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 2025 AGM – Chair’s address and CEO’s presentation Sydney, 19 November 2025. Actinogen Medical ASX: ACW (“ACW” or “the Company”) is pleased to release the Chair’s address and CEO’s slide presentation to this morning’s Annual General Meeting commencing at 11am (AEDT) in Sydney. The AGM will be held at the offices of K&L Gates, Level 31, 1 O’Connell Street’, Sydney NSW 2000. This AGM is an in-person only meeting. The Chair’s address and CEO’s presentation slides are attached to this announcement. View this announcement on our InvestorHub: https://investors.actinogen.com.au/link/rkD6NP 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 Disclosure Committee 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 and Depression and hopes to 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 will be fully enrolled by the end of 2025 with initial results from an interim analysis in late January 2026 and final topline results in mid Q4 2026. 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 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 video, 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 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. 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 19 November 2025 Actinogen 2025 AGM Chair’s Address Good morning, fellow shareholders, my name is Geoff Brooke, and I am the Chair of Actinogen Medical Limited. On behalf of the Board of Directors and staff of the Company it is a pleasure to welcome you to the Actinogen 2025 Annual General Meeting. Thank you for your time and continued support as we reflect on a year of meaningful progress and look ahead with optimism. The financial year ended 30 June 2025 was one of significant advancement for Actinogen, set against a backdrop of renewed optimism in the biotechnology sector. Globally, investor sentiment toward small cap biotechs has rebounded, particularly for companies progressing into later stages of clinical development such as ourselves. This has been evident in both the United States and Australia, where capital has begun rotating back into high-quality biotech assets. Actinogen is well- positioned in this environment, with our lead asset, Xanamem® , rapidly advancing through a pivotal phase 2b/3 trial in Alzheimer’s disease. In addition, we successfully completed a phase 2a trial in major depressive disorder in August 2024 which demonstrated good clinical benefit on depressive symptoms with the 10 mg daily dose. Following a successful meeting with the FDA to define the future path to approval, further development in this indication is currently paused so the Company can focus its efforts on the Alzheimer’s disease program for now. Let me expound on our core focus—Alzheimer’s disease. This condition remains one of the most urgent and challenging healthcare issues of our time. Over 55 million people worldwide are affected, and despite recent therapeutic developments, there is still no cure. The approval of anti- amyloid infusion therapies, while a step forward, has shown only modest benefit and comes with significant limitations. This underscores the need for next-generation treatments—particularly those that are safer and more accessible, effective, and easier to administer. Xanamem is a novel, oral small molecule therapy designed to modify disease progression by targeting brain cortisol—a mechanism that sets us apart in the field. To our knowledge, there is no other drug in development for central nervous system diseases that works in this way. We are proud to be contributing to the global effort to slow, halt, or even reverse the cognitive and functional decline associated with Alzheimer’s disease. Our progress would not be possible without the exceptional leadership of our executive team. I would like to acknowledge Dr. Steven Gourlay, our CEO, for his strategic vision and scientific expertise. Under his guidance, the company has maintained strong momentum and operational discipline. We were also pleased to welcome Mr. Andrew Udell as Chief Commercial Officer during the year. Andy brings deep commercial experience that will be invaluable as we prepare for later- stage development and eventual product launch. I also extend my sincere thanks to our broader executive team, employees, and key contractors. Their professionalism and dedication have been ® 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 instrumental in maintaining a highly effective clinical development program and the corporate operations required of a publicly listed biotechnology company. Turning to governance, our Board remains committed to the highest standards of oversight and strategic leadership. During