Waltham, Mass.– Ventus Therapeutics has begun dosing participants in a Phase 2 clinical trial evaluating VENT-03, an investigational oral small-molecule cGAS inhibitor, in patients with lupus. VENT-03 is the most advanced oral cGAS inhibitor currently in clinical development and the first to complete a Phase 1 study before progressing into a Phase 2 trial in patients.
Discovered using Ventus’ ReSOLVE platform, VENT-03 targets the cGAS pathway, which is known to drive inflammation, cell senescence, and cell death. The pathway has been linked to a range of autoimmune conditions, age-related inflammatory disorders, and cardiometabolic diseases.
“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 multicenter, randomized, double-blind, placebo-controlled Phase 2 study includes an open-label extension and is designed to assess the efficacy and safety of VENT-03 in patients with active skin disease associated with lupus. Researchers will evaluate the drug’s impact on interferon-stimulated and inflammatory gene signatures in both blood and skin, as well as its effect on clinical disease severity. The study will also measure changes in systemic disease activity using established lupus scales and track a broad biomarker panel, including markers related to cardiac function and senescence.
Top-line results from the 28-day placebo-controlled portion of the trial are expected in the second half of 2026, with open-label extension data 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 inflammatory and immunological 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.”
