<img src="https://ml-eu.globenewswire.com/Resource/Download/97ece598-a26e-433e-943f-4b50098d0267?size=2" nborder="0" align="left" hspace="5" vspace="5" title="NMD_Logo3_reg.jpg" alt="NMD Pharma"/><ul type="disc"><li style="text-align:justify;">New publication identifies neuromuscular junction transmission failure as a novel mechanism contributing to sarcopenia, with preclinical studies showing that ClC-1 inhibition improves neuromuscular transmission and muscle function</li><li style="text-align:justify;">NMD Pharma is advancing a multi-asset ClC-1 portfolio targeting both rare neuromuscular diseases and more prevalent skeletal muscle disorders, including moderate-to-severe sarcopenia</li></ul> Aarhus, Denmark, 23 July 2026 – NMD Pharma A/S, a clinical-stage biotechnology company focused on developing novel therapies to restore skeletal muscle health, today announced the publication of new clinical and preclinical research in The Journal of Clinical Investigation identifying neuromuscular junction (NMJ) transmission failure as a key and potentially reversible contributor to age-related muscle weakness and sarcopenia. The collaborative research was led by W. David Arnold, M.D., Executive Director of the NextGen Precision Health Initiative and Professor of Physical Medicine and Rehabilitation at the University of Missouri, together with an international team of neuromuscular and aging researchers. The study demonstrated that older individuals with clinically significant muscle weakness (a hallmark of sarcopenia), exhibit NMJ transmission failure, with the severity of NMJ transmission failure closely associated with the severity of muscle weakness. Importantly, small-molecule inhibition of the skeletal muscle-specific ClC-1 ion channel enhanced muscle excitability and improved NMJ transmission, resulting in increased muscle function in aged rodent models exhibiting NMJ deficits similar to those observed in weak older adults. The findings identify a previously underappreciated postsynaptic mechanism of age-related muscle weakness and provide a biologically grounded rationale for targeting ClC-1 in sarcopenia. “These findings significantly advance our understanding of age-related muscle weakness,” said lead author Dr. W. David Arnold, Executive Director of the NextGen Precision Health Initiative and Professor of Physical Medicine and Rehabilitation at the University of Missouri. “Aging muscle may not simply receive a weaker nerve signal—it can become less able to reliably translate that signal into muscle activation. By targeting ClC-1, we believe we have the opportunity to restore the muscle’s responsiveness to nerve signalling and address a potentially important underlying driver of weakness and functional decline.” The publication further strengthens NMD Pharma's long-term strategy of advancing therapies designed to restore reliable skeletal muscle activation across diseases characterized by impaired muscle function. The Company's lead clinical-stage asset, ignaseclant, is establishing the foundation of NMD Pharma’s ClC-1 platform across multiple rare neuromuscular diseases. Building on this clinical and translational foundation, NMD Pharma is advancing next-generation ClC-1 programs designed to expand the platform into more prevalent skeletal muscle disorders, beginning with moderate-to-severe sarcopenia. "Our primary objective is to restore muscle function in patients whose daily lives are limited by muscle weakness and decline in physical function," said Thomas Holm Pedersen, Ph.D., Chief Executive Officer of NMD Pharma. "We believe that restoring reliable skeletal muscle activation has the potential to improve muscle strength, physical function, mobility, and independence by addressing a fundamental biological mechanism underlying impaired muscle function. Beyond these direct functional benefits, our emerging scientific hypothesis is that a healthier, more consistently activated skeletal muscle may also help preserve the broader physiological functions of skeletal muscle that contribute to healthy aging, resilience, and quality of life." NMD Pharma's next-generation programs are supported by the Company's integrated discovery and translational platform, combining deep expertise in skeletal muscle biology, ion channel pharmacology, electrophysiology, medicinal chemistry, and neuromuscular clinical development. About the Publication The article, “Neuromuscular junction failure in sarcopenia is linked to NaV1.4 loss and reversed by ClC-1 inhibition,” was published in The Journal of Clinical Investigation. The study integrated clinical electrophysiological assessments in weak older adults with mechanistic and interventional studies in aged rodent models. The authors concluded that NMJ transmission deficits represent a key, reversible contributor to sarcopenia and identified ClC-1 inhibition as a potential therapeutic approach for addressing age-related muscle weakness. The full paper can be accessed online <a href="https://www.globenewswire.com/Tracker?data=RNVtKwKHTAuNy-y0bWm48YNJPACrBshc3Q8gSuZUL1QuFk2uHcmdieOGiQZf5yAc0cElJYDBKODDp8L42f8U6M0Jv31h_rVCp7YS47sfe7E=" rel="nofollow" target="_blank" title="here">here</a>. Recent and ongoing NMD Pharma clinical trials In February this year, NMD Pharma announced promising topline results from its Phase 2a SYNAPSE-CMT study evaluating ignaseclant in patients living with Charcot-Marie-Tooth disease (CMT) types 1 or 2. The study showed consistent and clinically meaningful functional improvements across muscle strength, motor performance, and patient-reported outcomes in patients with CMT. The Company has also completed a Phase 1b/2a study in adults with SMA with top-line results expected in H2 2026. In addition, topline results from a Phase 2b study in gMG with AChR and MuSK positive autoantibodies are expected in Q1 2027. These