7:04AM Omeros reports additional positive clinical data for its drug candidate to treat cognitive disorders; PDE10 target engagement continues to increase with well-tolerated doses (OMER) 11.79 : Co announced additional positive data from its Phase 1 program for OMS824, the lead compound in Omeros' phosphodiesterase 10 (PDE10) program. This latest clinical trial evaluated the extent to which OMS824, at a dose higher than previously reported, binds to PDE10, an enzyme expressed in the region of the brain that has been linked to a wide range of diseases that affect cognition. OMS824 achieved an average of 63% engagement at PDE10 and did not trigger the dose-limiting side effects seen with other PDE10 inhibitors. These data further support advancing OMS824 through clinical trials in patients with cognitive disorders. Last month, co started a Phase 2 trial evaluating the drug in patients with schizophrenia and plans to start a Phase 2 trial in Huntington's disease later this year.
The results reported today were in healthy male subjects receiving OMS824 once daily for seven days at a dose higher than those previously evaluated in the target-engagement clinical trial. Positron emission tomography (PET) scans were used to measure the binding activity of OMS824 to PDE10 in the brain. An average of 63% occupancy at PDE10 was seen in the basal ganglia, the region of the brain that plays a critical role in cognition. The drug was well tolerated with mild somnolence as the only apparent side effect.
While the level of target engagement seen in this PET trial is significantly higher with lesser side effects than has been reported for any other PDE10 inhibitor in development, a recently completed Phase 1 clinical pharmacokinetic trial with 10 days of OMS824 dosing achieved ~ 50% higher plasma concentrations than in the PET trial, and all side effects were mild and well-tolerated, and most were self-limiting. PET data were not obtained in this pharmacokinetic trial but, based on modeling of all data obtained in the OMS824 Phase 1 program, it is estimated that the drug engaged the PDE10 enzyme at levels substantially greater than 63%. Co is now planning to evaluate a higher dose of OMS824 in the PET trial to confirm this estimate.
