Semaglutide(Anya Biopharma)

Ventyx Biosciences’ Phase 2 data showed a significant reduction in cardiovascular risks in patients with obesity through NLRP3 inhibition, a closely-watched target in neurologic and cardiometabolic drug development. After the readout was announced on Wednesday, the biotech’s stock $VTYX was up more than 85% on Thursday morning. That said, the future of VTX3232 could hinge on the ambitions of Sanofi, which paid $27 million in September 2024 to snag the rights to first negotiation for the once-daily oral NLRP3 inhibitor. Sanofi has acted on similar rights, having bought Vigil Neuroscience earlier this year after getting the negotiation rights to the biotech’s Alzheimer’s disease drug in 2024. “This is the first time we’re publicly disclosing this data, so [Sanofi] has not had a chance to see it. I’m hoping some of them have seen it today,” Ventyx CEO Raju Mohan said Wednesday during an analyst call. It’s unclear how long Sanofi gets to “review the results and determine if they have an interest in the molecule,” according to a Stifel note. A Sanofi spokesperson didn’t respond to a request for comment. The company is scheduled to report its third-quarter results on Friday. “Ultimately, NLRP3 could be a high-value target for big pharma,” Jefferies analysts wrote in a note. NLRP3 inhibitors tamp down on inflammation to lower cardiovascular risks, but they may also have the potential to treat neurological disorders. VTX3232 has completed a Phase 2 biomarker trial in patients with early forms of Parkinson’s disease. The target has attracted the interest of both drug giants and small biotechs working in cardiometabolic and neurologic R&D. That includes Novo Nordisk-partnered Ventus Therapeutics , Tenvie and NodThera , which is backed by Sanofi Ventures. Roche is also working on a Phase 1b oral candidate called selnoflast from its acquisition of Inflazome in 2020 for $448 million upfront. In the Phase 2 trial results, Ventyx said VTX3232 led to “significant reductions” in cardiovascular disease threats. The trial tested the experimental medicine alone and in combination with Novo Nordisk’s GLP-1 semaglutide. The primary endpoint of the trial was safety and tolerability. Ventyx said rates of adverse events for patients on its drug were “comparable to placebo.” On the key secondary endpoint, looking at inflammation, patients taking VTX3232 had a 64% reduction in high-sensitivity C-reactive protein (hsCRP) in the “full analysis set” at week 12 relative to baseline. There was a 3% increase in that measure in the placebo group. The p-value came in at p<0.0001. Meanwhile, the drug also led to statistically significant drops in lipoprotein(a) and liver inflammation, and it helped move interleukin-6 levels below the threshold for cardiovascular risk, according to Ventyx. The drug did not lead to weight loss, either as a single agent or in combination with semaglutide. The data are “now showing conclusively that NLRP3 inhibition has no effect in humans in promoting weight loss,” Mohan said on the call. Stifel analysts said it was “puzzling” that there was no effect on weight, given the signals in mouse models. But “the impact on biomarkers could support a path forward” for the drug in reducing cardiovascular risks, they wrote. Novartis bet $1.4 billion last month to get an anti-IL-6 drug via its acquisition of Tourmaline Bio , and Novo is also developing an IL-6 called ziltivekimab, which is in Phase 3 trials . “The potential for an ‘oral IL-6’ clearly has wide-ranging potential across a range of CV diseases with ongoing outcomes studies expected over the 2026/27 timeframe for Novo’s ziltivekimab, which represents a meaningful datapoint for the space,” the Stifel analysts wrote.