CLC-1 inhibitors(NMD Pharma)

NMD Pharma Publishes Comprehensive Data Package for NMD670 in Science Translational Medicine ClC-1 is a chloride ion channel specifically expressed in skeletal muscle cells that normally dampens muscle fiber excitability and is involved in regulating muscle fiber excitability during exerciseClinical and preclinical data supports the notion that ClC-1 inhibition is a novel and highly translational therapeutic approach to improve symptoms in myasthenia gravis and, potentially, other diseases with compromised neuromuscular transmissionNMD670, a skeletal muscle targeted ClC-1 inhibitor, is in clinical development for the treatment of patients with generalized myasthenia gravis, spinal muscular atrophy, and Charcot-Marie- Tooth disease Aarhus, Denmark, 21 March 2024 – NMD Pharma A/S, a clinical-stage biotech dedicated to developing novel and improved treatments for patients living with neuromuscular diseases, today announces the peer-reviewed publication of comprehensive data sets demonstrating, for the first time, the ability of CIC-1 inhibition to restore muscle function in patients suffering from myasthenia gravis (MG) and in animal models of MG. These data are published in the journal Science Translational Medicine in a paper titled ‘First in class CIC-1 inhibitor improves skeletal muscle function in animal models and patients with myasthenia gravis.’ ClC-1 is a skeletal muscle specific chloride ion channel that plays important roles for regulating neuromuscular transmission and muscle fiber excitability during exercise. NMD Pharma’s lead development candidate, NMD670, a novel, selective, and orally bioavailable ClC-1 inhibiting small molecule, is used in the preclinical and clinical studies. NMD670 is a muscle-targeted therapy which aims to enhance the activation of skeletal muscle fibers and to improve muscle strength and endurance. Thomas Holm Pedersen, Chief Executive Officer of NMD Pharma and senior author of the paper, commented, “This paper summarizes years of work here at NMD Pharma and Aarhus University, firstly establishing neuromuscular transmission deficits in patients impacted by myasthenia gravis and then demonstrating that ClC-1 inhibition can reverse these deficits and improve the muscle function both in animal models and humans. These data provide important proof-of-mechanism as we progress our Phase 2 trial in spinal muscular atrophy and plan for the initiation of two other Phase 2 trials in AChR and MuSK antibody positive myasthenia gravis and Charcot-Marie-Tooth disease this year.” Dr Jorge A. Quiroz, Chief Medical Officer at NMD Pharma, added, “Myasthenia gravis is a rare neuromuscular disease that compromises the signal transmission between motor neurons and skeletal muscle fibers. As a result, patients have impaired skeletal muscle function and often experience severe muscle weakness and fatigue. Our aim at NMD Pharma is that our development candidates will reduce the burden and improve the lives of patients suffering from these debilitating neuromuscular diseases.” Today's publication in Science Translational Medicine highlights the successful translation of preclinical work with NMD670, which restored skeletal muscle function in a rat model of MG, to meaningful improvements in MG patients. It includes the randomized, placebo-controlled, single-dose, 3-way cross-over Phase 2a clinical study, investigating the efficacy, pharmacodynamics, and safety of a single dose of orally administered NMD670 in 12 patents with MG, showing clinically relevant and statistically significant improvements in the Quantitative Myasthenia Gravis (QMG) total score alongside a favorable safety profile. Access the full paper in Science Translational Medicine online here: www.science.org/doi/10.1126/scitranslmed.adk9109 In October 2022, NMD Pharma announced positive topline data which established the first clinical proof-of-mechanism of NMD Pharma’s novel CIC-1 chloride channel inhibitor approach in patients impacted by MG. In November 2023, NMD Pharma announced that it had raised €75 million (~$80 million) in a Series B financing to complete three Phase 2 studies with NMD670, the Company’s lead ClC-1 inhibitor in AChR and MuSK antibody positive MG, spinal muscular atrophy, and Charcot-Marie-Tooth disease. -END- Contacts NMD Pharma A/SThomas Holm Pedersen, CEOE-mail: contact@nmdpharma.com ICR ConsiliumMary-Jane Elliott / Ashley Tapp / Lindsey Neville E-mail: NMDPharma@consilium-comms.com Tel: +44 (0)20 3709 5700 About NMD PharmaNMD Pharma A/S is a clinical-stage biotech company developing a first-in-class platform of small molecule therapies selectively targeting the skeletal muscle chloride ion channel (ClC-1) for the treatment of severe neuromuscular disorders. The Company was founded on more than 15 years of muscle physiology research with a focus on regulation of skeletal muscle excitability under physical activity. NMD Pharma has built a world-leading muscle electrophysiology platform leveraging the in-depth know-how of muscle physiology and muscular disorders, small molecule modulators, enabling technologies and tools as well as in vivo pharmacology models for discovering and developing proprietary modulators of neuromuscular function. The Company has built significant clinical and development expertise as its programmes have progressed through the clinic. NMD Pharma has raised ~€155 million from investors including Novo Holdings, Lundbeckfonden BioCapital, INKEF Capital, Roche Venture Fund, and Jeito Capital. Find out more about us online at http://www.nmdpharma.com.

