Actinogen Medical’s Xanamem shows meaningful antidepressant activity in Phase 2 trial
Published: 20:37 23 Jul 2026 EDT
Actinogen Medical Ltd (ASX:ACW, OTC:ATGGF) this week reported encouraging evidence that its lead drug candidate Xanamem® (emestedastat) may offer a novel treatment approach for major depressive disorder following publication of Phase 2 trial results in the peer-reviewed British Journal of Psychiatry.
The proof-of-concept study found that Xanamem demonstrated clinically meaningful antidepressant activity in patients with difficult-to-treat depression and cognitive impairment, supporting further investigation of the drug’s brain-cortisol control mechanism.
Antidepressant benefit strengthens over time
The randomised, double-blind, placebo-controlled trial enrolled 165 participants with clinically significant residual major depressive disorder and measurable cognitive impairment.
Most participants continued taking an existing antidepressant alongside either Xanamem 10 milligrams daily or a placebo during the six-week treatment period, followed by four weeks of blinded observation.
The antidepressant benefit compared with placebo was strongest at week 10, when Xanamem produced a 2.7-point improvement on the Montgomery-Åsberg Depression Rating Scale, reaching statistical significance.
Among the 46% of patients taking background selective serotonin reuptake inhibitor medication, the treatment benefit increased to 4.2 MADRS points.
The delayed improvement was consistent with the time required for chronic cortisol-related effects to emerge or reverse.
Xanamem was also found to be safe and well tolerated.
“These results are highly encouraging for the Xanamem 10 mg daily dose that is also being used in the Alzheimer’s disease program. The trial demonstrates that the drug penetrates the brain and there is a signal of clinically meaningful activity to improve depression symptoms in a difficult-to-treat MDD patient population," Professor Michael Berk AO, academic psychiatrist and co-author, said.
“There remains a significant unmet medical need for therapies such as Xanamem that have a novel mechanism of action and can be safely combined with existing depression treatments.”
Cognition improves independently of depression
While participants in both treatment groups recorded substantial improvements in cognitive symptoms, the study found no evidence that Xanamem provided a cognitive benefit over placebo.
The results also challenged the previously held belief that cognition necessarily improves alongside depressive symptoms, with researchers finding no correlation between improvements in cognition and improvements in depression.
The study authors concluded that Xanamem may represent a novel antidepressant worthy of further investigation, although additional depression trials will depend on future funding and partnership arrangements.
Alzheimer’s trial approaching key results
Actinogen is primarily developing Xanamem as a potential treatment for Alzheimer’s disease, where elevated cortisol is associated with cognitive decline and damage to brain cells.
The company’s pivotal XanaMIA Phase 2b/3 study is evaluating Xanamem in 247 patients with mild-to-moderate, biomarker-confirmed Alzheimer’s disease in Australia and the United States.
Topline results are expected in November 2026 and will include an initial assessment of Xanamem’s impact on psychiatric symptoms.
Chief medical officer Dr Dana Hilt said antidepressant activity could prove beneficial for Alzheimer’s patients, who frequently experience depressive symptoms.
“Anti-depressant activity may be a useful feature of Xanamem treatment for Alzheimer’s disease and help to improve well-being and quality of life in these patients,” Hilt said.
About Actinogen Medical
Actinogen Medical is developing treatments for neurological and neuropsychiatric conditions associated with dysregulated brain cortisol.
Xanamem is a first-in-class, once-daily oral therapy designed to reduce cortisol levels in key brain regions by inhibiting the 11β-HSD1 enzyme, without disrupting the body’s essential adrenal cortisol production.
The drug has been studied in more than 500 volunteers and patients across eight clinical trials and has demonstrated a favourable safety profile and clinical activity in depression and Alzheimer’s disease.
