Announcement PDF 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 2024 Previous Corresponding Reporting 01 July 2022 to 30 June 2023 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) 6,519,931 $ and % increase/(decrease) over previous corresponding period (2,061,008) (24.02%) (58,653,188) 6,743,175 12.99% (58,653,188) 6,743,175 12.99% 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 (20.00) cents (20.78) cents (20.00) cents (20.78) cents 5.95 cents 18.00 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 2024 is attached. 6. Signed Signed in accordance with a resolution of the Directors. Signed ______________________________ Date: 30 August 2024 Paul Rennie Managing Director EXPLORING THE POSSIBILITIES ANNUAL REPORT 2024 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 discovering, 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. Contents 01 Highlights 31 Consolidated Statement of Cash Flows 02 Chairman and Managing Director’s Report 32 Consolidated Statement of Changes in Equity 06 Chief Medical Officer’s Report 33 10 iPPS: Effect Size Determines Phase 3 Potential  otes to the Consolidated Financial N Statements 55 13 Directors’ Report Consolidated Entity Disclosure Statement 21 Remuneration Report 56 Directors’ Declaration 28 Auditor’s Independence Declaration 57 Independent Audit Report 29 61 Shareholder Information Consolidated Statement of Profit or Loss and Other Comprehensive Income 63 Corporate Governance Statement 30 Consolidated Statement Financial Position 64 General Information 65 Corporate Directory Paradigm Biopharmaceuticals Limited ABN 94 169 346 963 HIGHLIGHTS 5X 600 In PARA_OA_008, rescue medication use was 5 times lower in the twice weekly iPPS group compared to placebo. Subjects randomised in Stage 1 Para_OA_002. $7.3m AUD R&D Tax Incentive received for FY 2023 claim. Indicative Phase 3 Trial Site Locations • Australia • Belgium • Canada • Czechia • Poland • United Kingdom • United States Key Highlights from FY 2024 During FY 2024 Paradigm completed clinical trials for MPS I & VI and the PARA_OA_008 and PARA_OA_002 clinical trials. iPPS demonstrates 12-month duration Structural improvements at 6-months PARA_OA_002 Stage 1 completion Paradigm reported significant new phase 2 PARA_OA_008 data demonstrating improvements in patient-reported outcomes of WOMAC pain, function and PGIC scores for participants receiving 2mg/kg twice weekly iPPS compared to placebo at Day 365. A 6-week twice weekly course of subcutaneous iPPS was shown to increase cartilage thickness and volume and to reduce bone marrow lesions and synovitis from baseline on MRI follow-up at 6 months. The first stage of the harmonised phase 3 clinical program was completed during the period. 120 sites were activated across seven countries completing the randomisation of 600 subjects demonstrating the effectiveness of Paradigm’s recruitment initiatives. Paradigm Biopharmaceuticals Limited Annual Report 2024 01 CHAIRMAN AND MANAGING DIRECTOR’S REPORT $30.1m AUD Capital raise Capital raise in October 2023 comprising $18 million AUD institutional placement and fully underwritten $12.1 million AUD entitlement offer. Paul Rennie Chairman and Managing Director “Paradigm Biopharmaceuticals made significant advancements in FY 2024 with clinical programs in knee osteoarthritis (OA) and mucopolysaccharidosis (MPS). The Company reported outstanding phase 2 data de-risking iPPS for musculoskeletal disorders and engaged in major regulatory discussions with the FDA to advance the 2mg/kg dose for the phase 3 OA program.” Dear Shareholders, As Chair and Managing Director, I am pleased to provide you with key clinical, regulatory and business highlights from the 2024 financial year. Paradigm Biopharmaceuticals Ltd (Paradigm or the Company), is a late-clinical-stage drug development company headquartered in Melbourne, Australia and established in 2014 based on the insight that the properties of injectable pentosan polysulfate sodium (iPPS) could have not only a notable potential in treating musculoskeletal disease but also provide a significant commercial opportunity for shareholders. Paradigm’s mission is to develop and commercialise iPPS for the treatment of pain associated with musculoskeletal disorders driven by injury, inflammation, aging, degenerative disease, infection or genetic predisposition. The company’s lead asset is utilising iPPS for the treatment of knee OA. In FY 2024, our focus was on expanding the potential of iPPS in treating knee osteoarthritis (OA) while simultaneously completing the final recruitment and analysis of the stage 02 Annual Report 2024 1 dose-ranging study of our phase 3 OA program. Paradigm achieved significant milestones, including outstanding data readouts from the phase 2 clinical study PARA_OA_008. This study demonstrated that iPPS