The NTX-253 Phase 1 programme is finished: Neurosterix, the schizophrenia-focused company spun out of Addex Therapeutics, announced on 8 October 2026 that it has completed Phase 1 studies of NTX-253 and plans to move the drug into Phase 2 in patients. NTX-253 is an oral, selective positive allosteric modulator (PAM) of the muscarinic M4 receptor, a target the company describes as validated for schizophrenia.
The announcement is a milestone rather than a data release. The company says the studies provided important safety and pharmacokinetic information, but it has not published numbers. This article sets out what was tested, what is still undisclosed, and why an M4 modulator is a target worth watching.
NTX-253 Phase 1 at a glance
- Drug: NTX-253, an oral M4 positive allosteric modulator.
- Indication: schizophrenia.
- Status: Phase 1 completed; Phase 2 in schizophrenia planned.
- Announced: 8 October 2026, via Addex, which holds a 20% equity interest in Neurosterix.
- Results published: none yet. No safety, pharmacokinetic or dose figures were given.
What the study tested
According to the earlier description of the trial, the Phase 1 programme had two main parts and enrolled both healthy adults and adults with stable schizophrenia:
- Single ascending dose (SAD): healthy volunteers received one oral dose of NTX-253 or placebo in escalating cohorts. This part included a food-effect cohort and a separate cohort measuring drug levels in cerebrospinal fluid (CSF), which shows how much of the drug reaches the brain’s surrounding fluid.
- Multiple ascending dose (MAD): participants took NTX-253 or placebo once daily for 10 consecutive days at escalating doses, including two cohorts of adults with stable schizophrenia whose antipsychotics were withdrawn for up to eight days before dosing.
The primary goals were safety, tolerability and pharmacokinetics (how the drug is absorbed and cleared), including steady-state levels in the multiple-dose part. Combining healthy volunteers and patients in one study is designed to save time, which the company’s chief executive, Tim Dyer, has said could accelerate development timelines.
What has not been disclosed
- Safety and tolerability findings, including any adverse events.
- Pharmacokinetic values and CSF exposure data.
- Evidence of target engagement at the M4 receptor.
- Participant numbers and dose levels.
- The design, size and start date of Phase 2.
Until those details appear in a full disclosure, conference presentation or registry entry, the only fair reading is that the study met the bar for the company to proceed. That is a meaningful step, but Phase 1 studies are not designed to show whether a drug works.
How to read a Phase 1 completion announcement
Early-stage announcements are written to be positive, and the words “completed” and “advancing” say little about the underlying data. A Phase 1 study can be completed with a perfectly clean safety record, or with a dose-limiting problem that simply led the company to choose a lower dose. The announcement does not distinguish between these. What would be informative is the margin between the dose expected to be useful in Phase 2 and the highest dose tested, the pattern of side effects such as nausea, dizziness or heart-rate changes, and how much drug reached the cerebrospinal fluid.
Another point worth noting is that antipsychotics were withdrawn in the patient cohorts for up to eight days. That is a short window, appropriate for a safety study, but it means Phase 1 cannot say how NTX-253 behaves alongside a patient’s usual medicine or over weeks of treatment. Those questions belong to Phase 2.
Why target the M4 receptor?
Schizophrenia treatment has long relied on drugs that block dopamine receptors. They can control psychosis but often bring movement disorders, weight gain and other metabolic problems. Muscarinic receptors, which respond to the neurotransmitter acetylcholine, offer a different route: the M4 subtype influences dopamine signalling indirectly. The company says NTX-253 may reduce psychosis while avoiding the movement and metabolic effects linked to traditional dopamine blockers, and that preclinical studies showed robust antipsychotic-like activity and a favourable safety profile.
A positive allosteric modulator does not switch the receptor on directly. It makes the receptor more responsive to the body’s own acetylcholine, which in theory allows finer control and better selectivity than a drug that activates every muscarinic receptor. In our assessment, that selectivity is the central scientific bet: it needs to be shown in people, not only in animals.
Where this fits in the schizophrenia pipeline
Interest in muscarinic drugs grew after the first muscarinic-targeting antipsychotic, Cobenfy, was approved in the United States in 2024. That approval showed regulators will accept a non-dopamine mechanism, and it raised the commercial stakes for companies with more selective approaches. NTX-253 is one of several such efforts. For comparison, see how a different neurology programme progressed in our report on Cerevance’s Phase 3 results for solengepras in Parkinson’s disease.
Who is behind Neurosterix
Addex spun Neurosterix out in April 2024 with a $65 million Series A financing led by funds affiliated with Perceptive Advisors. Addex kept a 20% equity interest. The company focuses on central nervous system disorders, and NTX-253 is its lead schizophrenia programme.
What to watch next
- Presentation of Phase 1 safety and pharmacokinetic data.
- Confirmation of the Phase 2 design, size and timeline.
- Evidence that NTX-253 reaches the brain at doses that engage M4.
- Any financing needed to run Phase 2.
Frequently asked questions
What is NTX-253?
An investigational oral M4 muscarinic positive allosteric modulator being developed for schizophrenia.
Has NTX-253 been shown to work?
No. Phase 1 assesses safety and pharmacokinetics. Efficacy has not been reported.
What happens next?
Neurosterix plans to advance NTX-253 into Phase 2 in schizophrenia. Timing and design have not been disclosed.
What is the link with Addex?
Addex spun out Neurosterix in 2024 and retains a 20% equity interest.
Why is the M4 receptor interesting?
It modulates dopamine signalling indirectly, which may allow antipsychotic effects with fewer movement and metabolic side effects than dopamine blockers, according to the company.
How we reported this: we relied on the company’s announcement of 8 October 2026 and its earlier description of the trial design. Statements about the drug’s promise are company claims. Last updated: 9 October 2026. This article is news reporting and not medical advice.
