mitochondrial dysfunction, today announced that the U.S. Food and Drug Administration ("FDA") has accepted for filing its New Drug Application ("NDA") for elamipretide for the treatment of Barth syndrome. The NDA is supported by the positive data from the SPIBA-001 Phase 3 Natural History Control Study and additional supporting efficacy and safety data from the TAZPOWER Part 2 baseline-controlled trial. Elamipretide received Fast Track Designation in 2017, Orphan Drug Designation in 2018 and Rare Pediatric Disease Designation in 2020. "We are grateful that the FDA has listened to the voices of patients, families, and advocates who have been calling for a fair, appropriate, and complete review of elamipretide, which is the only medicine in late-stage clinical development for Barth syndrome," said Kate McCurdy, Chair of the Barth Syndrome Foundation. "This devastating disease has claimed the lives of too many of our children, loved ones, and friends. For those who survive past childhood, quality of life is severely diminished due to extreme muscle weakness, fatigue, and the constant threat of a life-threatening cardiac event. Our community desperately needs a treatment to enable us to live healthy and thriving lives." The FDA indicated that it is currently planning to hold an advisory committee meeting to discuss the application. The application was assigned a standard review designation, which the Company has asked FDA to reconsider. "We are pleased that the FDA has not only filed our NDA for Barth syndrome but has also committed to a transparent review process with its decision to convene an advisory committee," said Reenie McCarthy, Chief Executive Officer. "We welcome the input of committee experts to advise FDA on the seriousness of this devastating disease and the urgency of the unmet need, including in light of FDA's puzzling review designation. We look forward to working with the FDA through the review process." If approved, this would be the first marketing authorization for elamipretide, a first-in-class mitochondrial targeted therapeutic. Elamipretide is also in development for primary mitochondrial myopathy, with pivotal data from the fully-enrolled Phase 3 NuPOWER trial expected in late 2024. About Barth Syndrome Barth syndrome is an ultra-rare genetic condition characterized by cardiac abnormalities leading to exercise intolerance, muscle weakness, debilitating fatigue, heart failure, recurrent infections, and delayed growth. The disease is associated with reduced life expectancy, with 85% of early deaths occurring by age 5. Barth syndrome occurs almost exclusively in males and is estimated to affect one in 1,000,000 males worldwide or around 150 individuals in the United States. There are currently no FDA- or EMA-approved therapies for patients with Barth syndrome. Elamipretide has Orphan Drug, Fast Track and Rare Pediatric Designation from the FDA and Orphan Drug Designation from the EMA for the treatment of Barth syndrome. About Stealth BioTherapeutics Stealth BioTherapeutics is 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 heart, the eye, and the brain. The Company believes its lead product candidate, elamipretide, has the potential to treat rare diseases including Barth syndrome and primary mitochondrial myopathy and common age-related diseases including dry age-related macular degeneration. The Company is also evaluating a topical ophthalmic formulation of its second-generation clinical-stage candidate, SBT-272, for dry age-related macular degeneration. The Company has a deep pipeline of novel compounds under evaluation for rare neurological and cardiac disease indications following promising preclinical data. Media Contact Anna Stallmann Anna Stallmann Communications [email protected] Investor Relations Contact Austin Murtagh Stern Investor Relations [email protected] SOURCE Stealth BioTherapeutics Inc.

STEVENAGE, United Kingdom, Feb. 22, 2023 (GLOBE NEWSWIRE) -- NRG Therapeutics, Ltd., an innovative neuroscience company targeting mitochondrial dysfunction, is pleased to announce that it has been awarded a second $500,000 grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF), to support its lead drug discovery programme and the development of a novel treatment for Parkinson’s. NRG Therapeutics is applying breakthrough science in the field of mitochondrial biology to develop first-in-class treatments for Parkinson’s. Its approach is based on inhibiting the mitochondrial permeability transition pore (mPTP) in brain cells, which has been shown to be neuroprotective in several preclinical models of Parkinson’s and other neurodegenerative diseases. Having met the goals of the grant it received from MJFF in 2021, this second grant will support experiments to validate a novel mitochondrial drug target for Parkinson’s. The work will determine whether genetic deletion of this mitochondrial protein in vitro and in vivo protects brain cells, and therefore, whether drug modulation of this protein has the potential to improve Parkinson’s symptoms. The overall goal of the programme is to develop drugs that block the opening of the mPTP, an event which is triggered by high concentrations of calcium ions, leading to the death of dopamine-producing brain cells. NRG Therapeutics’ co-founder and CEO Dr Neil Miller said, “We have made great progress with our research funded by MJFF and we are delighted to have received a second award to fund further research to validate the molecular target for our mPTP inhibitors. There is a significant unmet medical need as all current treatments for Parkinson’s control symptoms but do not halt or slow progression of disease. Truly disease-modifying treatments for Parkinson’s and other neurodegenerative diseases remain the holy grail. It is our hope that our work could lead to new treatments that could positively change the lives of individuals with neurodegenerative disorders.” Classical ‘first-generation’ inhibitors of the mPTP, such as cyclosporin A, inhibit cyclophilin D (CypD), a protein that is believed to regulate the pore. However, all historical attempts to develop CypD inhibitors that can cross the blood-brain barrier have been unsuccessful. NRG has discovered novel ‘second-generation’ mPTP inhibitors that are small drug-like molecules, orally bioavailable and brain penetrant, and therefore have the potential for use in the treatment of chronic neurodegenerative disorders. NRG’s lead assets were identified through phenotypic screening in isolated mitochondria and have been shown to act independently of CypD. “Our mission is to support development of life-changing treatments to fulfill the unmet needs of people with Parkinson’s disease, and we are pleased to provide funding for a second project with NRG toward that goal,” said Alexandra Vaiana, PhD, MJFF’s Associate Director of Research Programs. Details of the MJFF’s most recently funded programs can be found HERE. These include NRG’s funded study ‘Validation of a Novel Mitochondrial Drug Target for Parkinson’s Disease’ HERE. Media enquiries (for NRG Therapeutics) Sue Charles, Charles Consultants - +44 7968 726585 sue@charles-consultants.com About NRG Therapeutics – NRG Therapeutics is a neuroscience drug discovery company building a pipeline of disease-modifying mitochondrial therapeutics to slow or halt the progression of neurodegenerative disorders such as Parkinson’s and Amyotrophic Lateral Sclerosis (ALS), also known as motor neurone disease (MND). The company’s pre-clinical pipeline of small molecule assets is based on inhibiting the mitochondrial permeability transition pore (mPTP) through a novel mechanism of action. Inhibition of the mPTP has been shown to protect neurones, reduce neuroinflammation and extend survival in pre-clinical disease models. Based at the Stevenage Bioscience Catalyst (SBC), UK, NRG Therapeutics is a private company with equity investment from Parkinson’s UK, Omega Funds and Brandon Capital. The company has also received grant funding from The Michael J. Fox Foundation, Innovate UK (Biomedical Catalyst Award), and is the industrial partner for a FightMND Drug Discovery grant awarded to WEHI (Walter and Eliza Hall Institute of Medical Research). Follow us on Twitter and LinkedIn.