Phase 2 results of Ventyx Bio Cardiovascular drug lead to talks with major pharmaceutical company

An investigational drug from Ventyx Biosciences produced statistically significant reductions in blood levels of a protein that is an indicator of cardiovascular risk, preliminary Phase 2 results that support the molecule’s approach to tackling what is emerging as a competitive inflammatory target for heart disease. The reading of the data also marks the start of negotiations with a major pharmaceutical company that has a prime position to obtain the 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 primary objective of the placebo-controlled Phase 2 study was to assess safety and tolerability, and the reported results exceeded that mark. It is the efficiency measures that attract investors’ interest.

The study included 175 patients with cardiovascular risk and obesity. Secondary objectives included measurements of the San Diego-based biotech’s drug on inflammation. This effect was assessed by a test measuring levels of C-reactive protein (CRP), a liver protein produced in response to inflammation. Results released after Wednesday’s market close show a rapid reduction in highly sensitive CRP (hsCRP) within about a week. This effect was sustained, with study participants receiving VTX3232 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 included participants who received at least one dose of study drug, results showed a 64% reduction in hsCRP at week 12 compared to baseline. The 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 that Tourmaline Bio is developing for the treatment of atherosclerotic cardiovascular diseases. 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 taken so far by the drug Ventyx, it has no future as a treatment for obesity. The study also included a group that received VTX3232 with semaglutide, the main pharmaceutical ingredient in Novo Nordisk’s obesity drug Wegovy. The drug Ventyx did not cause weight loss in the arm as monotherapy or in addition to Wegovy.

Speaking on a conference call Wednesday evening, Ventyx CEO Raju Mohan said the company has no expectations regarding NLRP3 inhibition in obesity because human biological data to date does not support it. The trial results can now put that question aside, he said. Additional data from the study will be presented at upcoming medical conferences.

Ventyx focused on VTX3232 two years ago, after the immunology drug that was its lead program met the primary endpoint in a Phase 2 study in plaque psoriasis, but with lower results than other drugs in a competitive class. VTX3232 will need to continue to demonstrate its competitiveness in the emerging class of NLRP3 inhibitors, studied in both neurodegenerative disorders and cardiometabolic applications. No NLRP3 inhibitors have yet been approved, but Mohan says the VTX3232 data stands out in the class in terms of safety and effectiveness.

Start-up Nodthera has reached phase 2 testing with NT-0796, an NLRP3 inhibitor in development for the treatment of obesity. The company is also studying this drug in Parkinson’s disease. BioAge Labs, which last year abandoned a licensed obesity drug candidate after a safety signal emerged in human trials, is now focusing on BG-102, an oral NLRP3 inhibitor discovered in-house in phase 1 development for obesity.

Roche’s pipeline lists selnoflast, a small molecule NPRP3 inhibitor (formerly RG6418), in phase 1 testing for potential applications in immunology and neurology. In 2022, Novo Nordisk paid $70 million upfront 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 pharmaceutical company to strike a deal for an NLRP3 inhibitor. Last year, Sanofi invested $27 million in Ventyx, which also gave the pharmaceutical giant first negotiating rights for VTX3232. Mohan said reading phase 2 data for the molecule now kicks off the round of negotiations with Sanofi, which did not have access to the data until Wednesday. Mohan declined to specify a timeline or give further details about the negotiations with Sanofi, but said the company would disclose more “at the appropriate time.”

“This is the first time we’ve publicly disclosed this data, so they haven’t had a chance to see it,” Mohan said of Sanofi. “I hope some of them saw it today. They will see it in their interactions with them as part of [right of first negotiation].”

In addition to cardiovascular indications, Ventyx is attempting to harness the brain-penetrating properties of VTX3232 to reduce neuroinflammation to treat early-stage Parkinson’s disease. Last June, the company released topline data from an open-label Phase 2a study showing the drug was safe and well tolerated, meeting the primary endpoint. The results also showed reductions in NLRP3-related indicators in cerebrospinal fluid and blood, as well as evidence that the drug hits its target. Ventyx said the results support advancing this program toward a placebo-controlled phase 2 test in Parkinson’s disease.

Photo: BrianAJackson, Getty Images