not only alleviates pain and enhances knee functionality but also shows promise in improving joint health, as evidenced by synovial fluid biomarker analysis and MRI imaging. Clinical OA Program Highlights In FY 2024, our focus was on expanding the potential of iPPS in treating knee osteoarthritis (OA) while simultaneously completing the final recruitment and analysis of the stage 1 dose-ranging study of our phase 3 OA program. Paradigm achieved significant milestones, including a readout from the phase 2 clinical study PARA_OA_008. In July 2023, Paradigm completed the first stage of its two-stage, adaptive, randomised, double-blinded, placebocontrolled, phase 3 PARA_OA_002 clinical trial. The trial involved randomising 600 participants across 120 sites in Australia, the US, Canada, the UK, Belgium, Poland, and Czechia. Paradigm Biopharmaceuticals Limited 600 Subjects randomised in stage 1 PARA_OA_002 Paradigm demonstrated its experience in clinical trial recruitment, randomising 600 participants globally. 113.25% Increased OA prevalence globally from 1990 to 2019. Globally, OA prevalence increased by 113.25%, from 247.5 million in 1990 to 527.8 million sufferers in 2019. Paradigm also requested an interim analysis be conducted by the independent Data Monitoring Committee to evaluate the performance of all treatment arms in stage 1. This analysis revealed that the doses: used in stage 1 (less than 2 mg/kg twice weekly) did not meet the pre-specified performance threshold based on previous outcomes with a 2 mg/kg twice weekly dosing regimen. The interim analysis, conducted ahead of schedule, assessed the effectiveness of three iPPS doses against a placebo. The analysis, which included data from the first 300 participants up to Day 56, provided additional insights to complement Paradigm’s previous phase 2 studies. This data determined the lowest effective dose of iPPS and contributed to preparations for the next stage of the phase 3 OA program. Paradigm’s PARA_OA_008 clinical trial reached a successful 12-month milestone reported in September 2023. The trial attained its primary endpoint of a change in one or more synovial fluid biomarkers and also delivered positive clinical data at Days 56, 168, and 365. Notable results at Day 365 include significant pain reduction, functional improvement and a substantial decrease in the use of rescue pain medication in the iPPS twice-weekly group. Early access programs had previously provided substantial testimonials that the effects of iPPS are durable for at least 12 months. It was crucial for Paradigm to validate these findings under clinical trial conditions, and the data confirmed that a single 6-week course of iPPS provided durable pain relief and functional improvement for up to 12 months. Progression of Phase 3 Program Additionally, quantitative MRI analysis from the phase 2 PARA_OA_008 trial reported in October 2023 demonstrated that iPPS treatment resulted in increased cartilage thickness and volume, and resolution or reduction of bone marrow lesions and synovitis. Specifically, the iPPS group saw an increase in overall cartilage thickness by 0.17mm and cartilage volume by 1.9%, compared to decreases in the placebo group. These results highlighted that iPPS not only treats OA symptoms but also preserves and regenerates joint tissues, establishing Paradigm as a leader in OA treatment innovation. The key elements addressed in the Type D response include the justification for the minimal effective dose, additional nonclinical studies completed to Good Laboratory Practice (GLP) standards In April 2024, Paradigm submitted a comprehensive response to the US FDA following a Type D meeting held on January 10, 2024. This submission included results from five nonclinical studies, data from the successful phase 2 clinical trial (PARA_OA_008), and clinical data from 600 participants dosed in stage 1 of the PARA_OA_002 trial. addressing previously noted adrenal findings, the draft clinical trial protocol, and a revised safety monitoring and mitigation plan. The submission was made through a request for review pathway, which does not have strict timelines under the Prescription Drug User Fee Act. Paradigm has utilised the time awaiting the agencies feedback effectively ensuring that the selected clinical trial sites that were high performing sites in stage 1 of the Phase 3 program remain updated to enable rapid start-up once we have agreement from the US FDA. “FY 2024 has been a year of clinical advancement delivering exceptional new data for Paradigm Biopharmaceuticals confirming the potential of iPPS for osteoarthritis. Our focus for financial year 2025 remains steadfast on delivering an innovative treatment for those suffering with osteoarthritis whilst creating value for our shareholders.” Paradigm Biopharmaceuticals Limited