Mitochondrial Respiratory Chain Deficiencies

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.

CT LVAS scans, analyzes CT images providing rich data on regional lung function—enables radiologists to furnish new levels of quantified, data-based correlation between function and structure to patients' physicians—using existing CT scanning equipment. LOS ANGELES, Nov. 22, 2023 /PRNewswire/ -- 4DMedical, the leading producer of advanced lung function imaging software has received FDA clearance for its CT-based ventilation product (CT LVAS™). CT LVAS, designed for use with computed tomography scans, joins 4D Medical's XV LVAS® imaging software cleared for use with fluoroscopy In the United States. The FDA clearance for CT LVAS dovetails with the upcoming 4DMedical product, CT:VQ™. CT:VQ will enable quantitative perfusion (blood flow) data and visualizations to be extracted from CT scans. Standard CT images provide clinicians with structural detail about patients' lungs—from which they try to infer information about disease and function. CT LVAS adds a wealth of data on lung performance on top of the structural detail of CT scans. This capability fills an information gap that enables radiologists to provide the objective, data-driven information that could materially inform diagnosis and treatment options. Greg Mogel, MD, consultant radiologist at 4DMedical notes, "Having assisted with image interpretation of CT LVAS exams in Australia, I've seen the diagnostic power of adding functional assessment to the structural information provided in standard non-contrast chest CTs. CT LVAS allows radiologists to provide a whole new dimension of lung health information to referring clinicians needing answers. I look forward to sharing this release at the upcoming RSNA." CT LVAS software processes existing CT scans using sophisticated algorithms derived from aerospace technology. These highly detailed reports include color-coded images of regional airflow and lung ventilation—overlayed on the patient's CT scan. CT LVAS uses a software-as-a-service model and requires no new capital equipment. Scans from existing CT equipment are uploaded for processing, where they are analyzed and returned to the radiologist as the Ventilation Report. CT LVAS measures lung ventilation in tens of thousands of locations in the lungs. The Regional Ventilation Visualizations provide region-specific ventilation at deep inspiratory breath-hold for a mid-coronal slice and three axial slices—Upper, Middle, and Lower. The regional ventilation data is quantified in lung volume change and regional lung ventilation heterogeneity. "I am excited by the impact CT LVAS will provide caregivers and patients in the U.S." says 4DMedical Founder and CEO Andreas Fouras. "As we head to RSNA, I am thrilled that reimbursement has been approved for our XV LVAS product designed for fluoroscopy, and to also share FDA clearance for CT LVAS in the U.S. We also look towards the commercial release of CT:VQ and the opportunity to combine and provide the two sets of highly quantified lung pulmonary information from CT LVAS and CT:VQ. In healthy lungs, ventilation and perfusion are well-matched, meaning that airflow and blood flow are equally distributed throughout the lungs. 4DMedical's CT:VQ technology will enable regional changes in ventilation and perfusion to be quantified and visualized, allowing a detailed assessment of V/Q mismatch. Clinically, these scans will primarily be used for diagnosing pulmonary embolism, but they can also be employed to assess conditions such as chronic obstructive pulmonary disease, pulmonary hypertension, and to evaluate pulmonary vascular disorders. Importantly, perfusion (blood flow) data and visualizations from CT:VQ can be combined with the ventilation data and visualizations provided by CT LVAS--for a highly quantified picture of lung performance. About 4DMedical 4DMedical Limited (ASX:4DX) is a global medical technology company that has created a step change in the capacity to accurately and quickly understand the lung function of patients with respiratory diseases. Through its flagship patented XV Technology®, 4DMedical enables physicians to understand regional airflow in the lungs and identify respiratory deficiencies earlier and with greater sensitivity as they breathe. This technology powers 4DMedical's FDA-cleared XV Lung Ventilation Analysis Software (XV LVAS) - the first modality to dynamically quantify ventilation throughout the lungs, and its FDA-cleared Computed Tomography-enabled counterpart software, CT LVAS. XV LVAS and CT LVAS reports are prepared using 4DMedical's Software as a Service delivery model using existing clinical imaging equipment or the Company's revolutionary XV Scanner. To learn more, please visit . CONTACT: Colin Reed [email protected] SOURCE 4DMedical