HMNC Brain Health and Spruce Biosciences have achieved a significant milestone in precision psychiatry with the first patient dosing in their Phase 2 TAMARIND trial, evaluating tildacerfont as a targeted treatment for major depressive disorder (MDD). The collaboration represents a novel approach to depression treatment, moving away from traditional trial-and-error methods toward biologically-driven patient selection.
Precision Approach to Depression Treatment
The TAMARIND trial (Tildacerfont as Antidepressant Medication and Relief in Depression) targets a biologically distinct subtype of MDD patients tied to hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Tildacerfont, a corticotropin-releasing factor type 1 (CRF1) receptor antagonist, has the potential to address hyperactive brain corticotropin-releasing factor (CRF) neurotransmission and aberrant functioning of the HPA axis in patients with MDD by blocking the CRF1 receptor.
"The initiation of the TAMARIND trial marks an exciting step forward and key milestone in our mission to redefine depression treatment by targeting its biological roots," said Hans Eriksson, M.D., Ph.D., MBA, Chief Medical Officer of HMNC.
Novel Patient Selection Technology
HMNC's proprietary investigational-stage patient selection tool utilizes genetic markers to identify MDD patients who are more likely to respond to CRF1 receptor antagonism. This approach aims to dramatically change the treatment paradigm in depression, going from a trial-and-error approach to selection of a specific intervention based on the individual patient's biology, thereby improving treatment efficacy and reducing both costs and time.
Professor Florian Holsboer, co-founder of HMNC and Head of the Scientific Advisory Board, noted: "Decades of research has revealed that excessive release of CRF in the brain is related to the stress response and may cause depression in a substantial portion of patients. This program exemplifies our approach of pairing precision patient selection with novel therapeutics to deliver more personalized solutions to patients."
Significant Market Potential
According to Javier Szwarcberg, M.D., M.P.H., Chief Executive Officer of Spruce, "Tildacerfont may modulate certain hormonal responses to stress, which has the potential to address up to 50% of the MDD patients worldwide using patient selection tool." The companies believe this precision approach could transform treatment for an area of significant unmet medical need.
Trial Design and Timeline
TAMARIND is a randomized, double-blind, placebo-controlled, Phase 2 proof-of-concept clinical trial evaluating the safety, efficacy, and tolerability of tildacerfont in 88 adults with MDD. Patients are selected utilizing HMNC's proprietary investigational-stage patient selection tool over an eight-week treatment period followed by a four-week follow-up period.
The primary endpoint is the change in depression total scores from baseline using the Hamilton Depression Rating Scale. The key secondary endpoint is the change in functional impairment as measured using the Sheehan Disability Scale. Other measures assess response, remission, and overall quality of life. The study is being conducted across eight sites in the United Kingdom.
Drug Profile and Safety
Tildacerfont is a potent and highly selective, non-steroidal, oral antagonist of the corticotropin-releasing factor type 1 (CRF1) receptor, which is the receptor for corticotropin-releasing factor (CRF), a hormone secreted by the hypothalamus. The CRF1 receptor is abundantly expressed in the brain and pituitary gland, where it serves as a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis.
Notably, no drug-related serious adverse events have been reported related to tildacerfont treatment in completed studies, supporting its continued development in this patient population.
Topline results from TAMARIND are anticipated in the first half of 2026, marking a critical milestone for both companies' precision psychiatry initiatives.
