RAG-17 / Ractigen Therap - LARVOL DELTA

Ractigen Therapeutics Announces Completion of Enrollment and First Dosing in Phase II Clinical Trial of RAG-17 for SOD1-ALS (The Manila Times) - "This Phase II trial (NCT06556394) is a randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of repeated intrathecal injections of RAG-17 in patients with SOD1 mutations."

Enrollment closed • Trial status • Amyotrophic Lateral Sclerosis

Ractigen Therapeutics...announced the successful closing of a new financing round exceeding $31 million (over RMB 200 million). (The Manila Times) - "Funding led by Guozhong Capital will accelerate...CNS asset RAG-17..."

Financing • Amyotrophic Lateral Sclerosis

Oligonucleotide-siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial. (PubMed, Nat Med) - P1 | "These results demonstrate a favorable safety outcome, supporting the continued clinical evaluation of RAG-17 for SOD1-ALS. ClinicalTrials.gov registration: NCT05903690."

First-in-human • Journal • P1 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Movement Disorders • NEFL • Plasma NfL • SOD1

Ractigen Therapeutics Announces Landmark Publication in Nature Medicine Highlighting Unprecedented Preclinical Efficacy and Positive First-in-Human Clinical Data for RAG-17 in SOD1-ALS (PRNewswire) - "Favorable Safety Profile: RAG-17 met its primary safety endpoint. It was well-tolerated, with no serious adverse events (SAEs) and no requirement for invasive mechanical ventilation up to the data cutoff. Treatment-emergent adverse events (TEAEs) were mild to moderate, transient, and manageable; Robust Biomarker Reductions: RAG-17 achieved substantial, progressive reductions in key biomarkers. In Cohort 1, mean cerebrospinal fluid (CSF) SOD1 protein decreased by 69% at Day 240, while plasma NfL—a critical marker of neuroaxonal damage—decreased by a mean of 62%, with individual nadirs reaching up to 85% below baseline....In aggressively progressing SOD1G93A mouse models, RAG-17 demonstrated remarkable efficacy even when administered significantly after symptom onset (postnatal days 126 and 151). Late-stage treatment extended survival by up to 75.8% (128.5 days) compared to controls, alongside restored motor function and preserved body weight."

First-in-human • P1 data • Preclinical • Amyotrophic Lateral Sclerosis

Phase II Trial Update (PRNewswire) - "Ractigen Therapeutics also reports that a Phase II clinical trial for RAG-17 is now underway. This randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of repeated intrathecal injections of RAG-17 in patients with SOD1 mutations. Since the first participant was successfully dosed on January 13, 2026, enrollment for two cohorts has been successfully completed."

Trial status • Amyotrophic Lateral Sclerosis

Ractigen Therapeutics…announced positive preliminary data from the single ascending dose (SAD) Phase I portion of its ongoing Phase I/II clinical trial of RAG-17. RAG-17 is a novel small interfering RNA (siRNA) therapeutic in development for the treatment of amyotrophic lateral sclerosis (ALS) patients with mutations in the superoxide dismutase 1 (SOD1) gene. (PRNewswire) - "Favorable Safety & Tolerability: RAG-17 was well-tolerated across all ascending dose cohorts. There were no serious adverse events (SAEs) or Grade3 treatment-emergent adverse events. Only three treatment-related adverse events were reported and all were mild ≥ 3 treatment-emergent adverse events; Profound Target Engagement: A single IT dose yielded rapid and durable reductions in the disease-driving protein. In the 150 mg cohort, the maximum reduction in cerebrospinal fluid (CSF) SOD1 reached 58.1% (blinded analysis) by Day 90, maintaining a clinically meaningful reduction through Day 210."

