On Aug. 25, 2025, AbbVie and Gilgamesh Pharmaceuticals announced a definitive agreement under which AbbVie will acquire Gilgamesh’s lead investigational candidate, currently in clinical development for the treatment of patients with moderate-to-severe major depressive disorder (MDD).

Psychedelic compounds, including 5-HT_2A receptor agonists, have gained recognition as potential treatments for mental health disorders, such as MDD, because of their demonstrated rapid, robust and durable antidepressant effects. However, existing agents in this class are hampered by their long duration of psychoactive experience.

Bretisilocin, a 5-HT_2A receptor agonist and 5-HT releaser, is a novel, next-generation psychedelic compound designed to address development challenges observed within this class of compounds. Bretisilocin has been shown to exert a shorter duration of psychoactive experience, while retaining an extended therapeutic benefit.

Positive topline results from a Phase 2a study of bretisilocin in MDD were recently announced, demonstrating a clinically impactful and statistically significant reduction in severity of depressive symptoms versus low dose active comparator, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. At Day 14, a single dose (10mg) of bretisilocin demonstrated robust antidepressant effect with a -21.6 point change from baseline in MADRS total score compared to a -12.1 point change from baseline for the low dose (1mg) active comparator (p = 0.003). Bretisilocin was well tolerated with no serious adverse events.

Under the terms of the agreement, AbbVie will acquire Gilgamesh’s bretisilocin program for up to $1.2 billion, inclusive of an upfront payment and development milestones. Additionally, as part of the transaction, Gilgamesh will spin off a new entity that will operate under the name Gilgamesh Pharma Inc. to hold its employees and other programs, including its oral NMDA receptor antagonist blixeprodil (GM-1020), cardio-safe ibogaine analog, M1/M4 agonist program and existing collaboration with AbbVie. The transaction is subject to customary closing conditions.