Dyne Therapeutics, Inc. announced that new preclinical data demonstrating the FORCE(TM) platform achieved delivery to the central nervous system (CNS) and robust pharmacological effects in the brain will be featured in an oral presentation at the American Society of Gene & Cell Therapy (ASGCT) 26(th) Annual Meeting, being held May 16-20, 2023 in Los Angeles. The FORCE platform was designed to overcome the limitations of delivering oligonucleotide therapeutics to muscle tissue by leveraging transferrin receptor 1 (TfR1). TfR1-mediated delivery has also been shown by the field to facilitate uptake of therapeutics by the CNS.

Many people living with rare muscle diseases also experience CNS symptoms that contribute to the burden of disease, including cognitive deficits and dysregulated sleep, which affect individuals with myotonic dystrophy type 1 (DM1). In data to be presented at ASGCT, intravenous (IV) administration of FORCE conjugate achieved delivery to the CNS via TfR1 in both non-human primates (NHPs) and the innovative hTfR1/DMSXL mouse model. The hTfR1/DMSXL model, developed by Dyne, expresses the human TfR1 and carries a human DMPK gene with more than 1,000 CTG repeats that represents a severe DM1 phenotype.

In NHPs, FORCE conjugate, a TfR1-binding Fab antibody conjugated to an antisense oligonucleotide (ASO), demonstrated broad distribution throughout the brain compared to an unconjugated ASO delivered either via intrathecal (IT) or IV administration. Similarly, FORCE conjugate delivered to the brain of hTfR1/DMSXL mice and demonstrated robust reduction of toxic nuclear DMPK RNA and foci. In the hTfR1/DMSXL model and NHPs, FORCE conjugate was well tolerated.