Helixmith Co. Ltd announces positive topline data from world's first gene therapy phase 1 study for CMT

SAN DIEGO, Nov. 9, 2021 /PRNewswire/ -- Gene therapy developer Helixmith announced today the results from a phase 1 study for Charcot-Marie-Tooth (CMT) involving Helixmith's lead product Engensis (VM202). It is world's first gene therapy trial completed for this debilitating hereditary neuropathy. This study was conducted at the Samsung Medical Center in Seoul, Korea by Professor Choi Byung-Ok, Professor of Neurology, Sungkyunkwan University School of Medicine, and Director, Korean Organization for Rare Diseases. The study involved 12 CMT participants of which 2 were mild and 10 were moderate in their severity.

This phase 1 study was done with 12 participants who had mild to moderate symptoms and CMTNS-v2 scores ranging from >2 and ≤20. The primary objective was to check safety, but several exploratory efficacy measurements were also collected, such as FDS, ONLS-Leg, CMTNS-v2, and MRI. The first three assays measure the level of fatigue and neuropathy. MRI measures the fraction of fat, which increases with muscle loss resulting from neuropathy.

Engensis continues to appear to be well-tolerated, consistent with observations made in other clinical studies done for painful diabetic peripheral neuropathy, amyotrophic lateral sclerosis, and critical limb ischemia. There were two drug-related adverse effects, ankle edema and injection site pruritus, which were assessed as possibly related. The participants recovered; therefore, dose was maintained throughout the study.

There was a trend of improvements in FDS and ONLS-leg. In the case of FDS, 7 participants showed score 1 improvement, while 5 others showed no change. For ONLS-leg, score 1 improvement was observed in 4 patients, and no change in 8 participants. On average, there was a change in 0.33 for 9 months.

Another efficacy measurement observed was CMTNS-v2. When all 9 items were counted, there was a score 2.17 reduction, a 14% change from baseline (p < 0.01) during the 9-month follow-up period. Of note, 3 items (sensory symptoms, pinprick sensibility, vibration) showed significant improvements relative to baseline values, suggesting potential therapeutic effects in sensory functions.

Muscle loss was estimated by measuring fat fraction by MRI. There was a 0.2% and 1.9% increase in fat fraction in gastrocnemius and tibialis anterior muscles, similar to historical data. However, when patients had more than 10% fat fraction at baseline, the magnitude of fat increase was much lower, ranging from -0.8% improvement to 1.2% depending on muscle areas, compared with a 3% increase per year in the same subgroup of CMT patients based on other studies. These data suggested that Engensis might slow down or improve muscle degeneration, consistent with data from pre-clinical research showing the control of gene expression involved in muscle degeneration or regeneration by Engensis.

In summary, Engensis achieved safety and tolerability endpoints in treated CMT patients, and there was a trend or indication of possible improvements in neuropathy symptoms and muscle quality. A larger phase 2 study is being considered for CMT patients having applicable disease scores to verify observations made from this phase 1 study.

About Charcot-Marie-Tooth disease

CMT is a disease that gradually damages motor neurons and sensory neurons in arms and legs, causing muscle weakness and walking disorders. CMT1A, the most common type of the disease, occurs due to PMP22 gene duplication and accounts for about 40% of all CMT patients, with approximately 8,000 patients in Korea and more than 1.2 million worldwide. Despite such prevalence, no curative treatment has been approved worldwide, only adjuvant therapies are currently available to patients. 

About VM202 (Engensis)

Engensis (VM202) is an innovative gene therapy drug that provides fundamental treatment through tissue regeneration. Built on 20 years of experience in gene therapy, Engensis is designed to overcome the limitations of previous DNA plasmid candidates by expressing therapeutic levels of protein and inducing durable therapeutic effects. Helixmith's non-viral plasmid DNA product, Engensis, is designed to express recombinant HGF protein in nerve and Schwann cells to promote nerve system regeneration and induce the formation of microvascular blood vessels. HGF has a short half-life (5 minutes or less) and is quickly removed from the body by the liver, creating an obstacle to effective treatment with previous injectable recombinant HGF protein products.

A single injection of Helixmith's proprietary plasmid DNA product expresses the HGF gene at levels 30-40 times higher than conventional plasmid DNA and provides sustained gene expression in mouse models for 2 weeks, with peak protein expression at Day 7 and a gradual decrease over the next week. To date, more than 500 patients have been treated with Engensis across ten clinical trials in six different diseases and conditions. Data from previous clinical studies suggest that Engensis is well-tolerated and has the potential to provide durable analgesic and/or symptomatic relief in a variety of disease settings. Beyond potentially alleviating pain, Engensis is designed to target the underlying causes of neuropathy through its predicted angiogenic and neuroregenerative properties. The US FDA recognized the potential for Engensis to meet the unmet need for this condition in 2018 by designating it as a Regenerative Medicine Advanced Therapy (RMAT) for the treatment of painful diabetic peripheral neuropathy, making it the first RMAT-designated gene therapy for a prevalent disease with over one million patients. This designation grants all the benefits afforded by the fast track and breakthrough designations, including priority review, to Engensis.

About Helixmith

Helixmith is a clinical-stage gene therapy company headquartered in Seoul, Korea, developing new and innovative biopharmaceuticals to address previously untreated diseases, and is listed on the KOSDAQ. The company has an extensive gene therapy pipeline, including a CAR-T program targeting several different types of solid tumors and an AAV vector program targeting neuromuscular diseases. Engensis (VM202), the most advanced pipeline candidate, is a plasmid DNA therapy being studied for painful diabetic peripheral neuropathy, diabetic foot ulcers, claudication, amyotrophic lateral sclerosis, coronary artery disease, and Charcot-Marie-Tooth disease.

SOURCE Helixmith USA Inc.

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https://www.helixmith.com/