Piramal’s NCE research shares preclinical efficacy data for two promising molecules

Piramal Life Sciences – NCE Research, a division of Piramal Enterprises Ltd (PEL), made poster presentations for drugs in early clinical development for metabolic disorders in two different sessions of the 74th Scientific Session of the American Diabetes Association (ADA) in San Francisco, California, USA. The presentations covered Piramal’s clinical stage GRP40 agonist, P11187 and Piramal’s clinical stage DGAT1 inhibitor P7435.

The P11187 presentation covered the preclinical pharmacological data in support of efficacy for a novel synthetic oral GPR40 partial agonist, P11187, which stimulates glucose-dependent insulin secretion.

The primary objective of the study was to evaluate the efficacy of P11187 to potentiate glucose-dependent insulin secretion. P11187 orally administered to both normal and diabetic mice and rats showed significant reduction in blood glucose levels. P11187 treatment in normal rats in the hyperglycemic clamp model results in considerable increase in glucose infusion rate and glucose-stimulated insulin secretion.

P11187 has been found to be a highly selective and potent partial agonist for these GPR40 receptors in humans, mice and rats. It is being developed for the management of Type II diabetes. Overall, P11187 has demonstrated glucose-stimulated insulin secretion and anti-hyperglycemic potential in rodent models of Type II diabetes with excellent safety profile. The drug is currently being tested in Phase I trial in the USA.

The P7435 presentation covered the preclinical data in support of efficacy for P7435, a novel, potent and selective, small molecule DGAT1 inhibitor in rodent models of hyperlipidemia and obesity. It also discussed the clinical results from a Phase I, randomised, double-blind, placebo-controlled study of single ascending doses (SAD) of P7435 in healthy male volunteers conducted in India.

The Phase I trial showed that P7435 was safe and well-tolerated when given in single doses from 10mg to 300mg to healthy male volunteers. The only adverse effect of the treatment seen was vomiting. The PK profile revealed that the increase in exposure from 10mg to 300mg of P7435 was dose-linear although less than dose-proportional.

In vivo data suggested that acute treatment with P7435 resulted in significant reduction in plasma triglyceride levels, and an increase in GLP-1 levels in the plasma along with sitagliptin. An overall reduction was observed in the body weight, food intake, cholesterol, epididymal fat pad weight, plasma glucose, plasma triglyceride, insulin, Steatorrhea and liver triglycerides of High Fat Diet (HFD) fed hamsters, ob/ob mice and SD rats when given a chronic treatment with P7435. On the whole, P7435 showed significant efficacy in rodent models of hyperlipidemia. The investigational drug is currently moving quickly through a Phase I trial in the US.

EP News Bureau – Mumbai