Announcement PDF ASX RELEASE 9 September 2025 Paradigm to Present at the Evans & Partners Small Cap Healthcare Conference 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, today announced it will be presenting at the 4th Annual Evans & Partners Small Cap Healthcare Conference on 9 September 2025. The presentation, delivered by Paradigm’s Founder and Managing Director Paul Rennie, will outline the significant burden of osteoarthritis disease and how Paradigm is seeking to address this unmet need through its ongoing global Phase 3 clinical trial of injectable pentosan polysulfate sodium (iPPS) for the treatment of knee OA. A copy of the presentation is available attached, or available via the company’s website via: https://investors.paradigmbiopharma.com/link/PBJlmP -EndsAbout 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 Evans & Partners 4 th A n n u a l S m a l l C a p Healthcare Conference MD | Paul Rennie Paradigm Biopharma Sep 2025 2 Disclaimer 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. Except as otherwise expressly stated in this presentation, Paradigm has not authorised any person to give any information or make any representation which is not contained in this presentation. Any such information or representation not contained in this presentation must not be relied upon as having been authorised by, or on behalf of, Paradigm. The Information should not to be relied upon for the making of any investment decision. Any investment in Paradigm is subject to a number of investment risks including the possibility of loss of capital invested and no return of income or payment of dividends. Neither Paradigm nor any other entity or person in or associated with Paradigm guarantees any return (whether capital or income) or generally the performance of Paradigm or the price at which its securities may trade. In particular, this presentation is not a recommendation, offer or invitation to subscribe for or purchase Paradigm securities. This presentation is not exhaustive of all of the information a potential investor or their professional advisers would require. This presentation does NOT constitute a “Prospectus" or a "Disclosure Document” (as defined in the Corporations Act 2001 (Cth) (“Corporations Act”)) and has not been, and will not be, lodged with the Australian Securities and Investments Commission or any other regulatory authority. Accordingly it is not required to contain, and may not necessarily contain, all of the information that a Prospectus or like Disclosure Document would be required to contain pursuant to the Corporations Act. This presentation does not take into account any specific objectives, financial situation or needs of investors. For these and other reasons, you are strongly recommended to obtain your own up to date independent legal, financial and investment advice – those acting without such advice do so at their own risk. This presentation may contain "forward-looking statements" which are not historical facts. Words such as “expect(s)”, “feel(s)”, “believe(s)”, “will”, “may”, “anticipate(s)” and similar expressions are intended to identify forward-looking statements. Any forward looking statements in this presentation are statements that are not historical facts, should be considered “at-risk statements” and not to be relied upon. These statements include, but are not limited to, statements regarding future clinical trial results, regulatory approvals, production targets, sales, staffing levels etc. All of such statements are subject to risks and uncertainties, many of which are difficult to predict and generally beyond the control of the Company, that could cause actual results to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include, but are not limited to: (i) the possible delays in and the outcome of pre clinical and clinical trials, (ii) risks relating to possible partnering or other like arrangements, (iii) the potential for delays in regulatory approvals, (iv) the unknown uptake and market penetration of any potential commercial products and (vi) other risks and uncertainties related to the Company’s prospects, assets / products and business strategy. This is particularly the case with companies such as Paradigm which operate in the field of researching, discovering, developing and commercialising potential treatments or other therapies. You are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof and Paradigm does not undertake any obligation to revise and disseminate forward-looking statements to reflect events or circumstances after the date hereof, or to reflect the occurrence