Annual Report 2024 03 CHAIRMAN AND MANAGING DIRECTOR’S REPORT continued MPS Clinical Program Highlights During the March 2024 quarter, Paradigm announced that the phase 2 MPS VI trial conducted in 2 sites in Brazil, successfully achieved its primary endpoint and showed positive results in several secondary outcomes. The main goal of the study was to assess the safety and tolerability of iPPS compared to a placebo. iPPS was found to be well-tolerated, with all adverse events classified as mild to moderate, mostly involving injection site reactions. The analysis confirmed that iPPS is a safe adjunctive therapy to enzyme replacement therapy for managing joint pain, stiffness, and functional disability associated with MPS VI. It was gratifying to see that all 13 participants in the study have chosen to either begin iPPS treatment, for those who initially received the placebo, or continue treatment following the conclusion of the clinical trial. This outcome highlights the positive benefits that patients receiving iPPS for MPS VI are experiencing in alleviating the effects of their disease. With these results, we resolved to conclude our R&D investment in the MPS program to concentrate our resources on the OA clinical program. Board Activities A key activity for the Paradigm Board during the first half of the financial year was to create and implement through a ‘yes’ vote at the 2023 Annual General Meeting, a new Employee Incentive Scheme that was in-line with our investors’ expectations. The Paradigm Employee Performance Rights Plan is the company’s long-term incentive (LTI) designed to motivate key employees towards our success while aligning their interests with those of the shareholders. The Paradigm Board developed this Plan with input from an external remuneration consultant and an employee share scheme specialist to ensure it meets best practices and shareholder expectations. The Plan involves granting performance rights to key employees, which convert to shares if certain conditions are met after a vesting period of three years. These conditions include achieving specific business targets, ensuring a minimum return for shareholders, and satisfactory employee performance. 04 Annual Report 2024 The Plan’s aim is to retain key employees over the long term, preserving corporate knowledge and enhancing shareholder value. Central to the Plan is the win-win-win principle, ensuring benefits for shareholders, the company, and employees. Each offer under the Plan includes performance targets tied to company goals and market benchmarks, ensuring employees are rewarded based on objectively measurable business outcomes and their individual performance. I would like to thank all our investors’ for approving this plan and aiding Paradigm to continue to attract and retain talented staff to the Paradigm organisation. Paradigm also saw a restructure of the Board through FY 2024 with both John Gaffney and Helen Fisher exiting their positions as Non-Executive Directors and the addition of Matthew Fry as a Non-Executive Director to the Paradigm Board. Matthew Fry’s appointment as a Non-Executive Director at Paradigm is a notable addition to the company’s Board. With extensive experience in the biopharmaceutical industry, Mr Fry brings a wealth of knowledge and strategic insight to Paradigm. His background in guiding companies through growth phases and his expertise in corporate governance have been invaluable assets for the Company. I would like to thank both John and Helen for their dedication to Paradigm over the last 9 and 3 years respectively. Key Operational Aspects A key focus of the 2024 fiscal year was containment of costs through a significant period toward the end of the first half with the conclusion of two phase 2 studies in MPS, the phase 2 PARA_OA_008 clinical trial and completion of enrolment and interim analysis of the PARA_OA_002 clinical trial. Whilst this period saw significant increases in R&D expenditure, administrative costs were reduced compared to prior periods to ensure Paradigm’s capital was focused on activities related to progressing iPPS and producing compelling data to support regulatory discussions. Paradigm’s cash position was bolstered on 30 October 2023, with Paradigm announcing a fully underwritten capital raise of $30.1M. This included Paradigm Biopharmaceuticals Limited a fully underwritten $18M institutional placement and a 1 for 10 accelerated non-renounceable entitlement offer of $12.1M, raised at $0.43 per share. The placement received strong participation from domestic and offshore institutional investors. As part of the capital raise, Paradigm issued 3 attaching listed options for every 4 new shares taken up in the capital raise. The options have an exercise price of $0.65 and expire on 30 November 2024. If exercised, these options