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 Appendix 4E and 2026 digital annual report Sydney, 27 August 2026. Actinogen Medical ASX: ACW (“ACW” or “the Company”) is pleased to announce its financial results for the year ended 30 June 2026. The Appendix 4E and 2026 digital annual report documents are attached. View this announcement on our InvestorHub: https://investors.actinogen.com.au/link/PB5nlr ENDS Investors Media Dr Steven Gourlay Michael Roberts George Hazim CEO & Managing Director Communications 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 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 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 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 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. 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 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 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. The peer-reviewed publication relating to this trial can be accessed for free via this link: https://tinyurl.com/ckm63z63. 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 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. 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 A P P E N D I X 4 E 1. Company details Name of entity ACTINOGEN MEDICAL LIMITED ABN or equivalent company reference Financial year ended (‘reporting period’) Financial year ended (‘previous corresponding period’) 14 086 778 476 30 June 2026 30 June 2025 2. Results for announcement to the market 30/06/2026 $ 30/06/2025 $ Change % Amount change $ Revenue from ordinary activities 499,858 685,253 -27.05% (185,395) Loss from ordinary activities after tax attributable to members (15,379,848) (14,732,263) 4.40% (647,585) Net loss for the period attributable to members (15,379,848) (14,732,263) 4.40% (647,585) Net tangible asset per share (a) 0.005 0.005 (a) Includes right-of-use asset 3. Statement of comprehensive income Refer to attached financial statements. 4. Statement of financial position Refer to attached financial statements. 5. Statement of cash flows Refer to attached financial statements. 6. Statement of changes in equity Refer to attached financial statements. 7. Dividends/distributions No dividends declared in current or prior year. 8. Details of dividend reinvestment plan Not applicable. 9. Details of entities over which control has been gained or lost during the period Not applicable. 10. Details of associates and joint venture entities Not applicable. 11. Any other significant information needed by an investor to make an informed assessment of the Company’s financial performance and financial position Refer to attached financial statements. 12. Foreign entities Not applicable. ACTINOGEN MEDICAL LIMITED A P P E N D I X 4 E 13. Commentary on results and explanatory information Actinogen Medical Limited (‘the Company’) incurred a net loss after tax for the financial year ended 30 June 2026 of $15,379,848 (2025: $14,732,263) Full year ended Full year ended 30/06/2026 30/06/2025 $ $ Interest revenue 499,858 685,253 Other income 12,673,927 5,489,600 Total revenue & other income 13,173,785 6,174,853 Research & development costs (19,027,365) (12,296,568) Employment costs (4,943,256) (4,434,666) Corporate & administration costs (2,000,387) (2,026,706) Finance costs (465,945) (48,890) Realised (loss) / unrealised gain on foreign currency 25,908 (14,381) Share-based payment expenses (1,723,316) (1,663,705) Amortisation expense (312,746) (312,746) Depreciation expense (right-of-use asset) (80,964) (80,964) Depreciation expense (office equipment) (25,562) (28,490) Total expenses (28,553,633) (20,907,116) Loss before income tax (15,379,848) (14,732,263) Income tax expense - - Loss for the year (15,379,848) (14,732,263) During the year there was a significant ramp up in expenditure activities by the Company across 35 different sites and multiple vendors, in multiple locations globally, as the XanaMIA Alzheimer’s disease trial reached peak enrolment. In order to support this ramp up in activity, employment costs increased during the period as the Company appointed new hires (Senior Clinical Project Manager, Medical Writer and Senior Clinical Trial Associate); as well as prior-year new hires completed a full year of employment (e.g. Chief Commercial Officer and Senior Director Portfolio and Program Manager). Finance costs increased due to the interest on the prior year loan that was issued on 30 June 2026 plus the interest on the existing loan issued on 27 January 2026, all being expensed in the current financial year. Corporate and administration costs remained constant. For further information, refer to the Directors’ Report and the Financial Statements. 14. Audit This report is based on accounts which have been audited. Dr Steven Gourlay Managing Director Sydney, New South Wales 27 August 2026 Authorised for release by the Board of Directors. Annual Report 2026 Actinogen is developing a revolutionary oral therapeutic, Xanamem® , which controls levels of the “stress hormone” cortisol in the brain, with the goal of improving the lives of patients and their families. Topline results from our first pivotal Alzheimer’s trial, evaluating its potential to slow disease progression, are expected in November 2026. ® Xanamem is a registered trademark of Actinogen Medical Limited Contents Disclaimer This annual report 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. Who we are IFC Highlights 2 The Xanamem pipeline 3 Progress has begun. The need remains 4 Cortisol and the Alzheimer’s brain 6 Elevated human brain cortisol levels linked to AD 7 Rigorous pivotal trial positioned for success 7 Chair’s letter 8 Chief Executive Officer’s letter 10 Vision and strategy 12 Operating & financial review 14 Board of directors 24 Executive leadership team 26 Directors’ report 28 Remuneration report (Audited) 31 Auditor’s independence declaration 44 Financial report 45 Directors’ declaration 70 Independent auditor’s report 71 Shareholder information 76 Corporate directory 79 Annual Financial Report 1 Highlights Imminent pivotal trial results in Alzheimer’s disease Achieved common understandings with the US FDA and the European Medicines Agency (EMA) on the pathways to marketing approvals in Alzheimer’s disease (AD), including agreement on the streamlined design of one further pivotal AD trial of Xanamem 10 mg versus placebo commencing in 2027 Pivotal Alzheimer’s disease trial remains on track for topline final results in November this year following three positive Independent Data Monitoring Committee (DMC) recommendations, including a confidential “non-futility” review of unblinded efficacy data in January Open label extension (OLE) phase of the XanaMIA trial commenced March 2026 with 89% of participants moving directly to the OLE at the end of the main trial, and a total of 108 now on treatment Completed manufacture of an additional batch of 10mg Xanamem tablets at Catalent (USA) for use in the OLE phase of the XanaMIA trial Peer-reviewed depression trial manuscript detailing positive anti-depressant activity published in British Journal of Psychiatry June-end cash balance of $16.7m provides cash runway beyond Alzheimer’s trial final results to mid‑2027 Strengthened IP protection through active national phase patent filings with the first national acceptances received for new patents covering Xanamem treatment of cognitive decline in healthy elderly people and key manufacturing steps Received $7.3 million research and development tax incentive (RDTI) rebate from the Australian Tax Office relating to the 2025 financial year Enhanced our relationships with key stakeholders by focusing on the importance and uniqueness of Xanamem’s brain cortisol control mechanism in AD and our impending pivotal trial data Actinogen Medical Limited 2 The Xanamem pipeline Progressing Xanamem in Alzheimer’s disease, major depressive disorder and other neurological indications Indication Preclinical Phase 1 Phase 2 Phase 3 Alzheimer’s disease Phase 2b/3 ongoing; positive interim results, final topline results expected November 2026 Phase 3 ready following successful Phase 2a MDD Open INDs Frontotemporal dementia Lewy-body dementia Parkinson’s disease Anxiety disorders Potential next indications Actinogen is developing Xanamem, a novel oral 11β-HSD1 inhibitor, for the treatment of Alzheimer’s disease. With enrollment complete in the pivotal XanaMIA Phase 2b/3 trial, the company is focused on advancing a differentiated therapeutic approach for patients living with one of the world’s greatest unmet medical needs. In addition to Alzheimer’s disease, Xanamem has demonstrated encouraging clinical activity in major depressive disorder and continues to offer potential across a range of neurological and neuropsychiatric disorders. As our lead development program advances, we will continue to evaluate future opportunities where the unique biology of brain cortisol inhibition may address additional diseases with significant unmet medical need. Annual Financial Report 3 CONTENTS Progress has begun. The need remains Recent therapeutic advances have demonstrated that modifying the course of the disease is possible, representing meaningful progress for patients, caregivers, physicians and researchers. At the same time, real-world experience has reinforced the limitations of current therapies and the significant unmet need that remains, highlighting the importance of developing additional treatment options that offer meaningful clinical benefit while addressing the practical needs of patients and physicians. The Alzheimer’s landscape continues to evolve beyond new therapies alone. Blood-based biomarkers are transforming how patients are identified, diagnosed and enrolled into clinical trials, creating opportunities for earlier intervention, more efficient drug development and, ultimately, a more personalized approach to patient care. Together, these scientific and clinical advances are reshaping the future of Alzheimer’s disease and reinforcing the need for continued innovation across multiple therapeutic approaches. The treatment of Alzheimer’s disease has entered an important new era Opportunity Innovation Progress Significant unmet need remains, reinforcing the need for additional therapeutic approaches Blood-based biomarkers are transforming diagnosis and enabling more efficient clinical trial enrollment Disease-modifying therapies have demonstrated that altering disease progression is possible Actinogen Medical Limited 4 Discussing the evolving Alzheimer’s treatment landscape and the potential impact of next-generation therapies designed to remove amyloid more rapidly, Prof. Marwan Sabbagh commented on the potential role for Xanamem: There will always be a market and opportunity for Xanamem. Professor Marwan Sabbagh Moreno Family Chair for Alzheimer’s Research, Professor of Neurology, Barrow Neurological Institute, Phoenix, Arizona, USA Annual Financial Report 5 CONTENTS