Leigh Disease

RADNOR, Pa.--( BUSINESS WIRE )-- Marinus Pharmaceuticals , Inc. (Nasdaq: MRNS), a pharmaceutical company dedicated to the development of innovative therapeutics to treat seizure disorders, today announced agenda topics and speakers for its upcoming Investor & Analyst Day on Friday, September 20 from 9:00 a.m. to 12:00 p.m. ET in New York. The event will feature presentations from Marinus’ leadership and key opinion leaders (KOLs) with a focus on the development program and commercial launch preparations for ZTALMY ® (ganaxolone) oral suspension CV in tuberous sclerosis complex (TSC). Marinus’ leadership will provide updated baseline patient demographics and characteristics from the Phase 3 TrustTSC trial and discuss the market opportunity in TSC. KOLs will share their clinical experiences with TSC, present new open label extension data from Marinus’ Phase 2 TSC clinical trial, and provide an overview on the burden of illness, current treatment landscape, and limitations. In addition, Marinus’ leadership will highlight how the Company is planning to expand its clinical pipeline with development programs in other neurodevelopmental epilepsies, pending the results of the TrustTSC trial which is expected to readout topline data in the first half of the fourth quarter of 2024. Marinus Speakers: Scott Braunstein, M.D., Chairman of the Board and Chief Executive Officer Steven E. Pfanstiel, Chief Financial Officer and Chief Operating Officer Joseph Hulihan, M.D., Chief Medical Officer Christy Shafer, Chief Commercial Officer Alex Aimetti, Ph.D., Chief Scientific Officer Sonya Weigle, Chief People and Investor Relations Officer Lisa Lejuwaan, Senior Vice President and Business Unit Lead, Rare Genetic Epilepsy KOL Speakers : Dr. Mary Kay Koenig, M.D., Director of the Center for Treatment of Pediatric Neurodegenerative Disease (CTPND), Director of Research for the Division of Child and Adolescent Neurology at the University of Texas McGovern Medical School Dr. Rajsekar R. Rajaraman, M.D., M.S., Director of the UCLA Tuberous Sclerosis Center of Excellence and the UCLA CDKL5 Center of Excellence, Associate Professor in Pediatric Neurology at UCLA Mattel Children's Hospital In-person attendance is open to invited research analysts and institutional investors. All others are invited to watch the live video webcast. Live questions will be taken by in-person guests, and virtual participants may submit questions through the webcast platform. To register for the video webcast, please visit the Investor Relations section of the Company's website at https://ir.marinuspharma.com/events-and-presentations/ . A replay of the webcast will be archived on the Investor Relations section of the Company's website following the event. Featured KOL Speaker Biographies: Dr. Mary Kay Koenig serves as the Director of the CTPND and Director of Research for the Division of Child & Adolescent Neurology at the University of Texas McGovern Medical School. Dr. Koenig attended the University of Texas in Austin where she received a Bachelor of Arts in Biochemistry. Following undergraduate school, Dr. Koenig received a Master's of Science in Microbiology at Southwest Texas State University followed by her Medical Doctorate at St. George’s School of Medicine. After medical school, Dr. Koenig completed a pediatrics residency at the University of Texas Medical Branch in Galveston and a fellowship in Child and Adolescent Neurology at The University of Texas Medical School. Upon completion of her fellowship, she joined the faculty and is now a tenured professor. She has served as the director for the UT Mitochondrial Center of Excellence since 2007, the co-Director for the UT Memorial Hermann Tuberous Sclerosis Clinic since 2007, and the Leigh Syndrome clinic director since 2013. Dr. Koenig strives to provide excellent clinic care and advance research for children afflicted with genetic neurodegenerative disease. She also works to mentor and educate junior faculty, fellows, residents, and medical students in the art of medicine and clinical research. Dr. Rajsekar "Raj" Rajaraman is an Associate Professor in Pediatric Neurology at the UCLA Mattel Children's Hospital. He completed his Pediatric Neurology residency, Clinical Neurophysiology fellowship, and Epilepsy fellowship training at UCLA. A native of New Jersey, Dr. Rajaraman completed his pediatrics residency at the Unterberg Children's Hospital at Monmouth Medical Center in New Jersey. During his pediatric residency, his exposure to seizures and the effects that epilepsy has on the patient and family led to him pursuing a career in pediatric epileptology at UCLA. Currently, his clinical and research interests involve all aspects of infantile spasms, as well as its effects in Tuberous Sclerosis and CDKL5 Deficiency Disorder. Dr. Rajaraman is currently the Director of the UCLA Tuberous Sclerosis Center of Excellence as well as the UCLA CDKL5 Center of Excellence. He is the primary investigator of over a dozen pharmaceutical and investigator driven clinical trials and studies. He has presented research at multiple conferences, including the American Academy of Neurology, Child Neurology Society, and the American Epilepsy Society, receiving achievements including the national 2014 American Epilepsy Society Young Investigator Award. Dr. Rajaraman has multiple publications on rare developmental epileptic encephalopathies (DEE). In addition to his clinical and research interests, Dr. Rajaraman is an active member of the American Academy of Neurology (AAN) and American Epilepsy Society (AES). He volunteers for the Epilepsy Foundation of Greater Los Angeles, including helping at their annual Walk to End Epilepsy at the Rose Bowl, as well as the Epilepsy Awareness Day at Disneyland. About Marinus Pharmaceuticals Marinus is a commercial-stage pharmaceutical company dedicated to the development of innovative therapeutics for seizure disorders. The Company’s product, ZTALMY ® (ganaxolone) oral suspension CV, is an FDA-approved prescription medication introduced in the U.S. in 2022. For more information, please visit www.marinuspharma.com and follow us on Facebook , LinkedIn and X .