will provide additional funding to support Paradigm’s phase 3 clinical program in osteoarthritis. FY 2024 has been a year of clinical advancement delivering exceptional new data for Paradigm Biopharmaceuticals confirming the potential of iPPS for osteoarthritis. The new data produced during the financial year was accepted for presentation at multiple global conferences including the Orthopedic Research Society and OARSI World Congress on OA. Our focus for financial year 2025 has been and remains steadfast on delivering an innovative treatment for those suffering with osteoarthritis whilst creating value for our shareholders. As we look forward to the rest of financial year 2025, we are well-positioned to commence our phase 3 clinical, and deliver on our strategic and corporate milestones, driving Paradigm towards sustained success and growth. I extend my heartfelt gratitude to our shareholders for their unwavering support as we progress on this journey at Paradigm. Additionally, I want to express my deep appreciation to the Paradigm team for their dedication, hard work, and accomplishments in FY 2024. I eagerly anticipate sharing more significant milestones with you in the coming year. On behalf of the Directors, Paul Rennie Chairman and Managing Director Melbourne, Victoria 30 August 2024 Paradigm Biopharmaceuticals Limited Annual Report 2024 05 CHIEF MEDICAL OFFICER’S REPORT 0.17mm Average increase in overall cartilage thickness across all knee compartments. Compared to a 0.09 decrease in the placebo group in PARA_OA_008. Dr Donna Skerrett Chief Medical Officer “Our dedicated efforts in advancing iPPS through clinical trials have yielded remarkable results, bringing us closer to offering a novel and effective treatment option for millions suffering from OA worldwide.” Dear Shareholders, As Chief Medical Officer at Paradigm Biopharmaceuticals, I am pleased to present the significant advancements we have made over the past year in our clinical programs, in the development of our lead candidate, injectable pentosan polysulfate sodium (iPPS), for the treatment of osteoarthritis (OA). This report highlights the key outcomes from our recent clinical trials and regulatory submissions, including the successful Phase 2 studies, the long-term durability of iPPS, and the critical next steps in our regulatory journey. These milestones underscore our commitment to addressing unmet medical needs with innovative therapies that improve patient outcomes and quality of life. The PARA_OA_008 clinical trial has been a cornerstone in establishing the efficacy of iPPS for the treatment of knee osteoarthritis. The trial involved 61 participants and focused on assessing the structural and long-term impact of a single 6-week course of iPPS administered at 2 mg/kg once or twice weekly compared to placebo. 06 Annual Report 2024 iPPS Demonstrates Significant Osteoarthritis Pain Reduction and Functional Improvement at 12 Months The PARA_OA_008 trial demonstrated that participants receiving twice weekly iPPS experienced significant and sustained reductions in pain over a 12-month period. WOMAC pain scores showed a statistically significant improvement at both Day 56 (p=0.045) and Day 365 (p=0.054) when compared to placebo, with 55% of participants achieving a clinically meaningful pain reduction of at least 30% by the end of the study. In addition to pain relief, the trial highlighted considerable improvements in physical function, as reflected by WOMAC function scores, which showed significant enhancements at Day 56 (p=0.017) and Day 365 (p=0.048) in the iPPS group compared to placebo. More than half of the participants (55%) receiving iPPS reported over a 50% improvement in function by Day 365. Patient-reported outcomes as measured by the Patient Global Impression of Change (PGIC), also indicated that participants in the iPPS group experienced a statistically significant overall improvement or Paradigm Biopharmaceuticals Limited 1 Year Pain reduction and functional improvement iPPS demonstrated one 6 week course provides up to 12 month pain relief and functional improvement in phase 2 PARA_OA_008. stabilisation in their OA condition, with a PGIC score of 3.74 at Day 365 compared to 1.96 in the placebo group (p=0.005). Additionally, the use of paracetamol as a rescue medication was over five times lower in the iPPS group compared to the placebo group at Day 365, underscoring the long-term efficacy of iPPS in managing OA pain. iPPS Reduces Cartilage Degeneration in Phase 2 Trial In addition to symptomatic relief, iPPS has shown promise in addressing the structural components of OA. The PARA_OA_008 study also focused on the impact of iPPS on cartilage thickness and overall joint health changes from baseline to Day 168 as measured by Magnetic Resonance Imaging (MRI). The quantitative