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SAN2465 – Rapid acting antidepressant 

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SAN2465

Rapid acting antidepressant devoid of psychotropic adverse effects

SAN2465 is a highly potent and selective negative allosteric modulator (NAM) of GABAA α5 containing receptors with a pharmacological profile different from conventional antidepressant therapies, novel NMDA-antagonist as well as psychedelic investigational drugs.

How SAN2465 work

SAN2465 has been tested in the chronic mild stress model of depression, which is widely acknowledged as the most valid animal model of depression with translational potential to human disease. In this model, SAN2465 has demonstrated rapid and sustained reversal of chronic stress-induced depressive-like symptoms, including anhedonia, anxiety, and cognitive impairment. The onset and robustness of the antidepressive effect was similar to ketamine, which was used as a positive control in the study. The data suggests that SAN2465 may induce rapid antidepressant effects like those observed with ketamine and esketamine (Spravato™), which has demonstrated clinical response within hours after the first dose in patients. Importantly, as opposed to ketamine and esketamine, negative modulation of GABAA α5 receptors is not anticipated to lead to significant adverse effects, as the expression of these receptors are more localized and mainly restricted to limbic areas.

 

Consequently, this innovative approach for the treatment of major depressive disorder differs substantially from conventional antidepressant drugs in its mechanism of action, and it has the potential to become a first-in-class rapid-acting antidepressant without the significant adverse effects associated with esketamine.

 

SAN2465 STATUS

Saniona’s novel rapid acting antidepressant candidate has been selected for preclinical development.