Ophthalmoplegia, Chronic Progressive External

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

ROCKVILLE, Md. and SUZHOU, China, Oct. 8, 2023 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, announces that the first patient with neovascular age-related macular degeneration (nAMD) has been successfully dosed in the Phase 3 clinical study (STAR) of efdamrofusp alfa (IBI302), a recombinant fully human anti-VEGF and anti-complement bispecific fusion protein. STAR is a randomized, double-masked, active-controlled Phase 3 clinical study to evaluate the efficacy and safety of intravitreal 8 mg IBI302 in subjects with nAMD to support the potential new drug application for IBI302 (CTR20232229, ClinicalTrials.gov Identifier: NCT05972473). A total of 600 subjects will be enrolled and randomized to 8mg IBI302 arm and 2mg aflibercept arm in a 1: 1 ratio: all subjects will have visits every 4 weeks (Q4W) for the entire study duration; subjects assigned to IBI302 arm will receive 8mg IBI302 intravitreal injections (Q4W) up to Week 8, followed by 8mg IBI302 intravitreal injections according to a personalized treatment intervals (PTI) dosing regimen; subjects randomized to the aflibercept active control arm will receive 2mg aflibercept intravitreal (Q4W) up to Week 8, followed by 2mg aflibercept intravitreal (Q8W). The primary endpoint is change from baseline in best corrected visual acuity (BCVA) letters in the study eye based on an average at week 44, 48, and 52. All subjects will continue to receive intravitreal injections up to Week 96, with a final study visit at Week 100. IBI302, the first-in-class bispecific fusion protein targeting VEGF and complement, can simultaneously inhibit VEGF-mediated signaling pathways and attenuate inflammatory responses mediated by complement activation. The results of the two Phase 2 clinical studies have demonstrated the favorable safety and efficacy of IBI302 in patients with nAMD, as well as the advantages of long-interval dosing: in terms of efficacy, improvements in BCVA, retinal thickness, and leakage and total area of neovascularization, with potential improvements in macular atrophy and fibrosis have been observed; The overall safety profile was favorable and similar to existing anti-VEGF agents. Professor Xiaodong Sun, Deputy Director of Shanghai General Hospital, Head of Ophthalmology Centre, Principal Investigator of the study, stated, "Currently, anti-VEGF drugs are the first-line treatment for nAMD. However, this treatment is associated with several limitations, such as frequent injections, long-term efficacy attenuation, and suboptimal outcomes for some patients, imposing significant inconvenience and economic burden to the majority of patients. Therefore, there remains a significant unmet clinical need. IBI302 as a global first-in-class anti VEGF-complement dual targeting drug, has demonstrated promising efficacy signals in completed Phase 1 and Phase 2 clinical studies, including improvements in visual acuity and reduction in retinal edema, while exhibiting favorable safety profiles. Preliminary positive signals have also been observed in the inhibition of fibrosis and macular atrophy. This has instilled great confidence in our researchers. We look forward to the upcoming Phase III STAR trial, and hope that IBI302 will not only overcome the current treatment limitations, prolong dosing intervals, reducing the burden of injections on patients, but also demonstrate its potential advantages in long-term anti fibrosis and macular atrophy improvement. This will ultimately offer a more patient-friendly dosing regimen and longer-lasting visual benefits to patients. " Dr. Lei Qian, Vice President of Clinical Development of Innovent, stated: " As globally the first anti-VEGF and anti-complement bispecific molecule, IBI302 is an innovative drug of Innovent with global proprietary right for the treatment of fundus diseases. The preliminary results of the Phase 1 and Phase 2 clinical studies have demonstrated a favorable safety and efficacy profile, we are encouraged to advance it into next stage of development. In the STAR study, our focus will not only be on improvement of visual acuity and retinal thickness but also on exploring the efficacy of 8mg IBI302 in extended dosing intervals. We look forward to the success of IBI302 in the STAR Phase 3 trial, to provide patients with a more effective and safe clinical treatment regimen as soon as possible." About neovascular age-related macular degeneration (nAMD) Age-related macular degeneration (AMD) is a chronic progressive ocular disease that affects the macula of the retina, resulting in central visual impairment, and its incidence increases with age. As a main type of AMD, nAMD accounts for 15% to 20% of all AMD patients and is the leading cause of central vision loss in AMD patients over 65 years of age. AMD has now leapt to the third leading cause of blindness in China with increasing incidence over years. The pathogenesis of nAMD has not been fully elucidated. It is generally recognized that increased VEGF over expression- induced angiogenesis is the main cause of nAMD. In addition, the inflammatory response mediated by abnormal activation of complement is also considered to be an important cause of AMD. Although ophthalmic anti-VEGF agents have brought significant visual benefits and alter the course of nAMD, the current frequent dosing (every 4 or 8 weeks) poses a heavy burden on patients, families, and the society. Besides, the visual benefits of anti-VEGF therapy are lost by years with prolonged treatment. In about two-thirds of patients with more than 7 years of follow-up, the visual benefit conferred by anti-VEGF therapy is greatly lost. Macular atrophy or retinal fibrosis is primarily responsible for the loss of visual benefits after long-term anti-VEGF treatment. Currently, drug development for nAMD mainly focuses on prolonging dosing intervals, and there are few drugs under development for macular atrophy or retinal fibrosis. About Efdamrofusp Alfa (IBI302) IBI302 is a recombinant fully human bispecific fusion protein of Innovent Biologics with global proprietary rights. The N-terminus is a VEGF domain that can bind to the VEGF family, block VEGF-mediated signaling pathway, inhibit vascular epithelium proliferation and angiogenesis, and improve vasopermeability and reduce leakage. The C-terminus of IBI302 is the complement binding domain that can inhibit the activation of the classic pathway and alternative pathway of complement through the specific binding of C3b and C4b, and reduce the inflammatory response mediated by the complement. IBI302 may exert its therapeutic effect by inhibiting both VEGF-mediated angiogenesis and complement activation pathways. About Innovent Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to discover and develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to discovering and developing, manufacturing and commercializing high-quality innovative medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, and ophthalmology diseases to enhance the quality of the patients' lives. Innovent has 10 products in the market, including TYVYT® (Sintilimab Injection), BYVASDA® (Bevacizumab Injection), SULINNO® (Adalimumab Injection), HALPRYZA® (Rituximab Injection), Pemazyre® (Pemigatinib Oral Inhibitor), olverembatinib, Cyramza® (Ramucirumab Injection), Retsevmo® (Selpercatinib Capsules), FUCASO® (Equecabtagene Autoleucel Injection) and SINTBILO® (Tafolecimab Injection). Additionally, 7 assets are in Phase III or pivotal clinical trials, and 17 more molecules are in early clinical stage. Innovent has also entered into 30 strategic collaborations with Eli Lilly, Roche, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. We strive to work with many collaborators to help advance the biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. Note: TYVYT®, BYVASDA®, SULINNO®, HALPRYZA®, olverembatinib, FUCASO® and SINTBILO® are not approved products in the United States. TYVYT® (sintilimab injection, Innovent) BYVASDA® (bevacizumab injection, Innovent) HALPRYZA® (rituximab injection, Innovent) SULINNO® (adalimumab injection, Innovent) Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan. CYRAMZA® (ramucirumab injection, Eli Lilly). Cyramza® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China. Retsevmo® (selpercatinib capsules, Eli Lilly). Retsevmo® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China. Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions. Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. SOURCE Innovent Biologics

