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 Final, 246th participant randomized and commenced treatment in Actinogen’s XanaMIA Alzheimer’s trial – topline results November 2026 Sydney, 18 December 2025. Actinogen Medical ASX: ACW (“ACW” or “the Company”) is pleased to announce that due to the recent accelerated screening and enrolment in the XanaMIA phase 2b/3 Alzheimer’s disease (AD) trial, the Company has randomized and commenced treatment of all participants. This means that topline, final results will be available in November next year. Key points: • XanaMIA is a randomized trial of 36 weeks treatment with Xanamem® or placebo in patients with mild- moderate Alzheimer’s disease followed by an open-label extension phase • Final and total enrolment is 246 participants (originally targeted 220), accounting for the expected, modest rate of discontinuations • Topline, final results are confirmed for November of next year (previously mid Q4) with full analysis completed in the months following • Data from the 26 additional participants boosts the statistical power of the trial • A webinar to discuss this announcement and related information will be held at 11am (Sydney time) today – details at the end of this announcement. The robust recent enrolment in the XanaMIA trial validates the attractiveness of Xanamem as an easy-to-use once-daily oral therapy for AD with a novel mechanism designed to control elevated brain cortisol (aka the “stress hormone”). The trial was designed using data from the analysis of 34 AD patients from the previous XanADu phase 2 trial with a diagnosis confirmed by elevated pTau181 levels. This analysis showed a large Xanamem benefit on the CDR-SB endpoint after just 12 weeks of treatment. Xanamem has also shown benefits on depressive symptoms in a recent phase 2 trial and in trials of cognition in cognitively normal, older volunteers. The XanaMIA trial is a double-blind, 36-week treatment, placebo-controlled, parallel group design trial in participants with mild to moderate AD and progressive disease, determined by clinical criteria and confirmed by an elevated level of the pTau181 blood biomarker. Participants receive Xanamem 10 mg or placebo, once daily, and its ability to slow progression of AD over 36 weeks of treatment is assessed with a variety of endpoints. The primary endpoint of 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. All past and present participants in the trial are eligible to receive active Xanamem 10 mg treatment in the open-label extension phase commencing in Q1 next year, even if they finished the main part of the trial in 2025. A formal interim analysis of safety and efficacy futility from the partially completed trial will be conducted by an independent Data Monitoring Committee (DMC) in late January 2026. The DMC comprises independent clinical and statistical experts who are not connected to the day-to-day conduct or analysis of the trial. The committee will review, in a highly confidential process, unblinded data for safety and efficacy futility from all available participant visits including many who will have completed the 36-week treatment period. ® 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 Topline final safety and efficacy results for the full 36 weeks of treatment from all participants will be available in November 2026. The final analysis will assess the difference in efficacy and safety between Xanamem and placebo-treated participants after the “double-blind” code is opened by the trial statisticians. Actinogen is grateful to the XanaMIA trial staff, participants with Alzheimer’s disease and their caregivers for their significant contributions and to those who have participated in previous Xanamem trials. Actinogen CEO and MD, Dr Steven Gourlay commented: “We are excited to be entering the final stage of the XanaMIA randomized controlled trial with confidence in our November 2026 timeline for topline final results. As the trial continues, the team will be busy commencing the open-label extension phase so that all participants can receive active Xanamem treatment for a longer period.” “We will be conducting the formal interim analysis of the trial in January, interacting with the European Medicines Agency on the path to approval in the EU and planning for the upcoming clinical and manufacturing programs. Xanamem has the potential to be a game-changer for Alzheimer’s patients because of its safety, ease-of-use and potential efficacy advantages.” Webinar today The Company will be holding a live webinar at 11am (Sydney time) today, 18 December 2025 to discuss this announcement and related information for the Xanamem program. CEO, Dr Steven Gourlay, CMO, Dr Dana Hilt, and CCO, Mr Andy Udell, will be available to answer questions from attendees. Pre-register immediately or register and