the year, we undertook a review of our governance practices and reassessed our Board skills matrix to ensure we are well-equipped for the company’s evolving needs. We continue to refine our governance framework to reflect our growth and increasing operational complexity. Transparency and accountability remain central to our approach, with key corporate policies and governance materials available on our website and supporting the execution of our long-term vision and annual priorities. I would like to thank my fellow Board members for their valuable contributions throughout the year. Their insight and commitment have been vital as we navigate the complexities of late-stage clinical development. We also acknowledge the important role of our scientific and medical advisory boards. Their guidance helps shape our clinical and regulatory strategy, ensuring we remain aligned with best practices and emerging opportunities. On the financial front, we strengthened our capital position through a successful raise of $11.1 million, comprising an $8.1 million placement and a $3.0 million Share Purchase Plan. Subscribers received listed options as part of the raise, and we now have two series of options trading on the ASX. This provides flexibility for shareholders and potential capital for future growth. In addition, we received a $9.0 million R&D tax incentive rebate for the 2024 financial year and secured access to a A$13.8 million non-dilutive loan facility backed by future R&D tax incentive rebates. The initial $3.0 million drawdown of that loan on 30 June 2025 was repaid in recent weeks from the $7.4 million in tax incentive rebates received for the $2025 financial year. These initiatives reflect our disciplined approach to capital management and our commitment to funding clinical development efficiently. Looking ahead, we view the new financial year with optimism. Last week we announced the positive outcome of our first meeting of the independent Data Monitoring Committee. The committee is responsible for reviewing the safety data for our pivotal XanaMIA Alzheimer’s trial and as we continue to derisk the programme, and advance towards critical value inflection points for the company, it is pleasing to see a positive response from the market. A key next milestone will be the interim analysis of efficacy and safety from the XanaMIA trial, expected in late January 2026. Assuming this is positive, it will provide strong momentum for the program and support on-going engagement with potential partners and stakeholders. Final topline results are now anticipated in mid Q4 2026 and are keenly awaited. In closing, I want to thank you—our shareholders—for your continued support and confidence in Actinogen. Your backing enables us to pursue our mission with focus and determination. We are entering a pivotal phase in our journey, and we look forward to sharing further updates with you as we work to deliver meaningful innovation for patients and value for shareholders. Thank you. 1 Dr Steven Gourlay MBBS PhD MBA: CEO & MD 19 November 2025 CEO’s AGM presentation 2 Management Team Experience 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 ACW AGM 19 November 2025 Oral Xanamem® Controlling brain cortisol to slow progression in Alzheimer’s disease and treat depression ® Xanamem is a registered trademark of Actinogen Medical Limited Xanamem’s unique mechanism of action 4 Click here for animation video ACW AGM 19 November 2025 Alzheimer’s disease market is large and growing 5 Growing Alzheimer’s Disease market – U.S. Large, unsatisfied and growing market ACW AGM 19 November 2025 Xanamem: Clear pathway to Alzheimer’s approval 6 • FDA 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 and ancillary studies • Ongoing XanaMIA pivotal clinical trial: • Brisk enrolment at 35 clinical centers in US and Australia, full enrolment Dec 2025 • Excellent safety profile maintained, positive first Data Monitoring Committee review • Interim analysis of safety and efficacy futility in late Jan 2026 • On-track for final results in mid Q4 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 ACW AGM 19 November 2025 Previous results that give the company confidence in a positive phase 2b/3 trial outcome in Alzheimer’s 7 1. Clinical benefit on depression symptoms in phase 2 (n = 165) 2. Large clinical benefit in pTau biomarker-positive Alzheimer’s patients (n = 34) 3. Human PET study showing high brain target engagement (n = 40) 4. Very strong cortisol scientific rationale in Alzheimer’s 5. Optimal trial design based on pilot data in pTau positive patients, CDR-SB endpoint ACW AGM 19 November 2025 -12 -10 -8 -6 -4 -2 0 Baseline Week 2 Week 4 Week 6 Week 10 Major depressive disorder phase 2a: benefit also seen in patients taking background SSRI anti-depressant (n=76) 8 EOT 2.6-point difference Cohen’s d = 0.38 p = 0.15 PT 4.2-point difference Cohen’s d = 0.64 p = 0.03 Abbreviations: SSRI, selective serotonin reuptake inhibitor MADRS LS mean change from baseline (± SE) Xanamem (n=37) Placebo (n=39) ON TREATMENT FOLLOW UP BETTER ACW AGM 19 November 2025 9 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 ACW AGM 19 November 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 3. Human PET study shows full target engagement 10 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 ACW AGM 19 November 2025 4. 