CLCN1

NMD Pharma Announces FDA Orphan Drug Designation Granted to NMD670 for the Treatment of Patients with Charcot-Marie-Tooth Disease This is the 2nd orphan drug designation granted to the skeletal muscle-specific drug therapy NMD670 Under this newly granted orphan drug designation, NMD670 is currently being evaluated in a Phase 2 clinical trial in adult patients with any genetically confirmed Type 1 or Type 2 CMT subtype NMD Pharma has three ongoing global clinical trials investigating NMD670 across rare neuromuscular diseases characterized by a high degree of patient impact and need, including a Phase 2 study in adults living with spinal muscular atrophy (SMA) type 3, a Phase 2b study in gMG patients, and this Phase 2 CMT study, with data readout(s) occurring from 2H/2025 through 1H/2026 6 January 2025 – NMD Pharma A/S, a clinical-stage biotech company dedicated to developing novel and improved treatments for patients living with neuromuscular diseases, today announces that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation (ODD) for NMD670, a novel, oral, small molecule inhibitor of the skeletal muscle-specific chloride ion channel ClC-1, for the treatment of Charcot-Marie-Tooth disease (CMT). CMT is a hereditary neuropathy characterized by muscle weakness and fatigue with no approved therapies. An estimated 136,000 individuals in the US have CMT and it is estimated that over 3 million individuals worldwide live with CMT. Clinical features of this rare neuromuscular disease include motor signs and symptoms such as muscle weakness, muscle atrophy, and fatigue, as well as sensory deficits that, in combination, may cause substantial reduction in quality of life. “NMD Pharma is committed to addressing the need of patients living with neuromuscular diseases such as CMT, and we are thrilled that the FDA has granted orphan drug designation to NMD670,” commented Thomas Holm Pedersen, Chief Executive Officer of NMD Pharma. “Based on positive results from preclinical studies and the recently published ESTABLISH1 CMT observational study, this designation not only highlights the urgent need for novel, effective treatments for this rare disease, but also underscores the therapeutic potential of our skeletal muscle-specific ClC-1 inhibitor approach to address the associated muscle weakness and fatigue.” In November 2024, NMD Pharma announced the initiation of a Phase 2 clinical trial, named SYNAPSE-CMT, of a twice daily oral dose of NMD670 over 21 days in 80 adult patients with any genetically confirmed CMT1 or CMT2 subtype, taking place across clinical sites in both the U.S. and Europe. Patients with CMT Type 1 and Type 2 in these geographies are encouraged to participate in the study, and for further information and a list of currently active trial sites, please look to clinicaltrials.gov under the identifier NCT06482437, or contact the Company at contact@nmdpharma.com. In addition, NMD670 was previously granted ODD by the FDA for the treatment of generalized myasthenia gravis (gMG) in September 2022. FDA ODD provides orphan status to therapies intended for the prevention, diagnosis or treatment of diseases affecting fewer than 200,000 people in the US. 1. Exploring SynapTic ABnormaLitIeS in Hereditary neuropathies 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 rare neuromuscular disorders and age-related neuromuscular diseases with high levels of patient unmet. 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. NMD670 is NMD Pharma’s lead development program. It is a first-in-class small molecule inhibitor of the skeletal muscle specific chloride ion channel 1 (CIC-1). NMD Pharma has demonstrated that CIC-1 inhibition amplifies the muscle’s responsiveness to weak signals, improving neuromuscular transmission and restores skeletal muscle function. This novel treatment approach has resulted in clinical evidence of CIC-1 inhibition in myasthenia gravis and preclinical evidence in spinal muscular atrophy, Charcot-Marie Tooth disease and sarcopenia. NMD670 has also been granted orphan-drug designation by the U.S. FDA for treatment of gMG. CMT encompasses a group of hereditary sensory and motor neuropathies that cause damage to peripheral nerves and their neuromuscular junction. Damage caused by CMT worsens slowly over time and can result in substantial reductions in mobility, independence and quality of life due to muscle weakness, fatigue and atrophy across skeletal muscle groups such as the legs, feet, arms, hands and potentially leading to diaphragm weakness and paralysis. CMT is often broadly grouped into demyelinating (CMT type 1) and axonal (CMT type 2) based on nerve conduction studies, but there are more than 160 subtypes of CMT based on their genetic causes, clinical features, and progression patterns. CMT affects approximately 136,000 individuals in the United States and 3.2 million worldwide, with first symptoms typically appearing during adolescence or early adulthood. The content above comes from the network. if any infringement, please contact us to modify.

