Announcement PDF ASX RELEASE 21 October 2024 Paradigm Investor Update Key Highlights • Protocol Submission: Paradigm will submit the revised Phase 3 (PARA_OA_012) protocol to the FDA by the end of October 2024, reflecting FDA feedback. • Trial Enhancements: Changes will improve patient convenience and reduce trial costs, enhancing overall efficiency. • CRO Selection: Four global CROs have been shortlisted for the Phase 3 trial, with final selection pending. • Next Steps: Following FDA review, enrolment is expected to begin in Q1 2025, starting with up to 10 Australian sites. • Board Confidence: Board and staff have purchased shares on-market, reinforcing confidence in the company’s progress. • Stock Options Expiring: If the PARO options expire without conversion, the Paradigm Board is considering various ways to reward our loyal shareholders who have supported us through this critical phase. Paradigm Biopharmaceuticals Ltd (ASX:PAR) (“Paradigm” or “the Company”), a late-stage drug development company, is pleased to announce its plan to submit the finalised protocol for its Phase 3 clinical trial (PARA_OA_012) to the U.S. Food and Drug Administration (FDA) by the end of October 2024. This submission will incorporate amendments that were suggested and agreed upon during a comprehensive review process with the FDA. Earlier this year, Paradigm submitted an initial draft phase 3 protocol to the FDA and, after receiving detailed feedback over five months and multiple review rounds internally by the US FDA, Paradigm has made the necessary revisions. Given the extensive engagement with the FDA, the Company is confident that the final protocol aligns with the FDA's expectations. Paradigm is optimistic about completing the 30-day review period smoothly once the protocol is submitted. Enhancements for Patient Convenience and Budget Optimisation Many of the changes recommended by the FDA are designed to enhance patient convenience and retention throughout the trial. These modifications are expected to streamline the trial process and potentially reduce overall costs. Paradigm anticipates that the adjustments will positively impact the Phase 3 trial budget. Global CRO Selection for Phase 3 Trial Throughout 2024, Paradigm has been consulting with global Contract Research Organisations (CROs) to conduct the PARA_OA_012 global trial. The Company has shortlisted four CROs, each having provided fixed pricing proposals based on the updated protocol. Paradigm will update investors on the selection of the CRO once a final decision has been made. Next Steps Once the protocol is submitted, Paradigm expects a 30-day review period before commencing pre-screening and enrolment for the PARA_OA_012 trial. Preparations are already underway at trial sites in both the U.S. and Australia. The Company will continue to keep investors informed about the Phase 3 trial, including updates on trial design and timelines following the FDA’s review. Paradigm is planning start-up activities in Australian sites initially with up to 10 sites across Australia to be utilised for the PARA_OA_012 clinical trial, with first patient enrolment expected in Q1 CY2025 Paul Rennie, Managing Director of Paradigm, stated: “Our ongoing collaboration with the FDA has been invaluable in refining our Phase 3 protocol. We are confident that the final protocol reflects the best pathway forward. The improvements we’ve incorporated, which enhance patient convenience and may reduce costs, further strengthen our position as we move into this critical stage. We look forward to sharing more updates as we progress through the trial and continue working towards securing approval for iPPS.” Board Update Paradigm Biopharma announces that Dr. Skerrett will be stepping back from her role as Executive Director following the conclusion of the 2024 Annual General Meeting (AGM). Dr. Skerrett will focus exclusively on her responsibilities as Chief Medical Officer (CMO) and the successful execution of Paradigm’s pivotal phase 3 clinical trial. Her deep expertise and commitment to advancing the trial remain a crucial asset as Paradigm moves toward this key milestone. Following this move, the Paradigm board will consist of three members, with a majority of independent directors. This structure ensures strong governance and oversight as the company continues to advance its strategic priorities. The Paradigm Board and staff have recently demonstrated their confidence in the company’s future by purchasing shares on-market. These purchases reflect the team’s commitment to driving the clinical program forward, particularly as we approach critical milestones in the phase 3 trial for iPPS. The company remains focused on advancing its clinical and regulatory objectives, and these investments underscore the shared belief in Paradigm’s long-term potential to deliver value for our shareholders. PARO Listed Options Paradigm acknowledges the upcoming expiry of the listed PARO options on 30 November 2024. As the company works tirelessly towards the start-up and execution of the phase 3 PARA_OA_012 clinical trial, we remain focused on driving long-term value for our shareholders. If the PARO options expire without conversion, the Paradigm Board is considering various ways to reward our loyal shareholders who have supported us through this critical phase. Paradigm remains committed to advancing our clinical trial and delivering meaningful progress as we approach this key milestone in the company’s journey. Employee Long Term Incentive Plan In the 2024 Notice of Meeting, Paradigm Biopharma has proposed awarding Executive Directors Paul Rennie and Dr. Donna Skerrett an aggregate of 2,900,000 Performance Rights, subject to Shareholder approval. This includes 1,200,000 Performance Rights for Dr. Skerrett (Resolution 6) and 1,700,000 Performance Rights for Paul Rennie (Resolution 7), issued under the Company's Incentive Performance Rights Plan. The value of these rights, based on the Black Scholes methodology, is $44,284 for Dr. Skerrett and $62,736 for Mr. Rennie. Additionally, the Paradigm Board has made the decision to cancel all 2023 LTI Performance Rights due to the delay in receiving the FDA’s Type D response and the resulting inability to achieve the targeted milestone of completing the phase 3 trial for iPPS for knee osteoarthritis and the subsequent NDA filing within the original timeframe. -EndsAbout Paradigm Biopharmaceuticals Ltd. 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 injectable (subcutaneous) pentosan polysulfate sodium (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 iPPS, such as in osteoarthritis (phase 3) and mucopolysaccharidosis (phase 2). 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. 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