Denovo Biopharma Partners With Orygen for Phase 2 Study of Pomaglumetad Methionil in Treating Psychosis

Denovo Biopharma today announced a partnership with Orygen, and plans to initiate a phase 2 investigator-initiated-trial studying pomaglumetad methionil (DB103) for first-episode psychosis (FEP) or clinical high risk (CHR) of psychosis.

Pomaglumetad methionil, a first-in-class psychiatric drug that selectively acts on the glutamic acid mGlu2/3 receptor, has no cross-reaction with other receptors in the central nervous system and therefore can avoid some usual adverse effects of currently-available psychiatric drugs. Professor Patrick McGorry, MD, will lead the study and Orygen in Parkville, Australia will sponsor the research.

“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 McGorry. “As a novel drug targeting the glutamate system, which plays a critical role in psychotic disorder, pomaglumetad presents an option to fulfill this unmet medical need. Given its excellent safety profile, it may be uniquely effective by addressing the shortcomings of other antipsychotics such as weight gain and prolactin elevation.”

This open-label, phase 2, feasibility trial will investigate the safety, tolerability, and acceptability of administering 2 daily doses of pomaglumetad methionil 40 mg, over the duration of 12 weeks in youth aged 18 to 25 years with insufficient response to a single first-line antipsychotic treatment in patients with FEP or failure of remission of CHR-positive symptoms and functional recovery in patients with CHR. Study nvestigators will also evaluate whether pomaglumetad methionil can reduce total symptomatology and dysfunction. The study has been approved by the Royal Melbourne Hospital Human Research Ethics Committee (Project 2024.289).

“Although pomaglumetad did not achieve statistically significant efficacy in a broad schizophrenia patient study, a subset of patients early in disease exhibited significantly greater improvement,” said Wen Luo, PhD, the chief executive officer of Denovo. “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. We are honored to work with the world-renowned team at Orygen, internationally recognized for its scientific leadership and extensive expertise in youth mental health research.”

Orygen is Australia’s leading nonprofit youth mental health organization; they have the largest concentration of youth mental health researchers, clinicians, and educators in the world. Orygen’s name comes from being the ORiginal mental health organization for the Youth GENeration.

According to previous research on pomaglumetad methionil, the drug showed promise as a novel antipsychotic in preclinical research but failed to show efficacy in clinical trials, but may be effective in certain patient populations.² Over a decade ago, research on pomaglumetad methionil as an adjunctive treatment with atypical antipsychotics was discontinued due to lack of efficacy.³ This new partnership and research marks a fresh start for the treatment option.

References

1. Denovo Biopharma announces partnership with Orygen on phase 2 study evaluating DB103 (pomaglumetad methionil) in treating psychosis. News release. February 11, 2026. Accessed February 11, 2026. https://www.globenewswire.com/news-release/2026/02/11/3236218/0/en/Denovo-Biopharma-Announces-Partnership-with-Orygen-on-Phase-2-Study-Evaluating-DB103-Pomaglumetad-Methionil-in-Treating-Psychosis.html

2. Sonnenschein SF, Grace AA. The mGluR2/3 agonist pomaglumetad methionil normalizes aberrant dopamine neuron activity via action in the ventral hippocampus. Neuropsychopharmacology. 2020;45(12):2106-2113.

3. Lilly stops phase III development of pomaglumetad methionil for the treatment of schizophrenia based on efficacy results. News release. August 29, 2012. Accessed February 11, 2026. https://investor.lilly.com/news-releases/news-release-details/lilly-stops-phase-iii-development-pomaglumetad-methionil