join at 11am (Sydney time) using the link below: https://investors.actinogen.com.au/webinars/VyEXvP-december-webinar A copy of the webinar presentation is attached to this announcement. At the conclusion of the presentation, there will be an opportunity for questions from webinar attendees. A recording of the webinar will be made available as soon as possible after the conclusion of the event on the Company’s InvestorHub: https://investors.actinogen.com.au/webinars/VyEXvP-december-webinar View this announcement on our InvestorHub: https://investors.actinogen.com.au/link/eNm4Jy 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 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 Medical Limited ACN 086 778 476 Suite 901, Level 9, 109 Pitt Street, Sydney NSW 2000 +61 2 8964 7401 | actinogen.com.au 3 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 impairment and depression and may study Fragile X Syndrome and other neurological and psychiatric diseases in the future. Reducing cortisol inside brain cells could have a positive impact in 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 unmet medical 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 220 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 endpoint of 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. The trial is now closed to recruitment, with initial results from an interim analysis expected in late January 2026 and final topline results 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 will evaluate safety and a limited number of efficacy endpoints such as the CDR-SB. The trial will commence in Q1 2026 and be 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 antidepressant therapy, and effects on cognition and depression were assessed. Trial results were reported in August 2024 and showed clinically and statistically significant benefits 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 assessment of 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, without affecting 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 approximately 400 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. 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 Actinogen Medical Limited ACN 086 778 476 Suite 901, Level 9, 109 Pitt Street, Sydney NSW 2000 +61 2 8964 7401 | actinogen.com.au 4 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 realised. ACTINOGEN MEDICAL ENCOURAGES ALL CURRENT INVESTORS TO GO PAPERLESS BY REGISTERING THEIR DETAILS WITH THE DESIGNATED REGISTRY SERVICE PROVIDER, AUTOMIC GROUP. Oral Xanamem® Controlling brain cortisol to slow progression in Alzheimer’s disease and treat depression Webinar Presentation Dr Steve Gourlay, CEO; Dr Dana Hilt, CMO; Mr Andy Udell, CCO 18 December 2025 ® Xanamem is a registered trademark of Actinogen Medical Limited 2 This presentation has been prepared by Actinogen Medical Limited. (“Actinogen” or the “Company”) based on information available to it as at the date of this presentation. The information in this presentation is provided in summary form and does not contain all information necessary to make an investment decision. This presentation does not constitute an offer, invitation, solicitation or recommendation with respect to the purchase or sale of any security in Actinogen, nor does it constitute financial product advice or take into account any individual’s investment objectives, taxation situation, financial situation or needs. An investor must not act on the basis of any matter contained in this presentation but must make its own assessment of Actinogen and conduct its own investigations. Before making an investment decision, investors should consider the appropriateness of the information having regard to their own objectives, financial situation and needs, and seek legal, taxation and financial advice appropriate to their jurisdiction and circumstances. Actinogen is not licensed to provide financial product advice in respect of its securities or any other financial products. Cooling off rights do not apply to the acquisition of Actinogen securities. Although reasonable care has been taken to ensure that the facts stated in this presentation are accurate and that the opinions expressed are fair and reasonable, no representation or warranty, express or implied, is made as to the fairness, accuracy, completeness or correctness of the information, opinions and conclusions contained in this presentation. To the maximum extent permitted by law, none of Actinogen its officers, directors, employees and agents, nor any other person, accepts any responsibility and liability for the content of this presentation including, without limitation, any liability arising from fault or negligence, for any loss arising from the use of or reliance on any of the information contained in this presentation or otherwise arising in