Announcement PDF ASX RELEASE 19 November 2025 2025 Annual General Meeting Chairman’s Address Dear Shareholders, As Chair and Managing Director, I am pleased to report on the strong progress Paradigm Biopharmaceuticals has delivered over the past 12 months. 2025 has been a year defined by operational execution, disciplined financial management, and meaningful strategic advancement as we continue to progress our pivotal Phase 3 clinical program in knee osteoarthritis (OA). 2025 marked Paradigm’s transition from planning to full execution of the global PARA_OA_012 Phase 3 program, the final step before potential registration of injectable pentosan polysulfate sodium (iPPS) for knee OA. Following extensive regulatory dialogue and careful protocol refinement, the U.S. FDA completed its 30-day protocol review without further questions. This outcome enabled Paradigm to efficiently advance into the ethics and regulatory approvals needed to activate trial sites across Australia and the United States. Site activation commenced in May 2025, led by our global CRO, Advanced Clinical, and by June we had successfully consented our first participant in Australia. Since then, screening and recruitment have continued to accelerate across both geographies, supported by refined inclusion criteria and strong site engagement. To further strengthen global oversight and enhance trial robustness, Paradigm recently engaged NBCD as a complementary CRO. NBCD brings additional on-the-ground regulatory and operational expertise across Europe and Asia, improving geographic diversity, governance efficiency, and data quality throughout the Phase 3 program. We remain firmly on track to achieve our key clinical milestones. Both the 25% and 50% recruitment markers are now in sight, with hundreds of participants currently progressing through screening. Our independent interim analysis remains scheduled for mid-2026, once half the study cohort reaches Day 112. This analysis will represent a major value inflection point for Paradigm, providing early efficacy signals and informing ongoing regulatory, commercial, and partnering discussions. While advancing iPPS remains our highest priority, 2025 was also notable for a strategic broadening of Paradigm’s osteoarthritis portfolio. In June 2025, we completed the acquisition of Proteobioactives Pty Ltd, securing global intellectual property rights for Pentacoxib™, a novel oral combination of PPS and a COX-2 inhibitor designed for earlier- stage OA and veterinary applications. This acquisition positions Paradigm across the full OA treatment continuum, addressing both early symptomatic disease with Pentacoxib and moderate-to-severe OA with Zilosul®. The veterinary development pathway for Pentacoxib also creates a capital-efficient route to generate early data and potentially revenue, supporting a measured and scalable expansion of our musculoskeletal pipeline. In response to clear feedback from shareholders during the 2024 AGM and subsequent meetings, the Board prioritised a balanced, flexible and minimally dilutive funding strategy in 2025. In December 2024, Paradigm successfully raised $16 million through an equity placement at $0.40 per share, enabling accelerated site activation and manufacturing readiness. In July 2025, we supplemented this with a US$27 million (approximately A$41 million) convertible note facility with Obsidian Global Partners, secured following a competitive international process. The Obsidian facility provides staged access to capital while preserving balance sheet strength and maintaining strategic optionality. Importantly, it provides funding runway through 100% recruitment and the interim analysis in mid-2026. Our Loyalty and Piggyback Option Program further supports a long-term, shareholder- aligned capital structure. While we acknowledge the options are not yet in the money, the potential for up to $112 million in future non-dilutive capital underscores Paradigm’s commitment to creating value for long-standing shareholders. We are focused every day on delivering the progress needed to ensure these options can be exercised and reward those who have supported the Company through this phase. 2025 has been characterised by disciplined execution across all operational pillars. Trial site selection, activation and recruitment scaling have been supported by global systems and experienced clinical, regulatory and operational teams. These efforts are designed to optimise data integrity, trial consistency, and overall probability of success. Early screening data demonstrates improved performance and lower screen-failure rates relative to previous studies, reflecting the refinements implemented after FDA feedback. Parallel progress continues across supply chain and CMC readiness, ensuring that commercial-scale manufacturing capability remains aligned with our clinical and regulatory timeline. As we enter the next phase of execution, Paradigm does so with strengthened operational momentum, increased regulatory clarity, and the financial runway required to deliver one of the most important milestones in the Company’s history, the interim analysis of the