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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?).

Reunion Neuroscience reported Monday that its psilocybin-like psychedelic candidate, RE104, significantly improved the symptoms of women with moderate-to-severe postpartum depression (PPD) in a mid-stage study — with some even seeing benefits after just one day. "We are encouraged by the results from our RECONNECT Phase II trial, which provide strong clinical validation for RE104 as a well-tolerated and effective treatment for PPD offering rapid relief with minimal interruption to daily activities," said Mark Pollack, Reunion's chief medical officer. Buoyed by the positive results, the company expects to launch a Phase III trial of RE104 in PPD next year; it's also planning to study the prodrug of 4-OH-DiPT in two separate indications. Rapid, safe responseThe RECONNECT study — funded by a $103-million series A raised last year — enrolled 84 women between the ages of 21 and 45 to receive either a single, 30-mg subcutaneous dose of RE104, or a 1.5-mg dose of the psychedelic as an active control. Reunion reported that some patients experienced clinically meaningful reductions in MADRS score on the first day after dosing, and maintained that response through the day 28 follow-up appointment. On day seven post-treatment, patients who received the 30-mg dose achieved a statistically significant 23-point reduction from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, versus a reduction of 17.2 points for the comparator group, meeting the trial's primary endpoint. At the one-week mark, 77.1% of patients who received the high RE104 dose had at least a 50% MADRS score improvement from baseline, with 71.4% meeting the criteria for being in remission. In comparison, only 61.6% and 41% of those in the control arm met the respective benchmarks. RE104 was generally well-tolerated, with the most common treatment-emergent adverse events (TEAEs) experienced by patients being nausea (43.9%) and headache (34.1%), which occurred primarily on the day of treatment.There were no reported serious TEAEs, such as suicidal ideation or behaviour. Four hours after treatment, 92.7% of patients were discharge-ready, differentiating RE104 from other psychedelic treatments such as psilocybin or LSD, which are associated with longer psychoactive experiences.Reunion also shared the preliminary results from a lactation study designed to evaluate whether it would be safe for women taking RE104 to breastfeed. The study found that the metabolites present in breastmilk was about 0.1% of the total 30-mg dose, which is an order of magnitude below the threshold deemed potentially harmful to an infant. Clinical plans Next up, Reunion will launch a pivotal Phase III trial of RE104 in PPD next year.But before that kicks off, it will start the Phase II REKINDLE study of RE104 in patients with adjustment disorder related to cancer and other medical illnesses in the third quarter of 2025.The company is also planning a Phase II trial of RE104 in an undisclosed significant mental health indication, which it hopes to begin in the first quarter of 2026.