DB105 / Denovo, Orion Corp, J&J - LARVOL DELTA

Regionally selective effects ofpirepematon catecholamine neurotransmissionupon local administration in cortical and subcortical brain areas (Neuroscience 2021) - "The alpha2c adrenoceptor antagonist ORM12741 was tested in a similar fashion, however limited to application in the PFC and sampling in the PFC and the striatum. This suggests that local cortical mechanisms are the main drivers of the pharmacodynamic effects of the compound. An alpha2c adrenoceptor-selective antagonist failed to produce similar effects, suggesting that the overall in vivo effects of pirepemat may derive from interactions of the agent at several receptors and/or circuits impacting PFC catecholamine output."

CNS Disorders • Parkinson's Disease

Application of the PET ligand [C]ORM-13070 to examine receptor occupancy by the α-adrenoceptor antagonist ORM-12741: translational validation of target engagement in rat and human brain. (PubMed, EJNMMI Res) - P1 | "ORM-12741 is a selective α-AR antagonist which penetrates the rat and human brain to occupy α-ARs in a manner consistent with its receptor pharmacology. Trial registration number and date of registration: ClinicalTrial.cov NCT00829907. Registered 11 December 2008. https://clinicaltrials.gov/ ."

Journal • CNS Disorders

COMPARISONS BETWEEN ADAS-COG 11 AND CDR SYSTEM MEASURES IN THE ASSESSMENT OF COGNITIVE DYSFUNCTION IN MILD TO MODERATE ALZHEIMER’S DISEASE. (CTAD 2019) - "In a recent Phase II study, the battery was used in conjunction with the Alzheimer’s Disease Assessment Scale - Cognitive Subscale (ADAS-cog), to assess the e ect of ORM-12741 on cognition in patients with mild to moderate Alzheimer’s disease... Statistically signi cant moderate and strong correlations were found between ADAS- Cog11 and the various CDR System measures including Word Recall, con rming the system’s validity in assessing cognition in Alzheimer’s disease patients. Additionally, the strongest correlations were observed for the accuracy to speed ratios, which is a novel finding. Such ratios capture two important aspects of cognition in patients with Alzheimer’s disease, decreased accuracy performance together with slowed response times."

Denovo Biopharma receives global rights to a novel late-stage drug for Alzheimer's disease from Orion Corporation for development as a personalized medicine (PRNewswire) - "Denovo Biopharma...today announced it has licensed ORM-12741 from Orion Corporation. Denovo gains global rights to develop, manufacture and commercialize ORM-12741...ORM-12741 is a selective, potent, first-in-class antagonist targeting the Alpha2C adrenoceptor (AR) that may be useful for neuropsyciatric indications such as Alzheimer's Disease, schizophrenia, and depression, among others."

Licensing / partnership

Orion Group half-year financial report January–June 2019 (GlobeNewswire) - "In the review period, Orion out-licensed the ORM-12741 molecule (alpha-2C-receptor antagonist) to Denovo Biopharma which plans to investigate its use in personalized medicine in the field of neuropsychiatry. The agreement does not have material financial significance for Orion at least for the time being."

Licensing / partnership

EFFICACY AND SAFETY OF ORM-12741 ON AGITATION/AGGRESSION SYMPTOMS IN PATIENTS WITH ALZHEIMER’S DISEASE: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY (ADPD 2019) - "Use of stabile cholinesterase inhibitor, memantine and SSRI medication was allowed. The results of the study do not support efficacy of ORM-12741 on agitation/aggression symptoms in patients with mild to moderate AD."

Clinical