Announcement PDF ABN 16 165 160 841 ASX RELEASE 30 May 2025 Annual Report – Year Ended 31 March 2025 Amplia Therapeutics Limited (ASX: ATX) today releases its Appendix 4E Preliminary Final Report YE 31 March 2025 and its 2025 Annual Report. This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics. Investor Contact: Dr Chris Burns Chief Executive Officer chris@ampliatx.com Media Contact: H^CK Director, Haley Chartres haley@hck.digital +61 423 139 163 About Amplia Therapeutics Limited Amplia Therapeutics Limited is an Australian pharmaceutical company advancing a pipeline of Focal Adhesion Kinase (FAK) inhibitors for cancer and fibrosis. FAK is an increasingly important target in the field of cancer and Amplia has a particular development focus in fibrotic cancers such as pancreatic and ovarian cancer. FAK also plays a significant role in a number of chronic diseases, such as idiopathic pulmonary fibrosis (IPF). For more information visit www.ampliatx.com and follow Amplia on Twitter (@ampliatx) and LinkedIn. - End - Level 17, 350 Queen Street, Melbourne VIC 3000 Email info@ampliatx.com www.ampliatx.com ANNUAL REPORT 1 FIGHT C 2024-2025 Amplia Therapeutics Ltd COVER ART Of Ether and Water IV Original Bokeh Painting by Jacquelyn Stephens. Reproduced with permission. jacquelynstephensart.com.au Amplia Therapeutics recognises and respects First Nations People and welcomes the work of all those who strive for health equality in Australia. 2 Contents Letter from the Chairman .......................................................................................... 4 CEO and MD Message ............................................................................................. 6 Meet the Team ........................................................................................................ 8 Company Snapshot .............................................................................................. 10 Year in Review ........................................................................................................ 12 ACCENT Trial in pancreatic cancer ...................................................................... 14 Amplia Targets US Market with Initiation of FOLFIRINOX Trial ........................ 16 Global Standards of Care: How Pancreatic Cancer Treatment Varies ................ 18 Our Values ................................................................................................................................ 20 Financial Report ............................................................................................................................... 21 Letter from the Chairman Dear Shareholders, On behalf of your Board I am delighted to share the Amplia 2025 Annual Report. We have made significant progress with our FAK inhibitor program in the past year and the strong support of our shareholders is a key contributor to that progress, thank you. A year ago we were in the very early stages of our pivotal Phase 2a trial with sites open in Australia and South Korea. We had ambitious targets with regard to recruitment of subjects and high hopes that we would produce data that established the tolerability, safety and efficacy of narmafotinib (AMP945) in patients with advanced pancreatic cancer and underpin the continued clinical development. As we passed essential milestones during the trial the belief grew stronger that we could make a real difference to patients with this very challenging cancer. We have shared this data publicly and appropriately, including presenting topline data from the first 26 patients at a major international cancer conference (AACR) in the USA in April 2025. Narmafotinib was discovered in Australia, and is a highly potent and selective inhibitor of the enzyme FAK, with a best-in-class profile. In the ACCENT trial, the drug is dosed in combination with standardof-care chemotherapy and the data to date strongly indicate that the addition of narmafotinib substantially enhances the activity of chemotherapy. Critically, the drug appears to be well tolerated and is therefore not adding additional burden to patients who are already managing health effects of the disease itself and the attendant side-effects from chemotherapy. To fully recruit the ACCENT trial (55 patients) two-months ahead of schedule is a credit to our Amplia team, the clinical teams at the sites in Australia and South Korea and to the many service organisations that are needed to ensure the complex integration and operation of all the activities. We are grateful to all involved and most importantly to the patients, who facing a major health challenge, generously choose to participate in a clinical trial. This year the Company assembled a world-class clinical advisory board comprising key opinion leaders in pancreatic cancer and oncology clinical research. The advisory board offers critical insight into the data being generated in our current clinical trial as well