Khondrion appoints Jasper Levink as Chief Financial and Business Officer NIJMEGEN, the Netherlands – 11 September 2024: Khondrion, a clinical stage biopharmaceutical company discovering and developing therapies targeting primary mitochondrial diseases, today announces the appointment of Jasper Levink MSc, as Chief Financial and Business Officer, effective immediately. Prof. Dr. Jan Smeitink, Chief Executive Officer at Khondrion, said: “We are delighted to welcome Jasper to the Khondrion Leadership Team as our new Chief Financial and Business Officer. His financial and business development experience will be extremely important as we continue to execute our strategy, progressing our late stage candidate, sonlicromanol, alongside the development of our pipeline and expansion of our clinical capabilities.” Jasper Levink, Chief Financial and Business Officer at Khondrion, added: “I am excited to be joining Khondrion at a pivotal time in its development, helping to drive the Company’s mission of bringing clinically meaningful medicines to patients living with devastating mitochondrial diseases. After the successful completion of four clinical trials of sonlicromanol and with preparations underway for registrational phase 3 studies, I am eager to bring my financial, operations and business development experience to the accomplished team and to work with medical and patient communities to leverage the transformational potential of sonlicromanol for people living with primary mitochondrial diseases.” Mr. Levink has over a decade of experience in business development and finance in biotech. Earlier roles include Partner and Managing Director at ttopstart, a boutique consulting company dedicated to business development and finance in biotech, and CBO at LenioBio, a German biotech pioneering the first eukaryotic cell-free protein expression platform. Recently he has taken up the role of CEO at SixtyFour Therapeutics, an early-stage biotech company developing therapies against autoimmune diseases. He will combine that role with his contributions to Khondrion. – Ends – Contacts: Khondrion BVProf. Dr. Jan Smeitink, CEOE-mail: info@khondrion.com Tel: +31-24-7635000www.khondrion.com ICR Consilium David Daley, Kris Lam Email: khondrion@icrhealthcare.com About KhondrionKhondrion is a clinical stage biopharmaceutical company developing therapies for patients with m.3243A>G primary mitochondrial diseases. The company’s lead asset, sonlicromanol, is a brain- penetrant, reductive and oxidative distress modulator with anti-inflammatory properties. One of the most advanced disease-modifying drug candidates for mitochondrial disease in development, sonlicromanol has been tested in four clinical trials in patients with m.3243A>G primary mitochondrial disease, as well as in the first wave of a 6-month Phase 2 study in children with genetically-confirmed primary mitochondrial diseases and who suffer from motor symptoms. The compound has been granted orphan drug designations for the treatment of MELAS, Leigh disease and patients with maternally inherited diabetes and deafness (MIDD) in Europe, and for all inherited mitochondrial respiratory chain disorders in the US. It has also been granted a Rare Pediatric Disease designation in the US for the treatment of MELAS. Sonlicromanol and other compounds from Khondrion’s proprietary library have the potential to be developed for a wide range of diseases and conditions with the aim of benefiting patients whose daily lives are severely impacted by mitochondrial impairment. For more information visit www.khondrion.com. About mitochondrial disease Mitochondrial disease occurs when mitochondria, found within all cells of the human body and responsible for producing the energy necessary for cells to function, are defective. This can result in a wide range of serious and debilitating illnesses occuring shortly after birth or later in life. Signs and symptoms of these can include: cognitive problems, learning disabilities, blindness, deafness, heart failure, diabetes, fatigue, intolerance to exercise, muscle weakness and gait problems, and stunted growth. Orphan diseases of the oxidative phosphorylation system like Leigh disease, MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) spectrum disorders, MIDD (maternally inherited diabetes and deafness), LHON (Leber's hereditary optic neuropathy) and other respiratory chain/ oxidative phosphorylation disorders, are all examples of mitochondrial disease.

