Dynacure Receives Rare Pediatric Disease Designation from U.S. Food and Drug Administration for DYN101 for Myotubular and Centronuclear Myopathies (CNM)

STRASBOURG, France and PHILADELPHIA, July 30, 2020 /PRNewswire/ -- Dynacure, a clinical stage drug development company focused on improving the lives of patients with rare and orphan disorders, announced today that the U.S. Food and Drug Administration (FDA) has granted rare pediatric disease designation for DYN101, an investigational antisense medicine designed to modulate the expression of dynamin 2 (DNM2), for the treatment of Myotubular and Centronuclear Myopathies (CNM).

Under the FDA's rare pediatric disease designation program, the FDA may grant a priority review voucher to a sponsor who receives a product approval for a "rare pediatric disease," which is defined as a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years and affects fewer than 200,000 people in the U.S. Subject to FDA approval of DYN101 for the treatment of CNM, Dynacure would be eligible to receive a voucher that may be redeemed to receive priority review for a subsequent marketing application for a different product candidate or which could be sold or transferred.

"The rare pediatric designation of DYN101 for CNM demonstrates the FDA's recognition of Myotubular and Centronuclear Myopathies as serious, life-threatening disorders that affect skeletal muscles from birth and progress over time," said Leen Thielemans (Ir, PhD, MSc), Chief Development Officer of Dynacure.

"Our clinical development strategy is to provide benefit to a wide range of CNM patients, including children affected by this progressive disease, by modulating DNM2 with DYN101," said Chris Freitag (M.D.), Chief Medical Officer of Dynacure. "We are very excited about this new designation and we expect to open a pediatric study end of 2021 in both the US and EU."

About Myotubular and Centronuclear Myopathies
Myotubular and Centronuclear Myopathies (CNM) are serious, rare, life-threatening disorders that affect skeletal muscles from birth. CNMs derive their name based on the central location of the muscle fiber nucleus, which is an abnormal finding observed in muscle biopsies. The disease is driven by mutations in multiple genes including MTM1, DNM2 and BIN1 and Dynacure scientists have discovered the link between an increase in DNM2 and the direct cause of the disease (Cowling et al 2014 JCI). There are many genetic forms of CNM including X-linked recessive (XLCNM/ Myotubular Myopathy), autosomal dominant (ADCNM), and autosomal recessive (ARCNM), which are all associated with poor prognosis. Centronuclear Myopathies affect between 4,000 and 5, 000 patients in the EU, US, Japan and Australia1.

About DYN101
DYN101, an investigational antisense oligonucleotide using Ionis' proprietary antisense technology, is designed to modulate the expression of dynamin 2 (DNM2) for the treatment of Myotubular and Centronuclear Myopathies (CNM). Preclinical studies have demonstrated that DYN101 has the potential to be disease modifying in CNM, with compelling preclinical efficacy in treating animal models of XLCNM and ADCNM2,3. Prevention and reversion of the disease was observed with a clear dose-dependent improvement in whole body strength and mice survival. The development plan for DYN101 was designed to be very broad and it is the only known program being investigated for most CNM populations, XLCNM and ADCNM. DYN101 has been granted Orphan Drug designations by the US FDA and EMA.

About the Phase 1 / 2 Study 'Unite-CNM' (DYN101-C101)
'Unite-CNM' (DYN101-C101) study is a multicenter, ascending dose study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of DYN101 in approximately 18 patients greater than 16 years of age with X-linked (XLCNM) or autosomal dominant CNM (ADCNM). Enrolled patients will have a run-in period or be rolled over from an ongoing natural history study, sponsored by the Institute of Myology in France, which includes 60 subjects that have XLCNM or ADCNM. While the Phase 1 / 2 study will primarily focus on finding an optimal dose of the drug via safety, tolerability and after 12 weeks of treatment, multiple domains of efficacy will also be assessed in an exploratory analysis, which include muscular function, respiratory function and muscle strength. After completing the Unite-CNM study, Dynacure expects to investigate a potentially registration-directed Phase 2 / 3 study (all age groups) that would include US and European sites.

1 Neuromuscul Disord. 2018 Sep;28(9):766-777. doi: 10.1016/j.nmd.2018.06.012. Epub 2018 Jul
2 Nat Commun. 2017 Jun 7;8:15661. doi: 10.1038/ncomms15661.
3 Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):11066-11071. doi: 10.1073/pnas.1808170115. Epub 2018 Oct 5.