Phase 3 PARA_OA_012 trial in mid-2026. In the near term, our focus remains on accelerating recruitment, maintaining data quality, driving operational efficiency, and we continue to assess regional licensing and strategic partnership opportunities to support global positioning for both iPPS and Pentacoxib™. With these two complementary assets, Paradigm is now uniquely positioned across the full osteoarthritis treatment spectrum, from early symptom management to potential disease- modifying treatment for moderate to severe OA. This portfolio breadth, combined with our strong clinical, regulatory, and manufacturing foundations, provides a compelling long-term value proposition. I would like to extend my sincere thanks to our shareholders for their confidence and support, to our clinical investigators and patients for their invaluable participation, to our employees and partners for their ongoing dedication, and to my fellow Directors for their continued guidance and commitment. 2026 will be a defining year for Paradigm, one in which we expect to complete recruitment, deliver the interim analysis, and advance the next stage of our growth strategy. Our purpose remains steadfast: to provide new hope to millions of people worldwide living with chronic pain. Thank you. Paul Rennie Chair and Managing Director Paradigm Biopharmaceuticals Ltd About Paradigm Biopharmaceuticals Paradigm Biopharmaceuticals Ltd. (ASX: PAR) is a late-stage drug development company driven by a purpose to improve patients’ health and quality of life by discovering, developing, and delivering pharmaceutical therapies. Paradigm’s current focus is developing iPPS for the treatment of diseases where inflammation plays a major pathogenic role, indicating a need for the anti-inflammatory and tissue regenerative properties of PPS, such as in osteoarthritis (phase 3). Forward Looking Statements This Company announcement contains forward-looking statements, including statements regarding anticipated commencement dates or completions dates of preclinical or clinical trials, regulatory developments, and regulatory approval. These forward-looking statements are not guarantees or predictions of future performance, and involve known and unknown risks, uncertainties, and other factors, many of which are beyond our control, and which may cause actual results to differ materially from those expressed in the statements contained in this presentation. Readers are cautioned not to put undue reliance on forward-looking statements. Authorised for release by the Paradigm Board of Directors. FOR FURTHER INFORMATION PLEASE CONTACT: Simon White Director of Investor Relations Tel: +61 404 216 467 Paradigm Biopharmaceuticals Ltd. ABN: 94 169 346 963 Level 15, 500 Collins St, Melbourne, VIC, 3000, AUSTRALIA Email: investorrelations@paradigmbiopharma.com Paradigm Biopharma For more information please visit: https://investors.paradigmbiopharma.com A N N U A L G E N E R A L M E E T I N G | 1 9 N O V 2 0 2 5 BOARD OF DIRECTORS PAUL RENNIE Chair & Managing Director Non-Executive Director Non-Executive Director AMOS MELTZER MATTHEW FRY 2 Paradigm Biopharma NOV 2025 Experienced team to drive clinical success and commercialisation LOGIN & 3 Paradigm Biopharma NOV 2025 For Support call: 1300 816 159 (within Australia) +61 2 8072 1479 (overseas) Go to https://investor.auomic.com.au/#/home Under Meeting menu, click on “Join Meeting” Follow the prompts to register your relevant holding(s) 4 02/12/21 4 Paradigm Biopharma How to Ask a Question Nov 2025 COMPANY UPDATE 5 Paradigm Biopharma NOV 2025 PAUL RENNIE, Managing Director Questions relating to Company Update Notice of meeting & formal business Company Update 01 02 03 Agenda This document, together with any information communicated by Paradigm Biopharmaceuticals Ltd ASX:PAR (known as “Paradigm”, “Paradigm Biopharma” or “the Company”), in any presentation or discussion relating to this document (collectively, “Information”) is confidential, and has been prepared by the Company on the condition that it is for the exclusive information and use of the recipient. The Information is proprietary to Paradigm and may not be disclosed to any third party or used for any other purpose without the prior written consent of the Company. The Information is based upon management forecasts and reflects prevailing conditions, which are accordingly subject to change. In preparing the Information, the Company has relied upon and assumed, without independent verification, the accuracy and completeness of all information available from public sources, or which was otherwise reviewed by it. In addition, the analyses are not and do not purport to be appraisals of the assets, stock or business of the Company. Even when the Information contains a kind of appraisal, it should be considered preliminary, suitable only for the purpose described herein and should not be disclosed or otherwise used without the prior written consent of Paradigm. The Information is provided on the understanding that unanticipated events and circumstances may occur which may have significant valuation and other effects. This Company presentation