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 11 [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 ACW AGM 19 November 2025 Interim XanaMIA results in late Jan 2026, topline final results mid Q4 2026 12 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 > 240) 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 > 240 participants by end 2025 • Interim analysis late Jan 2026 (efficacy futility & safety) 5. Optimal pivotal trial design & patient selection ACW AGM 19 November 2025 Strategic insights about commercialization and partnering in AD 13 1. Anti-amyloid infusions have a borderline risk-benefit profile 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 has potential to be a catalyst for commercial and partnering interest ACW AGM 19 November 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 14 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 ACW AGM 19 November 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 15 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 e.g. Xanamem approaches full disease stabilization over 18 months ACW AGM 19 November 2025 16 Worse performance Safety1: No serious adverse events related to Xanamem (n ~ 500) 3. Opportunity for consistent benefit across safety and key secondary measures Better performance Cognition composite Activities of daily living Patient & carer-reported outcomes Quality of life EXAMPLE SECONDARY ENDPOINT DATA (MEAN, 95%C.I.)2 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/ ) 2. Example means shown by triangles; where example 95% confidence interval (C.I.) lines cross the midline, it means the p values would > 0.05 ACW AGM 19 November 2025 17 4. XanaMIA catalyst for commercial & partnering events We know the commercial opportunity is huge: ✓ US Neurologists treating AD love the idea of a safe and effective, oral drug and indicate that uptake would be rapid in the first year ✓ Xanamem could easily move to first line therapy and displace many existing treatments ✓ Combinability with other small molecules and biologics a major plus ✓ Multiple potential commercialization partners are reviewing our confidential data We are planning for: ✓ Completion of one or more regional partnership deals ✓ Final results that excite multiple, global partnership bids ✓ Final results good enough for regulators to seriously consider expedited approvals ACW AGM 19 November 2025 Conclusion 18 ACW AGM 19 November 2025 Building momentum toward Alzheimer’s results 19 • On-track with XanaMIA pivotal trial for mild-moderate Alzheimer’s disease ✓ Full enrolment of > 240 participants in XanaMIA pivotal trial Q4 2025 ✓ Interim results late January 2026, topline final results mid Q4 2026 • Highly positive market research with about 100 US Alzheimer’s physicians ✓ More than 50% of their patients are good Xanamem candidates ✓ And 80% of physicians would prescribe Xanamem in the first 6 months • FDA agreement on streamlined path to Xanamem approval ✓ One other pivotal trial of 10 mg vs. placebo ✓ Standard clinical pharmacology and safety database requirements • IP portfolio strengthened with the prosecution of multiple new patents • Increased partnership interest and dataroom activity • Company funded beyond mid 2026 Numerous value-add near-term milestones ACW AGM 19 November 2025 Multiple near-term milestones in coming year Milestone Likely Timing Screening activities close, XanaMIAAD trial Oct 25 Full enrolment, 220 patients with AD, XanaMIAAD trial Dec 25 XanaCIDD MDD peer-reviewed journal publication Q4 25 / Q1 26 CTAD AD conference in San Diego ad Meetings at JP Morgan Healthcare conference week, San Francisco Mid Jan 26 Interim analysis XanaMIAAD trial Late Jan 26 ADPD AD conference in Copenhagen Q1 26 EMA Scientific Advice meeting for AD Q2 26 Clinical Trials Science Forum – focus on commercial planning Q2 26 BIO conference in San Diego Q2 26 AAIC AD conference in London Q3 26 Last patient completes 36-week treatment, 4-week follow-up Oct 25 Final results, XanaMIAAD trial Mid Q4 26 20 ACW AGM 19 November 2025 21 Q & A 21 ACW AGM 19 November 2025