TOKYO--( BUSINESS WIRE )--LUCA Science Inc., in collaboration with Osaka University and Washington University School of Medicine in St. Louis, announces the publication of a transformative study in Nature Metabolism demonstrating the potential of mitochondria transfer-based therapies to alleviate symptoms and reduce the morbidity and mortality in a Leigh Syndrome (LS) mouse model. LS is a severe and often fatal inherited mitochondrial disease for which no effective therapies currently exist. The study, titled "Mitochondria Transfer-Based Therapies Reduce the Morbidity and Mortality of Leigh Syndrome," was conducted by an international team of researchers led by principal investigator Dr. Jonathan Brestoff. The research offers compelling evidence that transplantation of healthy wild-type (WT) mitochondria can ameliorate the symptoms and extend the lifespan of Ndufs4–/– mice, a well-established model for studying mitochondrial disease in Leigh Syndrome. Leigh Syndrome is a devastating neurodegenerative mitochondrial disease caused by mutations in genes essential for mitochondrial metabolism, leading to severe metabolic dysfunction. It typically presents in infancy or early childhood with severe symptoms such as muscle weakness, developmental delays, breathing difficulties, and seizures, often leading to a shortened lifespan. This study breaks new ground by showing that wild-type bone marrow transplantation, or administration of isolated mitochondria, can restore mitochondrial function in multiple organs, improve neurological outcomes, enhance energy expenditure, and extend lifespan in LS-affected mice. “Patients with LS and their families are in need of new therapies, and I hope that our studies open the possibility of using mitochondria transplantation to treat LS and other mitochondrial diseases,” said Dr. Jonathan Brestoff, senior author and Assistant Professor of Pathology and Immunology at WashU School of Medicine in St. Louis. “We are excited to present these findings, which demonstrated a convincing preclinical proof-of-concept in the therapeutic potential of mitochondria transfer in treating inherited mitochondrial diseases,” said Dr. Rick C. Tsai, one of the co-authors and CEO at LUCA Science. “We have established a manufacturing process that enables the production of off-the-shelf MRC-Q, and we are ready to initiate GMP development activities to advance MRC-Q towards clinical development. The study’s key findings include: - Wildtype Bone Marrow Transplantation: WT bone marrow transplantation led to significant improvements in the morbidity and mortality of Ndufs4–/– mice, correlating with the release of extracellular mitochondria and transfer of healthy mitochondria to diseased cells across multiple organs. - Autologous Mitochondria Transfer: Administration of isolated WT mitochondria extended lifespan, improved neurological function, and enhanced energy expenditure in LS-affected mice. - Cross-Species Mitochondria Transfer: Remarkably, storable human M itochondria o R ganelle C omplex Q (MRC-Q) by LUCA Science Inc. administered to Ndufs4–/– mice also ameliorated the symptoms of LS, suggesting the broader applicability of MRC-Q as biopharmaceutical therapies. This publication marks a significant milestone in the field of mitochondrial medicine and underscores the potential of mitochondria transfer as a therapeutic strategy for treating complex mitochondrial disorders. LUCA Science remains committed to advancing this research with the ultimate goal of developing effective treatments for patients suffering from mitochondrial diseases. The full paper is available in the latest issue of Nature Metabolism TITLE: Mitochondria transfer-based therapies reduce the morbidity and mortality of Leigh syndrome DOI: 10.1038/s42255-024-01125-5 LINK: https://www.nature.com/articles/s42255-024-01125-5 About LUCA Science Inc. LUCA Science is a pioneering biotechnology company focused on developing innovative therapies based on mitochondrial biology. The company’s mission is to harness the power of mitochondria to treat a wide range of diseases, including neurodegenerative disorders, cardiovascular diseases, and metabolic conditions. With cutting-edge research and a commitment to improving patient outcomes, LUCA Science is leading the way in mitochondrial medicine.