FDA Clears IND for Neurocrine and Nxera's Oral M1 Agonist NBI-1117567 in Alzheimer's Cognition
核心洞察
Neurocrine Biosciences has received FDA IND acceptance for a Phase 2 study of NBI-1117567 in Alzheimer's cognition, triggering a $10 million milestone payment to partner Nxera Pharma (搜索).
NBI-1117567 is an investigational oral muscarinic M1 receptor (搜索) preferring (M1/M4) selective agonist discovered using Nxera's proprietary NxWave drug discovery platform.
The compound is the third in the companies' muscarinic agonist portfolio to reach Phase 2, following direclidine (搜索) (NBI-1117568) in Phase 3 and NBI-1117570 in Phase 2.
Neurocrine Biosciences has received IND acceptance from the U.S. Food and Drug Administration for a Phase 2 study of NBI-1117567 ("NBI-'567") in Alzheimer's cognition, the company and its partner Nxera Pharma (搜索) announced. The clearance advances an orally administered, muscarinic M1 receptor (搜索) preferring (M1/M4) selective agonist into mid-stage testing in an indication both companies describe as an area of significant unmet medical need globally, including in Japan.
NBI-'567 was discovered using Nxera's proprietary NxWave drug discovery platform, a GPCR structure-based discovery engine. Neurocrine acquired the rights to develop and commercialize the compound from Nxera.
Milestone Payment and Portfolio Progress
The IND acceptance triggers a US$10 million milestone payment from Neurocrine to Nxera under the terms of their agreement. Nxera said the payment is expected to be recognized in full as revenue in the third quarter of its fiscal year 2026.
According to Christopher Cargill, President and CEO of Nxera Pharma (搜索), NBI-'567 is the third compound in the muscarinic agonist portfolio to receive approval to proceed to a Phase 2 study. "This follows direclidine (搜索) (NBI-1117568), the first NxWave-designed molecule to advance into a Phase 3 study, and NBI-1117570, which is currently in Phase 2," Cargill said.
Cargill added: "Alzheimer's cognition remains an area of significant unmet medical need globally, including in Japan, and we believe NBI-'567 has the potential to contribute meaningfully to improving outcomes for patients. We look forward to sharing further updates on progress across the muscarinic agonist portfolio."
Targeting M1 and M4 Receptor Subtypes
Muscarinic receptors are fundamental to activating signaling pathways in the brain. Five muscarinic acetylcholine receptors are involved in neurotransmission, and selectively targeting two of these subtypes — M1 and M4 — is an approach that has been clinically evaluated, with M1 positioned as a potential drug target for cognition and M4 for psychosis. NBI-'567 is described as an M1 preferring (M1/M4) selective agonist.
Collaboration Terms
Nxera Pharma (搜索) and Neurocrine Biosciences entered a collaboration and licensing agreement in November 2021 to develop novel muscarinic receptor agonists for the treatment of schizophrenia, dementia and other neuropsychiatric disorders. Under the agreement, Neurocrine gained development and commercialization rights to a broad portfolio of novel clinical and preclinical subtype-selective muscarinic M4, M1 and dual M1/M4 receptor agonists discovered by Nxera.
Neurocrine is responsible for development costs associated with the programs globally, except for M1 agonists being developed in Japan. Nxera retains rights to develop M1 agonists in Japan for any indication, with Neurocrine receiving co-development and profit share options. Nxera is eligible to receive R&D funding plus development, regulatory and commercial milestones of up to US$2.6 billion, with further product royalties, provided the criteria under the agreement are satisfied.
Nxera Pharma (搜索) operates at key locations in Tokyo and Osaka (Japan), London and Cambridge (UK), Basel (Switzerland) and Seoul (South Korea), and is listed on the Tokyo Stock Exchange (ticker: 4565).