VENT-03 / Ventus Therap - LARVOL DELTA

Discovery of VENT-03: a potential first-in-class cGAS inhibitor currently in Ph2 for SLE (ACS-Fall 2026) - "Details of the medicinal chemistry campaign to improve potency, physicochemical properties and PK parameters will be discussed including particulars of binding mode and mechanism-of-action. A summary of preclinical indication validation studies and phase 1 human PK results will also be included."

Infectious Disease • Inflammation • Inflammatory Arthritis • CGAS • STING

Ventus Therapeutics Announces First Patient Dosed in Phase 2 Clinical Trial of VENT-03, a Novel Small Molecule cGAS Inhibitor, in Patients with Lupus (Businesswire) - "The Phase 2 study is a multicenter, randomized, double-blind, placebo-controlled trial with an open-label extension, designed to assess the efficacy and safety of VENT-03 in patients with lupus with active skin disease....Top-line data from the 28-day placebo-controlled portion of the trial is expected in the second half of 2026, with data from the 2-month open-label extension to follow."

P2a data • Trial status • Cutaneous Lupus Erythematosus • Systemic Lupus Erythematosus

SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS IN HEALTHY VOLUNTEERS OF VENT-03, A NOVEL cGAS INHIBITOR FOR THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS (EULAR 2025) - "VENT-03 was safe and well-tolerated in healthy volunteers, demonstrating a favorable pharmacokinetic profile and robust target engagement. The efficacy of VENT-03 in SLE patients with active cutaneous manifestations will be evaluated in an upcoming Phase 2a stud."

Clinical • PK/PD data • Cardiomyopathy • Dermatomyositis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Myositis • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • CGAS

Ventus Therapeutics to Present Phase 1 Results for VENT-03, a First-in-Class cGAS Inhibitor, at LUPUS 2025 (Businesswire) - P1 | N=72 | "Ventus Therapeutics...today announced the upcoming presentation of the Phase 1 safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) results of VENT-03 at the 16th International Congress on Systemic Lupus Erythematosus (LUPUS 2025), taking place from May 21-24 in Toronto, Canada....The study results show that VENT-03 was safe and well tolerated up to single doses of 2000 mg once daily (QD) and multiple dosing of 900 mg QD for 10 days, which are substantially higher than our anticipated Phase 2 dose. The proportion of participants with adverse events (AEs) in the MAD cohorts was similar for VENT-03 and placebo (79% vs. 75%), and the vast majority of AEs in the study were mild and considered unrelated to the study drug."

P1 data • Lupus • Systemic Lupus Erythematosus

Ventus Therapeutics Announces Publication in Nature’s Communications Chemistry Describing the Structure-based Optimization of a New Series of cGAS Inhibitors (Businesswire) - "The publication provides insights into the mechanism of action and binding mode of known cGAS inhibitors, including the identification of key structural differences driving potency shifts between species. Investigators leveraged these findings to inform a structure-based design approach, which they used to develop a novel, highly potent cGAS inhibitor. This work provides the framework for rational and efficient optimization of cGAS inhibitors and potential preclinical translational strategies, adding to Ventus’ growing body of research on cGAS biology....'We will commence our first Phase 2 trial for VENT-03 in patients with lupus in 2025 and are planning additional trials given the strong biological evidence supporting the role of cGAS in the pathogenesis of multiple diseases.'...VENT-02 is a best-in-class, brain-penetrant, oral NLRP3 inhibitor....is expected to enter Phase 2 development in osteoarthritis in obese patients later in 2025."

New P2 trial • Preclinical • Lupus • Osteoarthritis

Discovery of VENT-03: A Novel Clinical cGAS Inhibitor for the Treatment of SLE and Other Autoimmune Diseases (ACR Convergence 2024) - "VENT-03 is a first-in-class molecule with excellent drug-like properties that targets a central driver of autoinflammation, cGAS. We anticipate the inhibition of cGAS in humans by VENT-03 will suppress multiple drivers of SLE pathology, including DNA-driven Type I IFN activity and NF-kB driven pro-inflammatory cytokines. VENT-03 therefore presents a unique therapeutic approach to the treatment of autoimmune diseases for which there remains a great unmet medical need."

