Back-to-back failures in psoriasis and Crohn’s disease have forced Ventyx Biosciences to abandon the development of its investigational oral TYK2 inhibitor VTX958.
Ventyx Biosciences on Monday announced that its investigational TYK2 blocker VTX958 missed its primary endpoint in a Phase II Crohn’s disease trial, forcing the San Diego-based biotech to discontinue development of the candidate.
The company did not provide specific data in its announcement, only revealing that VTX958 was unable to significantly improve mean scores in the Crohn’s disease activity index—a widely used tool for quantifying the symptoms and severity of Crohn’s disease—from baseline to 12 weeks, compared with placebo.
VTX958 delivered a dose-dependent and nominally significant treatment effect on endoscopic response, which was assessed through endoscopy and is a high-priority treatment goal. Both the 225-mg and 300-mg doses of the TYK2 inhibitor also resulted in a larger reduction in C-reactive protein and fecal calprotectin levels versus placebo, suggesting a beneficial effect on inflammation.
In terms of safety, the Phase II trial found VTX958 to be overall well-tolerated and its adverse event profile was consistent with what had been established in prior studies.
With Monday’s disappointing readout, Ventyx “does not anticipate conducting additional clinical trials of VTX958 with internal resources,” according to the company. The biotech will conduct further analyses of the Phase II data for VTX958 “to better understand the discordance between symptomatic and endoscopic response.”
VTX958 is an orally available and highly selective allosteric blocker of the TYK2 protein, which otherwise functions as a regulator of both the innate and adaptive immune responses. TYK2 plays a central role in type I interferon, IL-12 and IL-23 signaling. According to Ventyx’s website, VTX958’s mode of action can help dampen inflammation—the hyperactivation of which underpins several autoimmune disorders—while preserving overall immune function and protection.
However, this proposed mechanism does not seem to play out in the clinic. In November 2023, despite hitting its primary endpoint in a Phase II study, Ventyx announced that it was shelving its plans for VTX958 in moderate to severe plaque psoriasis.
“We are disappointed by the magnitude of efficacy observed,” CEO Raju Mohan said at the time, adding that the findings “do not support further development of VTX958 in the highly competitive psoriasis and psoriatic arthritis indications.”
In December 2023, Ventyx laid off approximately 20% of its staff, according to an SEC filing.