of or non-occurrence of any events. In addition, the past performance of Paradigm cannot be assumed as indicative of the future performance. There is NO guarantee of future performance, Including that Paradigm will achieve its stated objectives / milestones, that its forecasts will be met or that forward looking statements will be realised - actual results and future outcomes will in all likelihood differ from those outlined herein. Neither Paradigm nor any of its advisers, agents or employees make or give any express or implied representation, warranty or guarantee that the information contained in this presentation or otherwise supplied by or on behalf of Paradigm is complete or accurate or that it has been or will be audited or independently verified, or that reasonable care has been or will be taken in compiling, preparing or furnishing the relevant information. Paradigm does not take any responsibility for any inference, interpretation, opinion or conclusion that any person may draw or form from this presentation. To the maximum extent permitted at law, Paradigm and all of its representatives, directors, partners, employees or professional advisers exclude all direct and indirect liability arising out of or in connection with any use or reliance of the information contained or described within this presentation. Other than to the extent required by law (and only to that extent), the Parties do not make any representation or give any assurance, guarantee or warranty (express or implied) as to, nor assume any responsibility or liability for, the authenticity, origin, validity, accuracy, suitability or completeness of, or any errors in or omissions from, any information, statement or opinion contained in this Presentation or any accompanying, previous or subsequent material or presentation. Not an offer This presentation may not be released to US wire services or distributed in the United States. The new fully paid ordinary shares in Paradigm have not been, and will not be, registered under the US Securities Act of 1933 and may not be offered or sold in the United States except in transactions exempt from, or not subject to, the registration requirements of the US Securities Act and applicable US state securities laws. The distribution of this presentation in the United States and elsewhere outside Australia may be restricted by law. Persons who come into possession of this presentation should observe any such restrictions as any non-compliance could contravene applicable securities laws. See “International Offer Restrictions" for more information Paradigm Biopharma Sep 2025 What is Osteoarthritis Kellgren and Lawrence Grade Overview • A degenerative joint disease causing pain, swelling, and stiffness. • Restricts movement, daily activities, and quality of life. • Affects entire joints (cartilage, bone, ligaments, muscles). • Can lead to mental health issues, sleep disturbance, and social withdrawal. • • Most common in knees, hips, spine, and hands. Chronic, progressive, and a leading cause of disability. Risk Factors & Management Impact • Age, sex, obesity, joint injury, overuse, metabolic disease, genetics. • Exercise, weight management, physical therapy, braces. • NSAIDs, Opioids for pain control. • Joint replacement surgery in severe cases. Schematic from BioRender.com Paradigm Biopharma Osteoarthritis By Numbers Zilosul® is a non-opioid subcutaneous injectable aimed to treat pain and function in moderate-to-severe osteoarthritis. 1. 2. 3. 4. 5. 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/. 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. 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. National Institute of Health; Emerging drugs for osteoarthritis; Hunter DJ and Matthews G 16(3): 479–491; 2011 September. Global Pricing Research conducted by Paradigm.US, UK Germany, France People affected by OA Globally1 Moderate – to – Severe OA3 m+ 528 65 Knee OA most prevalent2 OA patients dissatisfied with current treatments4: m+ 365 81 Knee OA is the most common form of OA, accounting for around 69% of all cases, followed by hip and hand OA2. • • Sep 2025 Significant TAM Prevalence continues to rise due to ageing, obesity and injury. % of all OA % Target uptake: 10% dissatisfied market Zilosul indicative price: US$2500 per year5 4 Paradigm Biopharma Unmet Need • • • Effective Non-validated Ineffective Opioids *Royal Australian College of General Practitioners hold a ‘strong against’ recommendation High economic burden: OA costs the US healthcare system over $136B annually1. Strong demand for alternatives: A