connection with it. The information presented in this presentation is subject to change without notice and Actinogen does not have any responsibility or obligation to inform you of any matter arising or coming to their notice, after the date of this presentation, which may affect any matter referred to in this presentation. This presentation is not for general distribution or third party reliance or use. This presentation contains certain budget information, forecasts and forward looking statements that are based on the Company’s management’s beliefs, assumptions and expectations and on information currently available to management in respect of which there is NO guarantee of future performance. Such budget information, forecasts and forward looking statements involve known and unknown risks, uncertainties, and other factors which may cause the actual results or performance of Actinogen to be materially different from the results or performance expressed or implied by such forward looking statements. These risks and uncertainties include, but are not limited to the performance of Actinogen in its clinical trials including whether it's technology proves to be a safe and effective treatment, market penetration, competition from any other similar products, intellectual property risks (including securing rights in technology and patents) and global economic conditions. Furthermore, Actinogen's research, product development, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. There is no guarantee that Actinogen will obtain the required approvals, licences and registrations from the relevant authorities in jurisdictions in which it operates. Actinogen or others could identify product and efficacy issues relating to the safety of our technology. Accordingly, all forward looking statements are based on numerous assumptions regarding the Company’s present and future business strategies and the political and economic environment in which Actinogen will operate in the future, which are subject to change without notice. Past performance is not necessarily a guide to future performance and no representation or warranty is made as to the likelihood of achievement or reasonableness of any forward looking statements or other forecast. There is no guarantee that Actinogen will achieve its stated objectives/milestones, that any of its forecasts will be met or that forward looking statements will be realised. You are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof, and we do not undertake any obligation to revise and disseminate forward-looking statements to reflect events or circumstances after the date hereof, or to reflect the occurrence of or non-occurrence of any events. Neither Actinogen nor any other entity or person in or associated with Actinogen guarantee any return (whether capital or income) or generally the performance of Actinogen or the price at which its securities may trade. Any investment in Actinogen is subject to investment risks including the possibility of loss of capital invested and no return of income or payment of any dividends. To the maximum extent permitted at law, Actinogen and all of its representatives, directors, officers, partners, employees or professional advisers (Parties) exclude all direct and indirect liability arising out of or in connection with any use or reliance of the information contained or described within this presentation. Other than to the extent required by law (and only to that extent), the Parties do not make any representation or give any assurance, guarantee or warranty (express or implied) as to, nor assume any responsibility or liability for, the authenticity, origin, validity, accuracy, suitability or completeness of, or any errors in or omissions from, any information, statement or opinion contained in this presentation or any accompanying, previous or subsequent material or presentation. Disclaimer Webinar presentation 18 December 2025 3 Online Q&A Webinar presentation 18 December 2025 1. Open the chat function in the bottom right corner 2. Type your question into the text box 3. Click “enter” or the send button to submit your question 4 Management Team Experience & track record matters Board of Directors Dr. Geoff Brooke Chairman MBBS; MBA Dr. Steven Gourlay CEO & MD MBBS; FRACP; PhD; MBA Mr. Malcolm McComas Non-Executive Director BEc, LLB; FAICD; SF Fin Dr. George Morstyn Non-Executive Director MBBS; PhD; FRACP CD Dr. Nicki Vasquez Non-Executive Director PhD Dr. Dana Hilt Chief Medical Officer MD Dr. Steven Gourlay CEO & MD Will Souter Chief Financial Officer BComm, LLB Andrew Udell Chief Commercial Officer MBA Cheryl Townsend VP Clinical Operations RN, M Health Law Fujun Li Head of Manufacturing PhD Michael Roberts Head of IR & Comms B.Ec (Hons), CPA, FFIN Webinar presentation 18 December 2025 Alzheimer’s disease