Benzinga | May 14, 2021 07:07AM EDT

Dyne Therapeutics Highlights Presentation Of New Preclinical Data From Its Myotonic Dystrophy Type 1 Program During American Society of Gene & Cell Therapy Annual Meeting

Dyne Therapeutics, Inc. (NASDAQ:DYN), a muscle disease company focused on advancing innovative life-transforming therapeutics for people living with genetically driven diseases, is presenting new preclinical data from its myotonic dystrophy type 1 (DM1) program during the American Society of Gene & Cell Therapy (ASGCT) 24th Annual Meeting today, including results demonstrating sustained knockdown of toxic human nuclear DMPK RNA, the genetic basis of the disease.

"We are excited to present these data at ASGCT, which continue to validate our FORCE(tm) platform and our approach to developing a potential therapy for people living with DM1. In particular, we are seeing impressive reductions in toxic human nuclear DMPK RNA with twice the duration and at half the dose compared to the data we reported in January of this year in the same model," said Romesh Subramanian, Ph.D., chief scientific officer of Dyne. "This reinforces the advantage of the FORCE platform and its potential to enable targeted delivery of therapeutic oligonucleotides to muscle and supports our goal of offering monthly or less frequent dosing. We believe the preclinical hTfR1/DMSXL model that we developed establishes a new standard to evaluate pharmacodynamics in DM1 and has the potential for translation to human disease."

Dyne's lead DM1 candidate consists of an antigen-binding fragment antibody (Fab) conjugated to an antisense oligonucleotide (ASO) to enable targeted muscle tissue delivery 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. 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 January 2021, Dyne reported data showing that two doses (2 x 10 mg/kg) of its lead DM1 candidate resulted in significant toxic human nuclear DMPK knockdown at 14 days. New data being presented at ASGCT are consistent with these findings, with the candidate demonstrating an approximately 40 percent reduction in DMPK heart foci at 14 days.

Dyne expanded its analysis in the hTfR1/DMSXL model to evaluate the administration of a single, low 10 mg/kg dose of its lead DM1 candidate after 4 weeks. These new data show sustained DMPK knockdown at 4 weeks: 51 percent in the diaphragm, 46 percent in both the heart and tibialis anterior, and 42 percent in the gastrocnemius. Dyne's candidate was well tolerated in the hTfR1/DMSXL studies.

Additionally, Dyne is reporting during ASGCT new in vitro findings from DM1 patient cells with approximately 380 and 2,600 CTG repeats, where its candidate showed a robust, dose-dependent reduction in DMPK RNA, nuclear foci and correction of splicing defects as measured by BIN1 exon 11 inclusion. The results in the cell line with approximately 2,600 CTG repeats are particularly notable given the severity of DM1 disease represented.

"At Dyne we are focused on delivering disease-modification for patients, and the DMPK knockdown we are observing in our hTfR1/DMSXL model is consistent with the range that genetic studies suggest can be clinically meaningful," said Joshua Brumm, president and chief executive officer of Dyne. "These latest findings further strengthen the dataset we've already assembled, showing reduction in nuclear foci and splicing correction in patient cells, as well as splicing correction and reversal of myotonia in the well-validated HSALR in vivo model. We believe we are well positioned as we continue to advance our DM1 program toward the clinic."

Data from Dyne's DM1 program are being featured during the following presentations at ASGCT today and will be made available in the Scientific Publications & Presentations section of Dyne's website following the meeting:

Presentation: Splice Correction and Reduction of Toxic DMPK RNA In Vitro and In Vivo Utilizing Novel Antibody Targeted Antisense Oligonucleotides

Scientific Symposium: Hot Topics and Remaining Challenges in RNAi and Oligonucleotide Therapy for 2021

Time: 10:26 a.m. ET

Oral Presentation: The FORCE(tm) Platform Achieves Robust Knock Down of Toxic Human Nuclear DMPK RNA and Foci Reduction in DM1 Cells and in Newly Developed hTfR1/DMSXL Mouse Model (Abstract #247)

Session: Oligonucleotide Therapeutics

Time: 1:15 p.m. ET

DM1 Program Webcast

Dyne will host a live webcast event today at 4:00 p.m. ET to review the company's DM1 program and preclinical data, and the importance of targeting the genetic basis of the disease. Joining management on the webcast will be Charles Thornton, M.D., the Saunders Distinguished Professor of Neuromuscular Research at the University of Rochester. Dr. Thornton has been engaged in bench and clinical research on myotonic dystrophy for 30 years.

To access the event, please visit the Investors & Media section of Dyne's website at least 10 minutes before the start time in order to register: https://investors.dyne-tx.com/events/event-details/dm1-program-webcast. The replay of the webcast will be made available shortly after the event and remain accessible for 90 days. The corresponding slide presentation will also be available at the time of the event.