Announcement PDF ABN 16 165 160 841 10th April 2024 ASX RELEASE AACR CONFERENCE PRESENTATION HIGHLIGHTS • Data from our Phase 1b ACCENT trial in pancreatic cancer has been presented at the prestigious American Association of Cancer Research annual meeting • The data summary highlights that narmafotinib in advanced pancreatic patients appears safe and well tolerated, with promising early signs of activity Melbourne, Australia: Amplia Therapeutics Limited (ASX: ATX), (“Amplia” or the “Company”) is pleased to announce that a poster, highlighting key data from the Phase 1b ACCENT trial, was presented overnight at the annual meeting of the American Association of Cancer Research, being held in San Diego, USA. The ACCENT trial is the company’s lead clinical program, exploring the activity of our best-in-class FAK inhibitor narmafotinib, in combination with standard-of-care chemotherapy, in advanced pancreatic cancer patients. The poster outlines the scientific rationale for the use of FAK inhibitors in pancreatic cancer treatment and details the clinical design of the ACCENT trial. Data highlights from the presented data for the 14 patients in the Phase 1b trial include: • Demonstration of the excellent pharmacokinetics of the drug in patients, supporting once-aday daily dosing • Excellent safety and tolerability data • Response data showing a disease control rate, as best response, of 100% (= 6 partial responses and 8 stable disease) • Evidence that the higher doses of 200 and 400 mg resulted in better outcomes • Promising duration on trial showing 9 of 14 patients stayed on trial for >5 months. A copy of the poster is attached to this announcement. Amplia’s CEO Dr Chris Burns commented: “We are delighted to present this early data from the ACCENT trial to the broader scientific and clinical community at such a high profile conference. Such disclosures allow us to discuss the data with world-leading experts in FAK biology and oncology drug development, as well as potential collaboration partners in pharma and biotech.” This ASX announcement was approved and authorised for release by the Board. - End 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 Level 17, 350 Queen Street, Melbourne VIC 3000 Email info@ampliatx.com www.ampliatx.com 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 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), Threads (@ampliatx) and LinkedIn. Phase 1b/2a of narmafotinib (AMP945) in combination with gemcitabine and nab-paclitaxel (Abraxane®) standard of care as first-line therapy in patients with advanced pancreatic cancer (ACCENT trial): interim analysis Terrie-Anne Cock1, Anthony Bishop1, Nicole Kruger1, Sarah McCormack1, Marion Harris2, Sumitra Ananda3, Lara Lipton4, Adnan Nagrial5, Nick Pavlakis6, Warren Joubert7, Laura Donato8, Jason D. Lickliter1, Christopher J. Burns1 1Amplia Therapeutics, Melbourne, Australia, 2Monash Medical Centre, Melbourne, Australia, 3Epworth Cancer Services Clinical Institute, Melbourne, Australia, 4Sunshine Hospital, Melbourne, Australia, 5Westmead Cancer Care Centre, Sydney Australia, 6GenesisCare, Sydney Australia, 7Greenslopes Oncology, Brisbane, Australia and 8 IQVIA Biotech, Sydney, Australia Best Response by RECIST v 1.1 Dosing Regimens Background Narmafotinib (AMP945) is a selective and orally bioavailable inhibitor of Focal Adhesion Kinase (FAK). All participants receive oral narmafotinib once daily at the selected dose on Day -8 to Day -2 (7 doses total) of a monotherapy Run-In period, prior to the first treatment cycle. Each 28-day treatment cycle includes IV nab-paclitaxel (Abraxane®) and gemcitabine on Days 1, 8 and 15, and oral narmafotinib priming on Days 3 to 6, 10 to 13, and 24 to 27, inclusive. Inclusion Aberrant FAK signaling has been implicated in the progression of cancer, where it is involved