Announcement PDF ASX RELEASE 29 August 2025 Financial Year 2025 Annual Report Paradigm Biopharmaceuticals Ltd (ASX:PAR) (“Paradigm” or “the Company”), a late-stage drug development company focused on delivering new therapies to address unmet medical needs, presents the FY25 Annual Report. FY25 was a pivotal year for Paradigm Biopharmaceuticals, marking the transition from regulatory preparation to active clinical execution of our global Phase 3 program. With strengthened operational foundations, strategic financing, and the expansion of the Company’s osteoarthritis pipeline, Paradigm continues to advance its mission of transforming the treatment landscape for osteoarthritis. Our efforts throughout the year have laid the groundwork for a major inflection point in FY26 as patient enrolment progresses and interim analysis approaches. Key Highlights of FY25 Global Phase 3 Trial Execution Underway • Paradigm transitioned from regulatory preparation to full execution of its pivotal Phase 3 trial (PARA_OA_012) for iPPS in moderate-to-severe knee osteoarthritis. The FDA accepted the final protocol without further comment in October 2024. • The Company finalised regulatory protocols, completed manufacturing of investigational product (iPPS and placebo), onboarded CROs, and implemented daily electronic pain reporting to reduce variability and bias. • By financial year-end, 27 clinical sites were initiated across Australia and the US, with patient screening underway, establishing strong momentum for recruitment into FY26. • The trial design incorporates 466 participants (233 per arm) and is powered at over 86% to detect a treatment effect size of 0.3. If the previously observed effect size of >0.4 is replicated, statistical power exceeds 98%, greatly increasing the likelihood of success. Strengthened Financial Platform to Support Key Milestones • A $16 million equity raise in December 2024 funded initial trial activities including CRO engagement, site contracting, and investigational product supply. • In July 2025, Paradigm secured a US$27 million (A$41.2 million) convertible note facility with Obsidian Global Partners to support full trial execution through interim analysis, ensuring financial runway for continued progress across key geographies. OA Pipeline Expansion Through Strategic Asset Acquisition • Paradigm broadened its osteoarthritis portfolio with the acquisition of Pentacoxib™, a novel oral PPS + COX-2 inhibitor combination targeting earlierstage OA. Early formulation exploration is planned, with a staged approach planned to assess development potential and alignment with Paradigm’s end-toend OA treatment strategy. Outlook for FY26 Paradigm enters FY26 with strong operational momentum, having moved from regulatory groundwork to the active execution of its global Phase 3 clinical trial evaluating Zilosul® (iPPS) for moderate-to-severe knee osteoarthritis. Patient enrolment has commenced at clinical sites across Australia and the United States, and the Company is progressing toward its next key milestone: achieving 50% recruitment by the end of calendar year 2025. This will enable the planned interim analysis in mid-2026, an important inflection point for validating the program and unlocking further clinical and commercial value. The Company has focused its resources on building the infrastructure required to ensure timely and efficient execution of the trial. With accelerating site activations and a robust operational framework in place, Paradigm is well-positioned to sustain recruitment momentum and deliver statistically meaningful results. The design of PARA_OA_012, which includes strong powering assumptions, validated endpoints, and smart-deviceenabled pain reporting, has been structured to minimise bias and maximise the likelihood of replicating previous Phase 2 outcomes. Alongside the iPPS program, Paradigm is advancing early formulation development for Pentacoxib™, a novel oral combination of PPS and a COX-2 inhibitor targeting patients with earlier-stage osteoarthritis. This initiative supports the Company’s broader objective to address the full OA disease spectrum and expand future commercial opportunities across both human and veterinary segments. The Board and Executive team remain focused on achieving the clinical, regulatory, and commercial milestones required to drive shareholder value. The Company is confident that ongoing delivery of operational milestones, including patient recruitment and trial execution, will support a more accurate reflection of the underlying value of the iPPS program. Importantly, this progress underpins the potential conversion of the loyalty options issued in February 2025. As Paradigm progresses toward this critical data