Denovo Biopharma Partners with Orygen for Phase 2 Trial of Novel Glutamate-Targeting Drug in Early Psychosis
Key Insights
Denovo Biopharma (search) has partnered with Orygen (search) to initiate a Phase 2 investigator-initiated trial studying DB103 (pomaglumetad methionil) for first-episode psychosis (search) and clinical high risk of psychosis (search) in young patients aged 18-25 years.
The open-label feasibility trial will evaluate safety, tolerability, and efficacy of 40 mg twice-daily dosing over 12 weeks in patients with insufficient response to first-line antipsychotics.
Pomaglumetad methionil is a first-in-class psychiatric drug that selectively targets the glutamate mGlu2/3 receptor (search), potentially avoiding common side effects of current antipsychotics such as weight gain and prolactin elevation.
Denovo Biopharma (search) LLC has announced a strategic partnership with Orygen (search) to launch a Phase 2 investigator-initiated trial evaluating DB103 (pomaglumetad methionil) for treating first-episode psychosis (search) (FEP) and clinical high risk (CHR) of psychosis. The study, led by Professor Patrick McGorry, M.D., and sponsored by Orygen in Parkville, Australia, represents a novel approach to addressing unmet medical needs in young patients with psychotic disorders.
Addressing Treatment Gaps in Early Psychosis
"Despite the introduction of antipsychotic medications over a decade ago, treatment options for a substantial minority of young patients with FEP or CHR of psychosis remain limited," said Patrick McGorry, M.D., the study's lead investigator. McGorry emphasized that pomaglumetad's unique mechanism of action targeting the glutamate system (search), which plays a critical role in psychotic disorders, presents an opportunity to fulfill this unmet medical need.
The drug's excellent safety profile may offer particular advantages by addressing common shortcomings of other antipsychotics, including weight gain and prolactin elevation, according to McGorry.
Trial Design and Patient Population
The open-label, Phase 2 feasibility trial will investigate the safety, tolerability, and acceptability of administering two daily doses of 40 mg pomaglumetad methionil over 12 weeks. The study targets young people aged 18-25 years who have shown insufficient response to a single first-line antipsychotic treatment in FEP cases, or failure of remission of CHR-positive symptoms and functional recovery in CHR patients.
The trial will also assess whether pomaglumetad can reduce total symptomatology and dysfunction in this patient population. The study has received approval from the Royal Melbourne Hospital Human Research Ethics Committee (Project 2024.289).
Novel Mechanism of Action
Pomaglumetad methionil represents a first-in-class psychiatric drug that selectively acts on the glutamic acid mGlu2/3 receptor (search) with no cross-reaction with other receptors in the central nervous system. This selective targeting mechanism enables the drug to potentially avoid common side effects associated with psychiatric medications currently on the market.
The compound was originally licensed from Eli Lilly, which had completed 37 clinical trials involving more than 3,800 subjects. According to Denovo, pomaglumetad methionil has demonstrated significant promise when applied to appropriate patient subpopulations through personalized medicine approaches.
Previous Clinical Experience
Wen Luo, Ph.D., Denovo's Chief Executive Officer, acknowledged that while pomaglumetad did not achieve statistically significant efficacy in a broad schizophrenia (search) patient study, a subset of patients early in disease exhibited significantly greater improvement. This finding supports the rationale for focusing on early-stage psychosis patients in the current trial.
"The study of pomaglumetad in patients with psychosis marks an important step forward in our mission to develop innovative and transformative therapies for psychiatric conditions," Luo stated. "We are honored to work with the world-renowned team at Orygen (search), internationally recognized for its scientific leadership and extensive expertise in youth mental health research."
Company Pipeline and Precision Medicine Approach
Denovo Biopharma (search) positions itself as a clinical-stage biopharmaceutical company that uses novel biomarker approaches to execute efficient clinical trials in targeted patient subpopulations to increase the probability of success. The company maintains seven late-stage drugs in its pipeline addressing major unmet medical needs in central nervous system diseases and oncology, with most being first-in-class drugs with global rights.
The company recently achieved a significant milestone with a positive pivotal study of DB104 (liafensine) in patients with treatment-resistant depression (search) who carry a Denovo-discovered novel ANK3 (search) biomarker, which was published in JAMA Psychiatry.