Genaera has announced interim Phase I safety and pharmacokinetic data and new preclinical data on trodusquemine, its lead drug candidate for the treatment of type 2 diabetes and obesity.
Interim results from Genaera’s second Phase I clinical trial of MSI-1436, a novel inhibitor of PTP1B, demonstrated that the drug was well-tolerated by the overweight and obese volunteers with type 2 diabetes at anticipated therapeutic dose levels with a very low level of adverse events and no evidence of serious adverse events.
Moreover, pharmacokinetic (PK) profiles of MSI-1436 in the four cohorts of the study showed a consistent pattern with minimal subject-to-subject variability. Linearity of peak trodusquemine concentration was observed across the range of doses studied. Values for a wide range of endocrine and metabolic biomarkers as well as evaluations of mood and cognition were also found to be stable in subjects receiving all levels of the drug or placebo during the trial.
These positive study MSI-1436C-103 results are expected to enable further study to fully validate proof-of-concept of MSI-1436 in an ascending multiple-dose clinical trial planned to begin later this year.
Data were also presented from preclinical studies which demonstrated that systemically administered MSI-1436 crossed the blood-brain barrier and functionally inhibited PTP1B in the hypothalamus.
In this study, rats were administered a single dose of MSI-1436 one day prior to receiving insulin; 30 minutes post-insulin, hypothalami were harvested to determine the level of phosphorylated-insulin receptor beta (IR-beta), a target of PTP1B. Previous studies had shown that MSI-1436 is a reversible, noncompetitive inhibitor of PTP1B with the ability to cross the blood brain barrier.
In the hypothalamus, MSI-1436 enhanced the insulin-induced phosphorylative state of the insulin receptor, which confirms the functionality of MSI-1436 in this key regulatory center of the brain. According to the company, the combination of central and peripheral inhibition makes MSI-1436 a promising therapeutic candidate for both obesity and type 2 diabetes.
Comments