point, the Company will continue to explore potential pathways to earlier commercialisation and is committed to initiatives that support long-term value creation and ensure regional and global access to innovative therapies for osteoarthritis. Hear From Our Founder and Managing Director To hear more about Paradigm’s FY25 progress and future plans, watch the video update from Founder and Managing Director, Mr Paul Rennie, here: https://investors.paradigmbiopharma.com/link/P2zdVP -Ends- 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 or may contain 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. To learn more please visit: https://paradigmbiopharma.com Approved 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 APPENDIX 4E Preliminary Final Report to the Australian Stock Exchange Name of Entity Paradigm Biopharmaceuticals Limited ABN (ABN 94 169 346 963) Year Ended 30 June 2025 Previous Corresponding Reporting 01 July 2023 to 30 June 2024 Period 1. Results for Announcement to the Market $ Revenue from continuing activities (Loss) from continuing activities after tax attributable to members Net (loss) for the period attributable to members Dividends (distributions) 7,105,400 $ and % increase/(decrease) over previous corresponding period 663,131 10.29% (18,770,745) (39,960,105) (68.04%) (18,770,745) (39,960,105) (68.04%) Amount per security Franked amount per security Final Dividend N/A N/A Interim Dividend N/A N/A Record date for determining entitlements to the dividends (if any) N/A Brief explanation of any of the figures reported above necessary to enable the figures to be understood: N/A 2. Key ratios Basic earnings per ordinary security (cents per share) Diluted earnings per ordinary security (cents per share) Net tangible asset backing per ordinary security (cents per share) Current Period Previous corresponding period (Restated) (5.97) cents (20.03) cents (5.97) cents (20.03) cents 5.33 cents 6.23 cents 3. Control Gained Over Entities Having Material Effect Name of entity (or group of entities) N/A Date control gained N/A Profit / (loss) from ordinary activities after tax of the controlled entity since the date in the current period on N/A which control was acquired. Profit / (loss) from ordinary activities after tax of the controlled entity (or group of entities) for the whole of N/A the previous corresponding period. 4. Audit/Review Status This report is based on accounts to which one of the following applies: (Tick one) The accounts have been audited  The accounts are in the process of being audited If the accounts are subject to audit dispute or qualification, a description of the dispute or qualification: N/A 5. Attachments Forming Part of Appendix 4E The Annual Report of Paradigm Biopharmaceuticals Limited for the year ended 30 June 2025 is attached. 6. Signed Signed in accordance with a resolution of the Directors. Signed ______________________________ Date: 29 August 2025 Paul Rennie Managing Director EXTRACTING TRUE VALUE WITH UNTAPPED POTENTIAL Annual Repor t 2025 Paradigm Biopharmaceuticals Ltd. is a late-stage clinical development company. We are driven by a purpose to improve patients’ health and quality of life by, developing, and delivering pharmaceutical therapies. Paradigm has a vision to be recognised as a global leader in the development and commercialisation of innovative pharmaceutical therapies. Paradigm’s values of innovation, transparency, adaptability, collaboration, respect, and accountability comprise the central pillars of the organisation and influence all activities and decisions. 1 2 6 Highlights Chairman and Managing Director’s Report Chief Medical Officer’s Report 8 12 20 Transforming the OA Landscape Directors’ Report Remuneration Report Auditor’s Independence Declaration 27 Consolidated Statement of Profit or Loss and Other Comprehensive Income 28 Consolidated Statement of Financial Position 29 Consolidated Statement of Cash Flows 30 Consolidated Statement of Changes in Equity 31 Notes to the Consolidated Financial Statements 32 Consolidated Entity Disclosure Statement 56 Directors’ Declaration 57 Independent Audit Report 58 Shareholder Information 62 Corporate Governance Statement 64 General Information 64 Corporate Directory 65 Paradigm Biopharmaceuticals Limited ABN 94 169 346 963 HIGHLIGHTS 27 sites A$6.3m initiated to date across US and Australia R&D Tax Incentive received for FY24 Claim 28th November 2025 Successful conclusion of 30-day FDA review period enabling Paradigm to proceed with the pivotal phase 3 clinical trial PARA_OA_012 PHASE 3 STUDY LOCATIONS United State of America 50 sites Australia 15 sites KEY HIGHLIGHTS Phase 3 trial execution underway Strengthened funding base to support trial