TDP-43 Proteinopathies

Fabio Dorigotti brings over 25 years of clinical development experienceJoins Actimed following retirement of Frank Misselwitz London, UK – 16 January 2025. Actimed Therapeutics, a UK based clinical stage speciality pharmaceutical company focused on bringing innovation to the treatment of cancer cachexia and other muscle wasting disorders, announces the appointment of Dr Fabio Dorigotti as Chief Medical Officer (CMO) following the retirement of previous CMO, Frank Misselwitz MD. Prior to joining Actimed, Dr Dorigotti was CMO of Swiss biopharmaceutical company Quercis Pharma. He brings over 25 years of pharmaceutical industry experience spanning the full breadth of the clinical development process. Robin Bhattacherjee, Actimed CEO, commented: “I am very pleased to welcome Fabio as our new Chief Medical Officer as we focus on advancing our lead candidate ACM001.1 (S-pindolol benzoate) for cancer cachexia into late-stage clinical development. Fabio brings a wealth of relevant knowledge and experience and a proven track record of success. I would also like to take this opportunity to thank our retiring CMO Frank Misselwitz for his invaluable contribution to Actimed over the last several years and am delighted that he will retain his role as a Non-Executive Director on the Board of the company.” During his career, Dr Dorigotti has held inhouse roles of Head of Global Medical Affairs for CSL Vifor and Medical Affairs Director at Astrazeneca, and as Chief Strategy Officer and President of Global Clinical for Worldwide Clinical Trials, a full-service global contract research organization (CRO). He brings a strong track record of successful clinical development and product marketing approvals, alongside a deep understanding of FDA, EMA and other regulatory agencies. Dr Dorigotti commented: “Joining Actimed as CMO provides me with an exciting opportunity to bring my skills and experience to bear in the further development of products that could fill an unmet medical need and benefit patients with serious muscle wasting disorders. I look forward to collaborating with the excellent team at Actimed to help drive the further progress of this exciting candidate and the company.” *** About Actimed Therapeutics Actimed Therapeutics is a clinical stage speciality pharmaceutical company focused on bringing innovation to the treatment of muscle wasting disorders to transform the care of an underserved and vulnerable patient population. The lead area of focus for Actimed is specifically in cachexia. Cachexia is a wasting disease that is associated with cancer and other serious chronic illnesses and with significant morbidity and mortality. A significant number of cancer patients suffer from cachexia1 and it is estimated that cachexia is responsible for up to 20% of all cancer deaths2. A recent meta-analysis demonstrated that cachexia was associated with an 82% higher relative risk of mortality in patients with NSCLC versus no cachexia3. Despite its prevalence and devastating clinical effects, there is no globally approved drug for the treatment or prevention of cancer-related cachexia. The lead product of Actimed, S-pindolol benzoate (ACM-001.1) targets multiple pathways that drive cachexia and has generated promising proof of concept Phase 2a clinical data in cachexia patients, with further clinical studies in preparation. Actimed is currently preparing for further clinical studies in cancer cachexia having received an Investigational New Drug (IND) approval from FDA for S-pindolol benzoate in August 2023 for the treatment of cancer cachexia. Actimed also owns the global rights to its second asset, S-oxprenolol (ACM-002), which is being developed by the Company for the muscle wasting seen in amyotrophic lateral sclerosis (ALS) where loss of body mass and muscle wasting may impact survival⁴. Actimed was granted Orphan Drug Designation to S-oxprenolol for the treatment of ALS by the FDA in 2024. Actimed has licensed the global rights to develop and commercialise S-oxprenolol for cancer cachexia and any other indications outside of ALS to US company Faraday Pharmaceuticals. FOR MORE INFORMATIONActimed Therapeuticswww.actimedtherapeutics.com MEDiSTRAVA Frazer Hall, Erica HollingsworthTel: +44 (0)203 928 6900Email: actimed@medistrava.com ___________________________[1] Anker M et al., J. Cachexia, Sarcopenia and Muscle; 2019: 10: 22 – 242 Argilés JM et al, Nat Rev Cancer 2014; 14:754-623 Bonomi P. et al. The mortality burden of cachexia in patients with non-small-cell lung cancer: A meta-analysis; International Conference of Sarcopenia, Cachexia and Wasting Disorders, June 17 – 18 2023, Stockholm, abstract 2-18, page 139⁴ Wolf J et al., PMID 28184974 DOI: 10.1007/s00115-117-0293

NEWTON, Mass.--( BUSINESS WIRE )--Inflammasome Therapeutics ( https://www.inflam.com/ ), a clinical-stage biotech company developing novel, first-in-class dual inflammasome inhibitors for prevalent ophthalmic and neurodegenerative diseases, today announced positive topline 3-month data from a clinical trial of its K8 implant in patients with geographic atrophy (GA), the most serious form of dry age-related macular degeneration (AMD). Positive efficacy and safety data were observed at 3 months after a single injection of K8 in this study conducted at the University of Kentucky (NCT06164587). In the 5 patients with bilateral GA who received a K8 implant in one eye, there was a mean reduction in GA lesion growth of 66% at 3 months compared to the untreated contralateral eyes with GA (p = 0.029, mixed effects model), as measured by fundus autofluorescence (FAF) imaging by an independent masked reading center. Also, in all 5 patients, the GA lesions progressed