Neurosterix raises $105M Series B to take M4 modulator NTX-253 into Phase 2 for schizophrenia
The oral M4 modulator NTX-253 moves to Phase 2 in schizophrenia, a class where AbbVie's emraclidine failed in 2024. Andrew Miller, who built Karuna, is Executive Chair.
Neurosterix, a clinical-stage company, has closed a $105 million Series B round led by RTW Investments, according to techtimes.com techtimes.com
techtimes.comtechtimes.comOpen source ↗. The funds will move NTX-253, an oral, selective M4 muscarinic positive allosteric modulator, into Phase 2 trials in schizophrenia. Andrew Miller, who built Karuna Therapeutics, is Executive Chair of Neurosterix. Phase 1 was completed in October 2026. The company has not disclosed efficacy data, since Phase 1 trials in this indication mainly assess safety and pharmacokinetics.
How NTX-253 differs from Cobenfy
The FDA approved Cobenfy (xanomeline-trospium) in September 2024, the first schizophrenia treatment with a new mechanism of action since the early 1990s. Xanomeline is a dual M1/M4 agonist that activates the receptors directly. Trospium is added to prevent gastrointestinal side effects of peripheral muscarinic activation. Bristol Myers Squibb acquired Karuna for about $14 billion in late 2023.
NTX-253 is not an agonist. It binds a different site on the M4 receptor and amplifies the response when the body's own acetylcholine is already activating it. It is selective for M4 over the M1, M2, M3 and M5 subtypes and is orally bioavailable. Neurosterix argues that this selectivity reduces off-target muscarinic activation.
Emraclidine and the cooperativity question
Emraclidine, an M4-selective positive allosteric modulator from Cerevel Therapeutics (acquired by AbbVie), did not beat placebo in its EMPOWER Phase 2 trials in November 2024 techtimes.com
techtimes.comtechtimes.comOpen source ↗. Neurosterix attributes this to insufficient cooperativity, meaning how strongly the modulator amplifies the receptor's response to acetylcholine, rather than to the concept itself. According to the company, NTX-253 was designed with a higher cooperativity than emraclidine.
Two other M4 programs provide context. Bristol Myers Squibb reported about $105 million in Cobenfy revenue over the first three quarters of 2025, with quarterly sales of $27 million, $35 million and $43 million. The ARISE Phase 3 trial of Cobenfy as an add-on to existing antipsychotics missed its primary endpoint in April 2025. Neurocrine Biosciences' NBI-1117568, a selective M4 agonist that binds the orthosteric pocket, showed a statistically significant PANSS improvement versus placebo in Phase 2. Phase 3 trials of it are now enrolling.
