VRG50635 / Verge Genomics - LARVOL DELTA

Top line results of the phase 1b, open-label, multiple ascending dose study of VRG50635 in participants with familial and sporadic amyotrophic lateral sclerosis (ALS-MND 2025) - "Fifty-four participants entered Part 1, and 50 were dosed at 400 mg while 29 and 14 escalated to 600 and 800 mg, respectively. Median exposure duration was 27 (IQR 7–32) weeks, mean (standard deviation [SD]) daily dose was 450 (137) mg, and mean (SD) exposure was 1194 (972) ng/mL(2.8l M): 463 (482) on week 8 (N¼ 50), 1435 (982) on week 16 (N¼ 31), and 1676 (970) on week 24 (N¼ 25). Most participants treated for at least one month showed PD activity as measured by upregulation of plasma GPNMB (mean 3-fold increase for the full treatment period; 4-fold for weeks 24–40)."

Clinical • P1 data • Amyotrophic Lateral Sclerosis • Anorexia • CNS Disorders • Fatigue • GFAP • GPNMB • NEFL • Plasma NfL

Verge Genomics and Collaborators Identify Digital Clinical Biomarker Endpoints Sensitive to Short Term Disease Progression in the Pre-treatment Run-in Period of VRG50635 Proof-of-Concept ALS Clinical Trial (Businesswire) - P1b | N=54 | NCT06215755 | Sponsor: Verge Genomics | "Verge Genomics...today announced new findings demonstrating that multiple digital clinical biomarker endpoints can capture measurable disease progression during the eight-week, pre-treatment run-in period of the Phase 1b proof-of-concept study of VRG50635...for sporadic and familial amyotrophic lateral sclerosis (ALS)....Statistically significant measures of disease progression were identified across multiple endpoints after just 8 weeks of monitoring pre-treatment, which has the potential to revolutionize ALS clinical trial design....Dr. Diego Cadavid, Chief Medical Officer of Verge Genomics, will present these data in a platform session at the 77th Annual Meeting of the American Academy of Neurology in San Diego on Tuesday, April 8, 2025."

P1 data • Amyotrophic Lateral Sclerosis

Sensitivity of Digital Clinical Biomarker Endpoints to Detect Disease Progression during the 8-week Pretreatment Run-In Period in Proof-of-Concept ALS Study VGCS-50635-002 (AAN 2025) - "Objective:To investigate the changes in molecular and clinical disease biomarkers during the 8-week pretreatment run-in period of the VRG50635 amyotrophic lateral sclerosis (ALS) proof-of-concept study.Background:There is an unmet need for disease-modifying ALS treatments that slow progression, extend survival, and improve quality of life...During the 8-week pretreatment run-in period, SVC, ALS-FRS-R, and plasma NfL are mostly stable at the individual and group levels. Results will be presented for novel digital clinical biomarkers assessing whether they can measure disease progression over the 8-week run-in period."

Biomarker • Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Depression • Psychiatry • Plasma NfL

A Study of VRG50635 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=22 | Completed | Sponsor: Verge Genomics | Recruiting ➔ Completed

Trial completion

A Study of VRG50635 in Participants With Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P1 | N=54 | Active, not recruiting | Sponsor: Verge Genomics | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyotrophic Lateral Sclerosis • CNS Disorders

A Proof of Concept Study of the PIKfyve Inhibitor VRG50635 in Patients with Sporadic and Familial Amyotrophic Lateral Sclerosis (ANA 2024) - P1 | "There will be periodic assessments of safety after each dose escalation. Proof of concept will be determined after at least 40 study participants have completed Part 2 by examining all secondary and exploratory efficacy endpoints individually relative to the pre-treatment run-in period."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL • Plasma NfL

A Study of VRG50635 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Verge Genomics | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of VRG50635 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Verge Genomics

New P1 trial

A Study of VRG50635 in Participants With Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Verge Genomics

New P1 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

Verge Genomics Announces Initiation of Proof-of-Concept Study for the Treatment of Amyotrophic Lateral Sclerosis (ALS) with VRG50635 (BioSpace) - "Verge Genomics...today announced the initiation of its Phase 1b proof-of-concept study of VRG50635 for the treatment of sporadic and familial forms of amyotrophic lateral sclerosis (ALS). The study will assess the safety and tolerability of escalating doses of VRG50635, a potential best-in-class, small molecule inhibitor of PIKfyve, a therapeutic target for ALS discovered in diseased human tissues using CONVERGE, the company’s all-in-human, AI-powered platform."

Trial status • Amyotrophic Lateral Sclerosis • CNS Disorders

Verge Genomics Will Use Modality.AI in Its ALS Phase 1b Clinical Trial of Its Lead Drug Candidate VRG50635 (GlobeNewswire) - "Verge Genomics...announced that its Phase 1b proof-of-concept (POC) study of its lead drug candidate, VRG50635, will incorporate Modality.AI, the first automated, clinically validated, multimodal system to assess speech and language patterns. VRG50635 is a potential best-in-class small molecule inhibitor of PIKfyve that is in clinical development for amyotrophic lateral sclerosis (ALS) and is expected to move into Phase 1b in the coming months."

Trial status • Amyotrophic Lateral Sclerosis • CNS Disorders

Verge Genomics Announces Positive Safety and Tolerability Data from the Phase 1 Clinical Trial of VRG50635, a Potential Best-in-Class Therapeutic for All Forms of ALS (Businesswire) - P1 | N=80 | Sponsor: Verge Genomics | "Verge Genomics...today announced the completion of the Phase 1 clinical trial of VRG50635 in healthy adult volunteers. VRG50635 was dosed up to the maximum single and repeated doses planned, demonstrating a favorable safety, tolerability, and pharmacokinetic profile supportive of advancement into a proof-of-concept study in people with amyotrophic lateral sclerosis (ALS). Detailed results from the study will be presented at the upcoming European Network to Cure ALS (ENCALS) 2023 meeting being held in Barcelona, Spain from July 12-14, 2023....'We are extremely encouraged by these initial results which highlight the favorable safety and tolerability profile of VRG50635, and further validate the novel approach that Verge has taken to identify novel targets for complex diseases with high unmet need using human disease tissues and rapidly advancing compounds into proof-of-concept trials.'"

P1 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Proteinopathy

Verge Genomics to Incorporate Emerald Digital Health Technology into its ALS Phase 1b Proof-of-Concept Clinical Trial (Businesswire) - "Verge Genomics...announced that Emerald Innovations’ wireless digital health technology will be used to capture critical patient data in its planned Phase 1b proof-of-concept study of the PIKfyve inhibitor VRG50635, a novel therapeutic in clinical development for amyotrophic lateral sclerosis (ALS)....'The partnership between Verge and Emerald stems from a shared commitment to establish a data-driven approach to clinical trials.'"

Licensing / partnership • P1 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Proteinopathy

Verge Genomics Initiates First-In-Human Dosing in Phase 1 Trial of VRG50635, a Novel Therapeutic for Amyotrophic Lateral Sclerosis (Businesswire) - “Verge Genomics…announced today that the first subject has been dosed in a Phase 1 clinical trial of VRG50635. VRG50635 is a small molecule inhibitor of PIKfyve, a novel therapeutic target for amyotrophic lateral sclerosis (ALS) discovered by CONVERGETM, Verge’s all-in-human, AI-powered platform….This first-in-human study is a randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose design to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of VRG50635 in healthy volunteer subjects (Phase 1a) and multiple-dose study in patients with ALS (Phase 1b).”

Trial status • Amyotrophic Lateral Sclerosis • CNS Disorders