NMD Pharma Reports Results from the ESTABLISH Study – an International Observational Study of Neuromuscular Function in Charcot-Marie-Tooth Type 1 and 2

• Results from the study establish, for the first time, neuromuscular junction (NMJ) transmission deficit as a new disease characteristic in patients with Charcot-Marie-Tooth (CMT) type 1 and 2

• The level of NMJ transmission deficit in patients with CMT was associated with disease severity assessed through a range of clinical measurements of muscle strength and motor function

• The ESTABLISH study provides reliability and tolerability estimates for a range of electrophysiological and clinical outcomes which will be key to selecting outcome measures for future clinical trials in CMT

Aarhus, Denmark, 20 June 2023 – NMD Pharma A/S, a clinical stage biotech company developing first-in-class, small molecule ClC-1 inhibitors for neuromuscular disorders, presented the results from ESTABLISH1, an observational study of neuromuscular function in patients with the inherited neurological conditions CMT types 1 and 2 in a poster presentation yesterday at the Peripheral Nerve Society Annual Meeting (PNS) being held in Copenhagen, Denmark.

Results from the study establish, for the first time, neuromuscular junction (NMJ) transmission deficit as a new disease characteristic in patients with Charcot-Marie-Tooth (CMT) type 1 and 2. The level of NMJ transmission deficit in patients with CMT was associated with disease severity assessed through a range of clinical measurements of muscle strength and motor function. The study also provides important information on tolerability and reliability of clinical and electrophysiological outcomes which will aid the selection of relevant outcomes in future clinical trials.

The study compared electrophysiological assessments (single fiber electromyography (EMG) and repetitive nerve stimulation) and clinical testing (tests of muscle strength, fatigability, dexterity, and balance) between 21 patients with CMT types 1 and 2 and 10 healthy age-matched subjects. The international study was led by Dr. Henning Andersen, Aarhus University Hospital, and Dr. William David Arnold, NextGen Precision Health, University of Missouri*. Further information on the study can be found here

Prof. Dr. Henning Andersen, Department of Neurology at Aarhus University Hospital commented: “CMT is a highly debilitating disease with no approved treatments to provide a cure or alleviate symptoms in patients. Here we show that patients with CMT are characterized by deficits of the neuromuscular junction to effectively transmit signals from nerves to muscles and that the level of transmission failure correlates with the functional capabilities of the patients. This opens the door for pharmacologically targeting the transmission failure to improve symptoms in patients with CMT.”

Dr. William David Arnold, Executive Director at NextGen Precision Health, University of Missouri added: “We are excited to report the identification of an aspect of the disease that could represent a breakthrough in the identification of novel treatments for CMT.”

Jorge A. Quiroz, Chief Medical Officer of NMD Pharma, said: “With no currently approved treatments or therapies for this debilitating disease, uncovering NMJ transmission failure as a new disease mechanism in CMT represents a significant milestone for the development of new therapies including our novel ClC-1 inhibitor treatment approach. I would like to thank the Aarhus and Ohio teams for their great contributions to making this study a success and, most importantly, the patients and families participating in the Establish study.”

NMD Pharma plans to publish the full set of study results in a peer reviewed journal.

NMD Pharma is developing NMD670, a first-in-class small molecule inhibitor of the muscle specific chloride ion channel, the ClC-1 ion channel. NMD Pharma has pre-clinically demonstrated that ClC-1 inhibition can enhance neuromuscular transmission and, ultimately, skeletal muscle function and NMD670 has already demonstrated positive results in a Phase I and proof of mechanism study in patients with myasthenia gravis confirming safety, tolerability and initial efficacy data in subjects suffering from neuromuscular disorders.

1 Exploring SynapTic ABnormaLitIeS in Hereditary neuropathies

*At the time of conducting the Study Dr. William David Arnold was professor at Department of Neurology at The Ohio State University Wexner Medical Center. In September 2022, Dr. Arnold was appointed Executive Director of the University of Missouri System NextGen Precision Health Initiative and Professor at the University of Missouri in Columbia, Missouri.

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Contacts
NMD Pharma A/S
Thomas Holm Pedersen, CEO
E-mail: contact@nmdpharma.com

Consilium Strategic Communications
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 private biotech company leading in the development of novel first-in-class therapies for severe neuromuscular disorders. The Company was incorporated as a spin-off from Aarhus University, Denmark in 2015 and 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. NMD Pharma received initial seed financing in 2016 and have since raised ~€80 million from investors including Novo Holdings, Lundbeckfonden BioCapital, INKEF Capital, Roche Venture Fund, and Jeito Capital.

About the Department of Clinical Medicine: Aarhus, Denmark
Department of Clinical Medicine is Denmark’s largest health science institute conducting research in almost all medical specialities and hosting a large number of research centres. Most of our staff are employed part-time at the department and part-time as clinical staff at Aarhus University Hospital or one of the four regional hospitals in Central Denmark Region. The close collaboration between Aarhus University and Aarhus University Hospital ensures fast implementation of research results in clinical practice to the benefit of patients. Department of Clinical Medicine is located at Aarhus University Hospital, which has been awarded Denmark’s best hospital 13 times in a row.

About The Ohio State University
The Ohio State University Wexner Medical Center, based in Columbus, Ohio, USA, is a proud part of one of America’s largest and most comprehensive universities. On the university’s main Columbus campus, more than 56,000 students are able to choose from 14 colleges, 175 undergraduate majors and 240 master’s, doctoral and professional degree programs. Ohio State is consistently ranked as Ohio’s best and one of the nation’s top-20 public universities.
The university’s research innovations have attained world-class status, particularly in critical areas such as global climate change, cancer, infectious disease, neurosciences, advanced materials and ag-bio products that feed and fuel the world.

About Charcot-Marie-Tooth (CMT) disease
CMT encompasses a group of hereditary sensory and motor neuropathies that cause damage to peripheral nerves. Damage caused by CMT worsens over time and can result in the loss or alteration of sensation and atrophy of muscles in the legs, feet, arms and hands. There are several types of CMT which are differentiated by their effects on neurons and inheritance patterns caused by mutations on the X chromosome - both result in either abnormalities in myelination, axonal degeneration, or both. CMT affects approximately 2.6 million individuals worldwide with symptoms appearing typically at adolescence or early adulthood, however onset of the disease can occur at any age.