P1/2 data • Amyotrophic Lateral Sclerosis

Phase I Study of RAG-17, an siRNA Therapy Targeting SOD1, in Patients with SOD1-ALS: Preliminary Safety, Biomarker and Efficacy Data (AAN 2026) - "Conclusions RAG-17 demonstrates a favorable safety profile and compelling pharmacodynamic activity. The profound reduction in CSF SOD1 and plasma NfL following a single dose, combined with encouraging trends in clinical stability, highlights the efficiency of the SCAD™ delivery platform and supports RAG-17 as a promising therapeutic candidate for SOD1-ALS."

Biomarker • Clinical • P1 data • Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL • Plasma NfL • SOD1

Ractigen Therapeutics Announces First Patient Dosed in Phase II Clinical Trial of RAG-17 for SOD1-ALS (PRNewswire) - "The initial dosing occurred at Second Affiliated Hospital, Zhejiang University School of Medicine....This Phase II trial is a randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of repeated intrathecal injections of RAG-17 in patients with SOD1 mutations."

Trial status • Amyotrophic Lateral Sclerosis

Extended Study of RAG-17 in the Treatment of Amyotrophic Lateral Sclerosis Patients With SOD1 Gene Mutation (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Beijing Tiantan Hospital

New P1 trial • Amyotrophic Lateral Sclerosis • CNS Disorders • CSF NfL • Plasma NfL

Safety and Tolerance of RAG-17 in Amyotrophic Lateral Sclerosis Patients With SOD1 Gene Mutation (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Beijing Tiantan Hospital | Enrolling by invitation ➔ Completed | Trial completion date: Feb 2024 ➔ Jul 2024 | Trial primary completion date: Feb 2024 ➔ Jul 2024

Trial completion • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders • Plasma NfL • SOD1

RAG-17, a Novel siRNA Therapy for SOD1-ALS: Safety and Preliminary Efficacy from a First-in-human Trial (AAN 2025) - P1 | "The CREATION study demonstrates that RAG-17 is safe and exhibits potential efficacy in treating ALS patients. The results from this study highlight the therapeutic promise of RAG-17, offering new avenues for the management of ALS."

Clinical • P1 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Movement Disorders • Pain • NEFL • Plasma NfL • SOD1

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RAG-17 in Subjects With Amyotrophic Lateral Sclerosis (ALS) With Superoxide Dismutase Type 1 (SOD1) Gene Mutation (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Ractigen Therapeutics. | Not yet recruiting ➔ Recruiting

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders

Ractigen Therapeutics Announces First Patient Dosed in Phase I Clinical Trial for RAG-17 in SOD1-ALS (PRNewswire) - "Ractigen Therapeutics...announced the successful dosing of the first patient in the Phase I clinical trial of RAG-17, an innovative siRNA therapy targeting Amyotrophic Lateral Sclerosis (ALS) associated with superoxide dismutase 1 (SOD1) gene mutations at Second Affiliated Hospital of Zhejiang University School of Medicine. The Phase I clinical study is a randomized, double-blind, placebo-controlled trial designed to evaluate the safety/tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of RAG-17 in patients with SOD-ALS."

Trial status • Amyotrophic Lateral Sclerosis

RAG-17: A promising new gene silencing therapy for SOD1 ALS. Early safety and efficacy data from a first-in- human trial (ALS-MND 2024) - "Cells harboring chr7:76,009,472:C > T showed increased expression of CCDC146 at the mRNA (p = 0.0056, n =3) and protein levels. We also observed an exacerbation of ALS-associated phenotypes including increased TDP-43 mislocalization (100% increase, p = 0.024, n =3, t-test) and reduced dendritic arborization (p 0.05, n = 15) and completely rescued ALS-associated survival defects in iPSN derived from patients with both sporadic and C9ORF72-ALS (p <0.01, n = 15, Dunnett's test) irrespective of baseline CCDC146 expression."