as providing input into the design of our planned US trial. This second clinical study, investigating a combination of narmafotinib with a different chemotherapy to that used in the ACCENT study, is important strategically so that the Company can position narmafotinib as a drug that can be combined with the two main chemotherapy regimes used in treatment of advanced pancreatic cancer. The Company also announced a research collaboration with Korean biotechnology company Next&Bio. This collaboration builds on our ties in Korea, and will investigate new opportunities for our FAK inhibitors in pancreatic cancer. Lastly, and perhaps most importantly, the accelerated approval in the US of a new drug regimen which includes the first-generation FAK inhibitor defactinib, represents a milestone for development of FAK inhibiting drugs. The drug regimen has been developed by a US biotech for treatment of a subset of patients with the rare cancer low grade serous ovarian cancer. The treatment had previously received breakthrough designation from the FDA based on promising Phase 2 clinical data reported during the year. The Company successfully raised capital twice in the past financial year. We are grateful for the support of existing shareholders and pleased to welcome new investors to the register, including sophisticated 4 Institutional investors in the biotech space. The sector continues to be volatile, however we remain committed that our lead asset narmafotinib, and our development strategy, will deliver increasing shareholder value as our clinical dataset matures. Amplia has made great progress over the past year, and the available data from the ACCENT trial provides the confidence for ongoing development of narmafotinib as an integral part of this and other combinations. The momentum from ACCENT has built commitment and enthusiasm from the oncologist investigators involved in the trial. We are seeking every appropriate opportunity to communicate the data along with their feedback in scientific forums and in business partnering activities. On behalf of the Board I would like to acknowledge the hard work of the Amplia team, led by our CEO and Managing Director, Chris Burns, who continue to deliver on our plans in a timely and efficient manner. I thank my Board colleagues for their strategic guidance, careful governance and focused engagement with the planning and operation of Amplia. Our current activities, as we advance our clinical development, require careful attention to ensure that the right plans are delivered on time and on budget. While Chris Burns is our formal connection with the management team, we have many opportunities to engage and get direct feedback from our small but very experienced team. “ Finally, I would like to thank you, our shareholders, for your continued support of the Company, our exciting drug programs and the prospective benefits for patients with cancer. Amplia is in the advanced stages of developing a pipeline of small molecule inhibitors of FAK to meet urgent unmet needs in the cancer therapeutics space. This is an important body of work, which our investors can be proud to back – with value inflections imminent. Independent Non-Executive Chair, DR WARWICK TONG Dr Warwick Tong Independent Non-Executive Chair CEO and MD Message This last year has been another landmark year for Amplia Therapeutics. Our primary focus has been the clinical development of narmafotinib, and we have made great progress with the ongoing ACCENT trial. We have also been finalising plans for our US-based trial and conducting important preclinical work to explore the potential of narmafotinib in other cancer settings. The Amplia team and I have been truly excited to see the positive data coming from the ACCENT trial in advanced pancreatic cancer. Building on the initial signs of activity observed from the Phase 1b stage of the trial, reported last year, the trial enrolled well with the initial Phase 2a cohort of 26 patients being recruited by July. Six confirmed partial responses (PRs) from this cohort had been observed by September, a level of activity that indicated the combination of narmafotinib and the chemotherapies gemcitabine and Abraxane was sufficiently active for us to begin recruitment of the remaining 24 patients in the trial. We have continued to closely monitor these 26 patients, and by early March had observed 11 confirmed PRs and a median duration on trial of 208 days for this group, substantially better responses than for patients treated with the chemotherapy alone, based on historical data. The remaining 24 patients were again enrolled quickly, two months ahead of schedule, demonstrating the level of enthusiasm for the trial from our clinical trial sites in Australia and Korea. By the end of our business year (31 March 2025), for the fully enrolled cohort of 55 patients in total, 13 confirmed PRs had been observed. This has since increased to 15 confirmed PRs with 21 patients still on study. We look forward to reporting additional data as it becomes available. Our second clinical trial in pancreatic cancer is due to start mid-year, and we have been working diligently on supporting activities so that this trial can begin on time and run as efficiently as possible. The manufacture of sufficient quantities of drug to the high standards required has been completed over the year. In addition, we have undertaken further interaction with the US Food and Drug Administration (FDA) to ensure that the trial is fully compliant with FDA guidelines and in March 2025 reported the positive outcome from our Type D meeting with the FDA. Preclinical studies have focused on demonstrating the potential of narmafotinib in combination with other drugs being developed for the treatment of cancer. In particular, we have been interested in exploring how narmafotinib could enhance the activity of a new class of drugs called kRas inhibitors. There is substantial activity in developing kRas inhibitors by both pharma and biotech for various cancers, including pancreatic cancer; however, data from the most advanced compounds indicates that drug resistance amongst other issues may be problematic. We reported at an international conference at the beginning of this year that narmafotinib can enhance the activity of these drugs in preclinical cancer models, findings that may position narmafotinib as a key co-medication for these drugs to be truly successful. These are just some of the highlights from the Amplia team’s myriad achievements this year. Progress in regulatory activities, quality and Chemistry, Manufacturing and Controls (CMC), along with preclinical research, underpin much of our clinical success and I want to take the opportunity to thank our staff for their dedication and hard work. Finally, I wish to thank you, our Shareholders and investors, for your continued support and enthusiasm for our work. We remain focused on driving the development of narmafotinib forward to clinical success, and in so doing adding commercial potential to the Company and driving shareholder value. Dr Christopher Burns CEO and MD 6 “ We remain focused on driving the development of narmafotinib forward to clinical success, and in so doing adding commercial potential to the Company and driving shareholder value. CEO and MD, DR CHRISTOPHER BURNS Meet the Team Board of Directors WARWICK TONG MB ChB MPP GAICD Non-Executive Chairman of the Board Warwick is a NZ trained physician with more than 25 years’ experience in the Pharmaceutical and Biotechnology industry. Dr Tong was appointed as a Non-Executive Director on the 4th of May 2018 and Chairman on 25th May 2018. Dr Tong is also a member of the Audit Committee. CHRISTOPHER BURNS BSc (Hons) PhD GAICD Chief Executive Officer and Managing Director Chris is an experienced drug discovery leader having worked in various roles in pharma, biotech and academia for 30 years. Dr Burns was originally appointed as a Non-Executive Director on 4th May 2018 and was subsequently appointed as Chief Executive Officer and Managing Director on 5th December 2022. ROBERT PEACH PhD Independent Non-Executive Director Robert has over 30 years of drug discovery and development experience in the Pharmaceutical and Biotechnology industry. Dr Peach was appointed as an Independent Non-Executive Director on the 2nd September 2015 and is a Chair of the Remuneration Committee and a member of the Audit and Risk Committee. JANE BELL AM, BEc, LLB, LLM (Lond), FAICD Independent Non-Executive Director Jane is a banking and finance lawyer and non-executive director with more than 30 years’ experience in leading law firms, financial services and corporate treasury operations in Melbourne, London, Toronto, San Francisco and Brisbane. Ms Bell was appointed as an Independent Non-Executive Director on 12th April 2021 and is Chair of the Audit and Risk Committee. 8 Meet the Team Executive Team Scientific Advisers CHRISTOPHER BURNS BSc (Hons) PhD, GAICD Chief Executive Officer and Managing Director PROFESSOR MARGARET FRAME OBE, PhD FAK Biology Adviser RHIANNON JONES BSc (Hons) PhD, GAICD Chief Operating Officer PROFESSOR PAUL TIMPSON PhD FAK Biology Adviser DR JASON LICKLITER MBBS, FRACP Chief Medical Officer MARK DEVLIN BSc (Hons) PhD GradD Drug Dev MBA Scientific Adviser TIM LUSCOMBE BCom, CA, GIA (Cert) Chief Financial Officer ANDREW J. COOKE LLB Company Secretary CHARLOTTE MULDER BVSc (Hons), MBA Director Early Clinical Development TERRIE-ANNE COCK PhD Director Translational Science ADRIAN SULISTIO BEng (Hons), B. Com, PhD Manager Product Development NICOLE KRUGER BSc Director Clinical Operations Clinical Advisers DR JOSE IGLESIAS MD Clinical Adviser (Oncology) DR JORDAN BERLIN MD Clinical Adviser DR MITESH BORAD Clinical Adviser PROFESSOR NICK PAVLAKIS Clinical Adviser Company Snapshot Amplia Therapeutics Limited (ASX: ATX) is an Australian, clinical-stage, drug development company focused on the development Amplia’s pipeline drugs were originally developed by the of two potent, orally-available Cancer Therapeutics CRC (CTx), an Australian industry and academic collaboration that united bright minds inhibitors of Focal Adhesion at the country’s top cancer research institutes. The Kinase (FAK) for the Company’s lead therapeutic – originally known as AMP945 treatment of cancer and and now narmafotinib – was invented by a team of drug fibrotic diseases.​ discovery specialists including scientists from Monash Institute of Pharmaceutical Sciences, Peter MacCallum Cancer Centre, St Vincent’s Institute of Medical Research, the Walter and Eliza Hall Institute of Medical Research and Australia’s national science agency, CSIRO. Amplia was established to advance these promising drugs into clinical development and commercialisation – and is now well advanced on this journey. Our Technology Amplia Therapeutics is currently focused on the clinical development of two highly-promising drug candidates targeting Focal Adhesion Kinase (FAK). FAK inhibitors have been described as a ‘heavy punch’ to cancer, showing promising potential when used in combination with existing ‘standard of care’ therapies in the treatment of solid cancers. Our FAK inhibitors affect both the cancer cells themselves and the surrounding tissue, making tumours more vulnerable and responsive to currently used, and developmental, treatments. Pipeline 10 Focus on Oncology Focal Adhesion Kinase (FAK) is upregulated in many cancers where it supports cell survival and drives cell growth and migration. In addition, it is directly involved in several important biological processes in the tumour microenvironment i.e. the region surrounding the tumour; including the formation of fibrotic, scar-like tissue and generation of an immunosuppressed environment, both of which support tumour growth. When cancers become established in the body they often use these processes to improve their own survival. Amplia’s Cancer Program is directed at using its FAK inhibitors to block FAK activity in the cancer cells as well as the surrounding tissue, thereby blocking the above processes and making the tumours more susceptible to chemotherapy. Amplia’s lead drug candidate, narmafotinib, is a highly selective and potent FAK inhibitor that has shown promising results in preclinical studies for the treatment of pancreatic and ovarian cancers – both devastating, hard-to-treat diseases, in urgent need of new treatments. Most importantly, our clinical data in pancreatic cancer is also extremely promising (see page 14). Ovarian Cancer Pancreatic Cancer Pancreatic cancer is a difficult to treat cancer, with a low survival rate, typically detected late in disease progression. There were an estimated 4,600 diagnoses in Australia in 2024 and the estimated 5-year survival rate is 13%. Amplia has demonstrated the efficacy of narmafotinib in preclinical models of pancreatic cancer and is now undertaking a Phase 2 clinical trial in advanced pancreatic cancer in Australia and South Korea. Amplia has orphan drug designation and fast-track designation for pancreatic cancer from the US Food and Drug Administration (FDA). 11 Over 315,000 women develop ovarian cancer annually and high grade serous ovarian cancer (HGSOC) accounts for ≥90% of cases. HGSOC has poor prognosis with a 10-year survival rate of 15%. Platinum-based chemotherapy is the standard-of-care (SOC) treatment, however, nearly all recurrent HGSOC develop platinum-resistance limiting treatment options. Year in Review FY25 proved to be a productive year for Amplia Therapeutics, marked by significant progress in our flagship ACCENT clinical trial, notable regulatory achievements, and strategic positioning for future growth. The Company reached several critical milestones that validate our approach and strengthen our position as a leader in FAK inhibitor development. Clinical Trial - Well Advanced The ACCENT trial remained our primary focus throughout FY25. We successfully completed recruitment for both stages of the Phase 2a trial - first completing the initial 26-patient cohort and subsequently finishing full enrolment ahead of schedule with 55 patients in total. Our clinical results have been particularly encouraging. By the end of March 2025, 13 patients had achieved confirmed partial responses (representing at least 30% tumour shrinkage sustained for two months), positioning us well toward our target of 15 responses that would demonstrate superior efficacy compared to standard chemotherapy alone. The Phase 1b results, presented at prestigious conferences, including AACR and ASCO, showed a remarkable response rate of approximately 38% - significantly outperforming the 23% historical benchmark. Equally important was the FDA’s recognition of our progress, granting Fast Track Designation for narmafotinib in advanced pancreatic cancer - a designation reserved for therapies that may provide advantages over current treatments for serious conditions and opening up the possibility to access additional regulatory schemes including breakthrough designation and priority review. FY25 saw significant expansion of our international footprint. Our ACCENT trial successfully operated across multiple countries, with seven sites in Australia and five sites in South Korea. Our planned pancreatic cancer trial of narmafotinib combined with a different chemotherapy to that used in ACCENT, will be conducted in the US and Australia, under an IND application that was cleared by the US FDA last year. We have maintained an ongoing interaction with the FDA and changes to the trial protocol to speed up the development timeline have been reviewed and cleared by the FDA. Intellectual Property Amplia strengthened its intellectual property portfolio significantly, with key patents for narmafotinib granted in both Europe and Japan. These patents protect the specific chemical form of the drug currently in clinical development, securing our competitive position in major global markets. Research Collaborations and Pipeline Development Strategic partnerships enhanced our research capabilities during FY25. We initiated a collaboration with Korean biotech Next&Bio to test FAK inhibitors in combination with novel kRas inhibitors - expanding potential applications beyond pancreatic cancer to lung and colorectal cancers. Financial The Company successfully completed a $13.0 million capital raise during the December quarter, combining a placement and entitlement offer. This funding, along with strategic loan arrangements, provided the financial foundation to complete the ACCENT trial and advance our US FOLFIRINOX trial activities. We also successfully received our FY24 R&D Tax Incentive refund of $3.2 million, which allowed us to fully repay director loans and strengthen our balance sheet. 12 Future Outlook As we look ahead, Amplia is strategically positioned with multiple, near-term value drivers. The completion of ACCENT trial recruitment ahead of schedule provides earlier visibility to interim results, while our advancing US FOLFIRINOX trial represents significant expansion opportunities. With promising interim data already achieved, we are confident in our ability to deliver on our clinical objectives and advance narmafotinib toward potential regulatory approval. The foundations established in FY25 - from clinical validation to regulatory recognition to international expansion - now position Amplia for continued growth and value creation in the year ahead. April 2024 AACR Conference Presentation May 2024 $4.27m Offer Successfully Completed and ACCENT Trial Update May 2024 ASCO Conference Abstract June 2024 Amplia Establishes World Class Advisory Board July 2024 First 26 Patients Recruited in Phase 2A ACCENT Trial July 2024 Bioshares Conference Presentation July 2024 Sustained Reduction in Tumour Size Seen in Patients in Pancreatic Cancer Trial August 2024 Additional Patient Shows Sustained Reduction in Tumour Size in Pancreatic Cancer Trial August 2024 Granting of Key Chemical Form Patent in Europe and Japan August 2024 Amplia Receives R&D Tax Rebate Totalling $3.2 Million August 2024 Five Patients Record Sustained Reduction in Tumour Size in ACCENT Trial September 2024 FDA Fast Track Designation for Namafotinib in Advanced Pancreatic Cancer September 2024 Tumour Response in Sixth Patient Triggers Additional Recruitment in Pancreatic Cancer Trial October 2024 Recruitment Restarts in ACCENT Pancreatic Cancer Trial October 2024 Interim Data from ACCENT Pancreatic Cancer Trial Supports Continuation of Trial November 2024 Amplia Successfully Completes Institutional Placement November 2024 Amplia Enters into Preclinical Collaboration with Korean Specialist Drug Screening Company Next&Bio November 2024 Successful Completion of Retail Entitlement Offer December 2024 Positive New Data and Strong Recruitment in Pancreatic Cancer Trial January 2025 New Data for Narmafotinib Presented at International Conference January 2025 Completion of Recruitment of ACCENT Trial March 2025 Type D Meeting Outcome with US Food and Drug Administration March 2025 Encouraging Updated Data from Pancreatic Cancer Trial 13 ACCENT Trial in pancreatic cancer Since the launch of the ACCENT trial in August 2022, Amplia has achieved remarkable progress, completing full enrolment ahead of schedule and demonstrating compelling clinical results. What is the ACCENT Trial? Amplia is testing its FAK inhibitor narmafotinib (AMP945) in a Phase 1b/2a clinical trial in advanced pancreatic cancer patients, called the ACCENT trial. Narmafotinib is being added to the standard-of-care chemotherapy for advanced pancreatic cancer in Australia, a combination of two drugs called gemcitabine and nab-paclitaxel (Abraxane®). The trial is an open-label trial meaning all patients receive the experimental treatment and there is no control arm. Clinical data from the trial will be compared against published data from previous trials where gemcitabine and nab-paclitaxel have been studied in the identical patient population. The trial targets newly diagnosed patients who have advanced disease. For the Phase 1b stage, this included patients who have either locally advanced disease that cannot be removed surgically (nonresectable) or that has spread to other parts of the body (metastatic). For the Phase 2a stage, only patients with metastatic disease are included. The primary readout from the trial is Objective Response Rate (ORR). Secondary endpoints are Duration on Trial (DOT), Progression Free Survival (PFS) and Overall Survival (OS). Phase 1b to Phase 2a Transition Following completion of the Phase 1b stage of the trial, which identified a 400 mg daily dose of narmafotinib providing sufficient circulating drug levels to significantly block the activity of the FAK enzyme, the Company commenced Phase 2a of the trial. The objective of the first stage of the Phase 2a trial is to establish whether the proportion of responses to the drug is sufficient to warrant testing in a larger patient group. Analysis by expert biostatisticians identified that a clinical response (partial or complete response) in six or more patients out of 26 would be sufficient to continue enrolment of a further 24 patients. In total, there would be 50 patients in the trial, sufficient to generate statistically meaningful response data. Amplia opened recruitment for the Phase 2a portion of the trial in November 2023, with the first patient dosed in January 2024. Throughout 2024, Amplia announced a series of increasingly positive results from the Phase 2a portion of the ACCENT trial. The trial achieved its interim efficacy threshold progressively, with confirmed partial responses building from three patients in July 2024 to six patients by September 2024, triggering the continuation criteria for full enrolment. By December 2024, nine confirmed partial responses had been recorded from the initial 26 patient cohort, representing an objective response rate of approximately 35%, significantly better than the 23% reported for the historical trial being used as the benchmark. The median duration on trial for the 26 patients reached 172 days, representing a 47% improvement over the historical data of 117 days. 14 BREAKING NEWS Trial Recruitment Completed Ahead of Schedule The Company completed planned enrolment of the ACCENT Phase 2a clinical trial in January 2025, achieving full recruitment two months ahead of the original schedule. A total of 55 advanced pancreatic cancer patients have been enrolled in the study at trial sites in Australia and South Korea. As of May 2025, fifteen confirmed partial responses have been recorded in the trial, a level of response sufficient to demonstrate that the combination of narmafotinib and chemotherapy is superior to chemotherapy alone. In March 2025, 13 confirmed partial responses had been observed to date, with the median duration on trial for the first 26 patient cohort reaching 197 days, representing a 68% improvement over the historical data. Throughout the trial, narmafotinib has continued to be generally well tolerated by patients. No patients have withdrawn from the study due Looking Ahead to issues from narmafotinib. The rate and type of adverse events for With full enrolment completed the narmafotinib combination are very similar to that reported for ahead of schedule and compelling chemotherapy alone. interim data demonstrating both excellent tolerability and meaningful efficacy improvements over standard chemotherapy alone, the ACCENT trial positions narmafotinib as a promising new treatment option for advanced pancreatic cancer patients. Top-line data from the complete 55-patient dataset is planned for release in mid-Q3 2025. The success of the ACCENT trial validates Amplia’s approach to FAK inhibition in oncology and establishes a strong foundation for the Company’s broader clinical development strategy in addressing significant unmet needs in cancer treatment. ACCENT Hits the International Conference Circuit Data from the ACCENT has been presented at prestigious international scientific conferences, including the Keystone Meeting on the Tumour Microenvironment Banff, Canada, and the American Association of Cancer Research Annual Meeting in the United States. Both of these presentations have provided the Amplia team with the opportunity to engage with world-leading clinicians and scientists about the considerable potential of narmafotinib in pancreatic cancer treatment. Amplia Targets US Market with Initiation of FOLFIRINOX Trial Amplia has advanced its clinical development program by initiating a second major clinical trial exploring narmafotinib in combination with FOLFIRINOX, the preferred first-line treatment for advanced pancreatic cancer in the United States. While the ACCENT trial being conducted in Australia and Korea is investigating narma