Dragged by PhIII flop and shelved by AbbVie, a class of depression drugs finds new life at startup

23 Aug 2022
endpts.com
Acquisition
A month before Allergan revealed that it would be bought out by AbbVie for $63 billion, CEO Brent Saunders took a painful hit on one of his own acquisitions: In the wake of successive Phase III flops for the key depression drug from its $560 million deal to buy Naurex, Allergan marked a $2.5 billion writedown.
So when AbbVie swallowed Allergan, it left rapastinel — and the next-generation NMDAR modulators that came after it — sitting on the shelves.
Allergan chief Saunders takes a painful $2.5B hit on an ugly PhIII flop
By that time in 2020, the founders and crew at Naurex, including Joseph Moskal at Northwestern University, had already banded back together on a new venture named Gate Neurosciences and licensed preclinical programs from Eli Lilly to test out new ideas in precision neurology. They jumped on the opportunity to go after the legacy Naurex assets.
“Our conclusions from analyzing the data was that the molecule worked when it was dosed appropriately, in appropriately designed studies,” CEO Mike McCully told Endpoints News.
He added that Gate has been sharing with a broader group of scientists about the “tremendous amount of unpublished results that were within Allergan,” which is why after three years of quietly building, the biotech is now emerging from stealth.
There isn’t much he can share about the financing plans — except that AbbVie and Lilly are both shareholders — or clinical plans, except that a biomarker study is plotted for the fall and that his team has some ideas about how to identify patients most likely to benefit from Gate’s drugs.
But McCully is happy to talk about zelquistinel and apimostinel, the third- and second-generation NMDAR modulators licensed from AbbVie.
While targeting the same pathway of synaptic plasticity as NMDA receptor antagonistsNMDA receptor antagonists that have been approved to treat depression, such as J&J’s Spravato and Axsome’s Auvelity, the “-stinel” class of drugs goes downstream, he noted.
“So what you have when you have an NMDA receptor antagonistNMDA receptor antagonist is you are targeting GABA interneurons. That creates a dump of all of serotonin, dopamine, glutamate, all of that crashes in your brain,” he said. “That’s why you have this level of high doses of dissociation, hallucinations, all the psychedelic experience that happens with those drugs, and you have to make sure that you stay below that. […] So we have a unique way to target downstream on that which goes directly into the post-synaptic neurons and that is able to directly generate enhanced synaptic plasticity.”
A “pandemic baby” in McCully’s words, Gate has been staying lean and focused, with 10-plus employees alongside a network of advisors and part-time staffers. McCully said the next financing should fund the two lead programs to Phase II studies, before turning more attention to the other, earlier-stage drugs in the pipeline.
But the big idea, he noted, is that even as Big Pharma walked away from neuroscience research, a lot of academics and biotechs are still pushing it.
“Certainly Naurex was really a very early leader and ahead of its time in some of the work that was being done there,” McCully said.
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