XEN-D0501 and TRPV1 antagonists
XEN-D0501 is a selective, synthetic potent small molecule TRPV1 antagonist that was in-licensed in 2016. TRPV1 antagonists that down-regulate neurogenic inflammation, has demonstrated applications across pain and inflammatory diseases and potentially plays a role in obesity and diabetes. TRPV1 antagonists have been shown to 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 (non-diabetic) trial participants. 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 people living with obesity and type 2 diabetes. Further, PP-CT02, demonstrated that XEN-D0501 (administered as 4mg bi-daily for 28 days) – with statistical significance versus placebo – enhanced the endogenous insulin response to oral glucose.
Furthermore, ANP, a heart failure biomarker, was highly statistically significantly reduced. During 2023 we could report a 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.
Next up, PILA PHARMA will investigate the candidate in a pre-clinical setting with regards to generating weight-loss. This, if successful, will be followed with a clinical trial in people living with overweight but not diabetes.
The existing plans for PP-CT03, a clinical phase 2a trial to investigate the candidate in people living with overweight and type-2 diabetes, is also being prepared. The objective of this study is to identify the maximal tolerable dose of XEN-D0501 in people living with obesity and type 2 diabetes and to evaluate the safety profile following 3 months chronic treatment. In addition to the safety assessment, PP-CT03 will also include sufficient participants that should allow for efficacy readouts on reduction of body weight.
DISCOVERY OF TRPV1 AWARDED NOBEL PRIZE
IN 2021 DAVID JULIUS AND ARDEM WERE AWARDED THE NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE FOR THEIR DISCOVERIES OF RECEPTORS FOR TEMPERATURE AND TOUCH.
DAVID JULIUS UTILIZED CAPSAICIN, A PUNGENT COMPOUND FROM CHILI PEPPERS THAT INDUCES A BURNING SENSATION, TO IDENTIFY A SENSOR IN THE NERVENDINGS OF THE SIKN THAT RESPONS TO HEAT,TRPV1.
PILA PHARMA is the owner of a use-patent giving the exclusive right to treat diabetes and obesity with TRPV1 antagonists (Read the use-patent application here)