A genetically targeted approach to depression treatment has shown promising results in a large Phase 2b study of BH-200, a vasopressin V1b receptor antagonist, according to clinical-stage company HMNC Brain Health.

The OLIVE trial, conducted across eight countries in Europe, enrolled 338 patients with Major Depressive Disorder (MDD) and tested the effects of BH-200 given twice daily over eight weeks. Results showed a statistically significant and clinically meaningful reduction in depression symptoms across the full study population, with even stronger and earlier responses seen in a genetically defined subgroup.

Patients in this subgroup, representing 27% of the total cohort, showed a greater reduction in HAM-D17 depression scale scores (difference vs placebo: –4.47, p = 0.005) compared to the full group average (–2.98, p = 0.0003). These patients were identified using HMNC’s proprietary genetic selection tool based on vasopressin-related biomarkers and hypothalamic-pituitary-adrenal (HPA) axis activity.

“The OLIVE trial results confirm earlier data, validating vasopressin modulation as a viable mechanism in depression,” said Dr Hans Eriksson, chief medical officer at HMNC. “Our genetic tool helped identify patients with an early and robust treatment response, marking an important step forward for precision psychiatry.”

The company describes BH-200 as a selective modulator of the stress-response system that targets the HPA axis upstream from traditional monoamine-based antidepressants. BH-200 had already shown efficacy in a previous US-based Phase 2 trial. Combined, the two studies now represent data from over 600 patients.

The new findings support the idea that vasopressin signaling plays a key role in a biologically distinct subgroup of MDD patients — and that this can be identified in advance through genetics.

“This is what precision psychiatry aims to deliver,” said Maximilian Doebler, chief business officer at HMNC. “We’ve shown that it’s possible to predict early and strong responders before treatment begins. That has the potential to fundamentally shift how depression is treated.”

The OLIVE trial also found that BH-200 was generally safe and well tolerated. No serious adverse events were reported in the active treatment arm. The most common side effect was headache, and liver enzyme elevations were transient and resolved without clinical consequence.

Regulatory discussions for Phase 3 development are expected to begin shortly, with the company aiming to bring what could be the first precision-guided antidepressant into real-world clinical use.