DEP irinotecan presentation at ASCO 2024 Annual Meeting

ASX Announcement DEP® irinotecan presentation at ASCO 2024 Annual Meeting Melbourne, Australia; 4 June 2024: Starpharma (ASX: SPL, OTCQX: SPHRY) today provides a copy of the DEP® irinotecan presentation delivered at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting in Chicago, US. The presentation was part of a rapid oral abstract session and highlighted the final results of the DEP® irinotecan Phase 1/2 clinical trial, which were reported in full last week. More than 45,000 oncology clinicians, researchers, and pharmaceutical company representatives from around the world attended the ASCO Annual Meeting this year. Highly sought-after oral presentation slots are granted to studies that include significant breakthroughs and technologies likely to improve clinical oncology practice and patient outcomes. The clinical investigators involved in both the DEP® irinotecan and DEP® cabazitaxel studies are excited by the clinical data for these dendrimer -based medicines. They we re h ighly impressed with the selection of both abstracts for oral presentation at the ASCO Meeting, describing this as a significant achievement that recognises the positive clinical study findings for cancer patients. The DEP® irinotecan ASCO Meeting abstract (#3014) has been published in the Journal of Clinical Oncology (JCO) (Volume 42, Number 16)1. Dr Jia (Jenny) Liu, MD PhD FRACP, Medical Oncologist and Principal Investigator of the DEP® irinotecan trial at the Kinghorn Cancer Centre, St Vincent’s Hospital in Sydney, delivered the presentation overnight. The presentation is appended. 1 https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3014 2 About Starpharma Starpharma (ASX: SPL, OTCQX: SPHRY) is dedicated to helping patients with significant illnesses, such as cancer, achieve improved health outcomes and quality of life through the application of our unique dendrimer technology. Dendrimers are precise, synthetically manufactured, nanoscale molecules. Their unique properties —including their size, structure, high degree of branching, polyvalency, and water solubility—are advantageous in medical and pharmaceutical applications. Starpharma uses its dendrimer technology to develop novel therapeutics and to enhance the performance of existing pharmaceuticals. The Company’s portfolio includes multiple clinical-stage oncology products, which utilise its Dendrimer Enhanced Product (‘DEP ®’) drug delivery technology, as well as marketed products, including VIRALEZE ™ and VivaGel ® BV, which utilise SPL7013, a proprietary dendrimer with antimicrobial properties. Starpharma’s DEP ® drug delivery platform is being used to enhance the effectiveness of existing and novel therapies and to reduce drug-related toxicities through controlled and specified drug delivery. For more information about Starpharma, visit www.starpharma.com or connect with Starpharma on LinkedIn. WE Communications Hannah Howlett +61 450 648 064 WE-AUStarPharma@we- worldwide.com Starpharma Holdings Limited Cheryl Maley, Chief Executive Officer Justin Cahill, CFO and Company Secretary +61 3 8532 2704 [email protected] 4-6 Southampton Crescent Abbotsford Vic 3067 Disclosure This ASX Announcement was authorised for release by Chair, Mr Rob Thomas. Forward-Looking Statements This document contains certain forward -looking statements, relating to Starpharma’s business, which can be identified by the use of forward -looking terminology such as “promising”, “plans”, “anticipated”, “will”, “project”, “believe”, “forecast”, “expected”, “estimated”, “ targeting”, “aiming”, “set to”, “potential”, “seeking to”, “goal”, “could provide”, “intends”, “is being developed”, “could be”, “on track”, or similar expressions, or by express or implied discussions regarding potential filings or marketing approvals, or potential future sales of product candidates. 