at a much slower rate in the K8-treated eyes compared to the contralateral eyes. No drug-related intraocular or systemic safety issues were identified, and patients will receive a second K8 injection at month 3 of this 6-month trial. Given the extremely positive efficacy and safety data, the trial has now been expanded to 30 patients (60 eyes). “ We are excited to see such rapid and dramatic reduction of GA lesion growth within only 3 months following a single injection,” said Jayakrishna Ambati, M.D. , co-founder of Inflammasome Therapeutics. “Natural history studies have shown that in bilateral GA patients the lesion growth rates in the two eyes are almost identical, with less than 5% difference between eyes. Therefore, a 66% reduction in K8-treated eyes compared to contralateral eyes of the same patients provides strong evidence of efficacy. K8 has a unique mechanism of action whereby it blocks the effects of complement activation as well as numerous other inflammatory pathways in GA, a multifactorial disease. The rapid, profound, and uniform clinical efficacy seen in all 5 patients in this trial is consistent with the extensive preclinical data showing this multipronged protective action of K8. Remarkably, lesion growth was reduced irrespective of the FAF pattern, whether the lesions were fast- or slow-growing, location or duration of disease, or type of AMD drusen, demonstrating the broad-based action of K8,” continued Dr. Ambati. “ These initial clinical trial results are extremely encouraging, and we look forward to follow-up data from additional patients,” said Paul Ashton, Ph.D., CEO and co-founder of Inflammasome Therapeutics. “We are delighted that a single injection of K8 delivered via our unique drug-delivery technology achieved substantial and rapid efficacy that is much greater and faster than the approximate 20% reduction reported for the two FDA-approved drugs with monthly injections after 12 months. Furthermore, we believe that the statistical significance of the 66% reduction in lesion growth of 66% (p=0.029) compared to the untreated eyes seen with only 5 patients is indicative of the drug’s robust effect. Thus, K8 may present an opportunity to break through the efficacy ceiling observed with the approved anti-complement drugs in GA,” continued Dr. Ashton. The next phase of this 6-month trial will further evaluate safety and efficacy of K8 injected every 3 months in up to 30 participants with GA. The primary endpoints are safety and the difference in GA lesion growth in treated eyes versus contralateral untreated eyes. About Inflammasome Therapeutics and Kamuvudines Inflammasome Therapeutics ( https://www.inflam.com/ ) is a private, clinical-stage, biotech company developing novel, first-in-class, dual inflammasome inhibitors known as Kamuvudines for multiple ocular and neurological diseases. K8, delivered via a sustained-release intravitreous implant, is the Company’s lead product for retinal diseases such as GA. K8 has a unique, differentiated mechanism of action that enables it to block multiple toxic pathways that drive GA. GA affects approximately one million individuals in the US and more than eight million worldwide. In GA, multiple toxic substances including complement, retrotransposons, amyloid β , iron, and reactive oxygen species accumulate in the eye and trigger inflammasome activation as a final common pathway, which then causes cells in the macula to slowly die (atrophy). Over time, the area of atrophy grows in size and can lead to vision loss. The two currently FDA-approved drugs each target just a single toxic substance in the complement pathway but not the many other toxic substances seen in GA. They only modestly slow progression of GA, do not appear to slow down the rate of vision loss, and are associated with increased risk of developing wet AMD. The global annual market for GA has been estimated by Precision Business Insights to exceed $30 billion, and there is tremendous interest in developing new GA therapies. There are 40 interventional clinical trials for GA registered in ClinicalTrials.gov, almost all of which target individual toxic substances. In contrast, K8 blocks inflammasome activation caused by multiple toxic substances that accumulate in GA. Inflammasome Therapeutics believes this differentiated mechanism of action targeting the final common pathway could lead to improved, best-in-disease efficacy. Kamuvudines could also have application in a wide variety of neuro-inflammatory diseases such as ALS, Parkinson’s disease, Alzheimer’s disease, and Multiple Sclerosis. “ Preclinical data show impressive efficacy of Kamuvudine K9 in multiple neurodegeneration models,” said Dr, Ambati. Oral K9 is currently being tested in a clinical trial in subjects with Thyroid Eye Disease (NCT06467435). “ We have Kamuvudines specifically designed for neurological diseases that penetrate into the brain and central nervous system from a simple oral tablet. Inflammasome Therapeutics expects to begin clinical trials in some neurodegenerative diseases soon as well,” Dr. Ashton said. Dr. Ambati has spent more than a decade developing Kamuvudines and identifying their role in the inhibition of inflammasome activity that is now recognized to be the critical driving force of many chronic diseases. In a series of publications in journals such as Science and Nature , his group has described the basic research on GA and preclinical development of Kamuvudines: https://www.science.org/doi/10.1126/science.1261754 https://www.nature.com/articles/nature09830 https://www.science.org/doi/10.1126/sciadv.abj3658 https://www.science.org/doi/10.1126/sciimmunol.abi4493 Please visit www.inflam.com to learn more.

