Dyne Therapeutics, Inc. announced new preclinical data from its myotonic dystrophy type 1 (DM1) program demonstrating robust RNA knockdown of toxic human nuclear DMPK, the genetic basis of the disease. Dyne’s FORCE™ platform leverages the importance of transferrin 1 receptor, TfR1, in muscle biology as the foundation for its novel approach. TfR1, which is highly expressed on the surface of muscle cells, is required for iron transport into muscle cells. Dyne links therapeutic payloads to its TfR1-binding fragment antibody (Fab) to develop targeted therapeutics for muscle diseases. Dyne’s DM1 lead candidate consists of a Fab conjugated to an antisense oligonucleotide (ASO) to enable targeted delivery to muscle tissue to reduce accumulation of toxic DMPK RNA in the nucleus, release splicing proteins, allow normal mRNA processing and translation of normal proteins, and potentially stop or reverse the disease. These new preclinical data build on previous results showing significant reduction in cytoplasmic wild type DMPK RNA in a mouse model that expresses human TfR1(hTfR1). To assess the ability of its lead DM1 candidate to reduce toxic human nuclear DMPK RNA, Dyne developed an innovative hTfR1/DMSXL mouse model that expresses the human TfR1 and carries a human DMPK gene that represents a severe DM1 phenotype with more than 1,000 CTG repeats. In this model, two doses (2 x 10 mg/kg) of Dyne’s candidate resulted in significant toxic human nuclear DMPK knockdown at 14 days: 60% in the heart; 56% in the diaphragm; 54% in the tibialis anterior and 39% in the gastrocnemius. In the study, Dyne’s candidate was well tolerated. Dyne expects to share data from the hTfR1/DMSXL model at a scientific meeting during 2021. The new preclinical data from the hTfR1/DMSXL model are included in an updated corporate presentation available in the Investors & Media section of the Company’s website and add to the robust in vitro and in vivo findings generated previously in Dyne’s DM1 program: Reduction in nuclear foci and correction of splicing in DM1 patient cells; Correction of splicing and reversal of myotonia in well-validated HSALR model; Enhanced muscle distribution as evidenced by reduced levels of cytoplasmic wild type DMPK RNA in non-human primates (NHPs); Durability of response of up to 12 weeks after a single dose in a wild type mouse model; and Favorable tolerability observed in multiple NHP studies.