nelivaptan (BH-200) / HMNC Brain Health - LARVOL DELTA

Polygenic stratification reveals differential response to V1b antagonism in pre-exposed patients with major depressive disorder: a post-hoc analysis of the phase 2 OLIVE trial (CINP 2026) - "In one polygenically stratified subgroup of pre-exposed MDD patients, BH-200 demonstrated a clinically meaningful separation versus placebo at multiple time points. This stratification category also showed greater improvement in the overall MDD population earlier. These findings suggest that the combination of polygenic stratification and BH-200 treatment may benefit patients with treatment resistance."

Clinical • P2 data • Retrospective data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Vasopressin 1A and 1B receptor-mediated antinociception in a mouse model of cortical spreading depolarization. (PubMed, Pain) - "We examined the effect of selective vasopressin 1A receptor antagonist relcovaptan and vasopressin 1B receptor antagonist nelivaptan on SD-induced migraine-relevant behavior...However, there was no effect of either drug on opto-SD-induced grimace, photosensitivity, or locomotion. These data are consistent with an analgesic effect of endogenous vasopressinergic receptor activation in a mouse model of migraine."

Journal • Preclinical • CNS Disorders • Migraine • Mood Disorders • Pain • Psychiatry • THY1

Truncated depression rating scale outcomes in the OLIVE trial exploring a v1b antagonist and a genetic selection tool (APA 2026) - "Cohen's standardized effect sizes for change from baseline at week 8 were 0.46 for HAM-D6 and 0.44 for HAM-D17, and 0.41 for MADRS-6 and 0.42 for the original 10-item MADRS. The correlation between full and truncated scales was 0.75 (HAM-D) and 0.86 (MADRS). Conclusion : BH-200 demonstrated a high standardized effect size after 8 weeks of treatment compared to placebo, in comparison to other recent antidepressant trials (Hieronymus F, 2020)."

CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Antidepressant efficacy of BH-200 in patients classified by a genetic selection tool: Secondary endpoint results from the OLIVE trial (APA 2026) - "BH-200 showed improvement of depressive symptoms in MDD patients across several rating scales. These findings were consistently more pronounced in subgroup A . The reported ability to use a genetic tool to identify a subgroup of patients with MDD who respond favorably, marks an important milestone in precision psychiatry."

Clinical • CNS Disorders • Depression • Mood Disorders

Acute V1b vasopressin receptor antagonism ameliorates cardiovascular parameters in ovariectomized female rats subjected to chronic mild unpredictable stress. (PubMed, J Neuroendocrinol) - "Left ventricular (LV) function and aortic pulse wave velocity (aPWV) were assessed 1 h after either vehicle or nelivaptan, 10 mg/kg i.p. mean arterial pressure and heart rate were similar in gonadally intact control and CMS female rats but were significantly elevated from baseline values in CMS OVX and male rats...These findings support the concept that OVX females display cardiovascular responses similar to male rats when subjected to CMS. Systemic V1b R antagonism ameliorates aortic compliance in both male and OVX rats."

Journal • Preclinical • Cardiovascular • CNS Disorders • Depression • Psychiatry

Toward precision psychiatry: theoretical implications of bimodal response patterns to vasopressin V1b receptor inhibition in depression. (PubMed, Front Psychiatry) - P2 | "These findings support the hypothesis that nelivaptan effectively reduces depressive symptoms specifically in a subset of MDD patients, potentially identifiable by underlying HPA axis dysfunction. The confirmation of this hypothesis requires further studies integrating measures of HPA axis activity alongside response to nelivaptan treatment, facilitating precision psychiatry approaches for depression."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

HMNC Brain Health Completes Patient Randomization for Phase 2b OLIVE Trial for Major Depressive Disorder (GlobeNewswire) - "HMNC Brain Health...announced today the successful completion of patient randomization for its Phase 2b OLIVE trial. The trial is investigating the efficacy and safety of BH-200, a potent vasopressin V1b receptor antagonist, alongside a predictive companion diagnostic in patients with Major Depressive Disorder (MDD)....Initial results from the OLIVE trial are expected in Q2 2025."

P2b data • Trial status • Major Depressive Disorder