Ventus Therapeutics to Present Phase 1 Results for VENT-03, a First-in-Class cGAS Inhibitor, at LUPUS 2025

VENT-03 was well tolerated across dose cohorts

Pharmacokinetic profile supports once-daily dosing; pharmacodynamic results indicate robust target engagement

Phase 2 trial evaluating VENT-03 in patients with lupus expected to commence in 2025

WALTHAM, Mass. & MONTREAL--(BUSINESS WIRE)--Ventus Therapeutics, a clinical-stage biopharmaceutical company advancing two Phase 2 small-molecule programs for immunological, inflammatory, and neurological disorders, today announced the upcoming presentation of the Phase 1 safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) results of VENT-03 at the 16^th International Congress on Systemic Lupus Erythematosus (LUPUS 2025), taking place from May 21-24 in Toronto, Canada.

VENT-03 is the first oral small-molecule cyclic GMP-AMP synthase (cGAS) inhibitor to successfully complete a first-in-human Phase 1 study and was discovered using Ventus’ proprietary ReSOLVE^® platform. Data from the Phase 1 study, initially announced in October 2024, showed that VENT-03 was safe and well tolerated at all tested dose levels with a favorable PK profile enabling once-daily dosing.

“We are pleased to present at LUPUS 2025 the first reported Phase 1 results for a cGAS inhibitor, demonstrating that VENT-03 has the potential to become a first- and best-in-class therapy for lupus and other autoimmune disorders,” said Marcelo Bigal, M.D., Ph.D., President and CEO of Ventus. “Ventus is eager to unlock the potential of cGAS inhibition across multiple autoimmune diseases, with the first Phase 2 trial evaluating VENT-03 in patients with lupus to commence later this year.”

The Phase 1, double-blind, placebo-controlled, first-in-human trial included 72 healthy adult volunteers across single ascending dose (SAD) and multiple ascending dose (MAD) cohorts. 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. The PK profile of VENT-03 supports once-daily dosing with or without food, and the PD results demonstrate robust target engagement, supporting further clinical development.

“More than five million people worldwide are estimated to have a form of lupus. These patients can experience disease progression and severe symptoms that can affect quality of life, and currently available treatment options may not be able to adequately address these symptoms for all patients,” said Mona Kotecha, M.D., Chief Medical Officer of Ventus. “Through targeting cGAS, VENT-03 has the potential to become a safer and more effective treatment option for patients in need, addressing key unmet needs across multiple organ systems while providing the additional benefit of once-daily oral dosing. We look forward to sharing these results and to connecting with the wider lupus community at LUPUS 2025.”

Details of the poster presentation are as follows:

• Title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers of VENT-03, a Novel cGAS Inhibitor for the Treatment of Systemic Lupus Erythematosus
• Authors: Xavier Valencia, Kelly Pike, Loraine Warner, Conrad Winters, Jeanne Stewart, Ramsay Beveridge, Patrick Cyr, Nadine Fradet, Amandine Chefson, Ofer Spiegelstein
• Abstract Number: Poster 286
• Session Date: May 22^nd

About cGAS

cGAS is an intracellular pattern recognition receptor that is activated after binding to double-stranded DNA (dsDNA) in the cytoplasm. The presence of dsDNA in the cytoplasm is often the result of cellular dysfunction, which is a hallmark of many autoimmune and inflammatory diseases. Activation of cGAS leads to cGAMP formation, activation of STING, pronounced inflammation, and tissue damage. In both patients and preclinical models of disease, the cGAS pathway has been shown to be a key driver of lupus and other inflammatory diseases, such as rheumatoid arthritis, systemic sclerosis, dermatomyositis, and Sjögren’s disease.

About Ventus Therapeutics

Ventus Therapeutics is a clinical-stage biopharmaceutical company advancing two Phase 2 small-molecule programs for immunological, inflammatory, and neurological disorders. Using its proprietary drug discovery platform, ReSOLVE^®, the company has established a robust pipeline, including two wholly-owned programs. VENT-03 is a first-in-class, oral cGAS inhibitor expected to enter Phase 2 development for lupus in 2025. VENT-02 is a best-in-class, brain-penetrant, oral NLRP3 inhibitor in Phase 2 for Parkinson’s disease, and is expected to enter Phase 2 development for osteoarthritis in obese patients later in 2025. In addition, Ventus has out-licensed VENT-01, a peripherally-restricted, oral NLRP3 inhibitor in Phase 1, to Novo Nordisk A/S. For more information, please visit www.ventustx.com and engage with Ventus on LinkedIn.