Actinogen XanaMIA pivotal Alzheimer’s disease trial completes final patient visit, with topline results on track for November

This phase 2b/3, double-blind trial of oral Xanamem in 247 participants with mild to moderate Alzheimer’s disease and elevated pTau181 evaluates the potential benefit of targeting excess cortisol in the brain over a 36-week treatment period

SYDNEY, Australia, Sept. 23, 2026 (GLOBE NEWSWIRE) -- Actinogen Medical Limited (ASX: ACW) today announces that, following the final participant visit on 22 September in the USA, topline results for the XanaMIA phase 2b/3 Alzheimer’s disease (AD) clinical trial remain on track for November this year. This is the first Xanamem^® trial to evaluate the potential benefits of tissue cortisol control over a period longer than 12 weeks. Despite recent advances in Alzheimer’s disease treatment, substantial unmet need remains for therapies that can deliver meaningful clinical benefit, are easier to administer, and act through additional biological pathways.

Xanamem (emestedastat) is a promising oral enzyme inhibitor designed to control elevated levels of the “stress hormone” cortisol in the brain, which are associated with the onset and progression of AD. Elevated cortisol is also associated with ApoE4, the primary genetic risk factor for AD. Xanamem is a potent and highly selective enzyme inhibitor of 11β-HSD1, the cellular enzyme responsible for cortisol synthesis in tissues other than the adrenal glands, which is strongly expressed in regions of the brain important for cognition, including memory and executive function.

The XanaMIA trial is a randomized (1:1), double-blind, placebo-controlled phase 2b/3 trial evaluating Xanamem 10 mg versus placebo over 36 weeks, with a four-week follow up period. Participants are then eligible to enrol in an open-label extension phase and receive Xanamem 10 mg. The trial has now completed all patient visits, with 247 participants enrolled across Australia (45%) and the United States (55%).

Using elevated plasma pTau181 to select participants is a key feature of the trial. It has high validity for identifying AD in this population and is highly efficient compared with more complex methods such as amyloid brain scans or cerebrospinal fluid biomarkers. Elevated pTau181 also selects for participants with a more progressive disease course, increasing the trial’s power to detect a treatment effect for Xanamem and replicating the diagnostic profile of the phase 2a patient population where a large treatment benefit for Xanamem was observed (Taylor et al. 2024).

Enrolled participants had baseline clinical, genetic and laboratory characteristics similar to those reported in other trials of patients with mild to moderate AD:

1. Average age of 75 years
2. 49% female
3. 66% ApoE4 carriers (main AD genetic risk factor)
4. Mean (SD) pTau181 2.6 (1.3) pg/mL
5. Mean (SD) CDR-SB 4.3 (2.0) points.
   
   

Topline results from the trial are expected in November.

Dr Dana Hilt, the Company’s CMO commented:

“Xanamem is a unique oral therapy with the potential to become a transformational treatment option for patients and their families living with Alzheimer’s disease. Our key focus is to finalise high-quality data from the XanaMIA pivotal trial for release in November while planning streamlined pathways to the fastest possible regulatory approvals for Xanamem.” 

^® Xanamem is a registered trademark of Actinogen Medical Limited

About Actinogen Medical 
Actinogen Medical (ACW) is an ASX-listed, biotechnology company in the late clinical stages of development for Xanamem® (emestedastat), its novel oral therapy for Alzheimer’s disease and depression. The Company is based in Sydney, Australia with operations and clinical trials in Australia and the US. Xanamem has been studied in eight clinical trials with more than 500 people treated to date and has a promising safety and efficacy profile. ACW’s ongoing clinical trial, XanaMIA, is a phase 2b/3 pivotal trial of 247 participants with mild to moderate Alzheimer’s disease, treated for 36 weeks with Xanamem 10 mg or placebo, followed by an open-label extension phase with active Xanamem 10 mg for completing participants. In January 2026 an Independent DMC conducted an interim analysis of safety and efficacy futility and recommended the trial proceed to completion. The trial is now fully enrolled and will report topline, final results from the randomized phase in November this year.

About Xanamem (emestedastat)
Xanamem’s novel mechanism of action is to control the level of cortisol in the important areas of the brain through the inhibition of the cortisol synthesis enzyme, 11β-HSD1, without blocking normal production of cortisol by the adrenal glands. Xanamem is a first-in-class, once-a-day pill designed to deliver high levels of brain cortisol control in regions where 11β-HSD1 is highly expressed such as the hippocampus. Chronically elevated cortisol is associated with progression in Alzheimer’s Disease and excess cortisol is known to be toxic to brain cells. Elevated cortisol is also associated with depressive symptoms. Xanamem has demonstrated excellent brain target engagement and in human trials has shown potential to slow progression of Alzheimer’s disease and improve depressive symptoms in patients with moderately severe depression. To view Xanamem’s two-minute Mechanism of Action animation, click here.

Xanamem is an investigational product and is not approved for use outside of a clinical trial by the FDA or by any global regulatory authority. Xanamem® is a trademark of Actinogen Medical.

Disclaimer
This announcement and attachments may contain certain "forward-looking statements" that are not historical facts; are based on subjective estimates, assumptions and qualifications; and relate to circumstances and events that have not taken place and may not take place. Such forward looking statements should be considered “at-risk statements” - not to be relied upon as they are subject to known and unknown risks, uncertainties and other factors (such as significant business, economic and competitive uncertainties / contingencies and regulatory and clinical development risks, future outcomes and uncertainties) that may lead to actual results being materially different from any forward looking statement or the performance expressed or implied by such forward looking statements. You are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. Actinogen Medical does not undertake any obligation to revise such statements to reflect events or any change in circumstances arising after the date hereof, or to reflect the occurrence of or non-occurrence of any future events. Past performance is not a reliable indicator of future performance. Actinogen Medical does not make any guarantee, representation or warranty as to the likelihood of achievement or reasonableness of any forward-looking statements and there can be no assurance or guarantee that any forward-looking statements will be realized.

Dr. Steven Gourlay
CEO & Managing Director
E. steven.gourlay@actinogen.com.au

Investors
Will Souter
Investor Relations
E. will.souter@actinogen.com.au

Media
George Hazim
Media & Public Affairs Australia
E: georgehazim@mediaaffairs.com.au