Review article in high impact journal outlines the evidence that neurodegenerative diseases –including Parkinson's, Alzheimer's, ALS and Huntington's – can be addressed by boosting mitophagy, the quality control system cells use to remove dysfunctional mitochondria Strong evidence has emerged that deficient mitophagy is an underlying cause of neurodegenerative disease Momentum is building, with the first selective mitophagy enhancers aimed at modifying the course of neurodegenerative diseases entering clinical trials in the last 12 months CAMBRIDGE, England, Jan. 15, 2025 /PRNewswire/ -- Mission Therapeutics ("Mission"), a clinical-stage biotech company developing first-in-class therapeutics targeting mitophagy, today announces the publication of a review article titled Targeting mitophagy in neurodegenerative diseases in the journal Nature Reviews Drug Discovery. The peer-reviewed article can be viewed here. It outlines the progress scientists have made in identifying that mitochondrial dysfunction is a hallmark of neurodegenerative disease; how their understanding of the molecular pathways that underpin the mitophagy process has advanced; and the subsequent development of two molecular approaches – USP30 inhibition and PINK1 activation – which are now being tested in early-stage clinical trials. Dr Paul Thompson, Chief Scientific Officer at Mission Therapeutics, said: "Fresh scientific approaches are needed if we as a society are to address the growing burden of neurodegenerative diseases, which are becoming ever more common as populations age. This timely review outlines the significant potential that enhancing mitophagy has in tackling a wide range of neurodegenerative diseases including Parkinson's, Alzheimer's, amyotrophic lateral sclerosis (ALS) and Huntington's." Dr Laura Parton, Senior Director at Mission Therapeutics, said: "We now have a deep understanding of how the build-up of dysfunctional mitochondria can contribute to neurodegenerative diseases – and how we can go about addressing this problem with selective mitophagy enhancers, particularly those focussing on the USP30/PINK1/Parkin mitophagy pathway. After more than 30 years of research, the area is now coming to fruition, with three such drugs entering clinical trials in the last 12 months." The review was written by a team of renowned mitophagy experts from across industry and academia, including Mission scientists Dr Paul Thompson and Dr Laura Parton; Professor Miratul Muqit and Odetta Antico of Dundee University; and Dr Nicholas T. Hertz, co-founder of Mitokinin LLC. Mission Therapeutics is a global leader in discovering and developing innovative therapeutics that promote mitophagy, the quality control process cells use to remove dysfunctional mitochondria, thereby safeguarding their health and function. Effective mitophagy is particularly important for the ongoing health of neurons as, unlike most cells, they do not self-renew throughout an individual's lifetime. About Mission Therapeutics Mission Therapeutics is a world leader in discovering and developing novel therapeutics which promote the removal of dysfunctional mitochondria, promoting cell health and function. Mitochondria are energy producing organelles which require lifetime quality control through a ubiquitin-mediated clearance mechanism known as mitophagy. In certain situations, such as cellular stress, cell injury, and/or defects of the mitophagy process, the mitochondria can become dysfunctional and damaging to the cell, leading to reduced energy production, oxidative stress, inflammation and potentially cell death. Dysfunctional mitochondria are significant drivers of disease pathophysiology in acute kidney injury (AKI), Parkinson's disease (PD), heart failure, Duchenne's Muscular Dystrophy, IPF, mitochondrial diseases and Alzheimer's. USP30 is a deubiquitylating enzyme that constantly removes ubiquitin from mitochondria, providing a potential brake on clearance of dysfunctional mitochondria. Mission is currently developing two small molecule drugs, MTX652 (peripheral) and MTX325 (targeting the CNS) which, through inhibition of the mitochondrial DUB enzyme USP30, will promote clearance of dysfunctional mitochondria – consequently improving overall cellular health. Mission's USP30 inhibitors MTX652 and MTX325 could potentially be used to treat any disease or condition driven by mitochondrial dysfunction. Mission is backed by blue chip investors including Pfizer Venture Investments, Sofinnova Partners, Roche Venture Fund, SR One, IP Group and Rosetta Capital. SOURCE Mission Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED