biocrea and Pfizer jointly presented details on novel PDE10 inhibitors at the 241st ACS National Meeting & Exposition

biocrea, a biopharmaceutical company focusing on novel treatments for disorders of the CNS, today reported details on the design and synthesis of novel, brain-penetrating phosphodiesterase-10 (PDE10) inhibitors developed in collaboration with Pfizer Inc. The data were featured in joint presentations with Pfizer at the recent 241st ACS National Meeting & Exposition, an event organized by the American Chemical Society (ACS).

The data demonstrated that the scientists at Pfizer and biocrea were able to eliminate undesired activity on adenosine receptors and to considerably improve the compounds´ physicochemical properties and potency. The team had started with initial high-throughput hits characterized by low potency and selectivity. Further lead optimization led to a number of compounds with very robust activity in a range of preclinical models of anti-psychotic efficacy. Moreover, these PDE10 inhibitors produced low levels of catalepsy, suggesting a minimal risk for the induction of side-effects involving the extrapyramidal system (EPS), the most common adverse reaction observed with anti-psychotic drugs.

Phosphodiesterases (PDEs) have been identified as key regulators of intracellular cyclic nucleotide levels in the brain. Mechanistically, PDE10 inhibition has two major benefits, mimicking, the effects of antagonists of the dopamine-2 receptor, the current standard treatment for psychosis, and the effects of agonists of dopamine-1 receptors, which may decrease the side-effect liabilities while contributing to a pro-cognitive profile.

“The data presented at the 241st ACS National Meeting & Exposition underline the potential of our PDE10 inhibitor programs and the strong PDE expertise of our research team,” said Tom Kronbach, CEO of biocrea. “We are very pleased with the recent progress with our proprietary PDE10 inhibitors and are preparing a selected number of compounds for preclinical development.”

Formerly a division of Biotie Therapies, biocrea has emerged as one of the leading groups with unique expertise in the creation of novel, brain-penetrating PDE inhibitors. Following the expiry of its collaboration with Pfizer in 2010, biocrea has continued to design new scaffolds for brain-penetrating, best-in-class PDE10 inhibitors and has optimized new leads showing encouraging preclinical data in efficacy models. biocrea’s PDE10 inhibitors show exceptional potential for the treatment of all three symptom complexes of schizophrenia (namely hallucinations, negative symptoms and cognition deficits), and a growing body of evidence supports their utility as a new therapeutic option for Huntington’s disease.