Phosphodiesterase 10 (PDE10) is an enzyme that is expressed in areas of the brain strongly linked to diseases that affect cognition, including schizophrenia and Huntington's disease. Cognitive dysfunction occurs early in these diseases and is responsible for substantial disability. PDE10 inhibitors have been shown to be effective in multiple animal models of behavior and cognition, and there remain substantial unmet clinical needs with current treatments. Our proprietary compound OMS824 inhibits PDE10 and is being developed in clinical programs for the treatment of cognitive disorders, including schizophrenia and Huntington's disease. In schizophrenia, OMS824 may have, in addition to cognitive enhancement, beneficial effects on the positive (e.g., hallucinations) and negative (e.g., flat affect) symptoms of the disease. In Huntington's disease, OMS824 may improve motor and behavioral abnormalities as well as cognition. OMS824 may address other limitations of current treatments for both schizophrenia and Huntington's disease, for example, by avoiding the weight gain, hyperlipidemia, and the risk of sudden cardiac death associated with current antipsychotic medications as well as the depression and suicidal ideation seen with tetrabenazine, the only FDA-approved treatment for Huntington's disease.
We are conducting an ongoing Phase 1 clinical program evaluating the safety, tolerability and pharmacokinetics of OMS824 in healthy subjects. At the highest level of multiple-dosing administered, OMS824 was well tolerated and the only apparent drug-related adverse events were mild and self-limiting. As part of our Phase 1 clinical program, we are also conducting a clinical trial to evaluate the level of target interaction of OMS824 using positron emission tomography (PET) scans in healthy subjects by measuring the extent to which OMS824 binds to PDE10 in the striatum, a region of the brain that has been linked to a wide range of diseases that affect cognition. Quantitation of PET images showed that, at one evaluated dosage level, an average of 66% and a high of approximately 70% interaction at PDE10 were seen in the striatum. The drug was well tolerated in all subjects with mild somnolence as the main side effect. Unlike reported side effects for other PDE10 inhibitors in development, OMS824 is able to achieve high target interaction (a high to date of approximately 70%) without extrapyramidal symptoms (loss of muscle control, e.g., muscle rigidity, tremors, or involuntary muscle movements).
We are currently evaluating OMS824 in two Phase 2 programs: one in patients with stable schizophrenia and the other in Huntington's disease patients. Data from the Phase 2a schizophrenia clinical trial indicate that OMS824 can be administered in combination with standard antipsychotic medications and that, at tolerated doses, yields plasma concentrations that are predicted to achieve a high degree of PDE10 target interaction in the striatum. This opens the potential for OMS824 to be developed as monotherapy and/or as adjunctive treatment for cognitive impairment, acute exacerbation of symptoms, and/or inadequate response to antipsychotic medications.
The FDA has designated OMS824 as an orphan drug for Huntington's disease. OMS824 has also received Fast Track designation from the FDA for the treatment of cognitive impairment in patients with Huntington's disease.
As of February 15, 2014, we own five issued patents and one pending patent application in the U.S., and one issued patent and 23 pending patent applications in foreign markets that claim proprietary PDE10 inhibitors.