Ventus Therapeutics has announced the successful completion of its Phase 1 clinical trial for VENT-03, a novel, orally administered cyclic GMP-AMP synthase (cGAS) inhibitor. The trial, which involved 72 healthy adult volunteers, demonstrated that VENT-03 was safe and well-tolerated across a range of doses, with a pharmacokinetic profile suitable for once-daily dosing. These findings position VENT-03 as a potential first-in-class treatment for autoimmune and inflammatory diseases.
The Phase 1 trial assessed the pharmacokinetics, target engagement, safety, and tolerability of VENT-03. According to the company, no dose-limiting or dose-related toxicities, serious adverse events, or clinically significant changes in laboratory parameters, ECG, or vital signs were observed. All treatment-related adverse events were mild and transient.
Favorable Pharmacokinetics and Target Inhibition
VENT-03 exhibited a pharmacokinetic profile that supports convenient once-daily oral administration. Furthermore, the drug achieved plasma concentrations necessary for complete cGAS target inhibition, demonstrating robust pharmacodynamic activity. Ventus Therapeutics plans to present detailed data from the Phase 1 trial at an upcoming medical conference.
Targeting Lupus with cGAS Inhibition
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting millions worldwide. Current treatments, often injectable biologics targeting the type I interferon or BAFF pathways, address only certain aspects of the disease. Ventus Therapeutics is gearing up to initiate a Phase 2 trial with VENT-03 in SLE patients in 2025.
Xavier Valencia, M.D., Head of Clinical Development at Ventus, stated that a once-daily oral cGAS inhibitor has the potential to modulate both the type I interferon and BAFF pathways, impacting multiple facets of SLE and potentially providing superior efficacy compared to existing treatments. The cGAS pathway is activated by the presence of double-stranded DNA (dsDNA) in the cytoplasm, often resulting from cellular dysfunction, which is a hallmark of autoimmune and inflammatory diseases. Activation of cGAS leads to cGAMP formation, activation of STING, pronounced inflammation, and tissue damage.
Ventus' ReSOLVE™ Platform
Ventus Therapeutics utilizes its proprietary ReSOLVE™ platform to discover and develop differentiated small-molecule therapeutics. This platform combines AI/ML, structural biology, and biophysics to model protein dynamics, facilitating the development of high-quality small molecules for historically challenging targets. Marcelo Bigal, M.D., Ph.D., President and CEO of Ventus, emphasized that the profile demonstrated by VENT-03 qualifies it as a potential best-in-class anti-cGAS medication, underscoring the power of their ReSOLVE™ platform.
