Neurocrine Biosciences (NBIX) Study Result summary

Study design and objectives

• Phase II/2, multicenter, randomized, double-blind, placebo-controlled, multi-arm, dose-finding study of NBI-1117568 (NBI-568), a selective M4 agonist, in adults with schizophrenia at US inpatient sites.

• The study enrolled adults with marked to severe schizophrenia, using a 1:2 placebo to active randomization, with dosing arms of 20, 40, 60 mg QD, and 30 mg BID.

• Interim analyses by an independent committee guided dose escalation and addition of new arms, maintaining study blinding.

• Baseline PANSS scores averaged 96 across groups; demographic characteristics were balanced.

• The primary endpoint was change in PANSS total score from baseline at week six.

Efficacy results

• The 20 mg once-daily dose showed a statistically significant and clinically meaningful PANSS total score improvement of 18.2 points, placebo-adjusted difference of 7.5 points (p=0.011), effect size 0.61 at week 6.

• Statistically significant improvements were observed in Clinical Global Impression-Severity (CGI-S) and Marder factor subscales for both positive and negative symptoms.

• Improvements were observed as early as week one or three and sustained through week six.

• Other dose arms showed trends toward improvement but did not reach statistical significance.

• The efficacy profile is competitive with leading antipsychotics and muscarinic agents in development.

Safety and tolerability

• NBI-1117568 (NBI-568) was generally well tolerated across all doses, with discontinuation rates due to adverse events similar to placebo (5.0% vs. 4.3%).

• Most common adverse events were somnolence (10.7%), dizziness (9.3%), headache (8.6%), nausea (5.7%), and constipation (5.0%), generally mild or moderate; headache incidence was higher in placebo.

• No new safety signals or significant cardiovascular effects were identified; GI side effects and weight gain were minimal and comparable to placebo.

• No significant weight gain or increase in extrapyramidal symptoms compared to placebo.