Dynacure Presents New Preclinical Results on Muscle Targeting with Antisense Oligonucleotides at the 24th Annual International Congress of the World Muscle Society

STRASBOURG, France I October 2, 2019 I Dynacure, a clinical stage drug development company focused on improving the lives of patients with rare and orphan disorders, today announced two poster presentations at the 24th Annual International Congress of the World Muscle Society (WMS).  Dynacure is presenting new preclinical research supporting its lead antisense medicine, DYN101, and data from the prospective Natural History Study of Patients With Myotubular Myopathy and Other CentroNuclear Myopathies (NatHis-CNM) will be presented by the Institute of Myology.  DYN101 is an investigational antisense medicine designed to modulate the expression of dynamin 2 (DNM2) for the treatment of Centronuclear Myopathies (CNM).  Dynacure expects to initiate its first in human study, a Phase 1 / 2 study 'Unite-CNM', in the fourth quarter of 2019.  DYN101 is being developed in collaboration with Ionis Pharmaceuticals, the leader in RNA-targeted drug discovery. 

Preclinical mouse work has shown ASO-mediated DNM2 knockdown can efficiently correct skeletal muscle defects due to loss of MTM1, providing an attractive therapeutic strategy for this disease. Today at WMS, Dynacure scientists presented new preclinical data investigating skeletal muscle targeting of DNM2 reduction in mice with new palmitate-conjugated antisense. Effective muscle targeting will be an important step in translation of this approach to the clinic for patients.

"We are pleased to present new preclinical results at World Muscle Society that support our clinical approach of modulating DNM2 to treat CNM as well as data from a natural history study," said Belinda Cowling, Chief Scientific Officer of Dynacure.  "In preclinical models, we've demonstrated that antisense oligonucleotide knockdown can efficiently correct muscle defects in certain genetic forms, XLCNM and ADCNM, which represent a large portion of the treatable patient population.  This provides an effective therapeutic strategy to treat several forms of centronuclear myopathies due to the mutations in different genes.  In addition, the data measuring clinical changes over time collected from patients enrolled in the ongoing European natural history study will continue to inform our clinical plans.  We look forward to evaluating our lead therapeutic candidate DYN101 in patients with the initiation of our Phase 1 / 2 UNITE-CNM study."

24th Annual International Congress of the WMS
Poster Abstract: # P.104

Title: Skeletal muscle reduction of Dnm2 with antisense oligonucleotides in myotubular myopathy
Session: Poster session 2, Congenital myopathies: centronuclear and others
Date/Time: Wednesday, October 2, 2019 4:45 PM – 6:15 PM
Location:  Tivoli Gardens, Copenhagen, Denmark

Poster Abstract: # P.107

Title: Clinical changes over time in patients with centronuclear myopathy due to mutations in DNM2 gene enrolled in a European prospective natural history study
Date/Time: Wednesday, October 2, 2019 4:45 PM – 6:15 PM
Location:  Tivoli Gardens, Copenhagen, Denmark

The 2019 WMS poster can be accessed on Dynacure's website and further details on the WMS meeting can be accessed here: http://www.wms2019.com/

Centronuclear and myotubular myopathies, or muscle diseases, (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 for Centronuclear Myopathies

DYN101, an investigational antisense oligonucleotide using Ionis' proprietary antisense technology, is designed to modulate the expression of dynamin 2 (DNM2) for the treatment of Centronuclear Myopathies. 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, ADCNM and ARCNM.  In addition to investigating DYN101 for CNM, Dynacure aims to expand its use and explores additional indications where the overexpression of DNM2 is a disease-driving factor. 

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) is a European 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 XLCNM or 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 target attainment 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 European and US sites.   https://clinicaltrials.gov/ct2/show/NCT04033159?term=dynacure&rank=1

About Dynacure

Dynacure is a clinical-stage drug development company focused on improving the lives of patients with rare and orphan diseases. The Dynacure team leverages its proven track record in rare disease drug development to build a pipeline of novel drugs.  Dynacure is developing DYN101, an investigational antisense medicine designed to modulate the expression of dynamin 2 for the treatment of Centronuclear Myopathies, with Ionis Pharmaceuticals. Dynacure is also building a complementary research portfolio targeting other orphan disorders. The company maintains its headquarters in Strasbourg, France.  Dynacure's investors are Andera Partners, Bpifrance, IdInvest, Ionis Pharmaceuticals, Kurma Partners and Pontifax.

For more information, please visit www.dynacure.com.

SOURCE: Dynacure

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