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 CEO & CFO present at Bell Potter Healthcare Conference 2025 Sydney, 19 November 2025. Actinogen Medical ASX: ACW (“ACW” or “the Company”) is pleased to announce that its CEO, Dr Steven Gourlay and CFO, Mr Will Souter, will present at the Bell Potter Healthcare Conference 2025 today. The Company’s presentation is titled Oral Xanamem®: Controlling brain cortisol to slow progression in Alzheimer’s disease and treat depression. A copy of the presentation is attached to this announcement. Shareholders interested in viewing the Company’s presentation at the conference commencing at 1:00 pm can gain online access using the following link: https://bellpotterevent.com.au/healthcare-2025-ext/ View this announcement on our InvestorHub: https://investors.actinogen.com.au/link/eY2aWr 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 andother neurological andpsychiatric 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 neuropsychologicalburden 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, ® 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 once daily,and its ability to slow progression of Alzheimer’s disease is assessed with a variety of endpoints.The primary endpointof the trial is the internationally-recognized CDR-SB (Clinical Dementia Rating scale – Sum of Boxes). The trial is being conducted in Australia and the US. 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. 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 antidepressanttherapy,and effects on cognition and depressionwere assessed.Trial results were reported in August 2024 and showed clinically and statistically significantbenefits on depression symptoms with positive effects on the MADRS scale (a validated scale of depression symptom measurement) and the PGI-S (a valid patient reported assessmentof depression severity). Cognition improved markedly and to a similar extent in both Xanamem and placebo groups. About Xanamem (emestedastat) Xanamem’s novel mechanism is to control elevated levels of cortisol (aka the “stress hormone”) in the brain through the inhibition of the cortisol synthesis enzyme,11β-HSD1,withoutaffecting production of cortisol by the adrenal glands which is essential for the body’s normal functioning.Xanamem is a first-in-class,once-a-day pill designed to deliver high levels of cortisol control in key areas of the brain related to Alzheimer’s and other diseases such as the hippocampus and frontal cortex. To view Xanamem’s two-minute Mechanism of Action 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 eightclinical 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 productand is not approved for use outside of a clinical trial by the FDA or by any global regulatory authority. Xanamem® is a trademark of Actinogen Medical. Disclaimer This announcement and attachments may contain certain "forward-looking statements" that are not historical facts; are based on subjective estimates,assumptions andqualifications;and relate to circumstances and events thathave nottaken place and may nottake place.Such forward looking statements should be considered “at-risk statements” - notto 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 achievementor 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 Bell Potter Healthcare Conference 2025 Dr Steven Gourlay, CEO Mr Will Souter, CFO 19 November 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 Bell Potter Healthcare Conference 2025 3 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 Bell Potter Healthcare Conference 2025 4 ACW corporate snapshot* Bell Potter Healthcare Conference 2025 • Market cap of ~$175m significantly understates valuation upside in the success case for the current Alzheimer’s disease trial • Buyers have dominated ACW trading in CY25 following the removal of an overhang created by US fund BVF exiting all of its ASX positions including ACW • CEO Steve Gourlay has invested $2m personally to become the major shareholder with ~5% • Tight top 30% of the register comprising institutional and high net worth investors have continued to support the company through its pathway to this near-term value inflection point • Significant support from other high net worth and retail investors who recognize the value upside potential *ASX:ACW share price and volume trading chart 12 months to 17 November 2025 Xanamem’s unique mechanism of action 5 Click here for animation video Bell Potter Healthcare Conference 2025 Alzheimer’s disease market is large and growing 6 Growing Alzheimer’s Disease market – U.S. Large, unsatisfied and growing market Bell Potter Healthcare Conference 2025 Interim XanaMIA results in late Jan 2026, topline final results mid Q4 2026 7 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) Optimal pivotal trial design & patient selection Bell Potter Healthcare Conference 2025 Xanamem: Clear pathway to Alzheimer’s approval 8 • 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: • Brisk enrolment 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 Bell Potter Healthcare Conference 2025 Previous results that give the company confidence in a positive phase 2b/3 trial outcome in Alzheimer’s 9 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 Bell Potter Healthcare Conference 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) 10 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 Bell Potter Healthcare Conference 2025 11 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 Bell Potter Healthcare Conference 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 12 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 Bell Potter Healthcare Conference 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 13 [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 Bell Potter Healthcare Conference 2025 Strategic insights about commercialization and partnering in AD 14 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 Bell Potter Healthcare Conference 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 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 Bell Potter Healthcare Conference 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 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 Bell Potter Healthcare Conference 2025 16 17 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 Bell Potter Healthcare Conference 2025 18 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: ✓ Completing one or more regional partnership deals ✓ Final results that are good enough to excite multiple, global partnership bids ✓ Final results that are good enough for regulators to seriously consider expedited approvals Bell Potter Healthcare Conference 2025 Conclusion 19 Bell Potter Healthcare Conference 2025 Building momentum toward Alzheimer’s results 20 • 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 Bell Potter Healthcare Conference 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 21 Bell Potter Healthcare Conference 2025 22 Q & A 22 Bell Potter Healthcare Conference 2025 23 Contacts Mr Will Souter Chief Financial Officer M: +61 402 035 716 E. will.souter@actinogen.com.au Dr Steven Gourlay CEO & Managing Director P: +61 2 8964 7401 E. steven.gourlay@actinogen.com.au 23 Join the Actinogen Investor Hub: https://investors.actinogen.com.au/ Bell Potter Healthcare Conference 2025