Cortisol and the Alzheimer’s brain Alzheimer’s Risk & Progression Structural, functional & cognitive decline Neuroinflammation ↑microglial activity ↑cytokines Alzheimer’s Protein Pathology ↑amyloid beta ↑tau 11β-HSD1 Inhibitors ↓ brain cortisol Brain Tissue Damage ↓hippocampal volume ↓neurogenesis Long-term Intracellular Brain Cortisol Levels Aging, Alzheimer’s & Genetics ↑11β-HSD1 expression Chronic Stress ↑adrenal synthesis & systemic cortisol Failed HPA feedback “Stress” and/or genetic factors may drive multiple AD mechanisms via cortisol Xanemem’s 11β-HSD1 target: Genetic alterations are both protective (down) and a risk factor (up) for cognitive decline Increased 11β-HSD1 activity in the brain may drive long‑term local tissue cortisol “stress” resulting in brain tissue damage mediated by inflammation, direct toxicity and formation of toxic amyloid and tau proteins. Actinogen Medical Limited 6 Elevated human brain cortisol levels linked to AD Rigorous pivotal trial positioned for success Fully enrolled (n=247) across U.S. and Australia; topline results November 2026 • Blood pTau biomarker positive • Mild-moderate AD (NIA-AA criteria) •  CDR-SB at 36 weeks (functional and cognitive measure) •  Cognitive Test Battery •  Amsterdam Activity of Daily Living •  Fully enrolled (n=247) • Independent DMC interim review recommended trial continuation • Open-label ext. commenced •  Topline results November 2026 Population Primary Endpoint Key Secondary Endpoints Execution Follow-up & open label Double-blind, randomized treatment period (N = 247) 40 Weeks -4 0 36 Weeks 10mg Xanamem Placebo Screening NIA-AA=National Institute of Aging - Alzheimer’s Association; CDR-SB Clinical Dementia Rating Scale – Sum of Boxes 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 CSF cortisol (μg/dl) Cognitive Normal p<0.001 MCI Other MCI AD AD Dementia German Dementia Competency Network study Popp et al., 2015, Neurobiol. Aging 36:601–607 Annual Financial Report 7 CONTENTS Chair’s letter Dear Shareholder, I am pleased to present the Actinogen Medical Limited Annual Report for the financial year ended 30 June 2026, reflecting on a year of substantial achievement and disciplined execution. As we approach the release of topline results from the pivotal XanaMIA trial in Alzheimer’s disease later this year, we remain mindful of the significance of the opportunity before us. Should the trial prove successful, Xanamem has the potential to become an important new treatment for patients living with this devastating condition. Actinogen entered FY2026 with a clear focus: to successfully complete enrolment of the pivotal XanaMIA Alzheimer’s disease trial, progress through its interim analysis milestone, strengthen our regulatory and commercial position, and ensure the company remained appropriately funded through the delivery of topline results in November this year. I am pleased to report that each of these objectives was achieved. Pleasingly, the past year saw continued improvement in sentiment toward biotechnology companies globally, particularly those advancing innovative therapies through late-successful stage clinical development. Closer to home on the ASX there were some late-stage clinical failures that disappointed in other therapeutic areas. While markets continue to navigate geopolitical uncertainty, inflationary pressures and shifting interest rate expectations, investors increasingly focus on companies with differentiated science, credible regulatory pathways and meaningful near-term value inflection points. As we approach our first pivotal trial readout in November Actinogen is well-positioned with this profile. Executive leadership The successful execution of our strategy and achievement of our priorities is ultimately driven by the quality of our people. I would like to commend the outstanding performance of our executive leadership team, led by Dr Steven Gourlay. Successfully managing a global late-stage clinical development program requires exceptional scientific, operational and commercial expertise, and the leadership team has continued to execute with discipline, professionalism and determination throughout the year. I would also like to acknowledge our dedicated employees, clinical investigators, research partners and contractors whose efforts continue to underpin the company’s progress. Importantly, I extend my sincere thanks to the patients and families participating in our clinical trials. Their commitment is essential to advancing the development of new therapies for Alzheimer’s disease and other neurological conditions. Capital management Appropriate capital management remains one of the Board’s most important responsibilities. Our objective is to ensure the company has the financial resources required to execute its strategy while maintaining flexibility to respond to opportunities as they arise. As noted earlier, one of our key priorities during FY2026 was to ensure the company remained appropriately funded beyond the delivery of topline XanaMIA results. I am pleased to report that during the year, we strengthened our financial position through a combination of equity financing, R&D tax incentive receipts and non-dilutive funding initiatives. Actinogen Medical Limited 8 Following the positive interim analysis outcome from the XanaMIA trial in January, the company successfully completed a $16.8 million capital raising comprising a placement and share purchase plan, receiving strong support from both institutional and