NMD Pharma announces poster and oral presentations on skeletal muscle targeted ClC-1 therapy at two leading neuromuscular disease conferences ClC-1 is a chloride ion channel specifically expressed in skeletal muscle cells that normally dampens muscle fiber excitability and is involved in regulating muscle fiber excitability during exercise. ClC-1 inhibition could be a possible mechanism to improve muscle fiber activation to address muscle weakness and fatigue in neuromuscular diseases. Presentations include new preclinical data on CIC-1 inhibition and a design and status update on the ongoing Phase 2, SYNAPSE-SMA, trial of NMD670 in spinal muscular atrophy type 3. Aarhus, Denmark, 1 March 2024 – NMD Pharma A/S, a clinical-stage biotech dedicated to developing novel and improved treatments for patients living with neuromuscular diseases, today announces that it will present two posters at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference 2024 and one poster and one oral presentation at the 4th Scientific International Congress on SMA 2024. The presentations will provide a clinical study design and status update on the Phase II SYNAPSE-SMA trial of NMD670 in ambulatory adults with spinal muscular atrophy type 3. The SYNAPSE-SMA study is a proof-of-concept, Phase II, randomized, double-blind, placebo-controlled, 2-way crossover study to evaluate the efficacy, safety, and tolerability of NMD670. The study is an international multicenter study including sites in North America and Europe and the first subject was enrolled in September 2023. In addition, NMD Pharma will also be presenting a poster outlining pre-clinical results elucidating the mechanism of action for CIC-1 inhibition and its potential to improve neuromuscular transmission in neuromuscular diseases with transmission failure. Jorge A. Quiroz, EVP, and Chief Medical Officer at NMD Pharma: “We are looking forward to sharing updates on the ongoing Phase 2 SYNAPSE-SMA trial for NMD670, along with further insights into the mechanism of ClC-1 inhibition and its potential to enhance neuromuscular transmission improving muscle weakness and fatigue.” “There remains a significant unmet need for new treatments for severe neuromuscular diseases, including patients with SMA. NMD670 has already demonstrated positive clinical study results in a Phase I/II study in patients with myasthenia gravis (MG), and we are confident that it could also be beneficial for the treatment of patients affected by SMA.” The MDA Conference is taking place in Orlando, Florida from 3-6 March. Details of NMD Pharma’s poster presentations are below: Poster number: S114 Location: Poster Exhibit Hall, Hilton Orlando Date and time: Sunday March 3, 6:00pm – 8:00pm ET Poster number: M278 Location: Poster Exhibit Hall, Hilton Orlando Date and time: Monday March 4, 6:00pm – 8:00pm ET The 4th Scientific International Congress on SMA is taking place in Ghent, Belgium, from 14-16 March. : NMD Pharma be presenting one poster and one oral presentation at the congress. Details of NMD Pharma’s oral presentations are below: Oral Presentation: “ClC-1 inhibitor compound improves neuromuscular transmission and enhances skeletal muscle function in pre-clinical animal models of neuromuscular dysfunction” Location: Main Auditorium Date and Time: Saturday 16th March 9:30am CET -END- Contacts NMD Pharma A/S Thomas Holm Pedersen, CEO E-mail: contact@nmdpharma.com ICR Consilium Mary-Jane Elliott / Ashley Tapp / Lindsey Neville E-mail: NMDPharma@consilium-comms.com Tel: +44 (0)20 3709 5700 About NMD Pharma NMD Pharma A/S is a clinical-stage biotech company developing a first-in-class platform of small molecule therapies selectively targeting the skeletal muscle chloride ion channel (ClC-1) for the treatment of severe neuromuscular disorders. The Company was founded on more than 15 years of muscle physiology research with a focus on regulation of skeletal muscle excitability under physical activity. NMD Pharma has built a world-leading muscle electrophysiology platform leveraging the in-depth know-how of muscle physiology and muscular disorders, small molecule modulators, enabling technologies and tools as well as in vivo pharmacology models for discovering and developing proprietary modulators of neuromuscular function. The Company has built significant clinical and development expertise as its programmes have progressed through in the clinic. NMD Pharma has raised ~€155 million from investors including Novo Holdings, Lundbeckfonden BioCapital, INKEF Capital, Roche Venture Fund, and Jeito Capital. Find out more about us online at .