NMD Pharma Receives IND Clearance from the FDA to initiate a Phase 2 Clinical Trial of NMD670 in Charcot-Marie-Tooth disease in the US

AARHUS, Denmark I June 18, 2024 I NMD Pharma A/S, a clinical-stage biotech company dedicated to developing novel and improved treatments for patients living with severe neuromuscular diseases, today announces that it has received clearance from the US Food and Drug Administration (FDA) for its Investigational New Drug (IND) application to initiate a Phase 2 clinical trial, named SYNAPSE-CMT, of NMD670 in patients living with Charcot-Marie-Tooth (CMT) type 1 and type 2 disease. NMD670 is a first-in-class, muscle-targeted small molecule inhibitor of the skeletal muscle specific ClC-1 chloride ion channel.

The Phase 2 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the efficacy, safety, and tolerability of twice daily orally administered NMD670 over 21 days in approximately 80 adult patients with any genetically confirmed CMT1 or CMT2 subtype. Endpoints of the study include the 6-minute walk test, the 10-meter walk/run test, and the timed-up-and-go test, among other endpoints. The trial will take place at clinical sites in both the US and Europe, and it is expected to start enrolling patients soon.

In June 2023, NMD Pharma announced the results of ESTABLISH1, an international observational study of neuromuscular junction function in CMT types 1 and 2, at the Peripheral Nerve Society Annual Meeting. The results demonstrated that dysfunction at the neuromuscular junction is an unappreciated disease characteristic in patients with the inherited neurological conditions CMT types 1 and 2. The study revealed that nerves in the process of degeneration in patients with CMT transmit signals to skeletal muscle with varying degrees of weakness and deficits. The level of neuromuscular junction transmission deficit in CMT patients correlated with disease severity and motor function assessed through a range of clinical measurements of muscle strength and function.

Thomas Holm Pedersen, Chief Executive Officer of NMD Pharma, said: “Charcot-Marie-Tooth disease is a highly debilitating condition. There is no cure or approved medicines available to treat these patients, so there is an urgent need to develop treatments. Results from the ESTABLISH study highlight neuromuscular junction transmission deficits as a previously unrecognized disease characteristic in CMT. This gives us confidence that NMD670 has the potential to work within the skeletal muscles to improve and maintain clinically meaningful benefits for this underserved group affected by the disease.”

Allison Moore, CEO of the Hereditary Neuropathy Foundation (HNF) remarked: “NMD Pharma’s focus on developing treatments that address the symptoms of multiple subtypes of CMT represents a vital step toward dramatically improving patient’s lives. By alleviating the day-to-day challenges posed by this debilitating condition and potentially restoring function, NMD Pharma is providing hope and tangible benefits to those who need it most.”

“This is an exciting moment for the CMT community,” says Cleary Simpson, CEO of the CMT Research Foundation (CMTRF). “We are pleased to see NMD Pharma moving to Phase 2 with NMD670, a treatment with the potential for improving muscle function in people living with multiple types of CMT.”

“CMTA is extremely proud to have NMD Pharma as an Alliance Partner,” said Sue Bruhn, PhD, Charcot-Marie-Tooth Association (CMTA) CEO. “Their dedication to pioneering innovative treatments for CMT aligns perfectly with our mission to bring treatments to those affected by this devastating disease. We are thrilled with the FDA’s IND clearance for the NMD670 Phase 2 trial in CMT, this pivotal milestone brings us closer to effective treatments.”

By the end of 2024, NMD Pharma will have three ongoing Phase 2 trials using its skeletal muscle activation enhancing therapy in rare neuromuscular diseases characterized by a high degree of patient impact and unmet need. These include a Phase 2 study of NMD670 for adults living with spinal muscular atrophy (SMA) type 3, a Phase 2b study of NMD670 in generalised myasthenia gravis (gMG) both of which have already been initiated, and, following today’s news, a Phase 2 study of NMD670 in patients with CMT type 1 and type 2.

1 Observational Study of Neuromuscular Function in CMT type 1&2 and health controls (ESTABLISH) (NCT04980807)

About NMD Pharma
NMD Pharma A/S is a clinical-stage biotech company developing a first-in-class platform of small molecule therapies selectively and directly 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.

About NMD670
NMD670 is NMD Pharma’s lead development program which is being developed in 3 Phase 2 clinical studies. It is a first-in-class small molecule inhibitor of the skeletal muscle specific chloride ion channel (CIC-1). NMD Pharma has demonstrated that CIC-1 inhibition enhances weakened neuromuscular transmission and restores skeletal muscle function, and this novel treatment approach has demonstrated compelling preclinical and clinical data in animal models of myasthenia gravis, spinal muscular atrophy and a range of other neuromuscular disorders. 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.

About The Charcot-Marie-Tooth Association (CMTA)
CMTA is a community-focused, community-driven 501(c)(3) nonprofit organization with a mission to support the development of new treatments for CMT, to improve the quality of life for people with CMT, and, ultimately, to find a cure. As the leading global philanthropic funder of CMT research, CMTA unites the community with clinicians and industry experts to accelerate the advancement of treatments, with investments of more than $24 million since 2008. For more information, visit https://www.cmtausa.org.

About CMT Research Foundation (CMTRF)
The CMT Research Foundation (CMTRF) is a patient-led, non-profit focused on delivering treatments and cures for CMT. The foundation identifies significant obstacles or deficiencies impeding progress toward a cure and seeks out collaborators to address these issues. To date, CMTRF has funded 24 projects, of which 8 are completed. Of those 6 completed projects, 5 have clinical candidates. CMTRF’s mission to invest in promising science with high potential of leading to treatments and cures was proven effective and ground-breaking when DTx Pharma, with a CMTRF-backed program as its lead candidate, was acquired by Novartis for $1 billion. Founded by two patients who are driven to expedite drug delivery to people who live with CMT, the 501(c)(3) federal tax-exempt organization is supported by personal and corporate financial gifts. For more information, visit https://cmtrf.org.

About Hereditary Neuropathy Foundation (HNF)

The Hereditary Neuropathy Foundation (HNF), a patient advocacy and research non-profit with a mission to increase awareness and accurate diagnosis of Charcot-Marie-Tooth (CMT), support people living with CMT and their families with critical information to improve quality of life, and fund research that will lead to treatments and cures. HNF’s Therapeutic Research in Accelerated Discovery (TRIAD) is a collaborative effort with academia, government and industry to develop treatments for CMT. As part of TRIAD’s research consortium, the Global Registry for Inherited Neuropathies (GRIN) was established as a natural history study to collect and analyze patient-reported data and clinical scales, including the ONLS, CMT-FOM, CMTPedS, CMTInfS and the collection and curation of genetic reports and biospecimens. Most recently, GRIN’s natural history studies include digital health technologies for the development of innovative biomarkers for all CMT subtypes. For more information, visit https://www.hnf-cure.org.