NMD670 is an oral therapy designed to treat Charcot-Marie-Tooth disease. Credit: SkazovD / Shutterstock. The US Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to NMD Pharma’s oral lead development programme, NMD670, designed to treat Charcot-Marie-Tooth disease (CMT). A small molecule inhibitor of the skeletal muscle-specific chloride ion channel 1 (CIC-1), NMD670 entered the Phase II SYNAPSE-CMT trial last November, involving 80 adult subjects with genetically confirmed CMT1 or CMT2 subtypes. The study involves a twice-a-day oral dose over 21 days and is conducted across clinical sites in Europe and the US. The FDA’s ODD for the therapy follows a previous grant for the treatment of generalised myasthenia gravis (gMG) in September 2022. According to the company, the inhibition of CIC-1 can enhance muscle responsiveness to weak signals, potentially ‘improving’ neuromuscular transmission and restoring skeletal muscle function. This approach claims to have yielded clinical evidence of CIC-1 inhibition in myasthenia gravis and preclinical evidence in other conditions such as sarcopenia, CMT, and spinal muscular atrophy. NMD Pharma CEO Thomas Holm Pedersen said: “NMD Pharma is committed to addressing the needs of patients living with neuromuscular diseases such as CMT, and we are thrilled that the FDA has granted ODD to NMD670. “Based on positive results from preclinical studies and the recently published ESTABLISH CMT observational study, this designation not only highlights the urgent need for novel, effective treatments for this rare disease but also underscores the therapeutic potential of our skeletal muscle-specific ClC-1 inhibitor approach to address the associated muscle weakness and fatigue.” Marked by weakness in muscles, atrophy, fatigue, and sensory deficits, CMT significantly impacts the quality of life of those affected. The company noted that an estimated 136,000 people in the US and more than three million globally are living with this hereditary neuropathy.

NMD Pharma publishes new data on the role of ClC-1 inhibition in Charcot-Marie-Tooth in the Annals of Clinical and Translational Neurology Results from the ESTABLISH1 observational study confirms that neuromuscular junction (NMJ) dysfunction is an underappreciated disease characteristic in patients with Charcot-Marie-Tooth disease (CMT) types 1 and 2 affecting muscle function in patientsAdditionally, results from preclinical studies provide proof-of-mechanism for recovery of muscle function with ClC-1 inhibition using NMD670 in CMT mouse models Aarhus, Denmark, 18 December 2024 – NMD Pharma A/S, a clinical-stage biotech company dedicated to developing novel and improved treatments for patients living with neuromuscular diseases, today published new data in the journal Annals of Clinical and Translational Neurology with collaborators from the Aarhus University Hospital, University of Missouri, The Ohio State University, and Aarhus University. The peer-reviewed paper, entitled ‘Neuromuscular Transmission Deficits in patients with CMT and ClC-1 Inhibition in CMT animal Models,’ provides evidence that targeting the neuromuscular junction (NMJ) with ClC-1 inhibitors, such as NMD670, could enhance muscle function in patients with CMT, a rare neuromuscular disease. Clinical features of CMT include motor signs and symptoms such as muscle weakness, muscle atrophy, and fatigue, as well as sensory deficits that, in combination, cause substantial reduction in quality of life. Preclinical studies have previously implicated NMJ transmission deficits in muscle dysfunction in CMT. This study describes results from ESTABLISH1, an observational clinical study in CMT Type 1 and 2 patients and healthy patients in the US and Denmark, which confirms that patients with CMT, regardless of genotype, have notable NMJ transmission dysfunction that correlates with disease severity. In addition, the paper describes that the treatment of mouse models of CMT Type 1 (CMT1A) and CMT Type 2 (CMT2D) following partial inhibition of ClC-1 chloride channels and the application of nerve-stimulated muscle force, was shown to improve muscle contractile function with the addition of the novel small molecule ClC-1 inhibitor NMD670. W. David