Ventus Therapeutics Announces First Patient Dosed in Phase 2 Clinical Trial of VENT-03, a Novel Small Molecule cGAS Inhibitor, in Patients with Lupus

VENT-03 is the most advanced oral small-molecule cGAS inhibitor in clinical development

Trial designed to demonstrate proof-of-concept efficacy and safety in lupus as well as the potential of VENT-03 in additional I&I diseases, cardiometabolic conditions, and inflammaging

Top-line results expected in 2H 2026

WALTHAM, Mass. & MONTREAL--(BUSINESS WIRE)--Ventus Therapeutics, a clinical-stage biopharmaceutical company advancing multiple small-molecule programs for immunological, inflammatory, and neurological disorders, today announced that the first patient has been dosed in a Phase 2 trial of VENT-03 in patients with lupus. VENT-03, which was discovered using Ventus’ proprietary ReSOLVE^® platform, is the first oral small-molecule cyclic GMP-AMP synthase (cGAS) inhibitor to successfully complete a first-in-human Phase 1 study and to initiate a Phase 2 trial in patients. The cGAS pathway plays a prominent role in inflammation, cell senescence, and cell death, and has been implicated in a broad range of autoimmune and age-related inflammatory diseases as well as cardiometabolic disorders.

“For the more than five million people living with lupus worldwide, the disease presents a significant burden, with painful and often debilitating symptoms that can progress to multiple organ systems — including the kidneys, heart, lungs, and brain. Treatment choices remain limited, leaving significant unmet need,” said Mona Kotecha, M.D., Chief Medical Officer of Ventus. “In addition to clinical endpoints, our Phase 2 trial incorporates a robust panel of biomarkers, including general inflammation and cardiovascular biomarkers applicable to a broad range of diseases beyond lupus. VENT-03 provides a differentiated approach to treat autoimmune disease and has the potential to become a better and more convenient once-daily oral option for patients with limited available treatments.”

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. The key objectives are to evaluate the safety and efficacy of VENT-03 in changing the interferon-stimulated and inflammatory gene signatures in blood and skin, in addition to evaluating the effect of VENT-03 on clinical disease severity. Additional objectives are to assess the effect of VENT-03 on systemic disease activity using accepted systemic lupus scales and the impact of VENT-03 on a robust panel of biomarkers, including those measuring cardiac health and senescence. 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.

“This Phase 2 study of VENT-03 marks an important step in our efforts to demonstrate the broad potential of cGAS inhibition not only in lupus, but also in additional interferon-driven I&I diseases as well as cardiometabolic disorders and inflammaging,” said Marcelo Bigal, M.D., Ph.D., President and CEO of Ventus. “We look forward to sharing the results of this trial next year, which we believe will be a key step in unlocking the tremendous potential of VENT-03 as a pipeline-in-a-product.”

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, and is also implicated in cardiometabolic conditions and inflammaging.

About Ventus Therapeutics

Ventus Therapeutics is a clinical-stage biopharmaceutical company advancing multiple small-molecule programs for immunological, inflammatory, and neurological disorders. Using its proprietary drug discovery platform, ReSOLVE^®, the company has established a robust pipeline of wholly-owned programs: VENT-03, a first-in-class, oral cGAS inhibitor in Phase 2 for lupus with significant expansion opportunities in additional I&I diseases, cardiometabolic conditions, and inflammaging; VENT-02, a best-in-class, brain-penetrant, oral NLRP3 inhibitor in Phase 2 for Parkinson’s disease; and VENT-04, a first-in-class caspase-4/5 inhibitor in preclinical development. 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.