About XEN-D0501 and TRPV1 antagonists

XEN-D0501 is a selective, synthetic potent small molecule TRPV1 inhibitor that was in-licensed in 2016. The drug candidate is a small molecule currently formulated in a simple and stable tablet formulation.
TRPV1 inhibitors that down-regulate neurogenic inflammation, has demonstrated applications across pain and inflammatory diseases and potentially plays a role in diabetes and potentially other metabolic disorders like obesity. PILA PHARMA’s founder and current CSO Dorte X. Gram, is the inventor of the principle of treating diabetes and obesity with TRPV1 inhibitors – a discovery-by-surprise during her PhD studies at Novo Nordisk, Denmark. Here she discovered that TRPV1 inhibitors would prevent glucose intolerance and body weight gain in spontaneously obese pre-diabetic rats. These results pointed to a new and previously undiscovered role of TRPV1 in regulating both blood glucose and body weight. Prior to in-licensing, XEN-D0501 had been found to have a good safety profile in other (non-diabetic) patient groups.
PILA PHARMA has to date completed two phase 2a clinical trials (PP-CT01 and PP-CT02), that both demonstrated that XEN-D0501 is well tolerated by in people living with obesity and type 2 diabetes. Further, in PP-CT02, it was demonstrated that XEN-D0501 (administered as 4 mg bi-daily for 28 days) - with statistical significance versus placebo - enhanced the endogenous insulin response to oral glucose. ANP, a cardiovascular biomarker for heart failure, was also highly statistically significantly reduced.
During 2023 the Company could report very good tolerability of XEN-D0501 following 13 weeks administration of very high doses in 2 animal species, and XEN-D0501 can thus progress into longer clinical trials. A preclinical study in two different rat models of obesity were conducted at the end of 2025 and start of 2026. Initial results showed no effects, but later analyses showed that the used formulation resulted in insufficient exposure, yielding significantly lower levels than anticipated as compared to previously conducted 13-week rat toxicity studies. Given the low exposure observed, the data do not allow for conclusions regarding effect on body weight. The Company will continue its evaluation in clinical trials, where dose and exposure can be adequately controlled.
The next step is now to submit a clinical trial application for a dose-finding study in people living with obesity (PP-CT04). Preparations for submitting clinical trial applications in people living with both obesity and type 2 diabetes (PP-CT03) as well as erythromelalgia (PP-CT05) is also ongoing. The ambition is to create a comprehensive and meaningful data package that supports XEN-D0501 as an oral, potential first-in-class drug candidate.