Announcement PDF Actinogen Medical Limited ACN 086 778 476 Suite 901, Level 9, 109 Pitt Street, Sydney NSW 2000 +61 2 8964 7401 | actinogen.com.au 1 ASX ANNOUNCEMENT Actinogen receives third positive Data Monitoring Committee recommendation for the XanaMIA Alzheimer’s disease pivotal trial Sydney, 18 June 2026. Actinogen Medical ASX: ACW (“ACW” or “the Company”) is pleased to announce receipt of the positive recommendation of the XanaMIA phase 2b/3 trial’s independent Data Monitoring Committee (DMC) to continue the trial without amendment. Topline final trial results are expected in November this year. Highlights: • The independent DMC comprises independent clinical and statistical experts who are not connected to the day-to-day conduct or analysis of the trial • The latest DMC meeting reviewed available safety data from all 247 XanaMIA trial participants (more than 100 with the full 36 weeks of treatment) and concluded that the trial should continue without amendment • In contrast to the January 2026 DMC meeting, where efficacy futility was evaluated in a confidential and prespecified interim analysis, the DMC was not asked to review unblinded efficacy at this meeting • Oral Xanamem ® 10 mg daily continues to demonstrate a promising safety profile in patients with mild to moderate Alzheimer’s disease treated for up to 36 weeks in the XanaMIA trial. Dr Steven Gourlay, Actinogen’s MD & CEO, said: “With the third positive independent safety review complete we are confident of the suitability of Xanamem for longer-term treatment. Xanamem has the potential to be a game-changer for Alzheimer’s disease given its potential product profile as a safe and effective oral medication with the ability to slow disease course progression significantly more than any approved therapy.” View this announcement on our InvestorHub: https://investors.actinogen.com.au/link/e9MNze ENDS Investors Media Dr Steven Gourlay Michael Roberts George Hazim CEO & Managing Director Investor Relations Media & Public Affairs Australia P: +61 2 8964 7401 M: +61 423 866 231 M: +61 417 516 262 E. steven.gourlay@actinogen.com.au E. michael.roberts@actinogen.com.au E: georgehazim@mediaaffairs.com.au ® Xanamem is a registered trademark of Actinogen Medical Limited Actinogen Medical Limited ACN 086 778 476 Suite 901, Level 9, 109 Pitt Street, Sydney NSW 2000 +61 2 8964 7401 | actinogen.com.au 2 Announcement authorised by the Board of Actinogen Medical Limited About Actinogen Medical Actinogen Medical (ACW) is an ASX-listed, biotechnology company developing a novel therapy for neurological and neuropsychiatric diseases associated with dysregulated brain cortisol.There is a strong association between cortisol and detrimental changes in the brain, affecting cognitive function, harm to brain cells and long-term cognitive health. Cognitive function means how a person understands,remembers and thinks clearly.Cognitive functions include memory, attention, reasoning, awareness and decision-making. Actinogen is currently developing its lead compound, Xanamem, as a promising new therapy for Alzheimer’s Disease. It has also conducted a phase 2 trial in patients with cognitive impairmentand depression andmay study Fragile X Syndrome and other neurological and psychiatric diseases in the future. Reducing cortisol inside brain cells could have a positive impactin these and many other diseases.The cognitive dysfunction,behavioural abnormalities,and neuropsychological burden associated with these conditions is debilitating for patients,and there is a substantial unmetmedical need for new and improved treatments. Clinical Trials The XanaMIA Phase 2b/3 Alzheimer’s disease trial is a double-blind, 36-week treatment, placebo-controlled, parallel group design trial in 247 patients with mild to moderate AD and progressive disease, determined by clinical criteria and confirmed by an elevated level of the pTau181 protein biomarker in blood.Patients receive Xanamem 10 mg or placebo, once daily,and its ability to slow progression of Alzheimer’s disease is assessed with a variety of endpoints.The primary endpointof the trial is the internationally-recognized CDR-SB (Clinical Dementia Rating scale – Sum of Boxes). The trial is being conducted in Australia and the US and is now closed to participant recruitment. It has passed an independent Data Monitoring Committee safety and efficacy futility review and final topline results are expected in November 2026. The XanaMIA-OLE Alzheimer’s disease open-label extension is an open-label phase of up to 25 months treatment where all participants will receive active Xanamem 10 mg once daily. The trial evaluates safety and a limited number of efficacy endpoints such as the CDR-SB. The trial commenced in March 2026 and is open to all former and current participants in the XanaMIA Phase 2b/3 trial. The XanaCIDD Phase 2a depression trial was a double-blind, six-week proof-of-concept, placebo-controlled, parallel group design trial in 167 patients with moderate, treatment-resistant depression and a degree of baseline cognitive impairment. Participants were evenly randomized to receive Xanamem 10 mg once daily or placebo, in most cases in addition to their existing antidepressanttherapy,and effects on cognition and depressionwere assessed.Trial results were reported in August 2024 and showed clinically and statistically significantbenefits on depression symptoms with positive effects on the MADRS scale (a validated scale of depression symptom measurement) and the PGI-S (a valid patient reported assessmentof depression severity). Cognition improved markedly and to a similar extent in both Xanamem and placebo groups. About Xanamem (emestedastat) Xanamem’s novel mechanism is to control elevated levels of cortisol (aka the “stress hormone”) in the brain through the inhibition of the cortisol synthesis enzyme,11β-HSD1,withoutaffecting production of cortisol by the adrenal glands which is essential for the body’s normal functioning.Xanamem is a first-in-class,once-a-day pill designed to deliver high levels of cortisol control in key areas of the brain related to Alzheimer’s and other diseases such as the hippocampus and frontal cortex. To view Xanamem’s two-minute Mechanism of Action animation, click here. Chronically elevated cortisol is associated with progression in Alzheimer’s Disease and excess cortisol is known to be toxic to brain cells. Cortisol itself is also associated with depressive symptoms and when targeted via other mechanisms has shown some promise in prior clinical trials. The recent XanaCIDD trial demonstrated clinically and sometimes statistically significant benefits on depressive symptoms, further validating the cortisol control mechanism for the Xanamem 10 mg oral daily dose. The Company has studied 11β-HSD1 inhibition by Xanamem in more than 500 volunteers and patients in eight clinical trials. Xanamem has a promising safety profile and has demonstrated clinical activity in patients with depression,patients with biomarker-positive Alzheimer’s disease and cognitively normal volunteers. High levels of target engagement in the brain with doses as low as 5 mg daily have been demonstrated in a human PET imaging study. Actinogen Medical Limited ACN 086 778 476 Suite 901, Level 9, 109 Pitt Street, Sydney NSW 2000 +61 2 8964 7401 | actinogen.com.au 3 Xanamem is an investigational productand 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. 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