contains forward-looking statements, including statements regarding anticipated commencement dates or completions dates of preclinical or clinical trials, regulatory developments and regulatory approval. These forward-looking statements are not guarantees or predictions of future performance, and involve known and unknown risks, uncertainties and other factors, many of which are beyond our control, and which may cause actual results to differ materially from those expressed in the statements contained in this presentation. Readers are cautioned not to put undue reliance on forward-looking statements. The rate and timing of enrolment of our clinical trials and the timing of top-line results of our clinical trials should be regarded as forward-looking statements and the actual dates could differ materially from the expectations and projections set forth in Company presentations or statements especially during a pandemic. DISCLAIMER 6 Paradigm Biopharma NOV 2025 COMPANY OVERVIEW Paradigm is advancing pentosan polysulfate sodium (PPS) as a novel, non-opioid therapy to transform the treatment of osteoarthritis. By targeting the underlying inflammation and structural degeneration that drive disease progression, Paradigm aims to deliver safer, more effective options that move beyond symptom relief. Mission Develop and commercialise safe, effective and non-opioid therapies for musculoskeletal diseases, targeting inflammation, pain relief, and disease modification. Unmet need • Osteoarthritis (OA) affects more than 500 million people worldwide and is the leading cause of pain-related disability in adults. • Current treatment options are largely symptomatic, relying on opioids or NSAIDs that offer limited long-term relief and carry significant safety risks. • The U.S. FDA has reinforced the urgent need for new non-opioid therapies for chronic pain, creating a supportive regulatory environment for novel OA treatments such as iPPS. OA Portfolio – Addressing full OA Spectrum • Early OA → Pentacoxib™ (oral PPS + COX-2) • Moderate to Severe → Zilosul® (injectable PPS) • Full OA Treatment Spectrum: Veterinary → Early Human OA → Moderate–Severe Knee OA 7 Paradigm Biopharma NOV 2025 COMPANY ACHIEVEMENTS 2025 YTD Phase 3 trial transitioned from setup to active dosing across AUS & US. Acquisition of Proteobioactives → broadened OA pipeline. Secured US$27m Obsidian funding facility, fully funded through interim analysis. Submission of Peer Review Publications. Advanced Clinical appointed as global CRO with NBCD engaged in a complementary role, broadening geographic footprint. 8 Paradigm Biopharma NOV 2025 Osteoarthritis By Numbers Zilosul® is a non-opioid subcutaneous injectable aimed to treat pain and function in moderate-to-severe osteoarthritis. 1. GBD 2019: Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. https://vizhub.healthdata.org/gbd-results/. 2. Long H, Liu Q, Yin H, Diao N, Zhang Y, Lin J et al. Prevalence trends of site-specific osteoarthritis from 1990 to 2019: Findings from the global burden of disease study 2019. Arthritis Rheumatol 2022; 74(7): 1172-1183. 3. Cieza A, Causey K, Kamenow K, Wulf Hansen S, Chatterji S, Vos T. Global estimates of the need for rehabilitation based on the Global Burden of Disease study 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020 Dec 19; 396(10267): 2006–2017. 4. National Institute of Health; Emerging drugs for osteoarthritis; Hunter DJ and Matthews G 16(3): 479–491; 2011 September. 5. Global Pricing Research conducted by Paradigm.US, UK Germany, France Moderate – to – Severe OA3 OA patients dissatisfied with current treatments4: Zilosul indicative price: US$2500 per year5 65% • Significant TAM • Prevalence continues to rise due to ageing, obesity and injury. People affected by OA Globally1 528m+ Knee OA most prevalent2 365m+ Knee OA is the most common form of OA, accounting for around 69% of all cases, followed by hip and hand OA2. of all OA Target uptake: 10% dissatisfied market NOV 2025 Paradigm Biopharma 9 81% UNMET NEED Current treatments (NSAIDs, steroids, HA) focus on short- term pain relief. OA costs the US healthcare system over $136B annually1. A safe, effective treatment with long-term benefits is urgently needed. High economic burden: Limited treatment options: Strong demand for alternatives: 1. GBD 2019: Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 10 Paradigm Biopharma NOV 2025 UNMET NEED Grafe 1 Minor OA Grade 2 Mild OA Grade 3 Moderate OA Grade 4 Severe OA Non-validated Effective Ineffective *Royal Australian College of General Practitioners hold a ‘strong against’ recommendation Invasive Analgesics,NSAIDS • Daily use • GI, CV risk with prolonged use. Opioids • Severe side-effects • Addictive *Hyaluronic Acid Injectable*Platelet-rich Plasma, *Stem Cells • Limited pain relief • Royal Australian College of General Practitioners hold a ‘strong against’ recommendation. Steroid injectable • Limited pain relief • Evidence of further cartilage degradation Surgery - Total Knee Arthroplasty • High cost • Patients opting for alternative treatments 11 Paradigm Biopharma NOV 2025 ADDRESSING FULL OA SPECTRUM Dual PPS-based therapies transforming osteoarthritis management across the full disease spectrum. Together, they aim to shift treatment earlier, reduce opioid reliance, and improve long-term outcomes. Aligned with FDA focus on non-opioid chronic pain solutions. 