NS-136 · program
NS-136 for Schizophrenia
NS-136, a selective muscarinic M4 receptor positive allosteric modulator, for schizophrenia — NeuShen Therapeutics' lead program and the indication the compound was designed for. The first-in-human Phase 1 (NS136HV101, NCT06345703: SAD/MAD/food-effect, 76 healthy adults, sites in Adelaide, Australia and Chengdu, China) started 2024-04-30 and, per the sponsor, completed in adult and elderly healthy volunteers with a favorable safety and pharmacokinetic profile. The Phase 2 (NS136SZ201, NCT07521683) is a randomized, double-blind, placebo-controlled, parallel-group study in acute schizophrenia run in China: ~150 patients randomized 1:1:1 to NS-136 80 mg QD, 120 mg QD, or placebo for 5 weeks, primary endpoint PANSS total score at week 5; first patient dosed 2025-11-19, led by Dr. Gang Wang (Beijing Anding Hospital). The sponsor states results are intended to support advancement to Phase 3 and evaluation in Alzheimer's-related psychosis/agitation; the FDA cleared a separate IND for a Phase 2 in agitation in Alzheimer's disease on 2026-01-02. Registry-estimated primary completion of the Phase 2 is November 2026. No regulatory designations have been disclosed for the schizophrenia program.
Development timeline
- UpcomingClinicalTrials.gov estimated primary completion of the Phase 2 study of NS-136 (80 mg and 120 mg QD vs placebo) in acute schizophrenia (primary endpoint: PANSS total score at week 5): November 2026 (estimated study completion December 2026).
- IND/CTA clearanceFDA clears IND for a Phase 2 study of NS-136 in agitation associated with Alzheimer's disease↗
- Phase 2 NS136SZ201 (NCT07521683) started per ClinicalTrials.gov (actual start date 2025-10-20); the sponsor announced the first patient dosed on 2025-11-19. Randomized, double-blind, placebo-controlled, multi-center study in acute schizophrenia in China (~150 patients; NS-136 80 mg QD, 120 mg QD, or placebo for 5 weeks; primary endpoint PANSS at week 5), led by Dr. Gang Wang, Beijing Anding Hospital. The same announcement stated Phase 1 had completed in China and Australia with a favorable safety and PK profile.
- First-in-human Phase 1 NS136HV101 (NCT06345703) started per ClinicalTrials.gov (actual start date): randomized, double-blind, placebo-controlled SAD/MAD plus open-label food-effect study in 76 healthy subjects, sites at CMAX Clinical Research (Adelaide, Australia) and Chengdu Xinhua Hospital (China). NeuShen announced first healthy volunteer dosed in Australia in a release carried on PR Newswire 2024-05-08; an IND had previously been submitted to China's NMPA.
- Trial startedFirst-in-human Phase 1 of NS-136 starts in healthy volunteers (Australia and China)
Readouts
- November 2026AnticipatedRegistry resultsNCT07521683
ClinicalTrials.gov estimated primary completion of the Phase 2 study of NS-136 (80 mg and 120 mg QD vs placebo) in acute schizophrenia (primary endpoint: PANSS total score at week 5): November 2026 (estimated study completion December 2026).
Clinical trials in Schizophrenia
NCT07521683NS136SZ201Phase 2Recruitingn=150
A Phase II Clinical Study to Evaluate the Efficacy and Safety of NS-136 in the Treatment of Schizophrenia
NCT06345703NS136HV101Phase 1Completedn=76
First-into-human Study of NS-136 in Healthy Subjects
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| NS-136 oral tablet (80 mg / 120 mg once daily) 80 mg or 120 mg PO once daily in the Phase 2 schizophrenia study NS136SZ201 (NCT07521683). The Phase 1 first-in-human study (NCT06345703) used an 'NS-136 tablet' in single-ascending-dose, multiple-ascending-dose and food-effect parts; the dose range was not disclosed in the registry record. | Oral | Once daily | — |
Mechanism of action
Selective positive allosteric modulator (PAM) of the muscarinic acetylcholine M4 receptor (CHRM4), a Gi/o-coupled class-A GPCR. Potentiating M4 signalling is thought to normalize striatal dopaminergic hyperactivity indirectly, treating positive symptoms of schizophrenia without direct dopamine D2 receptor blockade and its extrapyramidal side effects; the sponsor reports preclinical efficacy against both positive and negative symptoms and cites potential for cognitive benefit. The same mechanism class underlies emraclidine and NBI-1117568; NS-136 is positioned by NeuShen as a potential best-in-class follow-on. No binding or functional potency values, selectivity ratios, or structural information have been published.
| Target | Action | Affinity |
|---|---|---|
| M4primaryCHRM4 | PAM | —ⓘ |
← Full NS-136 compound page (identity, identifiers, all indications)
Sources
- NCT06345703 (NS136HV101) — First-into-human Study of NS-136 in Healthy Subjects — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT07521683 (NS136SZ201) — A Phase II Clinical Study to Evaluate the Efficacy and Safety of NS-136 in the Treatment of Schizophrenia — ClinicalTrials.gov (U.S. National Library of Medicine)
- NeuShen Therapeutics Announces Completion of Series A+ Round Financing (2026-01-28) — NeuShen Therapeutics
- NeuShen Therapeutics Announces FDA Clearance of IND Application for a Phase 2 Clinical Trial of NS-136 in Agitation in Alzheimer's Disease (2026-01-02) — NeuShen Therapeutics
- NeuShen Therapeutics Announces First Patient Dosed in Phase 2 Clinical Trial of NS-136 for Schizophrenia (2025-11-19) — NeuShen Therapeutics
- NeuShen Therapeutics Initiates First-in-Human Trial of NS-136, a Novel Selective M4 Receptor Positive Allosteric Modulator for the Treatment of Schizophrenia (2024-04-30) — NeuShen Therapeutics