Announcement PDF ABN 16 165 160 841 ASX RELEASE 9 April 2025 US CLINICAL TRIAL ACTIVITIES FOR NARMAFOTINIB NOW UNDERWAY HIGHLIGHTS • Trial initiation activities for the Company’s new pancreatic cancer trial have begun • A multinational CRO has been engaged to coordinate and manage the trial • Manufacture of drug product for exclusive use in the trial has been completed • This trial explores the combination of narmafotinib with the chemotherapy FOLFIRINOX in advanced pancreatic cancer patients Melbourne, Australia: Amplia Therapeutics Limited (ASX: ATX), (“Amplia” or the “Company”), is pleased to announce that trial initiation activities for the planned pancreatic cancer trial in the US have begun. This new trial will explore the combination of the Company’s best-in-class FAK inhibitor narmafotinib with the chemotherapy FOLFIRINOX in patients with advanced pancreatic cancer. This trial will be run under the Investigational New Drug (IND) application for narmafotinib cleared by the US Food and Drug Administration (FDA) last year 1. FOLFIRINOX is widely used as the first-line treatment for pancreatic cancer patients in the US, as well as parts of Europe. This chemotherapy, which consists of a mixture of four separate drugs, is different to the gemcitabine + Abraxane® chemotherapy routinely used in Australia and currently being employed in the Company’s ACCENT trial. FOLFIRINOX is often associated with greater haematological toxicity, however patient response (as measured by progression free survival (PFS) and overall survival (OS)) is generally accepted to be slightly improved over gemcitabine and Abraxane (see Table). PFS (months) OS (months) Gemcitabine + Abraxane (MPACT trial 2) 5.5 8.5 Gemcitabine + Abraxane (NAPOLI trial 3) 5.6 9.2 FOLFIRINOX 4 6.4 11.1 The Company has now formally entered into an agreement with a large multinational contract research organization (CRO) to coordinate clinical trial activities in the US. As part of this foundational work, clinical trial sites at selected major hospitals across the US have been approached to participate in the trial. To ensure timely recruitment for the trial, the Company has elected to also include a small number of trials sites in Australia. Up to seven (7) clinical trial sites may be engaged to commence recruitment once all approvals have been obtained. ASX Release 18 Jan 2024 New Engl. J. Med. 2013, vol. 369, p. 1691-1703 3 Lancet. 2023, Vol 402, p. 1272-1281 4 New Engl. J. Med. 2011, vol. 364, p. 1817-1825 1 2 Level 17, 350 Queen Street, Melbourne VIC 3000 Email info@ampliatx.com www.ampliatx.com To support the dose-escalation phase of this trial, the manufacture of a large batch of drug product has been completed at our US-based Contract Development and Manufacturing Organization. For this trial, as with the ACCENT trial, drug is administered orally as formulated capsules. Amplia CEO and MD Dr Chris Burns commented: “We are extremely excited to have signed up a worldclass CRO to coordinate running this trial and to have started engaging with trial sites. This represents an important next step in the development of narmafotinib by exploring the potential of the drug in combination with another widely used pancreatic cancer treatment.” This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics. About Narmafotinib Narmafotinib (AMP945) is the company’s best-in-class inhibitor of the protein FAK, a protein overexpressed in pancreatic cancer and a drug target gaining increasing attention for its role in solid tumours. The drug, which is a highly potent and selective inhibitor of FAK, has shown promising data in a range of preclinical cancer studies. Narmafotinib is currently undergoing a clinical trial (the ACCENT trial) where it is dosed in combination with the chemotherapies gemcitabine and Abraxane in first-line patients with advanced pancreatic cancer. About the FOLFIRINOX Trial Narmafotinib, in combination with the modified FOLFIRINOX chemotherapy regimen, will explore the safety, tolerability, efficacy and pharmacokinetics of the combination in newly-diagnosed patients with advanced (metastatic) pancreatic cancer. The trial is entitled ‘A Phase 1b/2a, Multicenter, Open Label Study of the Safety, Efficacy and Pharmacokinetics of narmafotinib in Combination with modified FOLFIRINOX in Pancreatic Cancer Patients’ and is being conducted under an open IND from the US FDA. Designed as a single-arm, open-label study, the trial will proceed in two parts, incorporating the principles of the FDA's Project Optimus guidance for developing new oncology therapies 5. Part A will explore a range of doses of narmafotinib (AMP945), taken once daily in combination with modified FOLFIRINOX administered every 14 days, for safety, tolerability, and pharmacokinetics. Part B of the trial is designed to identify the optimal daily dose of narmafotinib for future studies, by comparing two (2) doses identified from Part A, for safety, tolerability and efficacy. The trial is being conducted initially at sites in the US and Australia. The Company has previously presented data from preclinical studies demonstrating that the addition of narmafotinib to FOLFIRINOX improves survival in animal models of pancreatic cancer compared to animals treated with FOLFIRINOX alone. The Company will provide further updates on the trial as activity progresses. 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 5 https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus 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.