PDE7 inhibitor program, previously focused on movement disorders, was fueled by Daiichi’s candidates.
Omeros has amended its exclusive license to phosphodiesterase 7 (PDE7) inhibitors from Daiichi Sankyo to include addiction and compulsive disorders. The deal, originally inked in March 2010, gave Omeros rights to Daiichi’s preclinical PDE7 inhibitors for use in movement disorders like Parkinson disease and restless leg syndrome.
Omeros previously discovered a link between PDE7 and movement disorders and believes that it also is the first to link PDE7 to addiction and compulsive behavior. NIDA and The Michael J. Fox Foundation are collaborators on the firm’s PDE7 program. When Omeros first licensed PDE7 compounds from Daiichi, it expected to file an IND to start clinical trials this year. However, its movement disorder pipeline is at the lead-optimization phase.
“From the advanced Daiichi compounds we have already selected a clinical candidate, and we expect that addiction will provide us with a faster and less expensive development pathway for our PDE7 program,” states Gregory A. Demopulos, M.D., chairman and CEO of Omeros.
PDE7 appears to modulate the dopaminergic system, which plays a significant role in regulating both movement and addiction. Omeros says that in animal models of cocaine addiction, PDE7 inhibitors reduce cocaine self-administration, inhibit relapse induced by cues and stress, and facilitate drug abstinence in previously addicted animals. No effect on normal feeding was observed in the cocaine studies, suggesting that PDE7 inhibitors selectively reduce addiction-related behaviors, according to the firm.
In a similarly well-established animal model of binge eating, Omeros reported that PDE7 inhibitors demonstrated equally robust efficacy, again showing no effect on normal feeding behavior.
Omeros’ development pipeline for addiction already comprises peroxisome proliferator-activated receptor gamma (PPAR gamma). Two Phase II studies are being conducted by researchers at the New York State Psychiatric Institute. NIDA is funding substantially all costs of these studies, which are evaluating the effects of PPAR gamma agonists on oxycontin and heroin use.
Pilot human and preclinical data suggest that PPAR gamma agonists may be most effective in the treatment of addiction to opioids, alcohol, and nicotine and that they are less effective for treating addiction to psychostimulants such as cocaine and methamphetamine. In contrast, preclinical data suggest that PDE7 inhibitors may be effective in the treatment of addiction to cocaine, methamphetamine, and nicotine as well as compulsive behaviors, Omeros notes.
