#China #ALS #RAG-17 #Ractigen #Nantong

Ractigen Therapeutics Achieves Milestone with RAG-17 in Nature Medicine

In a groundbreaking development, Ractigen Therapeutics has announced the publication of pivotal research focused on RAG-17 in the esteemed journal Nature Medicine. This peer-reviewed publication details an unprecedented achievement in the preclinical efficacy and early clinical trials for RAG-17, an innovative small interfering RNA (siRNA) therapy aimed at treating amyotrophic lateral sclerosis (ALS) caused by mutations in the superoxide dismutase 1 (SOD1) gene.

The Journey from Bench to Bedside

RAG-17 utilizes Ractigen's proprietary Smart Chemistry-Aided Delivery (SCAD™) technology, which enhances the delivery of siRNA directly to the central nervous system (CNS). This novel approach is intended to silence the SOD1 gene, which has been linked to the progression of ALS. Remarkably, the publication highlights that the First-in-Human (FIH) trials of RAG-17 have successfully met all primary safety endpoints, with no serious adverse events reported.

Dr. Yilong Wang, who led the study and serves as the Principal Investigator at Beijing Tiantan Hospital, stated, "SOD1-ALS is not just a medical challenge but a race against time for patients. Current therapies leave much to be desired, hence the urgent need for more effective solutions. Our preliminary results indicate that RAG-17 holds substantial promise in offering such solutions."

Observations from Clinical Trials

In the open-label, dose-escalation clinical trial, six patients with SOD1-ALS received multiple intrathecal doses of RAG-17. The results were encouraging:

• - Safety: The treatment was well tolerated, showing no serious adverse events and no need for invasive mechanical ventilation during the trial period.
• - Biomarkers Improvement: Significant reductions in cerebrospinal fluid (CSF) SOD1 protein were observed, with a mean decrease of 69% by Day 240 of the study. Additionally, plasma neurofilament light chain (NfL) levels, a critical marker of neurodegeneration, dropped by an average of 62%.
• - Stabilization of Disease Symptoms: Some patients exhibited stabilization or slowed decline in their functional capabilities, particularly regarding respiratory health over the study period.

Unmatched Preclinical Results

The publication also delineated RAG-17’s impressive preclinical performance. In exploratory tests involving advanced-stage ALS in rodent models, RAG-17 demonstrated survival extensions of up to 75.8% when administered well after symptom onset. In rat studies, it significantly delayed disease symptom onset and preserved spinal motor neurons.

In cynomolgus monkeys, RAG-17 achieved a remarkable reduction of SOD1 mRNA levels in the spinal cord, establishing a long-lasting effect that opens the door to potentially less frequent dosing in humans.

Aiming for a New Standard of Care

“Achieving robust target engagement and transferring those results into human trials is an extraordinary milestone for RNA therapeutics,” remarked Dr. Long-Cheng Li, the Founder and CEO of Ractigen Therapeutics. “We're very excited about the implications of RAG-17 as a future standard treatment for SOD1-ALS.”

The full study titled, “Oligonucleotide-siRNA conjugate for SOD1 amyotrophic lateral sclerosis: A phase 1 trial”, is publicly accessible in Nature Medicine, marking a significant step forward in the quest for effective ALS treatments.

The Road Ahead

As Ractigen Therapeutics progresses with RAG-17, they remain committed to extending their reach within RNA therapies. The company aims to address pressing medical needs across various diseases, with a core focus on revolutionary treatments that can reshape patient care in neurology and beyond. The results thus far create hope for individuals grappling with ALS, offering renewed encouragement in the search for effective therapies.

For more information about Ractigen Therapeutics, please visit www.ractigen.com.