Findings support saRNA as a therapeutic strategy to compensate dystrophin’s function by upregulating UTRN expression with small activating RNA (saRNA) for the treatment of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD).
JIANGSU, CHINA, November 2, 2023 — Ractigen Therapeutics, a clinical stage biopharmaceutical company founded by the pioneers in RNA activation (RNAa), presented recent preclinical results at the annual meeting of the Oligonucleotide Therapeutics Society (OTS) in Barcelona, Spain. RNAa uses short duplex RNA known as saRNA to target and ‘turn up’ transcription of endogenous genes leading to restoration of their protein function. saRNA offers the ability to modulate traditionally undruggable targets and represents one of the few available technologies that can be translated into clinic to treat diseases by stimulating the expression of therapeutic genes with insufficient expression.
Key Data Highlights from OTS
The poster titled “Therapeutic development of saRNA for Duchenne muscular dystrophy by targeted activation of utrophin” illustrated a novel and translatable therapeutic strategy for DMD and BMD caused by any mutation of the DMD gene. In this study, candidate saRNAs were designed to target the promoter of human UTRN gene to activate its expression. Potent lead saRNAs were identified in human skeletal muscle derived cell lines and validated in transgenic mice bearing the human UTRN promoter. In a proof-of-concept efficacy study in MDX mice bearing the human UTRN promotor, systemic administration of a lead saRNA conjugated to Ractigen’s proprietary LiCOTM delivery system ameliorated muscle damage. The study also highlighted their LiCOTM technology which enables duplex RNAs (e.g., saRNA and siRNA) delivery to, and exerts durable activities in, the skeletal muscles and heart.
“We are very excited about the preclinical results of our utrophin activating saRNA and believe that our approach could represent an ideal therapeutic strategy that benefits all DMD and BMD patients,” said Long-Cheng Li, CEO of Ractigen Therapeutics. “We are fast-tracking this program and aim to initiating phase I trial in early 2025”
At the same OTS meeting, Ractigen presented a second poster titled, “SCAD: a platform technology for CNS delivery of duplex RNA by intrathecal administration”, which reports the development and validation of its proprietary duplex RNA delivery platform SCADTM (smart chemistry aided delivery) in rodents and nonhuman primates. SCADTM enables the delivery of saRNA and siRNA to the CNS via local injection (e.g., intrathecal) with broad biodistribution and potent and durable activity. The SCADTM platform has propelled Ractigen’s leading RNA program to the clinic for the treatment of ALS patients with SOD1 mutation.
About RAG-18
RAG-18 is a therapeutic saRNA designed to upregulate the expression of utrophin to compensate the function of dystrophin and treat Duchenne muscular dystrophy (DMD) and Becker muscular dystrophin (BMD) regardless of the location of DMD mutation. RAG-18 utilizes Ractigen’s proprietary Lipid-conjugated oligonucleotide LiCOTM delivery platform, which enables durable and potent activity in the skeletal muscle and heart via systemic administration. Data from preclinical studies indicate RAG-18 could be delivered to the skeletal muscles and heart to activate the expression of endogenous utrophin gene and ameliorated muscle damage caused by the mutation of mouse Dmd gene.
About SCADTM
SCADTM (smart chemistry-aided delivery) is Ractigen’s proprietary breakthrough platform technology for delivering dsRNA to the central nervous system (CNS) by conjugating a non-targeting single-stranded accessory oligonucleotide (ACO) to a duplex with “self-delivering” properties. SCADTM has broad distribution, and durable and potent activity in different parts of the CNS by intrathecal injection. The efficacy and safety of SCADTM delivery system is being validated in the clinic.
About Ractigen
Ractigen Therapeutics, founded in 2017 by pioneers of the RNA activation (RNAa) technology, is a clinical pharmaceutical company devoted to creating groundbreaking therapies based on oligonucleotide technologies including RNAa and RNAi. Supporting therapeutic development, Ractigen Therapeutics has also created a portfolio of delivery platforms including its scadTM and LiCOTM system, which allows efficient delivery of therapeutic oligonucleotides to hard-to-reach extrahepatic tissues and empowers pipeline development across several disease areas. The Company has completed +$50M Series A/A+ venture financing rounds with participation from reputed investors including Hillhouse Venture Capital, SDIC Venture Capital, Eisai Co., LC Ventures, CSSD Capital, Xianghe Capital, CCB Healthcare Growth Fund, Boyi Capital, and Longmen Capital.
