Tides Express | RAG-17, SOD1-Targeting siRNA Therapy for ALS by China-US Reconn, Administered to First Patient in Phase II Clinical Trial

This multicenter Phase II clinical trial is a multiple-dose, dose-escalation (MAD) randomized, double-blind, placebo-controlled study., aimed to evaluate the safety/tolerability, PK, PD, and preliminary efficacy of RAG-17 repeat dosing administered intrathecally in ALS subjects carrying SOD1 gene mutations. Participating institutions include Beijing Tiantan Hospital affiliated with Capital Medical University (Professor Yilong Wang's team), the Second Affiliated Hospital of Zhejiang University School of Medicine (Professor Zhiying Wu's team), West China Hospital of Sichuan University (Professor Huifang Shang's team), Fujian Medical University Union Hospital (Professor Zhangyu Zou's team), and the First Affiliated Hospital of Sun Yat-sen University (Professor Jinsheng Zeng's team).

This milestone marks the official entry of the study into Phase II.The initiation of the Phase II MAD stage is based on the positive results from the successfully completed Phase I Single Ascending Dose (SAD) study. The SAD study data demonstrated excellent safety and sustained biomarker modulation following a single dose of RAG-17, including significant reduction of SOD1 protein in cerebrospinal fluid (CSF) and improvement in plasma neurofilament light chain (NfL) levels. These results strongly validate the capability of our proprietary SCAD™ delivery platform to achieve targeted delivery to the central nervous system (CNS) in humans.

AboutALS

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord, leading to muscle weakness, paralysis, and ultimately death within 3 to 5 years after diagnosis. Mutations in the SOD1 gene account for approximately 10-20% of familial ALS cases and 1-2% of sporadic ALS cases. Currently, there remains an urgent clinical need for treatments that can effectively slow or halt the progression of ALS to improve patients' quality of life and extend survival.

AboutRAG-17

RAG-17 is an innovative siRNA drug independently developed by Ractigen Therapeutics, leveraging the company's proprietary SCAD™ (Smart Chemical-Assisted Delivery) platform technology. The drug aims to specifically and efficiently target and silence the mRNA expression of the SOD1 gene for the treatment of ALS patients carrying SOD1 gene mutations. Toxic gain-of-function caused by SOD1 gene mutations is a significant pathogenic factor in familial ALS. By effectively inhibiting SOD1 gene expression and reducing the production of toxic SOD1 protein, RAG-17 aims to protect neuronal function, thereby delaying or halting the progression of SOD1-ALS.

Previously, RAG-17 received Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) and was included in the pilot project of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) under the "Patient-Centered Rare Disease Drug Development Pilot Work Plan ('Care Program')".

AboutRactigen

Ractigen Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing breakthrough small nucleic acid drugs and disease treatment methods. Ractigen Therapeutics is one of the few global companies that simultaneously masters both intrahepatic and extrahepatic delivery for small nucleic acid drugs. It has developed several internationally leading small nucleic acid drug delivery platform technologies with independent intellectual property rights, including SCAD™, LiCO™, and GLORY™. Based on RNA activation technology and its self-developed Smart-TTC saRNA drug development platform, the company has established a highly differentiated small nucleic acid drug pipeline, with indications covering neurodegenerative diseases, neuromuscular diseases, cancer, metabolic diseases, and hematological disorders, providing innovative therapeutic solutions for undruggable targets and currently incurable diseases across various fields.