in promoting tumor growth, adhesion, angiogenesis, invasion, and migration, as well as immunomodulation and remodeling of the fibrotic tumor microenvironment2-4. FAK is frequently overexpressed in a variety of cancers, including pancreatic ductal adenocarcinoma (PDAC)4, a highly fibrotic and aggressive malignancy with a poor 5-year survival rate,5 in which high FAK expression correlates with poor prognosis6,7. ACCENT Study Overview ACCENT trial (NCT05355298) is a Phase 1b/2a, open label study of the pharmacokinetics, safety and efficacy of narmafotinib in combination with gemcitabine and nab-paclitaxel (Abraxane®) standard of care as first-line therapy in patients with advanced pancreatic cancer. The trial is a single-arm open label study conducted in two stages. Key Eligibility Criteria Exclusion • Diagnosis of metastatic or not surgically resectable PDAC • ECOG status of 0 or 1 • Measurable disease per RECIST 1.1 • Life expectancy ≥ 3 months • Acceptable hematologic and clinical laboratory chemistry values • Received prior systemic treatment for PDAC, except as a radiosensitizer, provided >6 months have elapsed since last dose and no toxicities >grade 1 are still present • Known brain metastases, unless treated and well-controlled for > 3 months • GI condition that could interfere with swallowing or absorption of medication Patient demographics: Part A dose escalation 14 patients were treated with narmafotinib + gemcitabine/nabpaclitaxel (Abraxane®) • Males n=7 (50%) • Females n=7 (50%) • Average age: 62 years old • Predominantly Caucasian Contact Terrie-Anne Cock Amplia Therapeutics Email: TerrieAnne@ampliatx.com Website: www.ampliatx.com References 1. 2. 3. 4. 5. 6. 7. 8. 400mg-->200mg Classification 400mg-->100mg 400mg 0 -20 -40 Partial response -60 -80 Best Overall Response (n) 14 CR 0 (0%) PR 6 (43%) SD 8 (57%) DCR (PR+SD) 14 (100%) PD 0 (0%) Not Evaluable 0 (0%) Investigator assessed • Narmafotinib combined with gemcitabine/nab-paclitaxel (Abraxane®) demonstrated promising dose related trend in the first 14 patients – with ORR of 43%. • This compares favorably with the reported response rate of 23% with gemcitabine/Abraxane® in the pivotal Phase III trial8. • Two patients had dose adjustments due to AEs from 400mg to 100mg and 400mg to 200mg Time on treatment 1 – withdrawn due to chemotoxicities 3 4 5 6 7 PD 8 PR Ongoing withdrawal for non-PD reasons 9 10 11 13 3000 100mg Narmafotinib 200mg Narmafotinib 14 0 50 100 150 200 250 300 350 Duration of Treatment (days) 400mg Narmafotinib 2000 100mg 200mg 400mg-->100mg 400mg-->200mg 400mg 1000 0 0 4 8 12 16 20 24 Hour Pharmacokinetics from single dose of narmafotinib (Day -8) • Narmafotinib-related events - the following occurred in more than one participant: diarrhea, gastroesophageal reflux disease, nausea, vomiting, fatigue, pyrexia, and macro-papular rash • No treatment related deaths and only two narmafotinib related SAEs: febrile infection, and fatigue • All other SAEs reported to date have either been unrelated or assessed as related to gemcitabine/Abraxane® • No dose limiting toxicities (DLTs) were noted in the 100 mg and 200 mg cohorts. A single DLT (Grade 3 Nausea >72 h) was reported at the 400 mg dose • Two patients had dose adjustments due to AEs from 400mg to 100mg and 400mg to 200mg • No MTD was defined for narmafotinib Grade 3 or above System Organ Class Related Unrelated Narma- Gemci- NabAny Not fotinib tabine Paclitaxel All Events Related Related (N=15) (N=14) (N=14) Preferred Term n (%) E Blood and lymphatic system disorders Gastrointestinal disorders Anaemia 0 1 (7) 1 1 (7) 1 1 (7) 1 0 1 (7) 1 Nausea Vomiting 1 (7) 1 1 (7) 1 1 (7) 1 1 (7) 1 1 (7) 1 1 (7) 1 1 (7) 1 1 (7) 1 0 0 1 (7) 1 1 (7) 1 1 (7) 1 1 (7) 1 1 (7) 1 1 (7) 1 0 1 (7) 1 1 (7) 1 0 0 1 (7) 1 0 1 (7) 1 0 2 (13) 3 2 (13) 3 2 (13) 3 2 (13) 2 3 (20) 5 Toxicity to various agents 0 1 (7) 1 1 (7) 1 1 (7) 1 0 1 (7) 1 Dehydration 0 1 (7) 1 1 (7) 1 1 (7) 1 0 1 (7) 1 Fatigue General disorders & administration site Febrile infection conditions Pyrexia Injury, poisoning & procedural complications Metabolism & nutrition disorders Participants who experienced multiple events within a category are counted only once in the specific category (n), however each instance of the event is counted (E). Percentage (%) of participants (n) are calculated based on the number of participants for the respective dose level (N). Conclusions 12 ng/ml Part A (Phase 1b), patients were enrolled in a 3+3 design to determine the narmafotinib recommended Phase 2 dose (RP2D), with dose-escalation (100, 200 and 400 mg), with a primary objective of determining recommended RP2D, and assessing safety and tolerability of oral narmafotinib administered prior to IV administration of gemcitabine and nab-paclitaxel in participants with advanced pancreatic cancer. Part B (Phase 2a) is a Simon’s two stage design, with the primary objectives of assessing safety, tolerability, and efficacy of the combination using RECIST v1.1 (central read by indep't reviewers). 200mg 2 Pharmacokinetics • Narmafotinib plasma PK samples were collected on Days -8, -7, 1, 3, 8, and 10 of Run-In/Cycle 1 • The PK for narmafotinib is dose-proportional across the dose range tested, and the half-life supports once a day dosing • The chemotherapy regimen used in this study did not impact narmafotinib PK Change from baseline (%) FAK is a non-receptor tyrosine kinase that acts through numerous key signaling pathways to mediate communication between cells and their environment and plays a crucial role in normal cellular stress response, acting to buffer healthy cells from dying when exposed to extreme cellular stress1. 20 100mg Safety • All patients who completed their first 28-day cycle of treatment elected to stay on narmafotinib • 9 of 14 patients on drug > 5 months • There was a dose dependent trend in duration of treatment with the highest dose of narmafotinib (400 mg QD) associated with the longest duration of treatment, 212 days (mean duration) Lim ST, Chen XL, Lim Y, Hanson DA, Vo TT, Howerton K, Larocque N, Fisher SJ, Schlaepfer DD, Ilic D. Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation. Mol Cell. 2008 Jan 18;29(1):9-22. Sulzmaier FJ, Jean C, Schlaepfer DD. FAK in cancer: mechanistic findings and clinical applications. Nat Rev Cancer. 2014 Sep;14(9):598-610. Dawson JC, Serrels A, Stupack DG, Schlaepfer DD, Frame MC. Targeting FAK in anticancer combination therapies. Nat Rev Cancer. 2021 May;21(5):313-324. Zhang Z, Li J, Jiao S, Han G, Zhu J, Liu T. Functional and clinical characteristics of focal adhesion kinases in cancer progression. Front Cell Dev Biol. 2022 Nov 2;10:1040311. Siegel RL, Miller KD, Wagle NS, Jemal A, Cancer statistics, 2023. CA Cancer J Clin 2023; 73, 17-48. Zaghdoudi S, Decaup E, Belhabib I, et al. FAK activity in cancer-associated fibroblasts is a prognostic marker and a druggable key metastatic player in pancreatic cancer. EMBO Mol Med. 2020;12(11):e12010. Jiang H, Hegde S, Knolhoff BL, et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med. 2016;22(8):851-860. Von Hoff DD, Ervin T , et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703  Dose escalation assessed 100 mg, 200 mg, 400 mg once daily  Excellent once a day, dose proportional pharmacokinetics  Safe and well tolerated  Narmafotinib combined with gemcitabine/nab-paclitaxel (Abraxane®) demonstrates promising activity, with investigator assessed response rate of 43%  Based on this promising Phase 1b data, 400 mg of narmafotinib has been selected for RP2D and the trial will proceed through Simon’s Two Stage design and enroll up to 50 patients as part of the Phase 2 expansion cohort