Clinical • Cardiovascular • Dermatomyositis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Myositis • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • CD8 • CGAS • TREX1

Ventus Therapeutics Announces Successful Completion of Phase 1 Clinical Trial of VENT-03, a First-in-Class, Orally Administered cGAS Inhibitor (Businesswire) - P1 | N=72 | "Ventus Therapeutics....today announced results from its Phase 1 clinical trial of VENT-03, the first cyclic GMP-AMP synthase (cGAS) inhibitor to successfully complete a first-in-human study. The Phase 1 trial evaluated the pharmacokinetics (PK), target engagement, safety, and tolerability of VENT-03 across a broad range of single and multiple ascending doses in 72 healthy adult volunteers....'We’re excited to continue leading the way in cGAS development and look forward to initiating a Phase 2 trial with VENT-03 in SLE in 2025'....In the Phase 1 trial, VENT-03 was safe and well-tolerated at doses far exceeding those planned for use in Phase 2 trials."

New P2 trial • P1 data • Systemic Lupus Erythematosus

Ventus Therapeutics Hosts Inaugural Program Spotlight: VENT-03, a First-in-Class cGAS Inhibitor (Businesswire) - "Ventus Therapeutics...announced today that it will host its inaugural Program Spotlight on VENT-03 on May 25th, 2023 at 11:00 AM ET...The virtual event will feature VENT-03, a first-in-class cGAS inhibitor in development for lupus and other inflammatory disorders...As part of the event, Ventus scientists, together with Dr. Victoria Werth, Professor of Dermatology and Medicine at Penn Medicine, will discuss the biology of the cGAS pathway and its importance in immunology. They will also review the current treatment landscape and the potential of VENT-03 as an effective treatment for SLE and present the clinical development plan for VENT-03, including an overview of Ventus’ differentiated translation to the clinic."

Clinical • Interferonopathies • Lupus Nephritis • Systemic Lupus Erythematosus

Ventus Therapeutics Provides Updates on cGAS Inhibitor Program at Keystone Symposium on Innate Immunity (Businesswire) - "Ventus Therapeutics...nnounced the details of two presentations to be made at the Keystone Symposium on Innate Immunity: From Innate Sensing to Adaptive Responses, being held April 16-19 in Snowbird, Utah....This presentation will mark the public debut of data showcasing the potency and pharmacokinetic profile of the company’s potential first-in-class cGAS inhibitor, VENT-03. Ventus’ portfolio of cGAS inhibitors have demonstrated modulation of key endpoints in models of lupus, dermal inflammation, and chronic kidney disease....'We are eager to share the latest VENT-03 data with our peers at the Keystone Symposium'...'We expect VENT-03 to be the first cGAS inhibitor ever to enter clinical trials and believe that the scientific community shares our excitement for this candidate’s potential to treat a rrange of immunological diseases, including lupus, systemic sclerosis, and dermatomyositis.'"

Clinical data • Aicardi Goutieres Syndrome • Interferonopathies

Ventus Therapeutics Nominates Potential First-in-Class cGAS Inhibitor VENT-03 as Inaugural Development Candidate in cGAS Franchise (Businesswire) - "Ventus Therapeutics...announced today the nomination of a potential first-in-class cGAS inhibitor, VENT-03, as the company’s first development candidate directed against cGAS. This represents the third development candidate nominated in the past 12 months to Ventus’ pipeline, following the nominations of VENT-02, a brain-penetrant NLRP3 inhibitor, and VENT-01, a peripherally restricted NLRP3 inhibitor that is partnered with Novo Nordisk....'We expect VENT-03 to be the first cGAS inhibitor to enter the clinic, with a clinical development plan tailored to provide multiple data readouts prior to Phase 2 trials.'"

New P1 trial • Aicardi Goutieres Syndrome • Cutaneous Lupus Erythematosus • Dermatomyositis • Familial Chilblain Lupus • Interferonopathies • Systemic Lupus Erythematosus • Systemic Sclerosis