02. 01. 03. 12 Paradigm Biopharma NOV 2025 ADDRESSING FULL OA SPECTRUM Grafe 1 Minor OA Grade 2 Mild OA Grade 3 Moderate OA Grade 4 Severe OA Under investigation • Pentacoxib™ (oral PPS + COX-2) – safe, non-opioid option for mild-to- moderate OA. • Applications across vetinary and human OA • Zilosul® (injectable PPS) Phase 3 program for moderate-to-severe OA with disease-modifying potential. • Current P3 program 13 Paradigm Biopharma NOV 2025 OA PHASE 3 14 Paradigm Biopharma NOV 2025 15 02/12/21 15 Paradigm Biopharma PARA_OA_012 PHASE 3 PROGRAM OVERVIEW Global Pivotal Phase 3 Trial Progressing Toward Mid-2026 Interim Analysis Nov 2025 01 03 02 04 05 Primary endpoint Change in average daily pain at Day 112; key secondary endpoints include WOMAC pain and function, PGIC, and imaging biomarkers. Study design 466-patient, randomised, placebo-controlled trial evaluating injectable pentosan polysulfate sodium (iPPS, Zilosul®) for moderate-to- severe knee OA. Dosing regimen 2 mg/kg twice weekly for six weeks (12 injections). Trial oversight Conducted under FDA Fast Track designation with Advanced Clinical as global CRO and NBCD engaged in a complementary role to expand operational reach and data robustness. Interim analysis Planned for mid-2026, when 50 % of participants reach Day 112; independent DSMB oversight in place. 16 02/12/21 16 Paradigm Biopharma PARA_OA_012 Phase 3 Site Locations by State Nov 2025 United States 45 sites Australia 11 sites 17 02/12/21 17 Paradigm Biopharma LEAD PROGRAM OSTEOARTHRITIS Phase 3 Achievements Nov 2025 Site Activations • 60 sites across Australia, US, Hong Kong and Moldova on track for full activation by December 2025. • New sites in Hong Kong and Moldova broaden diversity and support regional regulatory pathways including the “1+” framework. Enrollment • Hundreds in screening with strong conversion to randomisation. • Improved screen-failure rates vs PARA_OA_002 from refined criteria and site training. • Recruitment and retention on plan; interim analysis mid-2026 (50 % of patients, DSMB- overseen). Addition of NBCD as Complimentary CRO • NBCD engaged alongside Advanced Clinical to enhance operational reach across Europe & Asia. • Strengthens site activation, data quality and overall trial governance efficiency. 18 02/12/21 UPDATE C o m p a n y 18 Paradigm Biopharma NOV 2025 19 02/12/21 19 Paradigm Biopharma FINANCE Strong Capital Position to Deliver Key Milestones Nov 2025 Obsidian Facility 02 01 03 Key focus has been to secure flexible sources of capital while minimising shareholder dilution wherever possible. Each conversion to date under the US$27 million Obsidian facility has occurred at a higher price than a traditional equity raising would have achieved at the time. The most recent US$5 million drawdown increased cash reserves to approximately A$26 million, with US$15 million still available at the company’s discretion. 20 02/12/21 20 Paradigm Biopharma FINANCE Runway and Funding Outlook Nov 2025 Fully funded through to the mid-2026 interim analysis of the Phase 3 program. R&D investment averaging A$5–6 million per quarter as global site activation and recruitment continue to scale. Forecast cash outflows for Q4 CY25 of A$13–15 million, reflecting peak clinical execution period. Loyalty and Piggyback Options provide potential A$111.9 million in additional non-dilutive capital if exercised. Ongoing focus on targeted capital allocation and disciplined financial management to preserve balance-sheet strength. 21 02/12/21 21 Paradigm Biopharma OUTLOOK Nov 2025 Recruitment Completion (1H 2026) Global enrolment completion with strong retention and adherence. Regulatory Engagement Continued collaboration with key regulatory agencies on expedited approval pathways. Pentacoxib™ Development Formulation optimisation and progression of development for veterinary and early OA markets. Scientific Publications Preparation and publication of peer-reviewed papers from Paradigm’s clinical programs. Interim Analysis (Mid-2026) Key efficacy and safety readout to guide next regulatory and commercial steps. Confirmatory Trial Protocol and site planning underway; clearance anticipated post-IA. Commercial Strategy Advancing market-readiness and access planning in key regions. Loyalty Options Exercise of loyalty options providing non-dilutive funding. Key Focus (next 12 months) 22 02/12/21 22 Paradigm Biopharma NEWS FLOW & CATALYSTS Nov 2025 Upcoming Catalysts Event Target Date PARA_OA_012 – 25% & 50% Recruitment of participants 2H 2025* Regional licensing agreement(s) in OA Ongoing PARA_OA_008 – Phase 2 clinical trial data manuscripts peer reviewed and published. End of CY2025 PARA_OA_012 – 100% Recruitment 1H 2026* PARA_OA_012 Interim Analysis – 50% participants reach Day 112 Mid-2026* THANK YOU FOR YOUR ATTENDANCE 23 Paradigm Biopharma NOV 2025 For more information please visit: https://investors.paradigmbiopharma.com