milestones OA portfolio expanded via strategic acquisition Paradigm transitioned from regulatory preparation to full execution of its pivotal Phase 3 trial (PARA_OA_012) for iPPS in moderate-to-severe knee osteoarthritis. The FDA accepted the final protocol without further comment in October 2024, and by end of FY25, 27 clinical sites were activated across Australia and the US, with patient screening underway. A A$16 million equity raise in December 2024 funded initial trial activities including CRO engagement, site contracting, and investigational product supply. Post year-end, a US$27 million (A$41.2 million) convertible note facility was secured to fund trial execution through interim analysis, ensuring financial runway for continued progress across key geographies. Paradigm broadened its OA pipeline with the acquisition of Pentacoxib™, an oral PPS + COX-2 inhibitor combination targeting early-stage disease. This complements iPPS for moderate-to-severe OA and supports a full-spectrum treatment strategy. Paradigm Biopharmaceuticals Limited Annual Report 2025 1 CHAIRMAN AND MANAGING DIRECTOR’S REPORT In FY25, Paradigm Biopharmaceuticals made notable progress in advancing our pivotal Phase 3 clinical trial of injectable PPS (iPPS) for knee osteoarthritis (OA), while reinforcing operational stability through disciplined financial management, a strategic funding structure, and focused pipeline expansion. The Company listened to shareholder feedback and prioritised a robust capital strategy to ensure uninterrupted execution of our global clinical program, whilst minimising dilution and preserving long-term shareholder value. Paul Rennie Chairman and Managing Director $16m Dear Shareholders, AUD Equity Placement Completed Raised from institutional and sophisticated investors in Dec 2024. $27m USD Convertible Note Facility Secured Obsidian facility with initial USD $7m drawdown; announced July 2025. As Founder and Managing Director, I am pleased to report on the operational highlights of FY25. The past 12 months have seen Paradigm sharpen its execution focus, strengthen financial foundations, and position itself for long-term success as we progress our lead asset, iPPS, through its final phase of clinical development. Following comprehensive regulatory engagement and protocol refinement, Paradigm received the green light to proceed with the pivotal Phase 3 PARA_OA_012 trial. The U.S. FDA’s 30-day protocol review concluded without further queries, enabling immediate progression into obtaining ethics approval to support rapid site activation and patient recruitment across Australia and the United States. This was achieved by completing the ethics and regulatory groundwork needed to ensure consistent trial conduct across both jurisdictions. We have achieved operational momentum with a strong collaboration with our global Clinical Research Organisation, Advanced Clinical, and our clinical infrastructure now spans over 2 Annual Report 2025 Paradigm Biopharmaceuticals Limited 65 selected sites globally, with systems and personnel in place to manage recruitment, data collection, and safety oversight with speed and precision. Our high performing sites are fully engaged and the activation of study sites commenced in May 2025 with potential study participants now being screened for the study across multiple sites. With our focus remaining on the Phase 3 clinical program of iPPS, we have continued to evaluate avenues for the Company to grow and expand our pipeline, and in June 2025, we acquired the exclusive global rights to develop and commercialise a novel oral combination of PPS and a COX-2 inhibitor to treat early stage osteoarthritis. The acquisition strategically expands Paradigm’s osteoarthritis portfolio, enabling the Company to address a broader spectrum of disease severity, with the oral PPS + Coxib combination positioned for the large, under-served mild-to-moderate OA segment, and the iPPS program continuing to target patients with moderate to severe disease. Our initial focus for the oral combination will be on use in the veterinary field which will also support our transition to the human use. Funding and Financial Stability In direct response to shareholder feedback shared through the 2024 Annual General Meeting and broader investor engagement, the Board and Executive team undertook a competitive capital process to fund Paradigm through to the interim analysis of the Phase 3 study. The Company prioritised a structure that maintained strategic flexibility while ensuring sufficient runway to meet key clinical milestones. With our focus remaining on the Phase 3 clinical program of iPPS, we have continued to evaluate avenues for the Company to grow and expand our