DB105 (formerly ORM-12741) is a potential treatment for Alzheimer’s disease that was being developed by the Finnish pharmaceutical company Orion. Orion had been developing the drug in partnership with Janssen Pharmaceuticals, a subsidiary of Johnson and Johnson. Denovo Biopharma licensed the rights to ORM-12741 in June of 2019 to investigate its role in personalized medicine using its proprietary biomarker analysis methods. Denovo also relabeled the drug DB105.

This medication is intended to treat memory loss as well as neuropsychiatric symptoms in Alzheimer’s, such as aggression, delusions, social withdrawal, and mood swings.

How DB105 works

DB105  acts on the α 2c adrenergic receptor on brain cells. The role of this receptor in Alzheimer’s disease is not well understood, but it is thought to be involved in the release of neurotransmitters in the brain, especially in stressful situations. Neurotransmitters are chemical messengers that carry signals between nerve cells.

Studies in mice have shown that the α 2c adrenergic receptor may affect sensory processing, motor control, and emotion-related activities.

DB105 is an α 2c adrenergic receptor “antagonist.” This means that it binds to and blocks the receptor’s activity.

DB105 in clinical trials

Several Phase 1 clinical trials conducted in healthy volunteers demonstrated that DB105 is safe, well-tolerated, and can be taken orally.

DB105 was also tested for efficacy and safety in a Phase 2 clinical trial (NCT01324518) in 100 Alzheimer’s patients also taking cholinesterase inhibitors as standard treatment. Participants were given either a high dose of DB105 (200 mg), a low dose of DB105 (60 mg), or a placebo twice a day for 12 weeks. They were then assessed using the cognitive drug research computerized assessment system and the neuropsychiatric inventory.

Results showed a small but significant improvement in episodic memory, or memory about autobiographical events, in patients given either dose of DB105 compared to those who received placebo. Findings also suggested that DB105 may slightly improve neuropsychiatric symptoms. Overall, DB105 proved safe for use in Alzheimer’s patients.

A second, larger Phase 2 clinical trial (NCT02471196) in 308 Alzheimer’s patients focused more specifically on DB105’s potential effects on symptoms of agitation and aggression. This study was completed at the end of 2017, but results have not been published. Presumably, the results of the trial were not favorable as Orion has licensed the drug to Denovo Biopharma which specializes in genetic biomarker analysis of late-stage drugs that have failed larger clinical trials. According to their website, Denovo uses its proprietary biomarker technology to identify targeted patient populations for new clinical trial designs of these drugs, so future clinical trials of DB105 may be forthcoming.

 

Last updated: Aug. 29, 2019

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