Arnold, MD, Principal Investigator who led the international ESTABLISH1 observational study, commented: “With no currently approved therapies to provide a cure or alleviate symptoms, data from the ESTABLISH and preclinical studies represents a significant milestone in the development of a treatment. Here, the data shows that patients with CMT, regardless of genotype, are characterized by notable NMJ transmission dysfunction, and that the level of dysfunction directly correlates with the level of disease severity, further confirming the potential therapeutic value of ClC-1 inhibition to address the muscle weakness and fatigue associated with CMT.” Thomas Holm Pedersen, Chief Executive Officer of NMD Pharma, added: “This data provides further evidence of the crucial role of neuromuscular junction dysfunction in CMT patients. The impaired connectivity between the motor neuron and skeletal muscle at the neuromuscular junction in CMT patients presumably occurs because the axons are in a process of degeneration or are newly formed or forming neuromuscular junctions from axons nearby degenerated connections. It is very promising that NMD670 improves muscle contractile function in animal models of CMT, and we have already started evaluating the effect of NMD670 in a Phase 2 clinical trial which we initiated in November 2024.” The full manuscript is available online through the following link: Neuromuscular transmission deficits in patients with CMT and ClC‐1 inhibition in CMT animal models - Grønnebæk - Annals of Clinical and Translational Neurology - Wiley Online Library On 18 November, NMD Pharma announced that it had dosed the first CMT disease patient in its Phase 2 clinical trial of NMD670. NMD Pharma has three ongoing global clinical trials investigating NMD670 across rare neuromuscular diseases characterized by a high degree of patient impact and need, including a Phase 2 study in adults living with spinal muscular atrophy type 3 and a Phase 2b study in generalized myasthenia gravis patients. Further information on the study can be found here: Study Details | Safety and Efficacy of NMD670 in Adult Patients With Type 1 and Type 2 Charcot-Marie-Tooth Disease | ClinicalTrials.gov Exploring SynapTic ABnormaLitIeS in Hereditary neuropathies -END- Contacts NMD Pharma A/SDan Brennan, SVP Corporate and Commercial StrategyE-mail: contact@nmdpharma.com ICR HealthcareMary-Jane Elliott / Ashley Tapp / Lindsey Neville E-mail: NMDPharma@icrhealthcare.comTel: +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 rare neuromuscular disorders and age-related neuromuscular diseases with high levels of patient unmet. 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. About NMD670NMD670 is NMD Pharma’s lead development program. It is a first-in-class small molecule inhibitor of the skeletal muscle specific chloride ion channel 1 (CIC-1). NMD Pharma has demonstrated that CIC-1 inhibition amplifies the muscle’s responsiveness to weak signals, improving neuromuscular transmission and restores skeletal muscle function. This novel treatment approach has resulted in clinical evidence of CIC-1 inhibition in myasthenia gravis and preclinical evidence in spinal muscular atrophy, Charcot-Marie Tooth disease and sarcopenia. NMD670 has also been granted orphan-drug designation by the U.S. FDA for treatment of gMG. About Charcot-Marie-Tooth disease (CMT)CMT encompasses a group of hereditary sensory and motor neuropathies that cause damage to peripheral nerves and their neuromuscular junction. Damage caused by CMT worsens slowly over time and can result in substantial reductions in mobility, independence and quality of life due to muscle weakness, fatigue and atrophy across skeletal muscle groups such as the legs, feet, arms, hands and potentially leading to diaphragm weakness and paralysis. CMT is often broadly grouped into demyelinating (CMT type 1) and axonal (CMT type 2) based on nerve conduction studies, but there are more than 160 subtypes of CMT based on their genetic causes, clinical features and progression patterns. CMT affects approximately 136,000 individuals in the United States and 3.2 million worldwide, with first symptoms typically appearing during adolescence or early adulthood.