selnoflast (RG6418) / Roche - LARVOL DELTA

TOPLINE RESULTS OF A PHASE 1B STUDY TESTING AN NLRP3 INFLAMMASOME INHIBITOR IN EARLY-STAGE PARKINSON'S DISEASE (ADPD 2026) - "Selnoflast showed a favorable safety profile. The observed effect on peripheral and central NLRP3-related biomarkers suggests the potential of NLRP3 inhibition for the treatment of early-stage PD."

P1 data • CNS Disorders • Movement Disorders • Parkinson's Disease • NLRP3

RIVULET: A Study to Evaluate the Efficacy, Safety, Pharmacodynamics (PD), and Pharmacokinetics (PK) of Selnoflast in Reducing Vascular Inflammation in Participants With Atherosclerosis at Risk for Major Adverse Cardiac Events (clinicaltrials.gov) - P2 | N=162 | Not yet recruiting | Sponsor: Genentech, Inc.

Adverse events • New P2 trial • Atherosclerosis • Cardiovascular • Inflammation

Selnoflast reduces markers of systemic inflammation in participants with coronary artery disease and elevated C-reactive protein (AHA 2025) - "hsCRP levels were also comparable at BL, with greater mean reductions by Day 8 in the selnoflast group (–70.95% change, 1.35±1.01 mg/L) vs PBO (–29.45% change, 4.99±5.59 mg/L). Absolute reductions remained ≥55% through Day 29, with individual PBO-corrected decreases ranging from 25-66% (Fig 1B).ConclusionSelnoflast was well tolerated without notable safety signals relative to PBO, approached steady-state PK by Day 2, and demonstrated consistent reductions in inflammatory biomarkers IL-6 and hsCRP in patients with CAD and residual inflammation."

Cardiovascular • Coronary Artery Disease • Dyslipidemia • Inflammation • Myocardial Infarction • CRP • IL6 • NLRP3

A PHASE 1B STUDY TO TEST THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF SELNOFLAST IN EARLY-STAGE PARKINSON'S DISEASE: STUDY DESIGN AND BASELINE CHARACTERISTICS (ADPD 2025) - "Conclusions The recruited participants' baseline characteristics are in line with those of an early-stage PD population. The effect of selnoflast on activated microglia, as measured by TSPO-PET imaging and CSF NLRP3-related markers, may serve as proof-of-mechanism for NLRP3 inhibitors and other novel neuroinflammation targets."

Clinical • P1 data • PK/PD data • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • IL18 • IL1B • NLRP3

A Study to Investigate The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7486967 in Participants With Early Idiopathic Parkinson's Disease. (clinicaltrials.gov) - P1 | N=60 | Completed | Sponsor: Hoffmann-La Roche | Trial completion date: Jul 2025 ➔ Jul 2024 | Trial primary completion date: Jul 2025 ➔ Jul 2024 | Recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease • LRRK2 • NLRP3

A Study to Investigate The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7486967 in Participants With Early Idiopathic Parkinson's Disease (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting | Trial completion date: Jan 2025 ➔ Jul 2025 | Trial primary completion date: Jan 2025 ➔ Jul 2025

Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease • LRRK2 • NLRP3

A Study to Investigate The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7486967 in Participants With Early Idiopathic Parkinson's Disease (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Movement Disorders • Parkinson's Disease • LRRK2 • NLRP3

A randomized, double-blind phase 1b study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of the NLRP3 inhibitor selnoflast in patients with moderate to severe active ulcerative colitis. (PubMed, Clin Transl Med) - "Selnoflast was safe and well-tolerated. Selnoflast 450 mg QD achieved plasma and tissue exposure predicted to maintain IL-1β IC over the dosing interval. However, PD biomarker results showed no robust differences between treatment arms, suggesting no major therapeutic effects are to be expected in UC. The limitations of this study are its small sample size and indirect assessment of the effect on IL-1β in tissue."

Biomarker • Clinical • Journal • P1 data • PK/PD data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • IL18 • IL1B • NLRP3

A Study to Investigate The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7486967 in Participants With Early Idiopathic Parkinson's Disease (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Hoffmann-La Roche | Phase classification: P1b ➔ P1

Phase classification • CNS Disorders • Movement Disorders • Parkinson's Disease • LRRK2 • NLRP3

A Study to Investigate The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7486967 in Participants With Early Idiopathic Parkinson's Disease (clinicaltrials.gov) - P1b | N=72 | Recruiting | Sponsor: Hoffmann-La Roche

New P1 trial • CNS Disorders • Movement Disorders • Parkinson's Disease • NLRP3

"Selnoflast binds to NLRP3 & inhibits the creation of the NLRP3 complex ❌NLRP3 complex 👉⬇️inflammasome activation 👉⬇️microglia-induced neurodegeneration❓ Gennaro Pagano introduces the Phase I study now underway: https://t.co/KovBdEp73A #ADPD2023 @adpdnet #Parkinsons" (@VJNeurology)

CNS Disorders • Movement Disorders • Parkinson's Disease • NLRP3

Phase Ib Study Design Evaluating The Safety, Pharmacokinetics And Pharmacodynamics Of Selnoflast, A Novel NLRP3 Inflammasome Inhibitor In Early-Stage PD (AAN 2023) - "Results The study design will be described, including inclusion/exclusion criteria, safety, pharmacokinetics and pharmacodynamic parameters (CSF and positron emission tomography imaging) selected for this Phase Ib study. Conclusions To characterise a novel compound acting on the inflammasome, an innovative Phase Ib study design is needed to investigate safety, pharmacokinetics and pharmacodynamics."

Clinical • P1 data • PK/PD data • CNS Disorders • Movement Disorders • Parkinson's Disease • NLRP3

Selnoflast, a potent NLRP3 inhibitor - results from a phase 1b experimental medicine study in patients with Ulcerative Colitis (ECCO-IBD 2023) - "World J Gastroenterol. 2019"

Clinical • P1 data • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • CCL2 • CXCL1 • CXCL3 • CXCL5 • IL18 • IL1B • IL6 • NLRC5 • NLRP3 • TNFAIP6

PHASE IB STUDY DESIGN EVALUATING THE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF SELNOFLAST, A NOVEL NLRP3 INFLAMMASOME INHIBITOR IN EARLY-STAGE PD (ADPD 2023) - "Results The study design will be described, including inclusion/exclusion criteria, safety, pharmacokinetics and pharmacodynamic parameters (CSF and positron emission tomography imaging) selected for this Phase Ib study. Conclusions To characterise a novel compound acting on the inflammasome, an innovative Phase Ib study design is needed to investigate safety, pharmacokinetics and pharmacodynamics."

Clinical • P1 data • PK/PD data • CNS Disorders • Movement Disorders • Parkinson's Disease • NLRP3