Ventus Therapeutics Announces Nomination of VENT-04, a First-in-Class, Oral, Small-Molecule Caspase-4/5 Inhibitor, as a Development Candidate

Targeting caspase-4/5 has the potential to address a broad range of inflammatory conditions, including inflammatory bowel disease, hidradenitis suppurativa, severe asthma, and chronic obstructive pulmonary disease

VENT-04 is the seventh development candidate created using Ventus’ proprietary ReSOLVE^® platform

WALTHAM, Mass. & MONTREAL--(BUSINESS WIRE)--Ventus Therapeutics, a clinical-stage biopharmaceutical company advancing multiple small-molecule programs for autoimmune, inflammatory, and neurological disorders, today announced the nomination of VENT-04, a first-in-class, allosteric caspase-4/5 inhibitor, as a development candidate. Caspase-4/5 activation is intrinsic to dysbiosis, bacteria-induced IL-18 expression, and pyroptotic cell death, which are all adverse factors in diseases of high unmet need, including inflammatory bowel disease (IBD), hidradenitis suppurativa (HS), severe asthma, and chronic obstructive pulmonary disease (COPD).

“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 CEO 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 in epithelial and endothelial cells as well as immune cells such as macrophages. Emerging evidence shows that caspase-4/5 are key drivers of autoimmune diseases characterized by bacteria-mediated barrier disruption and downstream inflammation, such as IBD. In preclinical studies, VENT-04 demonstrated the ability to completely protect mice from gut barrier disruption and robustly inhibited the downstream inflammatory cascade, including clinically validated effectors of disease 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. However, 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 be a leader in demonstrating the therapeutic benefit of caspase-4/5 inhibition across a broad range of inflammatory diseases.”

About ReSOLVE^®

Ventus’ proprietary ReSOLVE^® platform combines the latest advances in artificial intelligence/machine learning, protein science, structural biology, and biophysics to substantially increase the speed and accuracy of small-molecule drug discovery. ReSOLVE^® is the only platform that can model all conformations of a protein, identify druggable pockets, characterize the dynamic water networks of a pocket, and use those water networks to generate a blueprint for small molecule binders, referred to as a hydrocophore^®. The hydrocophore^® enables rapid virtual screening of libraries containing billions of compounds, efficiently identifying potent and structurally unique chemical matter. ReSOLVE^® is both target agnostic and therapeutic area agnostic and can be applied to multiple stages of drug discovery, from target assessment to development candidate nomination.

About Ventus Therapeutics

Ventus Therapeutics is a clinical-stage biopharmaceutical company advancing multiple small-molecule programs for autoimmune, 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.