safe, effective treatment with long-term benefits is urgently needed. CV = Cardiovascular; GI = Gastrointestinal *Hyaluronic Acid Injectable*Plateletrich Plasma, *Stem Cells Steroid injectable Surgery - Total Knee Arthroplasty Grafe 1 Minor OA Grade 2 Mild OA 5 Invasive Analgesics, NSAIDS Limited treatment options: Current treatments (NSAIDs, steroids, HA) focus on short-term pain relief. Sep 2025 Grade 3 Moderate OA • • Daily use GI, CV risk with prolonged use. • • Severe side-effects Addictive • • Limited pain relief Royal Australian College of General Practitioners hold a ‘strong against’ recommendation. • • Limited pain relief Evidence of further cartilage degradation • • High cost Patients opting for alternative treatments Grade 4 Severe OA 1. Source: https://www.tandfonline.com/doi/full/10.1080/03007995.2023.2234727?scroll=top&needAccess=true&role=tab Paradigm Biopharma The picture can’t be displayed. Advancing iPPS Toward a Differentiated OA Therapy Robust data and regulatory 01 SAFTEY & EFFICACY PROFILE • Strong efficacy and safety shown across a broad dataset • Durable benefits sustained to 12 months in Phase 2 studies • Imaging and biomarker data suggest effects beyond symptom relief 02 PHASE 2 AND REAL-WORLD EVIDENCE • Multiple Phase 2 studies underpin Phase 3, showing consistent efficacy across patient types and timepoints • Real-world insights from Australia's SAS program show long-term benefits with repeat courses. 03 MECHANISM OF ACTION • Demonstrated across preclinical models and human studies • Anti-inflammatory, cartilage-protective, and matrix-restoring properties • Biomarker data from Phase 2 suggests activity beyond symptom relief momentum underpin a welldefined path through Phase 3 04 OPTIMISED PHASE 3 PROGRAM • Fast Track designation granted by FDA • Protocol refined following extensive FDA engagement (Type C and D meetings) • Endpoints, statistical powering, and assessment windows aligned with regulatory expectations Sep 2025 29/12/20 6 T h e p Paradigm Biopharma Confidence in IPPS Sep 2025 Clinical & Real-World Evidence iPPS Study Study Type Dosing Regimen Key Findings Ghosh et al. (2005) Randomised, double-blind, placebo-controlled (n=114) 3 mg/kg IM once weekly for 4 weeks Significant pain reduction at rest (out to 24 weeks); Improved joint stiffness and global assessment Kumagai et al. (2010) Open-label clinical trial (n=20) 2 mg/kg SC once weekly for 6 weeks Improved range of motion and pain reduction (out to 52 weeks); Reduced serum C2C (cartilage degradation marker) PARA_OA_005 Phase 2b (n=128) 2 mg/kg SC twice weekly for 6 weeks Clinically significant pain & function improvement; 5x lower rescue medication use; Sustained relief to 6 months PARA_OA_008 Phase 2 (n=61) 2 mg/kg SC twice weekly for 6 weeks Significant pain and function improvement out to 12 months; Reduced cartilage degradation biomarkers; MRI evidence of bone marrow lesion reduction PARA_OA_002 Phase 2b/3 (n=601) Dosing study, 6-week treatment, 18-week follow-up Confirmation of minimum effective dose for Phase 3 trial; Safety profile consistent across all doses TGA SAS Real-World (n>700) 2 mg/kg SC twice weekly Meaningful clinical improvements in pain and mobility 7 Paradigm Biopharma Phase 2: PARA_OA_008 Sep 2025 8 2 mg/kg IBW SC twice weekly v placebo for 6 weeks, followed up for 12 months (n=61) A single 6-week course of twice-weekly iPPS demonstrates durable clinical outcomes out to 12 months least squares adjusted mean Function WOMAC change from baseline. FAS. least squares adjusted mean Pain Reduction WOMAC change from baseline. FAS. p=0.045 p=0.054 Rescue medication use • 5x lower cumulative use of rescue medication in iPPS group. p=0.017 p=0.048 LS Mean Change +/- Standard Error FAS: Full Analysis Set WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index Paradigm Biopharma PARA_OA_008 Sep 2025 9 Top-Line Day 168 Quantitative MRI Results Changes in Cartilage Thickness from baseline • Twice weekly iPPS arm, demonstrated a consistent pattern of improvement in cartilage thickness across all key regions of medial and lateral compartments at 6 months • Placebo showed a loss in cartilage thickness in all key regions at 6 months. Cartilage Thickness (µm) Adj. CFB (abs.) LSM results by key regions of the medial and lateral compartments in knee • iPPS increased the cartilage thickness in the central medial femur by 60µm (0.06mm) compared to a reduction of -20µm (-0.02mm) in the placebo group at 6 months. • Placebo group demonstrated cartilage loss rate consistent with the natural progression of knee OA (-40µm or 0.04mm per year). Osteoarthritis Pivotal PH3 Trial Paradigm Biopharma Phase 3 Objectives Key objectives for the Phase 3 PARA_OA_012 study Primary Objectives • To evaluate the treatment effect of PPS on knee pain in participants with knee OA pain. (Weekly Average ADP Day 112) Key Secondary Objectives • To evaluate the treatment effect of PPS on knee pain function in participants with knee OA pain. (WOMAC Day 112) • To evaluate the effect of PPS treatment on PGIC in participants with knee OA pain. (PGIC Day 112) • To evaluate the efficacy of PPS treatment on knee pain, function, stiffness, and overall, in participants with knee OA pain. Secondary Objectives • WOMAC Pain and function assessments at multiple timepoints to Day 404. • IPPS effects on Rescue Medication use. • Structural changes via X-Ray and MRI from baseline day 168, 404 Sep 2025 11 29/12/20 Paradigm Biopharma. Sep 2025 PARA_OA_012 Interim Analysis (IA) Phase 3 trial design Follow-up Period: 52 weeks Treatment Period: 6 weeks • Conducted once 50% of subjects (~233) reach Day 112. • Plan assess efficacy and possible early conclusion of trial based on target effect size. • DSMB to conduct Interim Analysis. • Interim Analysis expected mid-CY26. Screening PPS 2 mg/kg N = 233* Placebo N = 233* Day 1 39 First Injection Last Inj. 56 84 112 Interim Analysis 140 168 224 280 336 404 End of Study Primary endpoint: Change from baseline in weekly ADP NRS pain score at Day 112. Secondary endpoints: Function, PGIC, rescue medication, biomarkers of disease progression, including MRI & X-Ray. *May be subject to change 12 Paradigm Biopharma The picture can’t be displayed. 29/12/20 Sep 2025 13 PARA_OA_012 – Powered for Success Statistical Power Based on Phase 2 Data Validates The table summarises modelled power at effect sizes established in Phase 2 studies. Effect Size (ES) Estimated Power (n=233/arm) • High statistical power supports confidence in replicating prior Phase 2 clinical benefit. • Model assumes observed Phase 2 variance and full sample size. 0.3 (Phase 2 pooled) >86% 0.4 >98% • Success estimates based on historical trial performance and standard assumptions*. * Does not account for executional risk. T h e p Paradigm Biopharma Sep 2025 14 Valuation (Market Capitalisation $Am) Company ASX PH3 Comparison Table Upside from current valuation P3 Trial Indication FDA Designations At IND Clearance Current Mesoblast Ltd (MSB) GVHD (paediatric refractory to standard of care) ~A$1,500 ~A$2,931 Immutep Ltd (IMM) Metastatic non-small cell lung cancer ~A$535 ~A$382 Dimerix Ltd (DXB) Focal segmental glomerulosclerosis (FSGS) Orphan ~A$90 (May-22) ~A$291 Neuren Pharmaceuticals Ltd (NEU) Phelan-McDermid syndrome (PMS) Orphan ~A$500 (Mar-22) ~A$2,250 Botanix Pharmaceuticals Ltd (BOT) Primary axillary hyperhidrosis ~A$190 (Oct-23) ~A$314 Paradigm Biopharmaceuticals Ltd (PAR) Osteoarthritis of the knee Fast track ~A$112 Source: Market capitalisations are approximate only. IRESS as of 12 August 2025. NEU, MSB and BOT have since completed PH3 studies and are in production likely to positively effect current market capitalisation above. The picture can’t be displayed. Paradigm Biopharma Sep 2025 15 29/12/20 Investment Highlights ü Multiple Positive Phase 2 Trials: Consistent efficacy and safety demonstrated across studies, with signals of disease-modifying activity on MRI and biomarkers. ü Real-World Evidence: Long-term benefits observed in Australia’s SAS program, including sustained improvements with repeat courses. ü Optimised Phase 3 Design: Refined following extensive FDA engagement, aligned with regulatory expectations, and powered to detect clinically meaningful effects. ü Fast Track Designation: Accelerated regulatory pathway secured with the FDA. ü Large, Unmet Global Market: 500M+ people affected by OA, 81% of patients dissatisfied with current treatments ü Near-Term Inflection Point: Interim analysis expected mid-2026 at 50% patient completion, representing a major value catalyst. T h e p Paradigm Biopharma Sep 2025 16 News flow & catalysts Event Upcoming Catalysts Target Date PARA_OA_012 – First participant dosed. Q3 2025 PARA_OA_012 – 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* *The above is a statement of current intentions as at the date of this presentation. Investors should note that the above upcoming events are subject to funding or new circumstances. Paradigm Biopharma Paul Rennie Managing Director Email: prennie@paradigmbiopharma.com Simon White Director IR Investor and Media Enquiries For more information please visit: https://investors.paradigmbiopharma.com Email: swhite@paradigmbiopharma.com Sep 2025 17