studies build on the previously reported positive Phase 2a results in gMG and support the potential of NMD Pharma’s skeletal muscle-targeted ClC-1 inhibition platform across neuromuscular diseases arising from both pre- and post-synaptic dysfunctions. -END- Contact NMD Pharma A/S Trine Juul Wengel, Communications Director E-mail: <a href="https://www.globenewswire.com/Tracker?data=4o1WM__LeqwWXurrDm5_7sB7RRmyWay91uQpCOJlj0mJN_OOKP39gdtXj1FOZMlCekFXJ0MrD_0bpoA2Kx8XTRJGfG5bJYHuBioLqR_fEas=" rel="nofollow" target="_blank" title="contact@nmdpharma.com">contact@nmdpharma.com</a>   ICR Healthcare Mary-Jane Elliott / Ashley Tapp / Lindsey Neville E-mail: <a href="https://www.globenewswire.com/Tracker?data=jUYH1bne3o2L7tBKXRx8-wA2V47zikSkQuJSqemD4fKJO8AGpHCl-GYn7U1qPCN0Snw_ctMyCC0qI-WV6lV7qFWvw7KFxPQrKbUlWL6CQWNVQD97Zl17ICumiD2cBWnl" rel="nofollow" target="_blank" title="NMDPharma@icrhealthcare.com">NMDPharma@icrhealthcare.com</a> Tel: +44 (0)20        3709 5700 About NMD Pharma NMD Pharma is a clinical-stage biotechnology company dedicated to enabling better lives through novel therapies designed to restore skeletal muscle health. Building on more than 15 years of pioneering research in skeletal muscle physiology, the Company is developing a portfolio of first-in-class ClC-1 modulators designed to restore reliable skeletal muscle activation and improve muscle function. The Company's lead investigational medicine, ignaseclant, is being evaluated across multiple rare neuromuscular diseases, while next-generation programs are designed to expand the platform into both rare neuromuscular diseases and more prevalent skeletal muscle disorders, beginning with moderate-to-severe sarcopenia. Leveraging deep expertise in skeletal muscle biology, ion channel pharmacology, electrophysiology, medicinal chemistry, and translational science, NMD Pharma has established a world-leading platform for discovering and developing therapies that translate advances in muscle biology into meaningful improvements in strength, physical function, and quality of life. Headquartered in Aarhus, Denmark, with operations in the United States, NMD Pharma has raised approximately $180 million from leading life science investors, including Novo Holdings, Lundbeckfonden BioCapital, INKEF Capital, Roche Venture Fund, and Jeito Capital. For more information, please visit <a href="https://www.globenewswire.com/Tracker?data=PK---omADkw6epo56zm-yZoKneBusHxuE1RiMIOCohtmpZMu2XbsgioGExqnRlhwm6DRifRDn1n5AIFZM1-ANtffmbEwcB2CY2sdulGFYIc=" rel="nofollow" target="_blank" title="www.nmdpharma.com">www.nmdpharma.com</a>. About ignaseclant (NMD670) ClC-1 is the predominant chloride ion channel in skeletal muscle and a central regulator of muscle excitability, helping skeletal muscle respond reliably to nerve signalling. NMD Pharma's investigational therapies selectively modulate ClC-1 to restore the muscle's ability to respond to normal nerve signalling, enhancing skeletal muscle activation, neuromuscular transmission, and muscle function. Emerging preclinical and translational evidence also suggests that ClC-1 modulation may support nerve-muscle connectivity and neuromuscular remodeling, providing the potential for more durable improvements in muscle function. Ignaseclant is the Company's lead investigational oral ClC-1 modulator and is currently being evaluated in clinical studies for Charcot-Marie-Tooth disease (CMT), spinal muscular atrophy (SMA), and generalized myasthenia gravis (gMG). Its clinical development has established the translational foundation of NMD Pharma's ClC-1 platform and is informing the design of next-generation ClC-1 modulators for both rare neuromuscular diseases and more prevalent skeletal muscle disorders, including moderate-to-severe sarcopenia. About Sarcopenia Sarcopenia is a progressive skeletal muscle disease that impairs muscle strength, physical function, and independence. Once considered an inevitable consequence of aging, it is now increasingly recognized as a disease of impaired muscle function—not simply loss of muscle mass. As the disease progresses to severe sarcopenia, declining physical performance can significantly compromise mobility, independence, and overall health, increasing the risk of falls, fractures, hospitalization, and mortality. Published studies suggest that approximately 10–27% of older adults meet current diagnostic criteria for sarcopenia, while 2–9% have progressed to severe sarcopenia, representing millions of individuals worldwide living with advanced functional impairment. Sarcopenia may develop not only with aging, but also in association with chronic illness, physical inactivity, malnutrition, and weight loss. Despite its substantial personal, societal, and healthcare burden, current management relies primarily on resistance exercise and nutritional optimization, and there are currently no approved pharmacologic therapies specifically indicated to treat sarcopenia. While several investigational therapies have attempted to increase muscle mass, translating those changes into meaningful improvements in muscle strength and physical function has remained a significant challenge. Growing evidence suggests that impaired neuromuscular function contributes to muscle weakness and physical decline, creating opportunities for therapies designed to restore reliable skeletal muscle activation and improve muscle function. <img alt="" src='https://ml-eu.globenewswire.com/media/NDM3NGU3MTQtMDdjOS00NWY1LWJjZjYtMTExY2RlMDM3ZDM1LTcwMDAxMjA0MC0yMDI2LTA3LTIzLWVu/tiny/NMD-Pharma.png' referrerpolicy='no-referrer-when-downgrade' />

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NMD Pharma Announces Publication Identifying Neuromuscular Junction Transmission Failure as a Novel Contributor to Age-Related Muscle Weakness

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