An experimental Ventyx Biosciences drug led to statistically significant reductions in blood levels of a protein that’s an indicator of cardiovascular risk, preliminary Phase 2 results that support this molecule’s approach of addressing what is becoming a competitive inflammation target for heart disease. The data readout also starts the clock on negotiations with a big pharma company that has the inside track for securing rights to the once-daily pill.
Ventyx’s drug, VTX3232, is an oral small molecule designed to block the NLRP3 inflammasome, a protein complex that regulates inflammatory signaling. The main goal of the placebo-controlled Phase 2 study was to evaluate safety and tolerability, and the results reported passed that bar. It’s the efficacy measures that are piquing the interest of investors.
The 175-patient study enrolled patients with cardiovascular risk and obesity. Secondary goals included measures of the San Diego-based biotech’s drug on inflammation. This effect was assessed by a test that measures levels of C-reactive protein (CRP), a liver protein produced in response to inflammation. The results reported after Wednesday’s market close show rapid reduction in high-sensitive CRP (hsCRP) within about a week. This effect was sustained, with study participants who received VTX3232 as a monotherapy showing a 78% reduction in hsCRP from baseline measured at week 12, compared to a 3% increase in hsCRP in the placebo arm.
In the full analysis, which includes participants who received at least one dose of the study drug, results showed a 64% reduction in hsCRP at week 12 relative to baseline. Results also showed statistically significant reductions in other biomarkers associated with cardiovascular risk, including IL-6, a signaling protein involved in inflammation. IL-6 is the target of pacibekitug, an antibody drug that Tourmaline Bio is developing for atherosclerotic cardiovascular disease. Last month, Novartis announced a $1.4 billion deal to buy Tourmaline and its Phase 3-ready IL-6 inhibitor.
Despite the encouraging cardiovascular measures for Ventyx’s drug so far, it does not have a future as an obesity treatment. The study also included a group that received VTX3232 with semaglutide, the main pharmaceutical ingredient in Novo Nordisk obesity drug Wegovy. The Ventyx drug did not lead to weight loss in the monotherapy arm or as an add-on to Wegovy.
Speaking during a Wednesday evening conference call, Ventyx CEO Raju Mohan said the company had no expectations for NLRP3 inhibition in obesity, as human biological data to date did not support it. The trial readout can now put that question to rest, he said. Additional data from the study will be presented at upcoming medical conferences.
Ventyx turned its focus to VTX3232 two years ago, after the immunology drug that was its lead program met the main goal of a Phase 2 plaque psoriasis study but with results that fell short of others in a competitive class of medicines. VTX3232 will need to continue to show it is competitive in the emerging class of NLRP3 inhibitors, which is being studied in both neurodegenerative disorders and cardiometabolic applications. No NLRP3 inhibitors have been approved yet, but Mohan contends VTX3232’s data stand out in the class in terms of safety and efficacy.
Startup Nodthera has reached Phase 2 testing with NT-0796, an NLRP3 inhibitor in development for obesity. The company is also studying this drug in Parkinson’s disease. BioAge Labs, which last year discontinued an in-licensed obesity drug candidate after a safety signal emerged in human testing, is now focused on BG-102, an internally discovered oral NLRP3 inhibitor in Phase 1 development for obesity.
Roche’s pipeline lists the small molecule NLRP3 inhibitor selnoflast (formerly RG6418) in Phase 1 testing for potential applications in immunology and neurology. In 2022, Novo Nordisk paid $70 million up front for a preclinical oral NLRP3 inhibitor developed by Ventus Therapeutics. Novo’s pipeline currently lists an oral NLRP3 inhibitor in Phase 1 testing for liver, kidney, and cardiometabolic diseases.
Sanofi could be the next big pharma company to strike a deal for an NLRP3 inhibitor. Last year, Sanofi made a $27 million equity investment in Ventyx that also gave the pharma giant the right of first negotiation for VTX3232. Mohan said the Phase 2 data readout for the molecule now starts the cycle of negotiations with Sanofi, which did not get a look at the data prior to Wednesday. Mohan declined to specify a timeline or offer other details of the negotiations with Sanofi, but said Ventyx would disclose more “at the appropriate time.”
“This is the first time we’re publicly disclosing this data, so they have not had a chance to see it,” Mohan said of Sanofi. “I’m hoping some of them have seen it today. They will see it in the course of interactions with them as part of [right of first negotiation].”
In addition to cardiovascular indications, Ventyx is trying to leverage the brain-penetrating properties of VTX3232 to reduce neuroinflammation as a way to treat early-stage Parkinson’s. This past June, the company reported topline data from an open-label Phase 2a study showing the drug was safe and well tolerated, meeting the main goal. Results also showed reductions in NLRP3-related indicators in cerebrospinal fluid and blood as well as evidence that the drug engaged its target. Ventyx said the results support advancing this program to a placebo-controlled Phase 2 test in Parkinson’s.
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