Clinical • STMN2 • TARDBP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RAG-17 in Subjects with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) Gene Mutation (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Ractigen Therapeutics. | Initiation date: Aug 2024 ➔ Dec 2024

Trial initiation date • Amyotrophic Lateral Sclerosis • CNS Disorders

Rag-17: a promising new gene silencing therapy for sod1-als- early safety and efficacy data from a first-in-human trial (Neuroscience 2024) - P1 | "Among the first three participants receiving at least four doses, two showed stabilization of ALSFRS-R scores, and one even demonstrated improvement in ALSFRS-R and forced vital capacity (FVC) compared to baseline. The final analysis is expected in July 2024.1"

Clinical • P1 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Pain • NEFL • Plasma NfL • SOD1

Ractigen Announces Positive Clinical Data for RAG-17 in ALS-SOD1 Treatment from Investigator-Initiated Trial (PRNewswire) - P1 | N=6 | NCT05903690 | "Results demonstrated that RAG-17, administered intrathecally, was well-tolerated across all dose levels. All adverse events were mild. Comprehensive safety evaluations, including laboratory assessments, vital signs, and electrocardiograms, further supported the favorable safety profile. Encouragingly, early signs of clinical benefit were also evident. Notable changes in clinical outcomes and key biomarkers indicate the efficacy of RAG-17 within this patient population...This promising data will be presented at three upcoming conferences: the 27th National Conference of Neurology in China this September, followed by Neuroscience 2024 in Chicago, USA, in October, and the 35th International Symposium on ALS/MND in Montreal, Canada, in December—one of the largest annual gatherings dedicated to ALS and motor neuron disease research."

P1 data • Amyotrophic Lateral Sclerosis • CNS Disorders

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RAG-17 in Subjects With Amyotrophic Lateral Sclerosis (ALS) With Superoxide Dismutase Type 1 (SOD1) Gene Mutation (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Ractigen Therapeutics.

New P1 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

Ractigen Therapeutics Receives IND Approval from China's NMPA to Initiate Phase 1 Clinical Trials for RAG-17 in SOD1-ALS Patients (PRNewswire) - "Ractigen Therapeutics...announces that the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has approved the Investigational New Drug (IND) application for the initiation of Phase 1 clinical trials in China for RAG-17, targeting Amyotrophic Lateral Sclerosis (ALS). The IND-opening study is a Phase I, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of RAG-17 in subjects with ALS carrying the Superoxide Dismutase 1 (SOD1) mutation."

New P1 trial • Amyotrophic Lateral Sclerosis

Safety and Tolerability of RAG-17 in the Treatment of Amyotrophic Lateral Sclerosis Patients With SOD1 Gene Mutation (clinicaltrials.gov) - P1 | N=6 | Enrolling by invitation | Sponsor: Beijing Tiantan Hospital

New P1 trial • Amyotrophic Lateral Sclerosis • CNS Disorders • Plasma NfL • SOD1

Ractigen Therapeutics Announces Dosing of First Patient in First in Human Trial of RAG-17 for the Treatment of SOD1-ALS (GlobeNewswire) - "Ractigen Therapeutics...announced the dosing of its first patient in the Company's First in Human (FIH) clinical trial for ALS patients with SOD1 mutation. RAG-17 is a siRNA drug designed to provide potent and durable knockdown of SOD1 protein in the central nervous system (CNS) of ALS patients to prevent motor neuron degradation and delay disease progression....The FIH trial is designed to evaluate the safety, pharmacokinetics, pharmacodynamics (reduction of CSF biomarkers) and immunogenicity of RAG-17 in ALS patients with a confirmed SOD-1 mutation. The study is being conducted at Beijing Tiantan Hospital."

Trial status • Amyotrophic Lateral Sclerosis • CNS Disorders

Ractigen Therapeutics Receives FDA Orphan Drug Designation for the novel oligonucleotide conjugate RAG-17 for the Treatment of Amyotrophic Lateral Sclerosis (ALS) (GlobeNewswire) - “Ractigen Therapeutics announced today that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to RAG-17, a novel siRNA modality for the treatment of Amyotrophic Lateral Sclerosis (ALS).”

Orphan drug • Amyotrophic Lateral Sclerosis • CNS Disorders