Announcement PDF ASX RELEASE 23 August 2024 CEO & Managing Director’s Presentation to Annual General Meeting Melbourne, Australia: Amplia Therapeutics Limited (ASX: ATX) (“Amplia” or the “Company”) is pleased to release the CEO & Managing Director’s presentation to the Company’s Annual General Meeting (YE 31 March 2024) to be held today. This ASX announcement is authorised for release by the Company Secretary. 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), Threads (@ampliatx) and LinkedIn. Level 17, 350 Queen Street, Melbourne VIC 3000 Email info@ampliatx.com www.ampliatx.com Annual General Meeting 23 August 2024 Dr Chris Burns CEO and MD ampliatx.com | @ampliatx DISCLAIMER This presentation (Presentation) contains summary information about Amplia Therapeutics market, regulatory and other relevant environments that will exist and affect Amplia’s business and Limited ACN 165 160 841 and its subsidiaries (the Company or Amplia) which is current as at 30 Jun operations in the future. The Company does not give any assurance that the assumptions will prove 2024. By attending an investor presentation or briefing, or accepting, accessing or reviewing this to be correct. There may be other factors that could cause actual results or events not to be as Presentation, you acknowledge and agree to the terms set out below. anticipated, and many events are beyond the reasonable control of the Company. Readers are Summary Information: This Presentation has been prepared for information purposes only and is cautioned not to place undue reliance on forward-looking statements. Forward-looking statements a summary only. It should be read in conjunction with Amplia’s most recent financial report and in this Presentation are only made as at the date of this Presentation and the Company does not other periodic and continuous disclosure information lodged with the Australian Securities undertake any obligation to publicly update or revise any of the forward-looking statements or to Exchange (ASX), which is available at www.asx.com.au. Subject only to any legal obligation to do so, advise of any change in assumptions on which any such statement is based. the Company does not have any obligation to correct or update the content of this Presentation. Industry data and third party information: Industry data and third party information used in this Not financial product advice: This Presentation does not, and does not purport to, contain all Presentation may have been obtained from research, surveys, reports or studies conducted by third information necessary to make an investment decision, is not intended as investment or financial parties, including industry or general publications. Neither Amplia not its representatives have advice (nor tax, accounting or legal advice) and must not be relied upon as such. This Presentation independently verified any such market or industry data. does not take into account the investment objectives, financial situation or needs of any particular Financial Information: This Presentation contains historical financial information based on the investor. Investors are encouraged to seek independent professional advice when deciding if an Company’s results for the 12 month period ending 30 Jun 2024. All financial information disclosed in investment in the Company is appropriate. The Company is not licensed to provide financial this Presentation is presented in Australian dollars unless otherwise noted. Any discrepancies product advice in respect of its own securities. This Presentation is not a prospectus, product between totals and sums of components in tables and figures contained in this Presentation are disclosure statement or other offering document under Australian law (or any other law). It is not, due to rounding. and does not constitute, an invitation or offer of securities for subscription, purchase or sale in any Disclaimer: To the maximum extent permitted by law, Amplia and its officers, directors, employees, jurisdiction. agents and advisers: (1) disclaim all responsibility and liability (including, without limitation, any Investment risk and past performance: An investment in Amplia shares is subject to known and unknown risks, some of which are beyond the control of the Company and its directors. The Company does not guarantee any particular rate of return or the performance of Amplia. 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They may include, without limitation, statements regarding plans, strategies and require in evaluating a possible investment in Amplia or acquisition of shares, or the likelihood of objectives and anticipated business developments. Forward-looking statements inherently involve fulfilment of any forward-looking statement. known and unknown risks, uncertainties and other factors that may cause Amplia’s actual results, performance and achievements to differ materially from statements in this Presentation. Forwardlooking statements are based on the Company’s good faith assumptions as to the financial, 2 SNAPSHOT Amplia is developing a pipeline of small molecule inhibitors of Focal Adhesion Kinase (FAK) - a validated target in cancer Amplia’s lead compound narmafotinib is the best-in-class FAK inhibitor in development Amplia’s ongoing trial of narmafotinib in advanced pancreatic cancer is showing the drug to be well tolerated by patients with promising signs of efficacy 3 DEVELOPMENT HIGHLIGHTS Phase 2a clinical trial in advanced pancreatic cancer underway Orphan Drug Designation from US FDA for pancreatic cancer and IPF* Well tolerated Promising signs of efficacy Interim readout planned for Q3 2024 7 years market exclusivity in US Assistance with development planning Tax credits for clinical costs Exemptions from certain fees Preparing for narmafotinib trial in pancreatic cancer in the US US FDA has cleared Amplia’s IND‡ application for a pancreatic cancer trial in the US In combination with FOLFIRINOX Compelling preclinical data in multiple disease models: Pancreatic cancer Ovarian cancer IPF* *Idiopathic Pulmonary Fibrosis ‡ Investigational New Drug 4 6 Narmafotinib is being positioned as the preferred agent to enhance activity of drugs for solid tumours CORPORATE SUMMARY ASX:ATX 12 month share price chart Share price (22-Aug-24) A$0.13 Shares on issue 274.21m Market cap (22-Aug-24) A$35.65m Cash at hand (30-Jun-2024) A$6.3m on a pro forma basis* Substantial Shareholders Platinum Investment Management Ltd Blueflag Holdings Pty Ltd Acorn Capital Ltd *After receipt of net FY24 RDTI refund 6 EXPERIENCED BOARD BOARD Warwick Tong Robert Peach Jane Bell Chris Burns MB ChB MPP GAICD Chair PhD Director LLB, LLM (Lond), FAICD Director PhD GAICD CEO and MD 7 EXPERIENCED MANAGEMENT SENIOR TEAM Rhiannon Jones Terrie-Anne Cock Charlotte Mulder Adrian Sulistio PhD GAICD COO PhD Director Translational Science BVSc (Hons) MBA Director Early Clinical Development B Eng (Hons), B Com, PhD Manager Product Development 8 Amplia’s drugs inhibit the enzyme Focal Adhesion Kinase (FAK) FOCAL ADHESION KINASE (FAK) FAK is a critical protein in cancer growth and spread, and in formation of fibrotic (scar) tissue Amplia’s drugs potently and selectively block the activity of the FAK protein Broad clinical potential Cancer Fibrosis Scarring 10 FAK INHIBITORS IN DEVELOPMENT Only 3 companies with bona fide FAK inhibitors in development Verastem Inxmed Selectivity Good DDI profile Clinical Notes Stage Safe and well tolerated Ph 2a Defactinib (Verastem) Promising data in Phase 2 LGSOC Ph 2 and 3 Ifebemtinib (Inxmed) High incidence of proteinuria (protein in urine) Ph 2 Amplia Narmafotinib (Amplia) Narmafotinib has a superior profile to other compounds: best-in-class Good PK profile PK = Pharmacokinetics DDI = Drug-Drug Interaction LGSOC = Low grade serous ovarian cancer 11 NARMAFOTINIB Drug-like small molecule Highly potent and selective Excellent PK; once-a-day dosing Minimal DDI* risk when combining with other drugs Selectivity Highly selective for FAK Narmafotinib Drug-like small molecule FAK FAK Activity Highly potent FAK inhibitor Biochemical assays IC 50 2.2 nM K 29 pM D Cellular assays Ovarian cancer cells (OVCAR 5) 0.1 Narmafotinib conc. (nM) *Drug-Drug Interaction 12 NARMAFOTINIB IN CANCER Extensive preclinical data showing narmafotinib activity in cancer models Early signals of efficacy from ACCENT clinical trial Multi-action of narmafotinib Anti-proliferative Reduces cell’s ability to proliferate and migrate Tumour (blue - cancer cells; green- fibroblasts; purple, grey and yellow - suppressive immune cells) Developing clinical datasets from Verastem and Inxmed further validate anti-cancer activity FAK inhibitors block critical pathways supporting tumour growth Synergy with chemotherapies Enhances activity of drugs and other therapies Anti-fibrotic Reduces scar-tissue in TME*, improving permeability to drugs Immunomodulatory Improves immune cell reactivity to tumour cells *Tumour Microenvironment 13 BROAD POTENTIAL FOR FAK INHIBITORS IN CANCER FAK inhibitors can enhance effects of existing therapeutic approaches in solid tumours Chemotherapy Radiotherapy ... but can also enhance newer targeted treatments Kinase Inhibitors Immune Checkpoint Inhibitors Antibodies and ADCs* Cell Therapies *Antibody Drug Conjugates 14 Clinical studies of narmafotinib in pancreatic cancer PANCREATIC CANCER An unmet need 13% Increasing Prevalence Estimated 66,000 diagnoses and 50,000 deaths in US this year* 5 year survival Difficult-to-treat: typically detected late in disease progression** Market size Global treatment market estimated over US$6 billon in 2023 4,500 diagnoses in AU in 2023** Projected to grow to † ~US$36 billion by 2036 * American Cancer Society (link) ** Cancer Australia (link) † Research Nester (link) 16 PANCREATIC CANCER Undisputed role of FAK in disease progression FAK gene Alteration frequency Over-expression and increased FAK activity FAK activity correlates with worse outcome Low levels active FAK = better survival High levels active FAK = worse survival Beneficial preclinical efficacy with FAK inhibition Narmafotinib decreases tumour fibrosis (collagen) Narmafotinib treatment improves survival in disease models ovarian pancreatic EMBO Mol Med 2020, 12, e12010 FAK inhibition synergises with SOC* chemotherapies and targeted therapies *Standard-of-care 17 Clinical data indicates narmafotinib safe and well tolerated with preliminary signs of efficacy ACCENT TRIAL DESIGN Dose Selected Phase 1b (Australia) Phase 2a (Australia and South Korea) 26 patients 14 patients Interim Analysis ≥6 PR Phase 2a (cont) (Australia and South Korea) 24 patients 400 mg* 200 mg 100 mg COMPLETED RECRUITED *Dose selected for Phase 2 19 ACCENT PHASE 1b Key trial read-outs following industry standard criteria Primary Endpoint: Objective Response Rate Secondary Endpoint: Duration on Trial Objective Response Rate categorised as: Complete Response (CR) - Disappearance of all tumour lesions; no new lesions Partial response (PR) - >30% decrease in tumour lesions; no new lesions Stable Disease (SD) - Tumour lesions have reduced in size by less than 30% or have shown either no growth or minimal growth (<20%) Progressive Disease (PD) - At least a 20% increase in tumour lesions; or new lesions 20 ACCENT PHASE 1b Narmafotinib in combination with standard of care gemcitabine and Abraxane® Orally-dosed narmafotinib in the days preceding weekly chemotherapy 3 Cohorts (100 mg, 200 mg, 400 mg) Orally-dosed (capsules) Once-a-day Safe and well tolerated All patients elected to stay on drug post cycle 1 One DLT*: uncontrolled nausea Fatigue (Grade 3 or below) in more than 1 patient likely drug related *DLT = Dose Limiting Toxicity 21 ACCENT PHASE 1b Best Response Preliminary signs of efficacy observed (all patients) Improved response rate (PR and SD) compared to historical gemcitabine/Abraxane alone Comparison to pivotal trial (2013)** Better objective response (tumour reduction) at higher doses 4 of 6 PRs with top dose narmafotinib Duration on trial significantly improved vs gemcitabine/Abraxane alone Average treatment time at top dose ~2x longer ACCENT Best Overall Response* n=14 Historical Best Overall Response** (n=431) Complete Response 0 (0%) <1% Partial Response 6 (43%) 23% Stable Disease (SD) 8 (57%) 27% Disease Control Rate (CR+PR+SD) 14 (100%) 50% Progressive Disease (PD) 0 (0%) 20% Not evaluable 0 (0%) 30% Classification * Investigator reviewed ** Independent review as part of MPACT trial (NEJM 2013: 369; 1691-1703) NB. Phase 1b trial not powered for efficacy 22 ACCENT PHASE 1b Preliminary signs of efficacy observed Tumour Reduction (% change from baseline) Improved response rate (PR and SD) compared to historical gemcitabine/Abraxane alone (individual patients) Comparison to pivotal trial (2013)** Better objective response (tumour reduction) at higher doses 4 of 6 PRs with top dose narmafotinib Duration on trial significantly improved vs gemcitabine/Abraxane alone Average treatment time at top dose ~2x longer * Investigator reviewed ** Independent review as part of MPACT trial (NEJM 2013: 369; 1691-1703) NB. Phase 1b trial not powered for efficacy 23 ACCENT PHASE 1b Preliminary signs of efficacy observed Duration on trial Improved response rate (PR and SD) compared to historical gemcitabine/Abraxane alone Comparison to pivotal trial (2013)** Better objective response (tumour reduction) at higher doses 4 of 6 PRs with top dose narmafotinib Duration on trial significantly improved vs gemcitabine/Abraxane alone Average treatment time at top dose ~2x longer * Investigator reviewed ** Independent review as part of MPACT trial (NEJM 2013: 369; 1691-1703) NB. Phase 1b trial not powered for efficacy 24 ACCENT PHASE 2a PRELIMINARY DATA Require 6 or more PRs to progress to 50 patient total enrolment By 21 August, 5 confirmed PRs have been observed at 4 month timepoint >30% reduction in tumour lesion size sustained over 2 months No new lesions In addition, 6 SDs also observed at this timepoint Reduction in tumour size (<30%), or no/minimal (<20% tumour growth) No new lesions 25 Summary CLINICAL FOCUS AND OPPORTUNITY Combinations in pancreatic cancer Combinations in ovarian cancer Preclinical evidence other solid cancers Gemcitabine and Abraxane (ACCENT trial) FOLFIRINOX (US trial with open IND) Platinum resistant disease Maintenance therapy post surgery Bile duct, oesophageal, head and neck cancer kRAS-mutant cancers (e.g. lung, colorectal) Other fibrotic cancers (e.g. liver cancer) 27 RECENT AND PLANNED MILESTONES 2H 2023 / 1H 2024 2H 2024 1H 2025 Complete Phase 1b ACCENT trial - October 26 Patients recruited ACCENT trial - July Completion enrolment 50 pts ACCENT trial March Korean regulatory approval - November 6 Confirmed PRs - September Initiation ovarian cancer trial - April First patient dosing Phase 2a ACCENT trial January Interim ACCENT trial data - October Initiation pancreatic cancer trial (combination FOLFIRINOX under IND) - April Clearance of IND - January Preclinical data (drug combination study) November Completion of CMC campaign - May Rolling regulatory submissions Capital Raise - May 28 Chris Burns PhD GAICD CEO and MD chris@ampliatx.com​ ampliatx.com | @ampliatx