pipeline, and in June 2025, we acquired the exclusive global rights to develop and commercialise a novel oral combination of PPS and a COX-2 inhibitor as a potential therapy for early stage osteoarthritis management. In December 2024, we secured an AUD $16 million placement to institutional and sophisticated investors at $0.40 per share. The placement was oversubscribed and supported by both existing and new shareholders, providing funding to commence global site recruitment and manufacturing readiness. In July 2025, Paradigm announced a USD $27 million (AUD ~$41.2 million) convertible note facility with Obsidian Global Partners. This facility was the culmination of a competitive global capital process conducted over several months. The Company received multiple proposals and selected Obsidian following significant due diligence by both parties. The structure was chosen for its alignment with Paradigm’s long-term development objectives, providing staged access to capital with minimal upfront dilution. An initial tranche of USD $7 million was drawn to support trial operations, with the balance available at the Company’s discretion. The terms of the facility were designed to preserve operational control and minimise dilution, providing funding certainty through: • Activation of all planned Australian and U.S. clinical sites, • Completion of 100% patient recruitment, • Delivery of interim analysis (expected mid-2026). Paradigm Biopharmaceuticals Limited Annual Report 2025 3 CHAIRMAN AND MANAGING DIRECTOR’S REPORT continued Importantly, the facility retains flexibility to accommodate other capital sources as Paradigm advances. The Company remains committed to pursuing non-dilutive options, including regional licensing agreements for iPPS in smaller or strategically aligned international markets. This staged approach ensures Paradigm is well-positioned to deliver on its core clinical milestones, while remaining agile to evaluate and execute on value-enhancing opportunities. Further enhancing our funding strategy, Paradigm launched a Loyalty and Piggyback Options Program in early 2025 to reward long-term shareholders. Eligible investors received one Loyalty Option for every four shares held, exercisable at $0.65, with a 12-month expiry. Upon exercising two Loyalty Options, holders receive one Piggyback Option exercisable at $1.00, expiring in February 2028. If fully exercised, the combined program could generate up to $112 million in additional non-dilutive capital. This capital strategy, layered across equity, convertible instruments, and shareholder-aligned incentives, provides Paradigm with the flexibility and strength to deliver clinical results without delay, while minimising dilution and preserving balance sheet strength. Board and Leadership Update Paradigm continued to strengthen its governance framework in FY25 to support operational growth. At the 2024 AGM, we officially welcomed Mr. Matthew Fry as a Non-Executive Director. Mr. Fry brings more than two decades of strategic and regulatory experience in global healthcare markets and has already played a valuable role in guiding our late-stage development efforts. Following the AGM, Dr. Donna Skerrett stepped down from her role as Executive Director. Dr. Skerrett remains fully engaged as Paradigm’s Chief Medical Officer, now dedicating her full attention to the successful execution of our Phase 3 program and future regulatory submissions. Her deep clinical leadership remains integral to Paradigm’s progress. 4 Annual Report 2025 The Board thanks both incoming and departing Directors for their contributions and remains committed to maintaining a balance of scientific, commercial, and governance expertise. With our clear vision for Paradigm in place, we have recently added a Global Head of Operations, a CMC Regulatory Associate and a Medical Director to strengthen execution of our clinical program and our broader strategic vision. These additions bring critical expertise to help our next phase of activities. Reflections from the AGM, EGM and the Year Ahead At the 2024 Annual General Meeting and 2025 EGM, I had the opportunity to personally engage with many of our investors. Your feedback was clear: ensure Paradigm remains well-funded, strategically agile, and focused on execution. We took this guidance seriously and made it a priority to deliver a funding structure that supports trial continuity, minimises dilution, and allows for value-accretive flexibility. FY25 was marked by intentional discipline, in trial design, cost containment, and capital deployment. We now have a clinical program in full execution mode, backed by regulatory clarity and adequate funding to reach a critical inflection point: the interim analysis. With