Psilocybin

Bretisilocin recently achieved a 94% remission rate in a phase 2 major depressive disorder trial. \n AbbVie has written the next chapter in its epic quest to treat psychiatric disorders, agreeing to buy a psychedelic drug candidate from Gilgamesh Pharmaceuticals for up to $1.2 billion. Bloomberg reported AbbVie was in talks about buying Gilgamesh—a Fierce 15 2024 winner—for around $1 billion last month. The final deal is a little different than those early reports suggested. Rather than buy all of Gilgamesh, AbbVie has agreed to acquire its bretisilocin program and let the biotech spin off other assets to create a new entity.AbbVie will pay up to $1.2 billion in upfront and development milestones for bretisilocin. The companies are yet to disclose the split between upfront and milestone payments. No regulatory or commercial milestones nor royalties are mentioned in the press release about the deal.The agreement will give AbbVie control of an asset that recently achieved a 94% remission rate in a phase 2 major depressive disorder (MDD) trial. Forty patients received two doses, about two weeks apart, and were evaluated almost one month after the first dose. Gilgamesh designed bretisilocin, also known as GM-2505, to act on the 5-HT2A receptor that is central to the psychedelic response to drugs such as LSD and psilocybin. One key advantage is bretisilocin has a shorter half-life than traditional psychedelics. The half-life could support the use of bretisilocin in the two-hour in-clinic framework that Johnson & Johnson established for its ketamine drug Spravato.At AbbVie, bretisilocin will slot into a well-established neuroscience unit. AbbVie has deals with Gedeon Richter, the source of the company’s antipsychotic blockbuster Vraylar, and is trying to generate a return from its $8.7 billion bet on Cerevel Therapeutics despite a phase 2 flop.For Gilgamesh, the deal provides Big Pharma support for bretisilocin and funding for other programs. The new entity, Gilgamesh Pharma, will house the biotech’s employees, other programs and existing pact with AbbVie. The other R&D programs include an oral NMDA receptor antagonist, an ibogaine analog and an M1/M4 agonist program.Citi analysts dubbed the deal an \"interesting play\" by AbbVie, citing bretisilocin\'s potential competitive clinical profile but also the risky nature of MDD drug development.Editor\'s note: This article was updated at 11:30 a.m. ET on Aug. 25 to include analyst insight.

Almost a month after rumours surfaced that AbbVie was weighing a $1-billion bid for Gilgamesh Pharmaceuticals, the company announced Monday it will acquire the neuroscience biotech's lead asset — the psychedelic depression candidate bretisilocin (GM-2505) — in a deal worth up to $1.2 billion.Bretisilocin is a serotonin 5-HT2A receptor agonist and 5-HT releaser currently in mid-stage development. Unlike psilocybin or LSD, which can keep patients in a psychoactive state for six to 10 hours, "bretisilocin has been shown to exert a shorter duration of psychoactive experience, while retaining an extended therapeutic benefit," the companies said in a joint release.Topline Phase IIa results suggest the drug may indeed deliver. In patients with moderate-to-severe major depressive disorder, a single 10-mg dose reduced Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline by 21.6 points after two weeks, compared with a 12.1-point reduction in patients given a low-dose active comparator. The antidepressant effect emerged within 24 hours and was durable after just two treatment sessions, Gilgamesh reported in May. Bretisilocin was also generally well tolerated, with no serious adverse events reported.Clinicians see the drug's shorter-acting profile as a potential advantage. "This compound acts in just a couple of hours, so that would position it to really compete well against other psychedelics that are further along but longer-acting," Brian Barnett, clinical director of the psychiatric treatment resistance program at Cleveland Clinic, recently said in an interview with FirstWord. He also suggested bretisilocin could prove to be "a nice alternative" to Johnson & Johnson's Spravato (esketamine), with more durable benefit.Monday's deal includes an upfront payment and development milestones. As part of the transaction, Gilgamesh will also spin out a new entity that will operate under the name Gilgamesh Pharma to hold its employees and remaining programmes, including its oral NMDA receptor antagonist blixeprodil (GM-1020), cardio-safe ibogaine analogue (GM-3009), M1/M4 agonist programme and non-hallucinogenic neuroplastogens, already the centre of an existing $2-billion tie-up with AbbVie (see – Spotlight On: Neuroplastogens hit the mainstream in 2024. What's next for trip-less psychedelics?).