ALN-SOD / Alnylam, Regeneron - LARVOL DELTA

An Update From GOALS, A Phase 1b/2 Trial Of ALN-SOD, An Intrathecally-Administered Small Interfering RNA Targeting SOD1, In Symptomatic SOD1-ALS (ENCALS 2026) - P1/2 | "Additional emerging data will also be presented.Conclusion In this first-in-human, phase 1b/2 trial in participants with SOD1-ALS, ALN-SOD, an siRNA against SOD1, was sufficiently safe and well-tolerated to proceed through dose escalation. Encouraging trends in CSF SOD1 and NfL provide early evidence that ALN-SOD could reduce SOD1 expression and neuronal injury in SOD1-ALS."

First-in-human • P1/2 data • Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL • Plasma NfL • SOD1

First in Human (FIH) Study of ALN-SOD in Adult Participants With Amyotrophic Lateral Sclerosis Associated With Mutation in the SOD1 Gene (SOD1-ALS) (clinicaltrials.gov) - P1/2 | N=54 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Jun 2031 ➔ Mar 2032 | Trial primary completion date: Jun 2031 ➔ Mar 2032

First-in-human • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

First in Human (FIH) Study of ALN-SOD in Adult Participants With Amyotrophic Lateral Sclerosis Associated With Mutation in the SOD1 Gene (SOD1-ALS) (clinicaltrials.gov) - P1/2 | N=42 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Phase classification: P1 ➔ P1/2 | Trial completion date: Apr 2029 ➔ Jun 2031 | Trial primary completion date: Apr 2029 ➔ Jun 2031

First-in-human • Phase classification • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Interim results from GOALS, a phase 1b trial of ALN-SOD, an intrathecally-administered small interfering RNA targeting SOD1, in symptomatic SOD1-ALS (ALS-MND 2025) - P1 | "In this first-in-human, phase 1b trial in patients with SOD1-ALS, ALN-SOD, an siRNA against SOD1, has been sufficiently safe and well-tolerated to proceed with dose escalation and continued study. Encouraging trends in CSF SOD1 and NfL have been observed to date and provide early evidence that ALN-SOD could reduce SOD1 expression and neuronal injury in SOD1-ALS. Reference 1."

P1 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • CSF NfL • NEFL

FIRST-IN-HUMAN STUDY DESIGN TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ASCENDING DOSES OF ALN-SOD IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS AND SOD1 VARIANTS (PACTALS 2025) - P1 | "Findings from this FIH study will guide the selection of ALN-SOD dosing regimens for assessment in the subsequent clinical development program. ORIGINAL PRESENTATION: Motor Neurone Disease Association (MNDA) 35th International Symposium 2024; poster presentation #CLT-07."

Clinical • P1 data • PK/PD data • Amyotrophic Lateral Sclerosis • CNS Disorders • SOD1

First-in-human study design to evaluate ALN-SOD in patients with ALS and SOD1 variants (JSNE 2025) - No abstract available

Clinical • P1 data • Amyotrophic Lateral Sclerosis

First-in-human study design to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ascending doses of ALN-SOD in patients with amyotrophic lateral sclerosis and SOD1 variants (ALS-MND 2024) - "Tofersen, a monthly intrathecally (IT) administered antisense oligonucleotide targeting SOD1, led to reductions in key disease-related biomarkers (SOD1 protein in cerebro-spinal fluid [CSF] and neurofilament light chain) (1). This FIH study will provide information about the safety, tolerability, pharmacokinetics, and pharmaco-dynamics of ALN-SOD in participants with SOD1-ALS. The results will guide selection of dosing regimens to assess in the subsequent clinical development program."

Clinical • P1 data • PK/PD data • Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL • SOD1

First in Human (FIH) Study of ALN-SOD in Adult Participants With Amyotrophic Lateral Sclerosis Associated With Mutation in the SOD1 Gene (SOD1-ALS) (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders

First in Human (FIH) Study of ALN-SOD in Adult Participants With Amyotrophic Lateral Sclerosis Associated With Mutation in the SOD1 Gene (SOD1-ALS) (clinicaltrials.gov) - P1 | N=42 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P1 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

Alnylam Pharmaceuticals Reports Fourth Quarter and Full Year 2021 Financial Results and Highlights Recent Period Activity (BioSpace) - “Submitted a CTA for ALN-APP, an investigational RNAi therapeutic for the treatment of Alzheimer's disease and cerebral amyloid angiopathy. The Company announces today that it has initiated a Phase 1 study of ALN-APP in patients with early-onset Alzheimer’s disease….Disclosed new programs, including ALN-SOD targeting SOD-1, in development for the treatment of SOD-1-Specific Amyotrophic Lateral Sclerosis (ALS)…”

New trial • Trial status • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders