Announcement PDF 2025-2026 Amplia Therapeutics Ltd ANNUAL REPORT 1 F I G H T C COVER ART Lakes Walk Original Illustration by Lilian Darmono. Reproduced with permission. 2 Amplia Therapeutics recognises and respects First Nations People and welcomes the work of all those who strive for health equality in Australia. Contents Letter from the Chairman ..........................................................................................4 CEO and MD Message .............................................................................................6 Year in Review .......................................................................................................... 8 ACCENT Trial in pancreatic cancer ................................................................... 12 Targeting kRAS ....................................................................................................... 14 Scaling Up .................................................................................................................. 16 The Next Wave of Targeted Therapy ...................................................................... 18 Financial Report ................................................................................................................ 20 3 Letter from the Chairman Dear Shareholders, On behalf of the Board, I am delighted to present Amplia’s Annual Report for 2026. The year has been marked by significant progress and accomplishments. The Company is poised for further growth as we develop our pipeline. Our primary objective is to advance clinical studies of narmafotinib in pancreatic cancer, as well as supporting studies to generate robust data that will inform subsequent clinical trials involving alternative combinations and facilitate expansion into new therapeutic areas. The ACCENT clinical trial has continued to deliver exciting data, offering new promise for patients with pancreatic cancer and driving both Company growth and commercial interest. The most recent data, reported to the market in March 2026, is another step in a long journey and continues to underpin the scientific rationale that drove the original commitment and investment in the potential of focal adhesion kinase inhibition (FAKi) in contributing to the management of cancer. Narmafotinib was discovered and had its early development within the Cancer Therapeutics Cooperative Research Centre (CTxCRC) headquartered in Melbourne and licensed to Amplia in 2016. After completion of the requisite safety and manufacturing studies, its first-in-human clinical study (Phase 1a) was completed in Melbourne in 2020. In August 2022, the first patient with pancreatic cancer was enrolled in the ACCENT Phase 1b dose-escalation trial. As this was the tail end of the Covid pandemic, recruitment was slower than anticipated, with this stage of the trial formally completed in October 2023 with 15 patients enrolled. The Phase 2a recruitment of ACCENT began in January 2024 and was fully enrolled by mid-February 2025 with a total of 55 patients on study. As of mid-March, four patients remain on trial and one patient is just completing two years of treatment. We describe in this report the very exciting mature data from the trial that was recently disclosed to the market. These data show that across all measures, the combination of narmafotinib and the chemotherapies gemcitabine and Abraxane® performs better, based on historical data, than the chemotherapy alone. This provides the continuing confidence for the Company to direct the required investment to progress narmafotinib into the next stage of clinical studies. The CEO’s letter details the positive state of discussions with the US FDA regarding the design and implementation of these later stage studies. Our second clinical trial in pancreatic cancer, the AMPLICITY trial, began recruiting patients in Australia this last year. This trial combined narmafotinib with the more aggressive chemotherapy FOLFIRINOX. This chemotherapy has been more widely used in the United States and Europe than Australia, especially for younger and fitter patients. The US trial sites for AMPLICITY completed initiation processes more slowly than anticipated, with only two sites ready to recruit patients by the end of March 2026. Due to the early occurrence of significant FOLFIRINOX-related toxicity, as determined by the clinical investigators, we recently elected to discontinue recruitment into this trial. Five patients remain on the trial and are continuing on treatment, and we are shifting our focus to initiate additional trials with other clinical combination treatments that have less severe side-effect profiles. The treatment landscape for pancreatic cancer has been rapidly evolving with a clear shift away from toxic chemotherapy. Whilst this has been the mainstay of treatment for many years, new drugs targeted to specific cancer-driving mutations are showing promise in clinical studies. These newer drugs (kRAS inhibitors, ADCs, 4 cell therapies) have the potential to become new ‘standards-of-care’, in many cases when combined with less toxic chemotherapy options such as gemcitabine and Abraxane. We at Amplia are watching these developments closely and firmly believe there is significant opportunity for narmafotinib to be an integral part of this new paradigm of treatment. By breaking down the fibrosis in the tumour microenvironment, enhancing immune activation, and by blocking resistance pathways, narmafotinib has great potential to enhance the activity of these new treatments, increasing durability and depth of response. Discussions with selected developers of these drugs are underway. We are paying significant attention to other cancers that have attributes that present additional opportunities for combination therapy with narmafotinib. One example, that we have discussed publicly, is ovarian cancer which is often characterised by a fibrotic nature and resistance to standard-of-care chemotherapy. The efficacy of, and tolerance to, narmafotinib in the ACCENT trial is also attracting attention from potential collaboration partners that are interested in enhancing their therapeutic efficacy in other solid tumours. We successfully raised $27.5 million to support our ongoing development activities and plans. We thank all our shareholders, institutional and retail investors, who continue to support Amplia along this development path and who show their commitment by that support. As Chair, I could not ask for more commitment and contribution from my fellow directors. As CEO and Managing Director, Chris Burns has been an inspirational leader for his team and has applied his combination of scientific and business acumen to laying out the right pathways for Amplia within the changing oncological scientific and business environment. We have a small, highly competent team dedicated to the success of Amplia. The achievements of the past year are a glowing example of this performance. Like a good Board should do, we regularly look inward at our skills and performance to assess how we need to adapt to the changing external environment and growing success of Amplia. As we move into a more commercial phase of our development we will continue to review Board capability and make-up. Dr Warwick Tong Independent Non-Executive Chair 5 The ACCENT clinical trial has continued to deliver exciting data, offering new promise for patients with pancreatic cancer and driving both Company growth and commercial interest. Independent Non-Executive Chair, DR WARWICK TONG “ CEO and MD Message This past year has been a watershed year for Amplia. As the ACCENT trial nears its end, the mature data coming from independent analysis of the clinical imaging data clearly demonstrates that narmafotinib is having a profound benefit for pancreatic cancer patients when combined with standard-of-care chemotherapy. With such strong data for narmafotinib, we are now actively planning for a registration-enabling study as well as exploring potential for additional clinical opportunities. The potential for clinical and commercial success for our lead program is now significantly enhanced. The ACCENT trial, which explores the combination of narmafotinib with gemcitabine and nab-paclitaxel (Abraxane® ) in newly diagnosed patients with advanced (metastatic) pancreatic cancer, has been running for over three years and we anticipate that the trial will be completed in Q3 this year. The study is an open-label trial meaning that all patients receive narmafotinib and chemotherapy, and we benchmark activity against historical data for the chemotherapy alone - we discuss the ACCENT data in more detail on page 12. To generate clinical data that will support a registrational filing for approval of narmafotinib, we need to conduct a controlled study where the activity of narmafotinib combined with gemcitabine and Abraxane is compared to the activity of gemcitabine and Abraxane alone. Planning for this study is progressing well, and this past year we worked with the US FDA and to achieve alignment on the clinical trial approach to determine the optimal dose of narmafotinib. Additional meetings with the FDA will be held in the coming months to address other questions related to the Phase 2b/3 study. Our second study in pancreatic cancer also began over this last year. This trial is exploring a combination of narmafotinib with the 4-drug combination chemotherapy, FOLFIRINOX, again in newly diagnosed patients with metastatic pancreatic cancer. FOLFIRINOX, generally considered a more aggressive treatment compared to gemcitabine and Abraxane used in the ACCENT trial, is a more commonly used treatment option for metastatic pancreatic cancer in the US and Europe, compared to Australia. The trial began in September 2025 at two sites in Australia with two additional sites in the US opening in early 2026. In April this year we announced discontinuation of recruitment into the trial because the FOLFIRINOX backbone appeared to be too toxic, limiting our ability to escalate the dose of narmafotinib to suitable levels. Five patients remain on study and important data will be generated from this small patient group and will be reported in due course. There is currently significant interest in the development of new drugs for pancreatic cancer. This is largely driven by the promising clinical data being reported for a new class of drugs called kRAS inhibitors. Whilst these drugs are showing promising efficacy in clinical studies, they still need to penetrate the fibrotic microenvironment, safety and tolerability remain an issue, and drug resistance has been shown to rapidly develop. Over this last year we have produced and reported data from preclinical studies showing that narmafotinib improves responses to kRAS inhibitors by modulating fibrosis and blocking emergent resistance pathways. We are speaking with potential collaborators regarding proof-of-concept clinical studies combining narmafotinib with kRAS inhibitors with the goal of initiating a study before the end of 2026. 6 The team at Amplia, along with our network of consultants and advisers, are working tirelessly to progress Amplia’s programs, and specifically our lead drug narmafotinib, toward key clinical and commercial milestones. CEO and MD, DR CHRISTOPHER BURNS “ As I write this letter, the Artemis II astronauts are on their return journey back to earth from their historic navigation of the dark side of the moon, an incredible feat of science and engineering. The development of new medicines is likewise a highly complex and multidisciplinary undertaking, requiring deep insights in fundamental disease biology, chemistry and clinical science, along with input and strategic planning from regulatory experts, intellectual property specialists, formulation and production scientists, and many others. The team at Amplia, along with our network of consultants and advisers, are working tirelessly to progress Amplia’s programs, and specifically our lead drug narmafotinib, toward key clinical and commercial milestones and I thank them all for their unwavering commitment to our own ‘moonshot’. I would like to express my gratitude to our shareholders and investors for your ongoing support and interest in our efforts. Our goal remains to advance narmafotinib toward clinical success, thereby enhancing the company’s commercial prospects and increasing shareholder value. Dr Christopher Burns CEO and MD 7 Year in Review Clinical Development Progress Amplia’s clinical programs remained the central focus of activities throughout the year. The ACCENT trial, evaluating narmafotinib in combination with the chemotherapies gemcitabine and nab-paclitaxel in advanced pancreatic cancer, continued to generate encouraging clinical data. Updated analyses reported during the year demonstrated continued improvement in key clinical endpoints compared with historical benchmarks for chemotherapy alone. The study has achieved a confirmed objective response rate of 36%, while median progression-free survival has reached approximately 7.7 months, comparing favourably with published results for standard chemotherapy regimens. In addition, median overall survival has reached 11.1 months, representing an approximate two-month improvement compared to chemotherapy alone. Data from the ACCENT trial were presented to the global oncology community at the ASCO Gastrointestinal Cancer Symposium in January 2026. Presentation at this prestigious specialist conference highlights the growing interest in FAK inhibition as a therapeutic strategy in pancreatic cancer and reinforces the clinical progress being achieved with narmafotinib. In parallel with the continued development of ACCENT, Amplia advanced its second pancreatic cancer study, the AMPLICITY trial. This study evaluates narmafotinib in combination with modified FOLFIRINOX, a different chemotherapy regimen used more frequently in the United States and parts of Europe, than in Australia. Following the observation of protocol-defined dose limiting toxicities associated with the mFOLFIRINOX chemotherapy regimen, Amplia discontinued further recruitment to the AMPLICITY trial. Importantly, no toxicity concerns were attributed to narmafotinib. Patients already enrolled in the study continue treatment with ongoing safety monitoring. In light of these findings and the evolving treatment landscape in pancreatic cancer, Amplia has elected to discontinue development of the AMPLICITY study and focus its resources on the ACCENT trial and future combination approaches involving alternative, less toxic therapeutic regimens. Regulatory Progress Amplia continued to work closely with regulators to prepare the narmafotinib program for later-stage development. During the year, the Company received positive feedback from the United States Food and Drug Administration (FDA) following a Type D meeting regarding the design of a planned registration-enabling trial. The FDA supported the proposed two-dose comparison strategy in the Phase 2b stage of the study, providing important clarity for the next phase of clinical development. These regulatory interactions represent an important step in defining the pathway toward potential registration of narmafotinib for pancreatic cancer. 8 Manufacturing and Operational Readiness As Amplia prepares for later-stage clinical development, significant progress has been made in manufacturing and operational activities. In early 2026, the Company successfully completed its first large-scale manufacturing campaign for narmafotinib, producing approximately 13 kilograms of active pharmaceutical ingredient under Good Manufacturing Practice (GMP) conditions. This milestone marks the successful transition of manufacturing from a research and development environment to a commercial-ready manufacturing setting and provides sufficient drug supply to support ongoing and planned clinical trials. This progress in Chemistry, Manufacturing and Controls (CMC) is a critical component of preparing narmafotinib for larger clinical studies and future regulatory submissions. Intellectual Property and Strategic Positioning Amplia strengthened its intellectual property portfolio during the year with the granting of a key patent in the United States and other countries, protecting the specific crystalline form of narmafotinib currently being developed clinically. The patent extends protection for the drug to at least 2040 in major pharmaceutical markets. The Company also expanded its international capital markets presence. During the year Amplia commenced trading on the OTCQB Venture Market in the United States, improving accessibility for US investors and supporting broader engagement with the global biotechnology investment community. In addition, Amplia extended its preclinical research collaboration with Korean biotechnology company Next & Bio. The collaboration continues to explore the potential of combining FAK inhibitors with emerging kRAS inhibitors, an area of growing interest in oncology drug development. Financial Amplia strengthened its financial position during the year through a combination of capital raising activities and continued support from government R&D incentives. The Company successfully completed a capital raising through a placement and share purchase plan, providing additional funding to support the continued development of narmafotinib and the expansion of the Company’s clinical programs. Amplia also received its annual R&D Tax Incentive rebate, further strengthening the Company’s balance sheet and supporting ongoing research and development activities. Looking Ahead Amplia enters the coming year with strong clinical momentum and multiple near-term value drivers. The continued maturation of the ACCENT dataset will provide further insight into the clinical benefit of narmafotinib in pancreatic cancer, whilst the Company explores clinical development in combination with other treatment regimens in pancreatic cancer and other solid tumour indications. Together with growing regulatory alignment, strengthened manufacturing capability and expanding international engagement, these developments position Amplia to advance narmafotinib toward the next phase of clinical development and unlock the significant potential of FAK inhibition in oncology. 9 Year in Review ASX Releases 10 US Clinical Trial Activities for Narmafotinib Now Underway ACCENT Data Update Presented at International Conference Amplia Appoints Dr Jason Lickliter as Chief Medical Officer ACCENT Trial Achieves Superiority over Chemotherapy Alone Pathological Complete Response in Pancreatic Cancer Trial Second Complete Response in ACCENT Pancreatic Cancer Trial Amplia Gains US Ethics Approval for Pancreatic Cancer Trial Additional Partial Response in Pancreatic Cancer Trial Another Partial Response in ACCENT Pancreatic Cancer Trial Amplia announces A$25m Placement and Launches A$2.5m SPP Australian Ethics Clearance for Pancreatic Cancer Trial Positive ACCENT Trial Topline Data Released Amplia Share Purchase Plan Raises $2.65 Million Australian Trial Sites Open for New Narmafotinib Trial Narmafotinib Adopted as Nonproprietary Drug Name in USA First Patient Dosed in New Pancreatic Cancer Trial Patent Allowance for Key Narmafotinib Patent in US April 2025 April 2025 May 2025 May 2025 June 2025 June 2025 June 2025 July 2025 July 2025 July 2025 July 2025 August 2025 August 2025 August 2025 September 2025 September 2025 September 2025 11 11 Additional Responses in ACCENT Pancreatic Cancer Trial Amplia Therapeutics to Significantly Expand U.S. Presence Amplia Receives R&D Tax Rebate Totalling $3.77 Million Amplia Commences Trading on U.S. OTCQB Venture Market Positive Response from US FDA to Amplia’s Type D Meeting Key narmafotinib Patent Granted in the US Additional Confirmed Response Reported-Investor Presentation Amplia Enters 2nd Agreement with Drug Screening Co Next Bio ACCENT Data Presented at 2026 ASCO GI Cancer Symposium Narmafotinib Large-Scale Manufacture Complete US Sites For AMPLICITY Pancreatic Cancer Trial Open Benefit of Narmafotinib in kRas-Mutated Cancer Models Amplia Reports Improved Responses and Survival in ACCENT trial October 2025 October 2025 October 2025 October 2025 November 2025 December 2025 December 2025 December 2025 January 2026 January 2026 February 2026 March 2026 March 2026 ACCENT Trial Maturing data show improved response and survival outcomes Over the past year Amplia Therapeutics has continued to generate encouraging clinical data from the ACCENT trial, further strengthening the evidence supporting narmafotinib as a potential new treatment option for patients with advanced pancreatic cancer. Recent independently analysed mature data have further strengthened these findings, demonstrating improvements in response rates and overall survival. The ACCENT study is evaluating Amplia’s lead drug candidate narmafotinib in combination with the chemotherapy regimen gemcitabine and nab-paclitaxel in patients with newly diagnosed metastatic pancreatic cancer. The study is designed as a Phase 1b/2a trial and aims to determine whether the addition of narmafotinib can enhance the effectiveness of standard-of-care chemotherapy. Encouraging responses Throughout the year the ACCENT trial has continued to demonstrate meaningful clinical activity. The study has achieved a confirmed objective response rate of 36%, comparing favourably with the historical response rate of around 23% reported for chemotherapy alone in similar patient populations, as outlined in the benchmark MPACT trial upon which ACCENT is based. This updated response rate reflects independent central review of the data using RECIST 1.1 criteria. Median progression-free survival has also reached approximately 7.7 months, exceeding the approximately 5.5 months typically reported for chemotherapy alone. In addition, median overall survival has reached 11.1 months, representing an approximately two-month improvement compared to chemotherapy alone. Importantly, the treatment combination has maintained a favourable tolerability profile. Adverse events observed in the trial have been broadly consistent with those expected from chemotherapy alone, with no additional toxicity burden observed with the addition of narmafotinib. These results continue to support the hypothesis that FAK inhibition may enhance the effectiveness of chemotherapy in pancreatic cancer, a disease where treatment options remain limited and clinical outcomes are typically poor. Growing international recognition The progress of the ACCENT trial has attracted increasing attention from the global oncology community. Updated data from the study were presented at the ASCO Gastrointestinal Cancer Symposium in January 2026, one of the leading international meetings focused on gastrointestinal cancers. The Company was selected to present further mature ACCENT data at the American Association of Cancer Research (AACR) Annual Meeting in April 2026, reflecting growing international recognition of the program. As additional patients continue to be followed in the study, the ACCENT dataset continues to mature and provide important insight into the potential role of narmafotinib in pancreatic cancer treatment. 12 13 13 Exceptional clinical responses observed During the year the ACCENT trial also delivered several particularly notable clinical outcomes. Amplia reported a complete pathological response, meaning that following treatment no remaining viable cancer cells were detected in tumour tissue removed during surgery. Pathological complete responses are extremely rare in pancreatic cancer and represent a highly encouraging signal of treatment activity. In addition, the trial has reported complete responses in patients with advanced pancreatic cancer, where all measurable evidence of tumour has disappeared following treatment. Following independent central review, a total of five complete responses have now been confirmed, representing a complete response rate of 7.8% (5/64), an unprecedented result in this indication. Such outcomes are uncommon in metastatic pancreatic cancer and highlight the potential for the narmafotinib combination therapy to produce deep and durable tumour responses in a disease where meaningful clinical breakthroughs remain urgently needed. Targeting kRAS A New Approach in Pancreatic Cancer Research A new wave of kRAS-targeted therapies is driving renewed optimism in pancreatic cancer, one of the most difficult cancers to treat. As the field evolves, attention is increasingly turning toward combination strategies designed to improve durability of response and overcome treatment resistance. More than 90% of pancreatic cancers are driven by mutations in a gene known as kRAS, which plays a central role in tumour growth and survival. Despite its importance, kRAS was long considered “undruggable”, frustrating researchers and limiting treatment advances for patients with one of the poorest survival rates in oncology. That is now beginning to change. Over the past few years, a new generation of kRAS-targeted therapies has entered clinical development, with early studies showing encouraging improvements in patient outcomes. Recent clinical data from advanced pancreatic cancer trials demonstrated survival outcomes significantly beyond those historically achieved with chemotherapy alone — results many experts have described as a major step forward for the field. These advances are driving intense global activity in kRAS research, with more than 60 kRAS inhibitors currently in clinical development across multiple tumour types. While these developments are highly promising, researchers increasingly believe that targeting kRAS alone may not be enough to deliver durable long-term responses. Pancreatic tumours are biologically complex. Dense fibrotic tissue surrounding the tumour can limit drug penetration, while interactions within the tumour microenvironment can promote localised immune-suppression. Further, resistance to drug treatment develops over time. As a result, the focus across the industry is rapidly shifting toward combination approaches — pairing kRAS inhibitors with therapies designed to target other aspects of tumour biology. This emerging strategy is particularly relevant for Amplia. 14 15 The Growing Potential of Combination Therapy in kRAS-Driven Cancer As kRAS-targeted therapies continue to advance, increasing attention is turning toward combination approaches designed to improve response rates, extend durability and address treatment resistance. Amplia believes narmafotinib may have an important role to play within this emerging treatment landscape. Narmafotinib targets Focal Adhesion Kinase (FAK), a protein closely associated with tumour fibrosis, cancer cell survival and the tumour microenvironment in pancreatic cancer. Research increasingly suggests that FAK signalling may contribute to resistance mechanisms in kRAS-driven tumours, making it a potentially valuable complementary target alongside kRAS inhibition. Preclinical data presented by Amplia at the AACR Special Conference on RAS Oncogenesis and Therapeutics demonstrated that narmafotinib enhanced the activity of kRAS inhibitors across multiple cancer models, including pancreatic, lung and ovarian cancers. The findings also suggested that narmafotinib may help disrupt resistance pathways that can emerge during kRAS inhibitor treatment, with the potential to improve both the depth and durability of anti-tumour responses. These findings align with a broader industry shift toward combination-based strategies that target multiple aspects of tumour biology, rather than relying on single-agent therapies alone. Amplia’s ongoing ACCENT clinical trial, evaluating narmafotinib in combination with standard-of-care chemotherapy in pancreatic cancer, reflect this broader approach and continue to build understanding of the role FAK inhibition may play in difficult-to-treat cancers. As the field of kRAS-targeted therapy continues to evolve, Amplia believes narmafotinib has considerable potential to contribute to the next generation of combination treatment strategies aimed at improving outcomes for patients with kRAS-driven cancers. Building the Case for kRAS Combination Strategies Earlier this year, Amplia presented preclinical data at the AACR Special Conference on RAS Oncogenesis and Therapeutics demonstrating the potential for narmafotinib to enhance the activity of kRAS-targeted therapies across multiple cancer models. The preclinical studies demonstrated: • Enhanced tumour growth inhibition when narmafotinib was combined with kRAS inhibitors • Sustained tumour suppression in patient-derived pancreatic cancer models • Reduced kRAS signalling and disruption of pathways linked to tumour proliferation • Activity across multiple kRAS mutation subtypes The findings support the potential role of FAK inhibition as part of future combination strategies in kRAS-driven cancers. Scaling Up Amplia reaches large scale manufacturing milestone As Amplia advances the clinical development of its lead FAK inhibitor, narmafotinib, the Company has also been strengthening the manufacturing capabilities needed to support larger clinical trials and future commercial supply. Earlier this year, Amplia achieved an important milestone with the successful large-scale manufacture of narmafotinib, marking a significant step in preparing the program for later-stage clinical development. Working with its contract development and manufacturing organisation (CDMO), the Company transitioned production from a research and development environment to a commercial manufacturing setting. The manufacturing campaign produced approximately 13 kilograms of active pharmaceutical ingredient (API) to the required purity and quality specifications. The 13 kg batch represents roughly one-tenth of the anticipated com