WALTHAM, Mass. — Ventus Therapeutics, a clinical-stage biopharmaceutical company developing small-molecule therapies for autoimmune, inflammatory, and neurological disorders, announced the nomination of VENT-04, a first-in-class, oral, small-molecule caspase-4/5 inhibitor, as a development candidate.
Targeting caspase-4 and caspase-5 may offer a new approach for treating a range of inflammatory conditions, including inflammatory bowel disease, hidradenitis suppurativa, severe asthma, and chronic obstructive pulmonary disease. Activation of these caspases plays a central role in dysbiosis, bacteria-driven IL-18 expression, and pyroptotic cell death, processes that contribute to disease progression in areas of significant unmet medical need.
VENT-04 is the seventh development candidate generated using the company’s proprietary ReSOLVE® platform and represents the second first-in-class program advanced by Ventus.
“There remains a significant unmet need in addressing diseases like IBD, where many patients are not adequately treated by current therapies, and there is a need for safe, oral medications,” said Marcelo Bigal, M.D., Ph.D., president and chief executive officer of Ventus. “VENT-04 is our second first-in-class program and seventh development candidate overall across three high-value, impactful targets, underscoring the power of our ReSOLVE® platform.”
Caspase-4 and caspase-5 are expressed across epithelial, endothelial, and immune cells, including macrophages. Growing evidence suggests these enzymes are key drivers of autoimmune diseases marked by bacteria-mediated barrier disruption and downstream inflammation. In preclinical studies, VENT-04 completely protected mice from gut barrier disruption and significantly inhibited inflammatory pathways, including clinically validated disease effectors such as TNF-α and LCN2.
“Developing potent and selective inhibitors against caspases has long been a challenge for drug development,” said Michael Crackower, Ph.D., chief scientific officer of Ventus. “Previously developed caspase inhibitors demonstrated efficacy in clinical trials, validating the therapeutic role of caspase inhibition, but they required high doses that led to toxicity and program discontinuations. Using our ReSOLVE® platform, we have identified selective, highly potent, allosteric caspase-4/5 inhibitors. VENT-04 has the potential to demonstrate the therapeutic benefit of caspase-4/5 inhibition across a broad range of inflammatory diseases.”
