Myonexus Therapeutics Announces the Initiation of a Trial for the First-Ever Gene Therapy for Beta-sarcoglycanopathy, Also Known as Limb-Girdle Muscular Dystrophy Type 2E

Myonexus Therapeutics, a clinical-stage gene therapy company developing first-ever corrective gene therapies for limb girdle muscular dystrophies (LGMD), in collaboration with Nationwide Childrens Hospitals Center for Gene Therapy and Sarepta Therapeutics, announced today the initiation of a clinical trial evaluating MYO-101, a novel gene therapy candidate for beta-sarcoglycanopathy, also known as LGMD2E. The goal is to deliver to skeletal and cardiac muscle a gene that codes for and enables robust and functional expression of the protein beta-sarcoglycan, the lack of which causes LGMD2E. The first patient in cohort 1 of the trial was dosed earlier in October and all patients in cohort 1 are expected to be dosed in 2018, with data expected by early 2019.

LGMD2E is a rare, degenerative and universally fatal form of muscular dystrophy caused by a genetic mutation. Progressive muscle fiber loss, inflammation and scarring in these patients causes degeneration of muscle strength and function. One of the leading causes of early mortality is cardiomyopathy caused by damage to the heart tissue.

By implementing highly precise vector technology, gene therapy has great potential to deliver functionally curative solutions for challenging rare diseases. Based on positive pre-clinical results in both efficacy and safety, we are confident in the vector and platform selected for MYO-101 and are hopeful that MYO-101 could be the first profound therapy for patients with LGMD2E, said Michael Triplett, Myonexus president and chief executive officer. We look forward to working with the LGMD community and believe that by listening and incorporating their feedback, together we will make a dramatic impact on the progression of this disease.

The Myonexus gene therapy platform, which uses the AAVrh.74 vector system, has been evaluated by a research team including Louise Rodino-Klapac, Ph.D. and Jerry R Mendell, M.D., and colleagues at Nationwide Childrens Hospital for more than 12 years before being licensed to Myonexus, an independent start-up company formed in 2017. Dr. Rodino-Klapac remains Myonexus chief scientific officer for the program while Dr. Mendell remains the principal investigator at Nationwide Childrens Hospital.

Pre-clinical studies of MYO-101 have demonstrated robust transduction of the vector to skeletal and cardiac muscle, with no therapy-limiting immune response. After a single administration of MYO-101 in a mouse model, greater than 95% of muscle cells produced the beta-sarcoglycan protein, and key parameters of function including strength and cardiac output were normalized. The treatment was associated with a positive increase in muscle fiber diameters, reduced scarring and fat infiltration, and improved overall activity compared with non-treated mice.

Having evaluated the vector used in MYO-101 for more than a decade, in pre-clinical studies we have seen the robust and consistent ability of the vector to transduce the skeletal and cardiac muscle and produce a significant restoration of the missing protein, said Dr. Louise Rodino-Klapac, who also serves as Vice President of Gene Therapy for Sarepta Therapeutics. If successful in our clinical trial, this could become the first corrective treatment for LGMD2E, a merciless disease that has invariably robbed patients of strength and then life.

MYO-101 is the culmination of many years of hard work and experimentation, said Dr. Jerry Mendell, Curran-Peters Chair of Research at Nationwide Childrens. It shares much in common with our microdystrophin gene therapy program for Duchenne muscular dystrophy, as it also targets the skeletal and cardiac muscles, addresses a crucial missing protein in the dystrophin-associated protein complex, and shares an identical viral capsid and promoter with the microdystrophin construct. We look to build on our learnings as we commence our first cohort of LGMD2E trial participants.

Myonexus is advancing a series of gene therapy programs as part of an ongoing collaboration with Sarepta (see announcement). The collaboration aims to deliver the first-ever corrective treatments for five distinct forms of LGMD. In addition to the clinical research underway on MYO-101, Myonexus is advancing four other candidates, all using the same AAVrh.74 vector: MYO-102 for LGMD2D, MYO-103 for LGMD2C, MYO-201 for LGMD2B, and MYO-301 for LGMD2L. Pursuant to the collaboration agreement, Sarepta will make milestone and other payments over a two-year evaluation period and has the option to acquire Myonexus at set terms at any time.

About Limb-Girdle Muscular Dystrophy (LGMD)

Limb girdle muscular dystrophies are genetic diseases that cause progressive, debilitating weakness and wasting that begins in muscles around the hips and shoulders before progressing to muscles in the arms and legs. LGMD2E affects between 1-in-200,000 to 1-in-350,000 newborns without regard to sex, race, or national origin. The disease usually presents before age 10 with difficulty running, jumping and climbing stairs. It progresses to loss of ambulation in the teen years, and often leads to death before age 30. There is currently no treatment or cure for LGMD type 2E.

About the LGMD2E Clinical Trial

This first-in-human, Phase1/2a placebo-controlled study will evaluate a single intravenous infusion of MYO-101 among children with LGMD2E between the ages of four and 15 years with significant symptoms of disease. The study is designed to evaluate up to two dose levels of the gene therapy candidate in two cohorts among nine patients (Cohort 1-3 is active at 5×1013 vg/kg; Cohort 2 will consist of 3:3 active to placebo patients at either 5×1013 vg/kg or at 2×1014 vg/kg if results from Cohort 1 justify dose escalation). Placebo patients will be eligible for cross-over after the year one biopsy results. For more information, visit; study identifier NCT03492346.

About Myonexus Therapeutics

Myonexus Therapeutics is a clinical stage, rare disease gene therapy company developing first ever treatments for limb girdle muscular dystrophies (LGMDs) based on research at Nationwide Childrens Hospital, a leader in neuromuscular gene therapy discovery and translational research. Myonexus Therapeutics pipeline includes three clinical stage gene therapy programs (LGMD2E, LGMD2D, and LGMD2B) and two preclinical gene therapy programs (LGMD2C and LGMD2L). Founded in 2017, Myonexus is headquartered in New Albany, Ohio. More information is available at

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