our global trial infrastructure in place and recruitment underway, we are entering the most important year in Paradigm’s journey to date. We also advanced operational capabilities to support downstream success. This included alignment of supply chain and manufacturing planning with our trial timelines, refinement of regulatory filings for future submissions, and active discussions with potential partners who recognise the potential of iPPS as a differentiated, non-opioid treatment for improvement of symptoms and disease progression of OA. Paradigm Biopharmaceuticals Limited I would like to thank our shareholders for their unwavering support, our clinical and operational teams for their tireless efforts, and our Board for their strategic guidance. FY26 represents a transformative chapter for Paradigm, and I look forward to updating you on our progress as we work toward our goal of bringing iPPS to patients suffering from OA. On behalf of the Board, Paul Rennie Chairman and Managing Director Melbourne, Victoria 29 August 2025 $112m AUD Potential Non-Dilutive Capital If all Loyalty and Piggyback Options are exercised by shareholders. Strategic Acquisition Paradigm broadened its OA pipeline with the acquisition of Pentacoxib™, an oral PPS + COX-2 inhibitor combination targeting early-stage disease. Mid-2026 Interim Analysis Milestone for PARA_OA_012 study Primary readout for efficacy and safety; a key value inflection point. With our clear vision for Paradigm in place, we have recently added a Global Head of Operations, a CMC Regulatory Associate and a Medical Director to strengthen execution of our clinical program and our broader strategic vision. These additions bring critical expertise to help our next phase of activities. Paradigm Biopharmaceuticals Limited Annual Report 2025 5 CHIEF MEDICAL OFFICER’S REPORT FY25 has been a pivotal year for Paradigm Biopharmaceuticals, marked by the transition of iPPS from preparatory regulatory stages into full-scale phase 3 clinical execution. As Chief Medical Officer, I am pleased to report strong momentum across multiple clinical milestones, reflecting the rigour, resilience, and responsiveness of our regulatory and clinical teams. Dr Donna Skerrett Chief Medical Officer 466 Dear Shareholders, patients Target recruitment for the PARA_OA_012 Phase 3 study in moderate-to-severe knee OA. 65 sites Across Australia and the U.S. actively progressing site initiation and recruitment. First patients consented Australia and the United States commenced screening and enrolment activities. 6 Annual Report 2025 The year commenced with a major regulatory achievement: the successful submission and subsequent acceptance of the updated Phase 3 protocol (PARA_OA_012) by the U.S. Food and Drug Administration (FDA). The 30-day FDA review period concluded without further queries and allowed Paradigm to move confidently into trial start-up mode and, an outcome that reflects the quality and completeness of our submission informed by prior extensive regulatory agency interactions. This clearance affirmed the selection of our dosing regimen (2mg/kg iPPS, administered twice weekly for 6 weeks), which was based on strong clinical data from earlier Phase 2 studies. Importantly, the FDA’s feedback was fully integrated into our trial design and statistical methodology, elevating the significance of structural change endpoints to support future regulatory filings and potential label differentiation. Complementing the FDA review, Paradigm received centralised ethics approvals in both Australia and the United States, via HREC and IRB processes respectively, streamlining site initiation by enabling harmonised approval across all local sites within each country. Paradigm Biopharmaceuticals Limited Site Activation and Patient Progression Following regulatory and ethics clearance, the clinical team shifted its focus to execution. Site initiation activities commenced in Q2 CY2025, initially in Australia, followed shortly thereafter by rollout across the U.S. We are now focussed on activating more than 65 global trial sites, including approximately 15 in Australia and up to 50 across the United States. Paradigm has already consented and commenced screening of the first participants, beginning with Australian patients and then U.S. patients. Our first participants are preparing to be dosed shortly, with enrolment expected to increase rapidly each week as more sites are activated. This progress marks a turning point for Paradigm. After years of rigorous development, we are now delivering on the promise of a global, registrational trial executed at scale and designed to generate robust data on the efficacy and safety of iPPS in moderate-to-severe knee