market is large and growing 5 Growing Alzheimer’s Disease market – U.S. Large, unsatisfied and growing market Webinar presentation 18 December 2025 Xanamem’s unique mechanism of action 6 Click here for animation video Webinar presentation 18 December 2025 Xanamem has a clear path to Alzheimer’s approval 7 • Recent FDA agreement confirms development pathway to US marketing approval using one additional pivotal trial of 10 mg vs. placebo and open-label safety studies • Clear guidance on manufacturing, ancillary studies • Ongoing XanaMIA pivotal clinical trial: • Full enrolment in US and Australia • Excellent safety profile maintained, positive first Data Monitoring Committee review • Interim analysis of safety and efficacy futility in late Jan 2026 using all available data • On-track for final results in November 2026 • Phase 3 planning commencing in parallel with discussions re potential partnerships Phase 2b/3 trial on track, FDA agreement streamlines development, EMA meeting 2026 Webinar presentation 18 December 2025 Highlights of Alzheimer’s treatment landscape Oral Xanamem is leading the charge with a potential game-changing new mechanism Mechanistic Admin Comments Older drugs - boosting acetylcholine or glutamate Oral Marketed since '90s/'00s, symptomatic only. Gastrointestinal side effects. Anti-amyloid protein immunotherapies IV/SubQ Marketed with challenges including variable reimbursement (e.g. not Aust.). Safety concerns including infusion reactions, brain swelling / bleeding - MRI monitoring required Second-gen anti-amyloid with “brain shuttle” IV/SubQ Late-stage trials e.g. Roche’s trontinemab. Likely to be safer than first-gen due to less binding to vascular wall amyloid Xanamem (emestedastat) control of elevated brain cortisol Oral Mid-first pivotal, phase 2b/3 trial. Promising: n~500, can be combined with older drugs. Once daily dosing Blarcamesine SIGMAR1 antagonist to block autophagy Oral One phase 2b/3 trial, regulatory approval recently rejected by EMA. Dizziness, increased rate serious side effects vs. placebo Anti-amyloid formation or toxicity Oral Most failed phase 2, some on-going trials in patient subgroups. Anti-tau protein immunotherapy IV/SubQ All trials have failed to date, more on-going 8 Webinar presentation 18 December 2025 Why does the company have confidence in a positive phase 2b/3 trial outcome? 9 1. Very strong cortisol scientific rationale in Alzheimer’s 2. Human PET study showing high brain target engagement (n = 40) 3. Large clinical benefit in pTau biomarker-positive Alzheimer’s patients (n = 34) 4. Clinically important activity of Xanamem on depression in phase 2 (n = 165) 5. Evidenced-based trial design & patient selection (n=246) Webinar presentation 18 December 2025 1. Very strong cortisol scientific rationale in Alzheimer’s ✓ Compelling evidence provided by the Australian Imaging, Biomarker & Lifestyle Study of Ageing (AIBL) study (2017)1 • Higher plasma cortisol leads to a much greater risk of developing AD • Accelerated effect of Αβ+ on decline in global cognition, episodic memory, and attention ✓ Individuals with the APOE-ε4 allele have higher CSF cortisol2 ✓ Multiple other studies support the association between cortisol and AD development and progression3-6 ✓ High cortisol and low folate predict probable Alzheimer’s disease after age 757 ✓ Higher CSF cortisol levels in AD patients are associated with more rapid clinical worsening and cognitive impairment8,9 10 [1] Pietrzak et al., 2017, Biol Psychiatry: Cognitive Neuroscience and Neuroimagery, [2] Lupien et al., 1998, Nat Neurosci 1:69–73; [3] Geerlings et al., 2015, Neurology 85: 1-8; [4] Lehallier et al., 2016, JAMA Neurology 73(2), 203-212; [5] Popp et al., 2015, Neurobiol. Aging 36:601–607; [6] Ennis et al., 2017, Neurology 88(4):371-378; 2:45-52; [6] Lupien et al., 2009, Nat Rev Neurosci 10:434–445; [7] Hinterberger et al., J Am Ger Soc 2013 61(4):648-651; [8] Cernansky et al., 2006, Am J Psychiatry 163:2164-2169; [9] Kornhuber & Jensen, 2015, Neurobiol Aging 36:601-607; Popp et al, 2015 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 Cognitive Normal MCI Other MCI AD AD dementia CSF cortisol (μg/dl) p<0.001 MEAN CSF CORTISOL LEVELS Webinar presentation 18 December 2025 Other 11β-HSD1 enzyme inhibitors have not achieved adequate brain levels Xanamem extensively binds to the 11β-HSD1 enzyme throughout the brain, with high post-treatment effects (absence of color) after 7 days at all doses, slightly less at a 5 mg dose. This is consistent with full hormonal pharmacodynamic activity seen in clinical trials with doses as low as 5 mg. SUVRcarotid 5 mg Xanamem Baseline After 7 days of daily dosing 10 mg Xanamem 20 mg Xanamem 2. Human PET study shows full target engagement 11 Journal of Alzheimer’s Disease 97 (2024) 1463–1475 Brain 11-Hydroxysteroid Dehydrogenase