MELAS Syndrome

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.

- Independent committee confirms FALCON study is powered for potential success with both alternative endpoints passing futility- -Committee confirms strong safety profile of KL1333- - Abliva to host conference call and webcast on Friday 19 July at 4:30 pm CET / 10:30 am ET – July 18, 2024 -- Abliva AB (Nasdaq Stockholm: ABLI), a clinical-stage company developing drugs for the treatment of rare and severe primary mitochondrial disease, today announced a positive outcome of the interim analysis for FALCON, the potentially registrational study evaluating KL1333 in patients with primary mitochondrial disease. The study evaluates fatigue and myopathy as alternative independent primary endpoints, only one of which is required for a successful study readout. The independent Data Monitoring Committee (DMC) recommended continuing the study without modification. The favorable recommendation by the DMC to continue the FALCON study with a total of 180 patients validates the overall study design and confirms the strong safety profile of KL1333. The DMC has reviewed the 24-week interim data from the Wave 1 patient cohort. In their analysis, the independent group conducted a pre-specified analysis of the conditional power of the two primary endpoints after 24 weeks of dosing. Both endpoints passed futility and the DMC recommended to include a total of 180 patients, increasing the probability of a positive readout upon completion of the full study. The DMC emphasized that KL1333 has a strong safety profile. No safety concerns or drug-related serious adverse events (SAEs) were seen after 24 weeks of dosing. The interim analysis was conducted by an independent committee to maintain the rigor of a blinded study. Statistical significance across the two primary endpoints will be evaluated at the conclusion of the full study. “We are pleased with the positive outcome of the interim analysis as it highlights the positive risk-benefit of KL1333, de-risking the full study, increasing our confidence in KL1333’s novel mechanism of action and the FALCON study design” said Ellen K. Donnelly, Chief Executive Officer of Abliva. “There are currently no approved therapies for mitochondrial disease and with over 85,000 people affected across the US and Europe, we believe KL1333 is well-positioned to address this high unmet medical need and reach blockbuster potential in key geographies. KL1333 has the potential for an expedited path to market and we are committed to rapidly advancing this important medicine towards approval, with plans to start the final wave of FALCON study recruitment in the second half of 2024.” Abliva will host an investor call on Friday, July 19, 2024, at 10:30 AM ET / 4:30 PM CET, to discuss the positive outcome of the interim analysis for FALCON. A live question and answer session will follow the formal presentation. To register, click here. If you would like to ask a question during the live Q&A, please submit your request to questions@lifesciadvisors.com. FALCON is a Phase 2, global, randomized, placebo-controlled, potentially registrational trial evaluating the safety and efficacy of KL1333 in adult patients with primary mitochondrial disease who experience consistent, debilitating fatigue and myopathy. Patients with mitochondrial DNA mutations who meet the eligibility criteria are randomized 3:2 to receive KL1333 (50mg-100mg) or placebo twice daily for 48 weeks. The two alternate primary endpoints assess chronic fatigue (using the PROMIS Fatigue Mitochondrial Disease Short Form) and muscle weakness (using the 30 second Sit-to-Stand test), the most common and debilitating disease expressions in mitochondrial disease patients. Primary mitochondrial disease affects the ability of cells to convert energy. The disease can manifest itself very differently depending on the organs impacted and the number of dysfunctional mitochondria in that organ. Historically viewed as clinical syndromes, our knowledge about the various mutations underlying mitochondrial disease has increased, improving our ability to identify and treat these patients. It is estimated that 125 people per million have primary mitochondrial disease. It often presents in early childhood and leads to severe symptoms, such as mental retardation, fatigue, myopathy, heart failure and rhythm disturbances, diabetes, movement disorders, stroke-like episodes, and epileptic seizures. Abliva’s lead candidate, KL1333, has been designed to treat chronic fatigue and myopathy (muscle weakness) in genetically confirmed adult patients with primary mitochondrial disease. Diagnoses can include MELAS-MIDD and KSS-CPEO spectrum disorders as well as MERRF syndrome. The drug candidate is intended for long-term oral treatment. KL1333 has the ability to restore the ratio of NAD+ and NADH, and thus leads to the formation of new mitochondria and improved energy levels. In a cohort of mitochondrial disease patients in a Phase 1a/b study, the patients who received KL1333 showed both improvements in symptoms of fatigue as well as functional improvements. KL1333 is currently being evaluated in a global, potentially registrational, Phase 2 study (the FALCON study) and has received orphan drug designation in both the USA and Europe as well as Fast Track designation in the USA. Abliva discovers and develops medicines for the treatment of mitochondrial disease. This rare and often very severe disease occurs when the cell’s energy provider, the mitochondria, do not function properly. The company has prioritized two projects. KL1333, a powerful regulator of the essential co-enzymes NAD⁺ and NADH, has entered late-stage development. NV354, an energy replacement therapy, has completed preclinical development. Abliva, based in Lund, Sweden, is listed on Nasdaq Stockholm, Sweden (ticker: ABLI). For more information, please visit www.abliva.com. Subscribe to our news and follow us on LinkedIn and YouTube. The content above comes from the network. if any infringement, please contact us to modify.

A new study from deCODE genetics uses pedigrees and sequence data from 64,806 Icelanders to shed light on the rate and nature of mutations in mitochondrial DNA (mtDNA) and the peculiar dynamics of its maternal transmission REYKJAVIK, Iceland, June 7, 2024 /PRNewswire/ -- In a paper published today in Cell, scientists from deCODE genetics, a subsidiary of Amgen, present the largest study to date of germline mtDNA mutations in humans and their transmission across 116,663 mother-child pairs. The study documents the astonishing extent of hypermutability at some positions in mtDNA, including the well-known deleterious A>G mutation at position 3243 which causes the MELAS syndrome. The mutation occurred 15 times in the 2,548 matrilineal pedigrees, but typically disappeared after several generations, due to its severe impact on the health of carriers. Continue Reading Kari Stefansson senior author on the paper and CEO of deCODE genetics with Agnar Helgason and Erla Rut Arnadottir, scientists at deCODE genetics and authors on the paper Strong aggregate evidence was uncovered for selection against many such short-lived deleterious mtDNA mutations in the pedigrees. The deCODE team also reported evidence for an extensive earlier episode of negative selection affecting mitochondria, called germline selection, where poorly functioning mitochondrial DNA molecules are discarded during the development of oocytes. Finally, they used the large number of transmissisons of mtDNA mutations in the pedigrees to reliably estimate that individuals inherit, on average, only around 3 units of mtDNA from their mothers – fewer than indicated by previous studies. "It is remarkable that the hundreds of thousands of mtDNA carried by oocytes are derived from only about three of the mtDNA molecules originally carried by the mother," noted Agnar Helgason, a corresponding author of the paper. "This drastic bottleneck determines the rapid rate at which new mutations in the mtDNA germline can become lost or fixed over just a handful of generations in a pedigree, and must be in part due to a selection process during the development of oocytes, where mtDNA molecules with deleterious mutations are removed from the germline." "This study takes us a few steps closer to understanding the basis of the extraordinary variation in mutation rates across the nucelotides of the mtDNA genome, even between different alleles at the same position", said Kári Stefánsson, CEO of deCODE and a corresponding author of the paper. "Unfortunately, it is the hypermutability of some pathogenic mutations that has made them so prevalent and thereby easier to discover. However, our findings suggest that many rarer pathogenic mtDNA mutations that are responsible for disease burden in human populations remain to be discovered." Video: Contact: Thora Kristin Asgeirsdottir deCODE genetics 354 894 1909 Email: thoraa@decode.is Photo - Logo - SOURCE deCODE genetics