osteoarthritis. Partnering with Advanced Clinical To support this landmark trial, Paradigm undertook a competitive evaluation of global Clinical Research Organisations (CROs). After a comprehensive due diligence process involving seven CROs and formal proposals from four, Advanced Clinical was selected as our CRO partner for PARA_OA_012. Advanced Clinical brings deep experience in osteoarthritis trials, strong operational systems, and a global site network spanning North America, Europe, and APAC. Their emphasis on patient engagement and site responsiveness has been integral to our activation strategy. Their team is fully embedded alongside Paradigm’s, enabling real-time responsiveness and quality oversight across regions. Trial Design and Scientific Rigor The PARA_OA_012 study is a randomised, double-blind, placebocontrolled trial of 466 participants. The study’s primary endpoint is change from baseline in average daily pain score at Day 112. Secondary endpoints include WOMAC scores (pain and function), Patient Global Impression of Change (PGIC), rescue medication use, and imaging-based structural outcomes (MRI and X-ray). An interim analysis is planned once 50% of participants reach the Day 112 follow-up mark. This milestone is anticipated in mid-2026 and will serve as a critical decision point regarding potential acceleration strategies and commercial planning. The scientific rigour underpinning this design, including endpoint harmonisation with regulatory guidance and statistical powering based on previous clinical data ensures that the trial is positioned to deliver high-quality, registrable evidence. Future Outlook The next 12 months will be critical. As sites continue to activate and recruitment accelerates, our focus will remain on execution, ensuring every component of trial conduct, from participant safety to data quality, is held to the highest standard. In parallel, we are progressing other non-clinical studies that will be necessary for the new drug application (NDA) dossier submission, refining regulatory dossier components for eventual wider agency submissions, and beginning early engagement with global medical thought leaders to support awareness and future uptake of iPPS. Paradigm remains committed to transparent clinical communication and to upholding the highest standards of research integrity. Our clinical governance framework is actively guiding all decisions, from protocol adherence to safety monitoring and we continue to maintain a strong working relationship with our CRO and independent Data and Safety Monitoring Board (DSMB). A Personal Note As I stepped down from the Paradigm Board following the 2024 AGM, I did so to dedicate my full attention to the successful delivery of this Phase 3 program. I remain deeply engaged with our clinical partners, investigators, and internal teams and have never been more confident in our direction. The transition from Board responsibilities has allowed me to focus exclusively on the scientific and clinical work that matters most, bringing forward a therapy with the potential to address a major unmet need for millions of patients living with OA. Closing Remarks 2 mg/kg iPPS dosing Dosing regimen agreed to proceed in PARA_OA_012. 50% enrolment milestone 233 subjects required to meet the Day 112 Primary Endpoint for the DSMB to conduct the Interim Analysis. 7 CROs assessed Competetive process conducted to select key CRO partner for execution of Phase 3 program. I wish to thank our dedicated clinical team, our global site investigators and coordinators, and our participants who have placed their trust in this program. I also thank the Board for its unwavering support and strategic clarity during a year of intense operational activity. FY25 was a year of execution, and FY26 will be a year of delivery. I look forward to sharing our progress with the Paradigm community as we move closer to demonstrating the clinical and structural benefits of iPPS for knee OA. Dr Donna Skerrett Chief Medical Officer New York City, New York 29 August 2025 Paradigm Biopharmaceuticals Limited Annual Report 2025 7 TRANSFORMING THE OA LANDSCAPE Osteoarthritis (OA) is the most common joint disorder worldwide, affecting more than 500 million people and placing a substantial burden on healthcare systems and quality of life. In the United States alone, over 32 million adults live with OA, with the knee joint being the most frequently affected site. The disease typically progresses from early, intermittent stiffness and discomfort to chronic pain, reduced mobility, and eventually joint failure. This often results in patients undergoing joint replacement surgeries after years of insufficient symptom control1. Despite the widespread global impac