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 senior management presentation to key stakeholders at the Alzheimer’s Association International Conference and internationally Sydney, 8 July 2026. Actinogen Medical ASX: ACW (“ACW” or “the Company”) will conduct a series of key stakeholder meetings over the coming weeks with potential global and regional commercialization partners in Alzheimer’s disease, key opinion leaders and international biotech experts. Many of these meetings will be conducted at the Alzheimer’s Association International Conference (AAIC) in London, UK, from July 12-15, 2026. The presentation focuses on the Company’s strong scientific rationale and prior clinical data supporting the XanaMIA pivotal trial of Xanamem® (emestedastat) in patients with mild to moderate Alzheimer’s disease. Topline final results from the trial are expected in November 2026. A copy of the presentation is attached to this announcement. View this announcement on our InvestorHub: https://investors.actinogen.com.au/link/eY0kLy 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 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. 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 ® 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 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. 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. 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 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 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. Advancing oral Xanamem® in Alzheimer’s Disease Fully enrolled phase 2b/3 pivotal trial | Topline data November 2026 Potentially game-changing product profile Corporate Presentation July 2026 ® Xanamem is a registered trademark of Actinogen Medical Limited 2 This presentation is dated June 2026 and 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. It should be read in conjunction with the Company’s most recent financial report and other periodic and continuous disclosure announcements lodged with the Australian Securities Exchange (”ASX”), which are available at www.asx.com.au under the Company’s ticker code (ASX: ACW). 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Disclaimer Corporate Presentation July 2026 3 Corporate and Xanamem highlights Validated mechanism with differentiated oral profile • Xanamem is a novel oral therapy targeting elevated brain cortisol, a well- established risk factor for Alzheimer’s disease and depression • Oral administration and favorable safety profile support broad use Biomarker-enriched pivotal trial with independent validation • XanaMIA phase 2b/3 pivotal trial (n=247) fully enrolled; open-label extension commenced; topline results November 2026 • January 2026 independent Data Monitoring Committee recommended the trial continue unchanged following unblinded interim review of safety and efficacy futility Regulatory clarity in the US and EU • Current pivotal trial expected to form part of registrational package for Alzheimer’s disease • FDA and EMA guidance support a streamlined marketing approval path requiring only one additional pivotal trial following positive XanaMIA results Corporate Presentation July 2026 Potentially game-changing oral therapy for CNS diseases in late-stage trials Strong capital position • Company funded into 2027 • Resources focused on execution of the XanaMIA trial and preparation for 2027 NEXT MAJOR VALUE INFLECTION Pivotal trial topline results November 2026 3 4 Management Team Board of Directors Dr. Geoff Brooke Chairman MBBS; MBA Dr. Steven Gourlay CEO & Managing Director 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 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 Comms B.Ec (Hons), CPA, FFIN Experienced leadership Proven experience in clinical development, manufacturing, regulatory & commercialization Corporate Presentation July 2026 4 5 Recent milestones Corporate Presentation July 2026 5 Clear regulatory pathway to approval in US and EU Regulatory guidance from FDA & EMA supports streamlined late-stage development Current trial • XanaMIA pivotal trial (n=247) expected to form key part of registrational package • Open-label phase has commenced with high uptake from main trial participants Regulatory engagement • FDA guidance September 2025, EMA May 2026 • Both aligned on clinical, manufacturing and ancillary studies Remaining clinical requirements • One additional single-dose phase 3 trial (10 mg vs placebo) required1 • Open-label safety trials • Limited number of clinical pharmacology and nonclinical studies Corporate Presentation July 2026 1. FDA and EMA may accept a single pivotal trial plus adequate supportive evidence for approvals under certain circumstances 6 Positive interim safety, efficacy futility reviews Independent Data Monitoring Committee chaired by expert Dr Hans Moebius Recommendation: • Jan 2026 “non-futile” recommendation to continue the XanaMIA trial without modification • Jun 2026 positive safety review without futility assessment Formal interim review process in January: • The Committee was not authorized to recommend early stopping for efficacy in order to preserve the trial’s statistical integrity and alpha • The Committee confidentially reviewed treatment group data on: ✓ Safety data from all enrolled participants (n=247) ✓ Approximately 37% of the expected final dataset across scheduled timepoints including 52 participants with Week 36 (end of treatment) data Corporate Presentation July 2026 Independent DMC reviews deliver positive continuation decisions, clearing safety and futility criteria ahead of November 2026 topline results 7 Open-label extension commenced March 2026 Long-term safety and efficacy durability extension to Phase 2b/3 Design • All participants offered active Xanamem 10mg after completion of double-blind phase • Initiated March 2026 with high initial enrolment (>80% continuation from main trial) Data contribution • ≥14 months additional safety exposure • Longitudinal assessment of CDR-SB, cognition, and activities of daily living • Observational comparison of early vs delayed treatment initiation • Potential to show durability of benefit Strategic impact • Expands cumulative safety database • Supports regulatory engagement • Informs durability of clinical effect Corporate Presentation July 2026 8 Positioned to meet a huge unmet medical need in Alzheimer’s disease Corporate Presentation July 2026 9 Strong physician interest and demand for Xanamem Global Alzheimer’s therapeutic market expected to exceed $20B by 2030 Quantitative survey of 91 U.S. neurologists treating Alzheimer’s disease (June 2025) Respondents each manage ~250 AD patients on average Corporate Presentation July 2026 Rapid adoption expected ~80% expect to prescribe within 6 months • 13% within first month • 41% within three months Early uptake anticipated among high-volume AD prescribers Significant market share potential ~50% projected peak share • 43% estimate 31–50% peak share • 14% estimate >50% peak share Broad eligibility supports substantial utilization Expected role in management 92% anticipate leading / definite role • 30% expect top-two agent • 0% indicate no role Oral profile and safety drive enthusiasm 10 -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 Anti-amyloid therapies only modestly slow decline Disease stabilization represents an important therapeutic aspiration Worse performance Ideal trajectory with disease stabilization Unmet need despite amyloid therapy Corporate Presentation July 2026 Additional therapeutic mechanisms remain an important area of investigation 11 -3 -2.5 -2 -1.5 -1 -0.5 0 0.5 donanemab all placebo all Potential for greater magnitude of effect on CDR-SB Xanamem phase 2a p- tau–positive patients showed near- stabilization Worsening of CDR-SB over 18 months Worse performance Modest benefit of donanemab (Kisunla) over 18 months1 1. Sims et al. JAMA 2023 336(6):512-527 Corporate Presentation July 2026 Xanamem may stabilize or slow CDR-SB progression more than other therapies SIMULATED PHASE 2B/3 DATA 12 Summary: commercial and partnering implications Structural Limitations of Anti-Amyloid Infusion burden, ARIA risk, and cost limit broad adoption Differentiated Oral Profile Xanamem is positioned with a favorable risk-benefit and ease-of-use profile XanaMIA as a Value Catalyst Phase 2b/3 readout is positioned to accelerate commercial and strategic partnering activity Corporate Presentation July 2026 Potential for Meaningful Stabilization Targeting elevated brain cortisol may enable functional impact beyond modest slowing 13 Positioned for clinical success Corporate Presentation July 2026 14 Watch MOA animation Targeting elevated brain cortisol in Alzheimer’s disease Xanamem selectively inhibits brain 11β-HSD1 while preserving adrenal cortisol function Elevated brain cortisol is associated with cognitive decline and neurodegeneration Corporate Presentation July 2026 15 Elevated brain cortisol and Alzheimer’s progression Human observational and biomarker data support cortisol as a disease driver • Higher plasma cortisol associated with increased AD risk (AIBL study) • Cortisol accelerates cognitive decline and interacts with Aβ pathology • APOE-ε4 carriers exhibit higher CSF cortisol levels • Elevated CSF cortisol correlates with more rapid clinical worsening Corporate Presentation July 2026 [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 16 Xanamem achieves high brain target occupancy Human PET imaging confirms brain 11β-HSD1 engagement SUVRcarotid 5 mg Xanamem Baseline After 7 days of daily dosing 10 mg Xanamem 20 mg Xanamem 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 Corporate Presentation July 2026 Reduction in tracer signal (loss of color) indicates high 11β-HSD1 occupancy - Strong occupancy observed across evaluated clinical doses 17 CDR-SB slowed in pTau-positive Alzheimer’s Phase 2a trial showed slowing of decline over 12 weeks (n=34) Corporate Presentation July 2026 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 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 18 Durable activity in phase 2 depression trial 10 mg demonstrated separation from placebo overall and on background SSRI therapy Corporate Presentation July 2026 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. *Planned phase 3 population MADRS LS mean change from baseline (± SE) Xanamem (n=37) Placebo (n=39) ON TREATMENT AND BACKGROUND SSRI THERAPY (n=76)* FOLLOW UP -12 -10 -8 -6 -4 -2 0 Baseline Week 2 Week 4 Week 6 Week 10 19 Better Performance Rigorous pivotal trial positioned for success Fully enrolled (n=247) across U.S. and Australia; topline results November 2026 40 Weeks -4 0 36 Weeks 10mg Xanamem Placebo Screening Double-blind, randomized treatment period (N = 247) Follow-up & open label Population Primary Endpoint Key Secondary Endpoints Execution • 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 NIA-AA=National Institute of Aging - Alzheimer’s Association; CDR-SB Clinical Dementia Rating Scale – Sum of Boxes Corporate Presentation July 2026 20 Well-established safety, industry-standard endpoints being used in current pivotal trial 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 Actinogen – Xanamem® (emestedastat)/) Corporate Presentation July 2026 Safety • Well-tolerated across clinical program • No serious adverse events related to Xanamem reported to date (n ~ 500)1 • No ARIA signal observed Robust XanaMIA endpoints • CDR-SB at 36 weeks is primary endpoint • Cognition (validated cognitive measures) • “Amsterdam” activities of daily living instrument (functional measures) 21 Summary: positioned for phase 2b/3 success Clear Biological Rationale Elevated brain cortisol implicated in cognitive decline and neuronal injury Demonstrated Brain Target Engagement High 11β-HSD1 occupancy confirmed by human PET imaging Consistent CNS Activity Across Indications Durable separation from placebo in Phase 2 depression trial Rigorous, Fully Enrolled Pivotal Trial 247 patients; interim continuation; November 2026 readout Corporate Presentation July 2026 Clinical Signal in Enriched Alzheimer’s Population CDR-SB slowing in pTau positive patients over 12 weeks 22 Summary Corporate Presentation July 2026 23 XanaMIA trial positioned as a game-changer Operational execution and regulatory alignment ahead of pivotal Alzheimer’s data Corporate Presentation July 2026 • On-track with XanaMIA pivotal trial in patients with mild-to-moderate AD ✓ Full enrolment of 247 participants achieved ✓ Positive interim analysis Jan 2026 followed by positive June safety review ✓ Topline results expected Nov 2026 ✓ Structured as a registrational trial aligned with FDA & EMA guidance • Executing on streamlined development path for Alzheimer’s disease ✓ Open-label extension XanaMIA trial phase opened in March 2026 ✓ N