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AbbVie is considering a $1-billion acquisition of Gilgamesh Pharmaceuticals, Bloomberg News reported on Wednesday, citing people familiar with the matter. The sources cautioned that talks are still ongoing, and it's possible that a deal may not be reached. If the purchase goes through, it will be AbbVie's second takeout of a central nervous system-focused company in less than a year. In October, the drugmaker paid $1.4 billion in cash to buy up Aliada Therapeutics and its Alzheimer's disease asset.AbbVie and Gilgamesh have an existing deal to develop a class of drugs, called neuroplastogens, capable of treating psychiatric disorders without psychoactive side effects. The pharma shelled out $65 million upfront when it inked the deal in May 2024, and it's on the hook for an additional $1.95 billion in option fees and milestones, plus tiered royalties. Since their agreement, however, Gilgamesh has revealed results from a Phase IIa study of lead candidate GM-2505, a short-acting 5-HT2A receptor agonist, in patients with major depressive disorder (MDD). While perhaps more comparable to Johnson & Johnson's Spravato (esketamine) than a neuroplastogen, the experimental drug led to an 18.5-point drop in Montgomery-Åsberg Depression Rating Scale (MADRS) scores within 24 hours of the first dose, and a 94% remission rate about a month after just two treatment sessions.A key opinion leader who spoke with FirstWord after the readout said the data suggest GM-2505 could be more efficacious than Spravato in treating MDD, and its two-hour monitoring requirement fits nicely with existing hospital infrastructure (see – KOL Views Q&A: Gilgamesh's next-gen psychedelic could challenge Spravato in MDD).In addition to GM-2505, Gilgamesh's pipeline includes GM-1020, an NMDAR antagonist in Phase II testing for MDD, as well as multiple undisclosed neuroplastogens in preclinical development for depression and anxiety. Gilgamesh is one of a handful of companies working on neuroplastogens — non-hallucinogenic compounds that mimic the therapeutic potential of psychedelics. For more on the space, see Spotlight On: Neuroplastogens hit the mainstream in 2024. What's next for trip-less psychedelics?

Gilgamesh Pharmaceuticals reported top-line results from its Phase IIa study of GM-2505, an experimental 5-HT2A receptor agonist and 5-HT releaser being developed for major depressive disorder (MDD). The drug achieved a 94% remission rate about a month after just two treatment sessions, the company said.The randomised study evaluated 40 patients with moderate-to-severe MDD who received either 10 mg of GM-2505 or a low-dose psychoactive comparator via intravenous infusion on the first day, followed by a 15-mg dose of GM-2505 for everyone on day 15.10-point advantageResults showed a significant and "clinically impactful" reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Within 24 hours of the first dose, patients on GM-2505 saw an 18.5-point drop in their depression scores.After two weeks, the 10-mg group had a 21.6-point reduction on MADRS, nearly 10 points better than those who had started on the low-dose psychoactive comparator. By day 29, following the second dose, the high-dose group had a 28-point reduction from baseline, with benefits lasting up to day 74 without additional treatment.The medication was well-tolerated with no serious adverse events reported, and most side effects resolved within two hours of administration.Later-stage trials"GM-2505's rapid and sustained antidepressant effect fits seamlessly into the existing two-hour, in-clinic treatment model," said CEO Jonathan Sporn. The company plans to advance GM-2505 into later-stage trials, alongside its other lead programme, an oral NMDA receptor antagonist called GM-1020 that is completing a Phase IIa study in MDD this year.The trial results come on the heels of Gilgamesh's $2-billion partnership with AbbVie last May, aimed at neuroplastogens that mimic the therapeutic potential of psychedelics without hallucinations or the need for in-office administration and supportive care. However, GM-2505 is not part of that collaboration (see – Spotlight On: Neuroplastogens hit the mainstream in 2024. What's next for trip-less psychedelics?).The field of neuropsychiatry saw a surge of investment and deal-making over the last year or two (see – Spotlight On: Neuropsychiatry startups take centre stage). Arguably one of largest deals in the space, Bristol Myers Squibb is banking that Cobenfy (xanomeline/trospium chloride), a key asset acquired through its $14-billion takeover of Karuna Therapeutics — and since approved for schizophrenia — can drive an entire pipeline of products. Meanwhile, AbbVie's $8.7-billion buyout of Cerevel Therapeutics hit turbulence after a key asset stumbled in two trials — though the company is still looking for a silver lining.