retail investors as well as a further $0.5 million from CEO, Steve Gourlay. The company also received its FY2025 Research and Development tax incentive rebate together with additional funding secured against future R&D tax incentive receivables. Collectively, these initiatives ensure that Actinogen remains funded beyond the anticipated release of topline XanaMIA results and provide the flexibility to continue advancing the company’s strategic priorities. Board, corporate governance and advisory boards The Board remains committed to maintaining the highest standards of governance, oversight and accountability. As Actinogen progresses through late-stage clinical development, strong governance and robust risk management remain fundamental responsibilities of the Board. During the year we continued to review our governance practices and assess the skills and capabilities required to support the company’s ongoing growth and increasing operational complexity. We remain committed to transparency and accountability, supported by a governance framework designed to provide effective oversight while enabling efficient decision-making. I thank my fellow directors for their dedication and invaluable contributions throughout what has been a significant year for the company. Their collective expertise across biotechnology, medicine, finance, regulation and corporate governance continues to provide important guidance and significant leadership and support to management and shareholders alike. The Board also acknowledges the important contribution made by the company’s scientific and clinical advisers. During the year, the establishment of a dedicated Alzheimer’s Disease Clinical Advisory Committee further strengthened access to external expertise as we prepare for the next phase of development and potential commercialization planning. Annual General Meeting This year’s Annual General Meeting will be held on 30 November 2026, and we look forward to engaging with shareholders and discussing the company’s progress, achievements and future opportunities. By that time we expect to have reported topline results from the Alzheimer’s trial which should make for a particularly important and informative meeting for shareholders. Further details regarding the venue and timing will be provided in due course. Outlook We enter the new financial year with a strong sense of purpose and optimism. Few biotechnology companies have the opportunity to advance a development program with the potential to meaningfully improve outcomes for patients living with Alzheimer’s disease. The Board believes Actinogen enters FY2027 exceptionally well positioned, having successfully completed the many preparatory activities required to reach this late stage of development. The pivotal XanaMIA trial remains on track for topline results in November 2026. These results have the potential to shape the future direction of the Xanamem program, inform future regulatory interactions, support commercial discussions and broader strategic opportunities available to the company. Alongside the anticipated trial outcome, we expect continued engagement with regulators, further advancement of commercial readiness initiatives and ongoing evaluation of partnering opportunities. In closing, I would like to sincerely thank you, our shareholders, for your continued support and confidence in Actinogen. The company has made substantial progress throughout FY2026 and is poised for pivotal trial results in November. On behalf of the Board, I thank you for your ongoing commitment and look forward to sharing further updates as we continue our efforts to deliver meaningful innovation for patients and long-term value for shareholders. Dr Geoff Brooke Chair 27 August 2026 If you have any questions relating to your shareholding in Actinogen, please contact Automic at hello@automicgroup.com.au or on 1300 288 664 (within Australia) or +61 2 9698 5414 (outside Australia). Visit the Automic website https://investor.automic.com.au/#/home to register as an ACW shareholder or log in to your existing account. Annual Financial Report 9 CONTENTS Chief Executive Officer’s letter Dear Shareholder, The last year has been the most important and productive in Actinogen’s history. We entered this period with strong momentum behind our pivotal XanaMIA Alzheimer’s disease trial program, and we continue to execute against our strategy to develop Xanamem safely and expeditiously. Our clear focus is to create value for both patients and shareholders. Actinogen’s focus on controlling excess cortisol in the brain represents a differentiated and innovative approach to treating Alzheimer’s disease. We are not aware of any other late-stage program pursuing the same mechanism in central nervous system diseases. Importantly, the scientific and clinical data created by Actinogen over the past 12 years continue to strengthen the argument that cortisol control may have clinically meaningful benefit for patients. Xanamem (emestedastat) is a remarkable small molecule therapeutic, uniquely capable of addressing diseases associated with dysregulated brain cortisol because of its demonstrated ability to reach its 11β-HSD1 target in the brain. To our knowledge, there is no other 11β-HSD1 molecule that crosses the blood-brain barrier and is in development for central nervous system (CNS) diseases. Attention is now sharply focused on delivering high-quality topline, final results for the pivotal XanaMIA Alzheimer’s disease trial in Nove