Type 1 Occupancy by Xanamem Assessed by PET in Alzheimer’s Disease and Cognitively Normal Individuals Victor L. Villemagne, Vincent Dor, Lee Chong, Michael Kassiou, Rachel Mulligan, Azadeh Feizpour, Jack Taylor, Miriam Roesner, Tamara Miller and Christopher C. Rowe Webinar presentation 18 December 2025 12 3. Large Xanamem benefit in high pTau181 patients Phase 2a biomarker study: major slowing of CDR-SB decline over 12 weeks (n=34) Journal of Alzheimer’s Disease 100 (2024) 139–150 Plasma pTau181 Predicts Clinical Progression in a Phase 2 Randomized Controlled Trial of the 11-HSD1 Inhibitor Xanamem® for Mild Alzheimer’s Disease Jack Taylor, Mark Jaros, Christopher Chen, John Harrison and Dana Hilt 0.36 0.98 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Baseline Week 12 Xanamem Placebo 0.6-point benefit @12 weeks Xanamem vs. Placebo • Mean 0.6 units • Median 0.8 units • p = 0.09 • Cohen’s d = 0.4 CDR-SB units Change from Baseline (SE) Worse performance Webinar presentation 18 December 2025 Interim XanaMIA phase 2b/3 results in late Jan 2026, topline final results Nov 2026 13 NIA-AA=National Institute of Aging - Alzheimer’s Association; CDR-SB Clinical Dementia Rating Scale – Sum of Boxes 40 Weeks -4 0 36 Weeks 10mg Xanamem Placebo Screening Double-blind, randomised treatment period (N = 246) Follow-up & open label Key Inclusion Criteria Primary Endpoint Key Secondary Endpoints Implementation • Blood pTau biomarker positive • Mild-moderate Alzheimer’s by NIA-AA criteria • CDR-SB (functional and cognitive measure) @36 weeks • Cognitive Test Battery (7 cognitive measures well- validated in the Alzheimer’s field) • Amsterdam Activity of Daily Living (functional measure) • Full enrolment at 15 Australian & 20 US sites of participants • Interim analysis late Jan 2026 (efficacy futility & safety on all available data) • Final topline results Nov 2026 5. Evidence-based trial design & patient selection Webinar presentation 18 December 2025 XanaMIA interim analysis and open-label phase detail Interim analysis late January 2026, open-label phase commences Q1 2026 Interim analysis of safety and efficacy futility • Independent Data Monitoring Committee made up of experienced clinical and statistics experts • Conducted in a highly confidential manner so that the company, investigators and trial personnel are kept “blinded” to patient treatment assignment (active Xanamem vs. placebo) • Uses data from all available participants and all completed visits at the time • Outcome will be a binary recommendation to continue (trial not futile) or stop (trial is futile or there is safety issue) Open-label phase starting in Q1 2026 • Active Xanamem 10 mg offered to all current and prior XanaMIA phase 2b/3 trial participants • No placebo control group • Provides longer term safety data for at least 12 months and observational data on key efficacy endpoints such as the CDR-SB, cognition and activities of daily living 14 Webinar presentation 18 December 2025 Strategic insights about commercialization and partnering in AD 15 1. Anti-amyloid infusions have a borderline risk-benefit profile and are expensive 2. Xanamem is being developed with a better risk-benefit and ease-of-use profile aimed at stabilizing the disease safely 3. Desired Xanamem benefits include multiple aspects of cognition and life functioning – ideally to halt Alzheimer’s decline completely 4. XanaMIA trial is a catalyst for commercial and partnering interest Webinar presentation 18 December 2025 -3 -2.5 -2 -1.5 -1 -0.5 0 0.5 donanemab all placebo all halt progression Worsening of CDR-SB over 18 months Modest benefit of donanemab (Kisunla) over 18 months 16 Worse performance Ideal trajectory with disease stabilization Drugs targeting other mechanisms like Xanamem are needed Unmet need despite amyloid therapy 1. Anti-amyloid drugs only modestly slow disease Ideally patients with AD would not worsen on treatment at all Webinar presentation 18 December 2025 -3 -2.5 -2 -1.5 -1 -0.5 0 0.5 donanemab all placebo all halt progression Worsening of CDR-SB over 18 months Modest benefit of donanemab (Kisunla) over 18 months 17 Worse performance If results are good, Xanamem could be many times more effective than other drugs 2. Potential for Xanamem to beat existing approved treatments on CDR-SB primary endpoint Webinar presentation 18 December 2025 e.g. Xanamem approaches full disease stabilization over 18 months 18 Safety • Well-tolerated • No serious adverse events related to Xanamem in whole program to date (n ~ 500)1 3. Well-established safety and potential to see consistent benefit on key secondary efficacy measures 1. No serious adverse events related to Xanamem have been reported across all clinical trials to date; various other safety data are reported in peer reviewed publications (see https://actinogen.com.au/xanamem