We have identified various PDE subtypes, including PDE1, PDE2, and PDE9, as compelling targets for drug discovery. We believe that inhibitors of these PDE subtypes may be useful in the treatment of various CNS and non-CNS disorders.
Our ITI-002 portfolio of compounds modulates CNS pathways that we believe are critical to addressing cognition and motor behavior through the inhibition of an important intracellular enzyme, phosphodiesterase 1, or PDE1.
Inhibitors of PDE1 block the breakdown of cyclic nucleotides (cAMP, cGMP), potentiating downstream intracellular signaling. The PDE1 enzyme is highly active in pathological or disease states and our PDE1 inhibitors are designed to reestablish normal function in these disease states. PDE1 inhibitors have minimal effect on normal function, only acting when cells are stimulated. These "on-demand" effects make this an exciting and novel approach for the treatment of disease. The mechanism of action of PDE1 inhibitors suggests therapeutic potential across a variety of neurological and cardiovascular diseases. The mechanism of action of PDE1 inhibitors suggests therapeutic potential across a variety of neurological and cardiovascular diseases The lead compound in our PDE1 portfolio, ITI-214, has been found to be safe and well tolerated in four Phase 1 clinical trials, in healthy volunteers as well as patients with schizophrenia. A program with ITI-214 in patients with Parkinson’s disease has been initiated.