Tag: schizophrenia

Company News: biocrea’s First-in-class PDE2 Inhibitor Demonstrates Strong Potential For The Treatment Of Cognitive Disorders

– Data on novel PDE2 inhibitor BCA909 presented at 24th ECNP Congress in Paris –

biocrea, a biopharmaceutical company focusing on novel treatments for disorders of the central nervous system (CNS), today announced data on its innovative CNS-penetrating PDE2 inhibitor. The compound, which is code-named BCA909, was selected as a candidate for preclinical development  earlier this year. It demonstrates strong potential for the treatment of diseases in which normal learning and memory is impaired, e.g. mild cognitive impairment, Alzheimer’s disease and schizophrenia. Details on the compound were presented at the 24th ECNP Congress of the European College of Neuropharmacology in Paris, France (Sept. 3-7, 2011).

To date, few PDE2 inhibitors have been pharmacologically characterized. While initial findings have been encouraging, suggesting pro-cognitive and anxiolytic efficacy, the compounds did not enter the brain in sufficient quantities. With BCA909, biocrea has developed a novel, potent and selective PDE2 inhibitor with excellent CNS penetration and an efficacy and safety profile suitable for further development for multiple disease indications.

During the ECNP congress, biocrea presented data from extensive preclinical studies in vitro and in animal models of learning and memory. The key findings demonstrate that BCA909 delivers significant pro-cognitive activity in models of cognitive impairment resulting from either disruption of cholinergic or glutamatergic neurotransmission. Furthermore, BCA909 does not induce tolerance, indicating that maintained pro-cognitive efficacy, achieved through modulation of multiple neurotransmitter systems, can be delivered by the novel PDE2 mechanism of action.

Preclinical development of BCA909 is ongoing.

Company News: biocrea and Pfizer Jointly Presented Details on Novel PDE10 Inhibitors at the 241st ACS National Meeting & Exposition

– Novel treatment opportunities for CNS diseases –

biocrea, a biopharmaceutical company focusing on novel treatments for disorders of the central nervous system (CNS), today reported details on the design and synthesis of novel, brain-penetrating phosphodiesterase-10 (PDE10) inhibitors developed in collaboration with Pfizer Inc. (NYSE: PFE). The data were featured in joint presentations[1] 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, (1) the effects of antagonists of the dopamine-2 receptor, the current standard treatment for psychosis, and (2) the effects of agonists of dopamine-1 receptors, which may decrease the side-effect liabilities while contributing to a pro-cognitive profile.

 

[1] Malamas M et al., 241st ACS National Meeting & Exposition Abstract 65 – Imidazo[1,5-a]quinoxalines as selective PDE10A inhibitors for the treatment of schizophrenia, http://redir.ec/Qr3C; Malamas, M. et al., 241st ACS National Meeting & Exposition Abstract 66 – Benzo[e]imidazo[5,1-c][1,2,4]triazines as selective PDE10A inhibitors for the treatment of schizophrenia, http://redir.ec/pl1Q


Company News: biocrea Announces Novel Treatment Opportunities for CNS Diseases

– Company has filed US patent on novel, brain-penetrating PDE2 and PDE10 inhibitors –

CNS company biocrea today announced it has filed a patent application covering its brain-penetrating inhibitors of phosphodiesterases. These compounds constitute a new generation of promising drug candidates to address several CNS disorders that are currently lacking effective treatment options. biocrea has submitted a patent application to the U.S. Patent Office (USPTO) covering compounds and uses of its proprietary PDE2 and PDE10 inhibitors.

While the inhibitors of PDE10 show excellent potential for the treatment of schizophrenia, Huntington’s disease and Tourette’s syndrome, the PDE2 inhibitors cover a whole spectrum of new biological activities and treatment opportunities. Moreover, biocrea’s brain-penetrating PDE2 inhibitors show promise for the treatment of drug-induced movement disorders.

biocrea’s patent application also comprises dual inhibitors of PDE2 and PDE10 as the combination of both modes of action in one molecule results in synergistic biological effects.

So far, validating the benefit of brain PDE inhibitors in CNS diseases has been difficult because access to brain PDEs is limited by the so-called “blood brain barrier” (BBB). The team of biocrea has overcome these limitations and developed brain-penetrating, highly specific PDE inhibitors that constitute a new generation of promising drug candidates for the treatment of CNS disorders. The most advanced compound of biocrea’s novel family of PDE inhibitors, a brain-penetrating, selective PDE2 inhibitor, has been selected to enter pre-clinical development.