Mitochondrial Respiratory Chain Deficiencies

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

NIJMEGEN, Netherlands, Nov. 1, 2023 /PRNewswire/ -- Khondrion, a clinical stage biopharmaceutical company discovering and developing therapies targeting primary mitochondrial diseases, today announced that the United States Patent and Trademark Office and the European Patent Office have granted patents covering the use of Khondrion's lead compound sonlicromanol as an [mPGES-1 inhibiting] anti-inflammatory agent. Sonlicromanol works in three distinct ways by modulating oxidative and reductive distress, along with anti-inflammatory properties. The compound is currently under investigation for its effectiveness in treating adult patients diagnosed with primary mitochondrial disease due to the m.3243A>G mutation in their mitochondrial DNA. This mutation is linked to various conditions such as classical MELAS and MIDD syndromes, CPEO, and mixed phenotypes. Sonlicromanol targets the key underlying mechanisms shared by many mitochondrial diseases, including high levels of reactive oxygen species, disrupted redox metabolism, and inflammation induced by PGE2. Research has demonstrated that sonlicromanol acts as a selective inhibitor of microsomal Prostaglandin E-synthase 1 (mPGES-1), contributing to its anti-inflammatory impact. Preclinical studies conducted in other disease models with elevated levels of cellular mPGES-1, such as particular prostate cancer cells, have displayed encouraging outcomes. These findings suggest a wider range of potential applications for sonlicromanol beyond its initial focus on primary mitochondrial diseases. "The distinctive triple mode of action of sonlicromanol has the potential to play an important role not just in primary mitochondrial diseases but also in in a range of rare and more prevalent disorders," said Prof. dr. Jan Smeitink, Chief Executive Officer at Khondrion. "This US and European patent issuance significantly strengthen our intellectual property portfolio and stands as a crucial step in the broader development of sonlicromanol." The US patent titled "Compounds as mPGES-1 inhibitors" was issued as U.S. patent No. 11,672,787 on June 13, 2023. Its European equivalent was granted on October 19, 2023 as EP 18808288. About Khondrion Khondrion is a clinical stage biopharmaceutical company developing therapies for patients with inherited mitochondrial diseases. Based on proprietary science and a deep biological understanding of mitochondrial dysfunction, the company is advancing its lead drug candidate sonlicromanol. Sonlicromanol is a first-in-class, oral small molecule targeting key underlying mechanisms of primary mitochondrial disease based on its uniquely differentiated triple mode of action: reductive distress modulation to help restore the cell's metabolism, oxidative distress modulation preventing ferroptotic cell death, and selective mPGES-1 inhibition resulting in anti-inflammatory effects. Based on the favourable benefit-risk profile shown across the clinical studies performed so far, Khondrion is finalizing the design of a global Phase 3 study which is currently foreseen to start in H2 2024. 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. Ongoing preclinical research of sonlicromanol shows potential broader applications of the drug in other rare diseases and more common disorders. For more information visit . About mitochondrial disease Mitochondrial disease is caused by defective mitochondria, which are present in all cells of the human body and are responsible for generating the energy necessary for cells to function. This can lead to a wide range of serious and debilitating illnesses that can appear shortly after birth or later in life. Signs and symptoms of these conditions may include issues with thinking, learning difficulties, blindness, deafness, heart failure, diabetes, fatigue, intolerance to exercise, muscle weakness walking difficulties, and stunted growth. Orphan diseases of the oxidative phosphorylation system like Leigh disease, MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) spectrum disorders including MIDD (maternally inherited diabetes and deafness), and other respiratory chain / oxidative phosphorylation disorders, are all examples of mitochondrial disease. MELAS spectrum disorders are some of the most frequently observed primary mitochondrial diseases, in which all patients are characterized by an underlying point mutation (m.3243A>G) in the maternally inherited MT-TL1 gene. Forward-looking statements This press release may contain certain forward-looking statements regarding, among other things, the results, conduct, progress and timing of the company's clinical trials and presentation of data from clinical trials for sonlicromanol. Although the company believes its expectations are based on reasonable assumptions, all statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the company's control. These statements may include, without limitation, any statements preceded by, followed by or including words such as "target," "believe," "expect," "aim," "goal," "intend," "may," "anticipate," "foreseen," "estimate," "plan," "project," "will," "can have," "likely," "potential," "should," "would," "could" and other words and terms of similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the company's control that could cause the company's actual results, performance or achievements to be materially different from the expected results, performance or achievements expressed or implied by such forward-looking statements. Except as required by law, the company assumes no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. Contacts: Khondrion BV Prof. Dr. Jan Smeitink, CEO E-mail: [email protected] Tel: +31-24-7635000 LifeSpring Life Sciences Communication, Amsterdam Leon Melens E-Mail: [email protected] Tel: +31-6-53816427 Logo - SOURCE Khondrion

Researchers have found an anti-aging function in a protein deep within human cells. Researchers have discovered that a protein called ATSF-1 controls a fine balance between the creation of new mitochondria and the repair of damaged mitochondria. Researchers at The University of Queensland have found an anti-ageing function in a protein deep within human cells. Associate Professor Steven Zuryn and Dr Michael Dai at the Queensland Brain Institute have discovered that a protein called ATSF-1 controls a fine balance between the creation of new mitochondria and the repair of damaged mitochondria. Mitochondria, with their own DNA, produce energy within cells to power biological functions but the toxic by-products of this process contribute to the rate at which the cell ages. "In conditions of stress, when mitochondrial DNA has been damaged, the ATSF-1 protein prioritises repair which promotes cellular health and longevity," Dr Zuryn said. As an analogy, Dr Zuryn likened the relationship to a race car needing a pitstop. "ATSF-1 makes the call that a pitstop is needed for the cell when mitochondria need repairs," he said. "We studied ATFS-1 in C. elegans, or round worms and saw that enhancing its function promoted cellular health, meaning the worms became more agile for longer. "They didn't live longer, but they were healthier as they aged." "Mitochondrial dysfunction lies at the core of many human diseases, including common age-related diseases such as dementias and Parkinson's. "Our finding could have exciting implications for healthy ageing and for people with inherited mitochondrial diseases." Understanding how cells promote repair is an important step towards identifying possible interventions to prevent mitochondrial damage. "Our goal is to prolong the tissue and organ functions that typically decline during ageing by understanding how deteriorating mitochondria contribute to this process," Dr Dai said. "We may ultimately design interventions that keep mitochondrial DNA healthier for longer, improving our quality of life," Dr Dai said. This research was published in Nature Cell Biology.