Announcement • May 28
Actinogen Medical Limited Announces Positive EMA Scientific Advice and Provides Update on Xanamem Alzheimer’s Disease Program Actinogen Medical Limited announced the successful outcome of its scheduled scientific advice meeting (written response) on Alzheimer’s disease (AD) with the European Medicines Agency (EMA). Actinogen and the EMA reached a common understanding of the pathway to marketing approval for AD in the European Union (EU). This includes agreements related to regulatory starting materials used in drug substance synthesis, design considerations for one additional pivotal clinical trial and the limited number of ancillary clinical pharmacology trials and nonclinical studies required. Key understandings include: Agreement on the suitability of the ‘Regulatory starting materials’ for the commercial manufacturing of Xanamem (emestedastat) drug substance; Design of one additional, well-controlled, pivotal (phase 3) trial to follow a positive XanaMIA pivotal trial – both use a 10 mg dose vs. placebo; Standard total number of people to be treated with Xanamem to be described in the Marketing Authorization Application – that is, the proposed makeup of the planned safety database consistent with EMA and FDA guidelines; Small number of ancillary clinical pharmacology trials to be conducted parallel with the next pivotal trial; Small number of nonclinical studies required to further characterize safety, metabolism and excretion pathways to be conducted parallel with the next pivotal trial. The outcome reached at this meeting aligns closely with the guidance received at an earlier meeting with the FDA’s Neurology-I Division in September 2025. With the new EMA advice, Actinogen now has a clear pathway and guidance towards marketing approvals in two key pharmaceutical markets. Approvals in the US and EU also contribute to approvals in many other countries and regions. The advice from both the FDA and EMA provides regulatory clarity for ongoing discussions with potential development and marketing partners. Topline results from the randomized phase of the XanaMIA pivotal Alzheimer’s disease trial of Xanamem 10 mg vs. placebo are expected in November this year. The trial enrolled 247 participants in the US and Australia with mild to moderate Alzheimer’s disease and elevated levels of plasma pTau181. Earlier this year the Independent Data Monitoring Committee (DMC) recommended the trial continue unchanged after a confidential assessment of unblinded safety and efficacy futility data. All XanaMIA participants are now potentially eligible to extend their treatment by participation in the Open Label Extension (OLE) phase. The OLE will provide valuable data on longer-term safety and efficacy trajectories. The XanaMIA trial is intended to serve as one of two pivotal trials supporting the earliest possible marketing approvals for Xanamem in multiple regions. If the trial results are strongly positive in November, the Company will also explore expedited approval pathways with relevant regulators while commencing the new pivotal phase 3 trial. The FDA recently announced a new policy supporting approval based on a single pivotal trial with adequate supporting evidence. Xanamem’s novel mechanism of action is to control the level of cortisol in the important areas of the brain through the inhibition of the cortisol synthesis enzyme, 11ß-HSD1, without blocking normal production of cortisol by the adrenal glands. Xanamem is a first-in-class, once-a-day pill designed to deliver high levels of brain cortisol control in regions where 11ß-HSD1 is highly expressed such as the hippocampus. Chronically elevated cortisol is associated with progression in Alzheimer’s Disease and excess cortisol is known to be toxic to brain cells. Elevated cortisol is also associated with depressive symptoms. Xanamem has demonstrated excellent brain target engagement and in human trials has shown potential to slow progression of Alzheimer’s disease and improve depressive symptoms in patients with moderately severe depression. 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. Major Estimate Revision • May 20
Consensus EPS estimates upgraded to AU$0 loss The consensus outlook for fiscal year 2026 has been updated. 2026 losses forecast to reduce from -AU$0.0026 to AU$0.00 per share. Revenue forecast unchanged from AU$11.0m at last update. Biotechs industry in Australia expected to see average net income growth of 2.8% next year. Consensus price target of AU$0.08 unchanged from last update. Share price fell 21% to AU$0.034 over the past week. New Risk • May 18
New minor risk - Market cap size The company's market capitalization is less than US$100m. Market cap: AU$129.3m (US$92.5m) This is considered a minor risk. Companies with a small market capitalization are most likely businesses that have not yet released a product to market or are simply a very small company without a wide reach. Either way, risk is elevated with these companies because there is a chance the product may not come to fruition or the company's addressable market or demand may not be as large as expected. In addition, if the company's size is the main factor, it is less likely to have many investors and analysts following it and scrutinizing its performance and outlook. Currently, the following risks have been identified for the company: Major Risk Earnings are forecast to decline by an average of 37% per year for the foreseeable future. Minor Risks Currently unprofitable and not forecast to become profitable over next 2 years (AU$35m net loss in 2 years). Market cap is less than US$100m (AU$129.3m market cap, or US$92.5m). 