Researchers found that altered B cell function in children with mitochondrial disorders led to a weaker and less diverse antibody response to viral infections. Researchers analyzed gene activity of immune cells in children with mitochondrial disorders and found that B cells, which produce antibodies to fight viral infections, are less able to survive cellular stress. In a new study, National Institutes of Health (NIH) researchers found that altered B cell function in children with mitochondrial disorders led to a weaker and less diverse antibody response to viral infections. The study, published in Frontiers in Immunology was led by researchers at the National Human Genome Research Institute (NHGRI), who analyzed gene activity of immune cells in children with mitochondrial disorders and found that B cells, which produce antibodies to fight viral infections, are less able to survive cellular stress. "Our work is one of the first examples to study how B cells are affected in mitochondrial disease by looking at human patients," said Eliza Gordon-Lipkin, M.D., assistant research physician in NHGRI's Metabolism, Infection and Immunity Section and co-first author of the paper. Mitochondria are important components of nearly every cell in the body because they convert food and oxygen into energy. Genomic variants in more than 350 genes have been linked to mitochondrial disorders with varied symptoms depending on which cells are affected. "For children with mitochondrial disorders, infections can be life threatening or they can worsen the progression of their disorder," said Peter McGuire, M.B.B.Ch, NHGRI investigator, head of the Metabolism, Infection and Immunity Section and senior author of the study. "We wanted to understand how immune cells differ in these patients and how that influences their response to infections." Around 1 in 5,000 people worldwide have a mitochondrial disorder. Examples of mitochondrial disorders are Leigh's syndrome, which primarily affects the nervous system, and Kearns-Sayre syndrome, which primarily affects the eyes and heart. While mitochondrial disorders are known to affect organs such as the heart, liver, and brain, less is known how they affect the immune system. Using a genomic technique called single-cell RNA sequencing, which analyzes gene activity in different cell types, researchers studied immune cells found in blood. These cells include different types of white blood cells that help the body fight infections. During stressful conditions, these cells produce a microRNA called mir4485. MicroRNAs are small strings of RNA that help control when and where genes are turned on and off. mir4485 controls cellular pathways that help cells survive. "We think that B cells in these patients undergo cellular stress when they turn into plasma cells and produce antibodies, and these B cells then try to survive by producing the microRNA to cope," said Dr. McGuire. "But the B cells are too fragile due to their limited energy, so they are unable to survive the stressful conditions." Researchers used a technique called VirScan to look at all past viral infections, assess how well the immune system fought those infections and see the effects of B cells and plasma cells on antibody production. With a weaker antibody response, the immune systems in children with mitochondrial disorders are less able to recognize and neutralize invading viruses and clear infections. Researchers aim to use the results of this study to guide future treatment of patients with mitochondrial disorders, noting that more translational studies are needed in this research area.