Obuprazine met the Phase 2b primary endpoint in schizophrenia, with all three doses improving PANSS scores versus placebo and the lowest dose showing the largest benefit.
Written By: Neha Vishwakarma, PharmD
Reviewed By: Pharmacally Editorial Team
Tortugas Neuroscience has reported positive Phase 2b results for obuprazine (TRTL-107), an investigational treatment for schizophrenia developed by its partner, Hansoh Pharma. Announced on October 12, 2026, the findings were presented at the 2026 European College of Neuropsychopharmacology (ECNP) Congress. All three obuprazine dose groups significantly improved Positive and Negative Syndrome Scale (PANSS) total scores versus placebo at Day 42, although the lowest dose produced the largest placebo-adjusted improvement.
Obuprazine’s Pharmacological Profile
Obuprazine is a dopamine D2/D3 receptor partial agonist, a serotonin 5-HT2A receptor antagonist and a 5-HT1A receptor partial agonist. This combination may support symptom control across multiple domains, although its proposed tolerability advantages require confirmation in larger studies.
Tortugas holds global commercial development rights outside Greater China, where Hansoh retains rights. Obuprazine is the most advanced candidate in Tortugas’ four-asset licensing agreement with Hansoh.
Phase 2b Trial Design
The randomized, double-blind, placebo- and active-reference-controlled trial enrolled 363 Chinese adults with acute schizophrenia across 24 clinical centers. Participants had required hospitalization within the two months before screening.
Patients were assigned to one of five groups: obuprazine 1.5–3.0 mg, 4.5–6.0 mg or 6.0–9.0 mg; aripiprazole as an active reference; or placebo. The primary endpoint was change from baseline in PANSS total score at Day 42.
All Three Doses Meet the Primary Endpoint
All three obuprazine dose groups achieved statistically significant improvements versus placebo, with reported p-values below 0.0001.
The placebo-adjusted PANSS total score differences were:
- 1.5–3.0 mg: −16.7 points (95% CI, −22.5 to −10.9)
- 4.5–6.0 mg: −13.2 points (95% CI, −18.9 to −7.4)
- 6.0–9.0 mg: −14.7 points (95% CI, −20.5 to −8.8)
In the lowest-dose group, the least-squares mean PANSS change from baseline was −28.6 points, compared with −11.9 points for placebo.
The lowest dose therefore produced the largest observed placebo-adjusted improvement. The results do not demonstrate a straightforward dose-response relationship, and the available topline data do not explain why the higher doses did not produce greater improvements.
Aripiprazole showed a placebo-adjusted PANSS difference of −12.1 points (95% CI, −19.1 to −5.1). Although the obuprazine groups had numerically larger improvements, the reported results do not establish statistical superiority over aripiprazole.
Improvements Across Symptom Domains
At Day 42, all three obuprazine dose groups reportedly improved significantly versus placebo on the PANSS positive and negative symptom subscales and the Marder cognitive factor.
At 1.5–3.0 mg, placebo-adjusted improvements were 5.3 points on the positive symptom subscale and 4.4 points on the negative symptom subscale, with both comparisons reporting p-values below 0.0001.
The company also reported higher responder rates in the 1.5–3.0 mg and 4.5–6.0 mg groups than in the placebo and aripiprazole groups as early as Day 14. Response was defined as a reduction of at least 50% in PANSS total score. However, the announcement did not provide the corresponding responder percentages, limiting independent assessment of the early-response signal.
Safety and Tolerability
Obuprazine was generally well tolerated in the six-week study. Discontinuation due to adverse events was approximately 2.1% with obuprazine and 2.5% with placebo. Hansoh reported that most treatment-emergent adverse events were mild to moderate and that no new significant safety concerns were identified.
However, detailed adverse-event rates were not disclosed. Further data on weight changes, akathisia, extrapyramidal symptoms, sedation and prolactin changes will be important for assessing the drug’s tolerability relative to established antipsychotics.
Development Plans and Clinical Implications
Tortugas plans to submit a US Investigational New Drug application for TRTL-107, while detailed Phase 2b findings are expected to be submitted for peer-reviewed publication. Hansoh has indicated that the results support further development toward Phase 3.
The findings provide an encouraging efficacy signal across all three tested dose groups, including improvements in positive and negative symptoms. However, the apparent advantage of the lowest dose requires further investigation, and numerical differences from aripiprazole should not be interpreted as proof of superiority.
The study’s six-week duration, exclusively Chinese population and limited publicly available safety and responder data constrain interpretation. Larger, longer-duration trials will be needed to establish the optimal dose, durability of benefit and longer-term safety. Obuprazine remains investigational and is not approved for schizophrenia.
Reference
Tortugas Neuroscience Announces Positive Phase 2b Results for Obuprazine (TRTL-107) in Schizophrenia Demonstrating Broad Symptom Improvement and Rapid Onset, Tortugas Neuroscience, 12 October 2026
Efficacy and Safety of Obuprazine (HS-10380) in Patients with Schizophrenia: A Phase 2b Randomized Placebo-and Active-Controlled Trial, PS01-1227_Li_A0 – o,.pdf
About the Writer
Neha Vishwakarma (LinkedIn) is a Pharm.D professional with experience in clinical pharmacy, pharmacovigilance, and clinical research. She has hands-on experience in ADR assessment, ICSR processing, medication safety, and clinical data evaluation. Her research background in surgical site infections and antibiotic use supports her focus on evidence-based healthcare writing.