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In particular, management’s expectations regarding the approval and commercialization of the product candidates could be affected by, among other things, unexpected trial results, including additional analysis of existing data, and new data; unexpected regulatory actions or delays, or government regulation generally; our ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; governmen t, industry, and general public pricing pressures; and additional factors that involve significant risks and uncertainties about our products, product candid ates, financial results and business prospects. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove in correct, actual results may vary materially from those described herein as anticipated, believed, estimated, or expected. Starpharma is providing this information as of the date of this document and does not assume any obligation to update any forward -looking statements contained in this document as a result of new information, future events or developments or otherwise. Clinical case studies and other clinical information given in this d ocument are given for illustrative purposes only and are not necessarily a guide to product performance and no representation or warranty is made b y any person as to the likelihood of achievement or reasonableness of future results. Nothing contained in this document, nor any information made available to you is, or shall be relied upon as, a promise, representation, warranty or guarantee as to the past, present or the future performance o f any Starpharma product. PRESENTED BY: Dendrimer-enhanced (DEP) SN38 (DEP irinotecan) in patients with advanced solid tumors: a Phase 1/2 trial Jia (Jenny) Liu1, Anna R. Minchom2, Alastair Greystoke3, Thomas R.J. Evans4, Debashis Sarker5, Anthony M. Joshua1, Cienne Morton5, Burak Aktas5, Rasha Cosman1, Dominika Chwialkowska3, Jeremy R.A. Paull6, Bernadette M. Jean-Francois6, Nicola J. Main6, Julia Le Meur6, Stephanie R. Edmondson6, Natalie Cook7 1The Kinghorn Cancer Centre, St Vincent’s Hospital, Sydney, Australia, 2The Royal Marsden Hospital NHS Foundation Trust, London, UK, 3Northern Centre for Cancer Care, Newcastle-Upon-Tyne Hospitals NHS Foundation Trust, Newcastle, UK, 4The Beatson West of Scotland Cancer Centre, Glasgow, UK, 5Cancer Centre at Guy’s, Guy’s and St Thomas’ NHS Foundation Trust, London, UK, 6Starpharma Pty Ltd, Abbotsford, Australia, 7The Christie Foundation Trust, Manchester, UK Dr Jia (Jenny) Liu, BSc(Med) Hons BMed MD PhD FRACP Dr Jia (Jenny) Liu, MD PhD FRACP Study sponsored by Starpharma Pty Ltd 3rd June 2024, 8:00-9:30 am PRESENTED BY: 2 Dr Jia (Jenny) Liu, MD PhD FRACP Results from DEP SN38 Phase 1/2 clinical trial in 114 patients with advanced solid tumors: Summary 2 Linker DEP dendrimer PEG SN38 1:1 ratio SN38:PEG DEP SN38 dendrimer nanoparticle 10-15 nm diameter 3. Promising efficacy in irinotecan-treated CRC and platinum-resistant/refractory ovarian cancer 1. Dendrimer technology has potential to deliver a range of payloads with improved safety / efficacy 2. DEP SN38 (12.5 mg/m2) well-tolerated, with mostly mild/moderate gastrointestinal and no cholinergic toxicity PRESENTED BY: Dr Jia (Jenny) Liu, MD PhD FRACP • 3D-poly-lysine dendrimers act as scaffold for delivery of a range of payloads, including cytotoxics1 • DEP SN38 does not require liver metabolism for conversion into active SN38 metabolite  reducing off-target toxicity • DEP SN38 retained in tumor microenvironment via enhanced permeability and retention (EPR1,2)  improved efficacy 3 Linker DEP dendrimer PEG SN38 1:1 ratio SN38:PEG 1. Kaminskas et al, Nanomedicine 2011, 6(6):1063-1084 2. Iyer et al, DrugDiscToday 2006, 11(17-18):812-818 DEP SN38 Dendrimer Nanoparticle Mechanism DEP SN38 dendrimer nanoparticle 10-15 nm diameter 32 SN38 / dendrimer DEP SN38 avoids liver metabolism TumorHealthy tissue Normal vasculature Leaky vasculature Free SN38 SN38 release over time DEP dendrimer drug conjugate EPR Effect PRESENTED BY: 4 Dr Jia (Jenny) Liu, MD PhD FRACP Q3W Phase 2 Mono Dose Expansion CRC n=20 Ovarian n=14 Pancreatic n=9 Breast n=5 Other n=12 Q2W Phase 2 Combo Dose Expansion CRC n=13^ Q2W Phase 2 Mono Dose Expansion Platinum-resistant ovarian n=5^ DEP SN38 Phase 1/2 Clinical Trial MONOTHERAPY DEP SN38 COMBINATION DEP SN38 + 5-FU/LV Q3W P1a Dose Escalation 10.0 mg/m2 n=1 12.5 mg/m2 n=6 P1b(i) Dose Assessment 15.0 mg/m2 n=11 Q2W P1b(ii) Dose Assessment 12.5 mg/m2 n=6 15.0 mg/m2 n=6^ Q2W P1b(iii) Combination Dose Confirmation 12.5 mg/m2 n=6^ All doses are expressed as mg/m2 SN38 RP2D: 12.5 mg/m2 • Multicenter first-in-human open-label trial1,2 • DEP SN38 administered IV q3wkly or q2wkly infusion without corticosteroid/atropine pre-medication • Dose expansion cohorts: colorectal, platinum-resistant ovarian • Primary objective: safety profile and RP2D • Secondary objectives: preliminary anti-tumor activity, tolerability, PK 1. EudraCT: 2019-001318-40 2. Liu et al, Mol Cancer Ther 2023, 22(12_Supplement):B039 Study Design ^G-CSF prophylaxis as determined by Investigator PRESENTED BY: 5 Dr Jia (Jenny) Liu, MD PhD FRACP BASELINE CHARACTERISTICS COLORECTAL OVARIAN PANCREATIC BREAST OTHER1 TOTAL Subjects enrolled (n, %) 55 (48%) 23 (20%) 15 (13%) 8 (7%) 13 (11%) 114 (100%) Subjects ongoing (n, %) 4 (7%) 2 (9%) 0 (0%) 0 (0%) 0 (0%) 6 (5%) Age (years) Median (range) 59 (31-78) 64 (42-74) 65 (48-76) 53 (42-66) 60 (38-73) 61 (31-78) Sex (n, %) Male 24 (44%) 0 8 (53%) 0 9 (69%) 41 (36%) Female 31 (56%) 23 (100%) 7 (47%) 8 (100%) 4 (31%) 73 (64%) ECOG PS 0 23 (42%) 6 (26%) 6 (40%) 2 (25%) - 40 (35%) 1 32 (58%) 17 (74%) 9 (60%) 6 (75%) 2 74 (65%) Stage at diagnosis III 2 (4%) 4 (17%) 0 (0%) 0 (0%) 2 (15%) 8 (7%) IV 53 (96%) 19 (83%) 15 (100%) 8 (100%) 11 (85%) 106 (93%) Prior systemic therapy (n, %) Irinotecan 54 (98%) 0 (0%) 11 (73%) 0 (0%) 3 (23%) 68 (60%) Platinum 29 (53%) 23 (100%) 9 (60%) 0 (0%) 12 (92%) 73 (64%) Taxanes 0 (0%) 23 (100%) 2 (13%) 7 (88%) 9 (69%) 41 (36%) Prior lines of therapy Median (range) 4 (2-9) 6 (3 to 9) 2 (2 to 5) 7 (3 to 12) 3 (1 to 6) 4 (1 to 12) 1Other cancer types included lung, upper gastrointestinal, and kidney. Patient Characteristics – All Treated Patients PRESENTED BY: 0 20 40 60 80 Abdominal Pain Constipation Decreased Appetite Vomiting Diarrhea Fatigue Alopecia Nausea 10.5% 12.3% 16.7% 37.7% 39.5% 45.6% 62.3% 68.4% 0% 0% 0% 0.9% 0.9% 3.5% 0% 1.8% Patients (%) All Grades ≥ Grade 3 Dr Jia (Jenny) Liu, MD PhD FRACP Treatment-related AEs in ≥10% patients (N=114) Non-hematological AEs Hematological / Lab AEs DEP SN38 is well-tolerated with a notable lack of severe GI toxicity and mostly mild/moderate AEs Mostly mild/moderate GI AEs, and lack of cholinergic effects Dose Level / Regimen DLT 12.5 mg/m2 Q3W G4 neutropenia >7 days 15 mg/m2 Q2W G3 febrile neutropenia 15 mg/m2 Q2W G3 neutropenic colitis RP2D 12.5 mg/m2 for Q2W and Q3W Delay, n (%) 27 (23.7%) Reduction, n (%) 12 (10.5%) Discontinuation, n (%) 4 (3.6%) DEP SN38 Safety and Tolerability Treatment-related dose modifications (N=114) TRAE DEP SN38 (Q2W, Q3W) Irinotecan† (Q3W) Diarrhea ≥ Grade 3 0.9% ~20% Vomiting ≥ Grade 3 0.9% ~10% Nausea ≥ Grade 3 1.8% ~10% Cholinergic Syndrome 0% 47% DEP SN38 GI toxicity profile improved vs known toxicity of irinotecan † https://www.medicines.org.uk/emc/product/6506- UK SmPC April 2022 N=114 N=765 0 20 40 60 80 Lymphopenia ALT Increased AST Increased Thrombocytopenia Leukopenia Anemia Neutropenia 13.2% 13.2% 15.8% 19.3% 21.1% 32.5% 57.9% 0.9% 1.8% 1.8% 0% 8.8% 7.0% 34.2% Patients (%) All Grades ≥ Grade 3 DEP SN38 cycles administered: median 4 (1 – 38 to date) PRESENTED BY: Dr Jia (Jenny) Liu, MD PhD FRACP CRC Efficacy Overview Efficacy Response DEP SN38 Monotherapy Q3W/Q2W (N=38) Median number of prior lines (range) 4 (2-9) RECIST 1.1 Evaluable (n) 31 DCR (n) 48% (15) ORR (n) 0% (0) Duration of response up to 72 weeks Median PFS [95% CI] 2.1 months [9.9-18.4] DEP SN38 + 5-FU/LV Combination Q2W (N=17) Median number of prior lines (range) 3 (2-6) RECIST 1.1 Evaluable (n) 14 DCR (n) 86% (12) ORR (n) 14% (2) Duration of response up to 45 weeks* Median PFS [95% CI] 4.2 months [14.5-26.2] * 4 patients ongoing treatment Evaluable: patients who received ≥ 1 dose DEP SN38 and a CT scan at ≥ ~week 8 after first dose. DCR: : Disease Control Rate (CR+PR+SD/RECIST Evaluable). 0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0 50.0 Weeks Patients 34 6 1 1 -8 -11 -12 -12 -13 -13 -26 -29 -31 -46 -60 -50 -40 -30 -20 -10 0 10 20 30 40 Best % Change in Sum of Target Lesion Size (RECIST 1.1) % change (nadir vs baseline) PFS: DEP SN38 Combination Therapy (n=17) PR SD PD CRC Combination Therapy (n=14) Median PFS = 4.2 months PRESENTED BY: Dr Jia (Jenny) Liu, MD PhD FRACP Ovarian Efficacy Overview Efficacy Response Total (n=23) Q2W (n=8) Q3W (n=15) DEP SN38 Monotherapy Median prior lines (range) 6 (3-9) 6 (4-8) 6 (3-9) RECIST 1.1 Evaluable (n) 18 7 11 ORR % (n) 22% (4†) 43% (3†) 9% (1) DCR % (n) 72% (13) 100% (7) 55% (6) Duration of response up to 62 weeks* up to 62 weeks* up to 33 weeks Median PFS [95% CI] 3.2 months [12.6 – 29.5] 9.3 months [14.4 – 56.3] 1.9 months [7.3 – 17.7] * 2 patients – ongoing treatment Evaluable Patients: received ≥ 1 dose DEP SN38 and a CT scan at ≥ ~week 8 after first dose. DCR: Disease Control Rate (CR+PR+SD/RECIST Evaluable). † Includes a patient with no target lesions had complete resolution in tumor ascites and pleural effusion. 20 16 10 9 8 4 3 0 0 -7 -8 -14 -17 -23 -38 -59 -100 -100.0 -80.0 -60.0 -40.0 -20.0 0.0 20.0 RECIST best % change (nadir vs baseline) 8 Complete resolution of soft-tissue tumor and tumor-related ascites in a patient with concomitant 98% reduction in CA-125 Best % Change in Sum of Target Lesion Size (n=17*) *Excludes one patient with no target lesions who achieved CR in ascites and pleural effusion PR SD PD Overall response RECIST best % change (nadir vs baseline) 36 23 19 2 -29 -29 -30 -34 -46 -46 -48 -48 -53 -58 -61 -63 -96 -98 -120 -100 -80 -60 -40 -20 0 20 40 60 CA-125 Best change from baseline (%) CA-125 biomarker reduced in >75% patients - up to 98% ↓ PRESENTED BY: 9 Dr Jia (Jenny) Liu, MD PhD FRACP Monotherapy DCR 48% Combo + 5FU/LV DCR 86%(n=55) (n=23) CA125  75% Q2W ORR 43% Q2W+Q3W DCR 72% Key Points 9 Linker DEP dendrimer PEG SN38 1:1 ratio SN38:PEG DEP SN38 dendrimer nanoparticle 10-15 nm diameter 0 20 40 60 80 Abdominal Pain Constipation Decreased Appetite Vomiting Diarrhea Fatigue Alopecia Nausea 10.5% 12.3% 16.7% 37.7% 39.5% 45.6% 62.3% 68.4% 0% 0% 0% 0.9% 0.9% 3.5% 0% 1.8% Patients (%) All Grades ≥ Grade 3 DEP SN38 (12.5 mg/m2) IV Q2W / Q3W well-tolerated, with mostly mild/moderate GI AEs, no cholinergic toxicity Promising efficacy in irinotecan-treated CRC and platinum-resistant/refractory ovarian cancer Dendrimer technology has potential to deliver a range of payloads with improved safety / efficacy Dendrimer nanoparticles offer a better way to deliver chemotherapy, focusing the treatment on cancer cells and sparing healthy tissue, helping to improve effectiveness and reduce side effects PRESENTED BY: 10 • Confirm efficacy of DEP SN 38 vs irinotecan in randomized trials • Explore synergy of DEP SN38 in combination with checkpoint / PARP inhibition • Dendrimer platform to improve efficacy and safety profile of different payloads Dr Jia (Jenny) Liu, MD PhD FRACP Future Directions PRESENTED BY: Acknowledgements 11 • Patients and their caregivers • All investigators, co-investigators and site support staff who conducted this trial • Sponsor: Starpharma Pty Ltd Dr Jia (Jenny) Liu, MD PhD FRACP

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