MRI (qMRI) findings from the PARA_OA_008 clinical trial highlighted the potential impact of iPPS on cartilage preservation in patients with knee osteoarthritis. At Day 168, participants treated with iPPS exhibited an increase in overall cartilage thickness, measuring 0.17mm (p=0.05) compared to overall decrease of -0.09mm in placebo as measure by qMRI. An overall increase in cartilage volume by 1.9% (p=0.07) was also reported in the iPPS group compared to a decrease of -1.58% in the placebo group, over the same period. This stark contrast underscores the ability of iPPS to effectively slow down or prevent the deterioration of cartilage, a critical factor in the progression of osteoarthritis. The placebo group’s significant cartilage thinning is consistent with the typical progression of osteoarthritis, where ongoing cartilage degradation leads to increased pain and loss of joint function. In contrast, the iPPS group not only avoided this deterioration but also maintained much of their existing cartilage thickness, suggesting that iPPS may play a protective role in joint health. Additionally, the iPPS-treated group demonstrated a 30% reduction in bone marrow lesions (BMLs), while the placebo group exhibited only a minimal reduction of 5%, emphasising the effectiveness of iPPS in addressing this key indicator of joint degeneration. The data also revealed that iPPS treatment led to a 20% reduction in synovitis (inflammation of the synovial membrane), whereas the placebo group showed no significant change in synovitis levels. The ability of iPPS to preserve cartilage that would otherwise deteriorate, highlights its unique position in the OA treatment landscape, setting it apart from conventional therapies that primarily target pain relief. PARA_OA_002 Stage 1 Interim Findings The 2024 financial year also saw Paradigm complete several critical steps in our phase 3 development plan for iPPS in knee OA. The PARA_ OA_002 clinical trial evaluating dosing successfully completed the recruitment of 600 subjects globally, marking a significant milestone in our journey toward bringing iPPS to market as a treatment for osteoarthritis. Paradigm Biopharmaceuticals Limited The success of this recruitment phase is also attributed to several strategic initiatives that were implemented to ensure timely and effective enrolment. Collaborations with specialised teams in patient recruitment and digital outreach played a crucial role in accelerating our efforts. Their expertise in engaging patients and innovative approaches to digital outreach allowed us to reach a diverse and broad patient population across multiple regions globally. The PARA_OA_002 trial represented a critical step in advancing iPPS toward regulatory approval. Stage 1 of this study focused on determining the lowest effective dosing regimen of iPPS in a larger population. During FY 2024 an interim analysis of the PARA_OA_002 clinical trial was conducted at a critical juncture to evaluate the effectiveness of the dosing regimens under investigation and to ensure the study was progressing as expected. This analysis was performed after 300 patients had Annual Report 2024 07 CHIEF MEDICAL OFFICER’S REPORT continued “This report highlights the key outcomes from our recent clinical trials and regulatory submissions, including the successful Phase 2 studies, the long-term durability of iPPS, and the critical next steps in our regulatory journey.” reached the 56-day follow-up, allowing the data monitoring committee to assess the early efficacy signals of the various doses in the study. The decision to conduct the interim analysis at this stage was driven by the need to make informed adjustments to the trial design if necessary and to compare to the 2 mg/kg twice-weekly regimen identified as optimal in previous studies ensuring that we could maximise the likelihood of achieving conclusive and meaningful results. The interim analysis of PARA_OA_002 highlighted that the dosing regimen of 2 mg/kg twice weekly, as identified in previous studies, remains the most effective. The data confirmed that doses lower than 2 mg/kg or less frequent dosing did not demonstrate the same level of efficacy. In January 2024, Paradigm held a Type D meeting with the U.S. Food and Drug Administration (FDA) to discuss critical aspects of the ongoing development of iPPS for osteoarthritis treatment. This meeting provided a platform for Paradigm to address key regulatory considerations and to align with the FDA on the next steps required to advance the program for registration. Following this meeting, Paradigm submitted a comprehensive written response to the FDA, which included data from five nonclinical studies, results from the successful PARA_OA_008 phase 2 clinical trial, and clinical data from over 600 participants dosed in stage 1 of PARA_OA_002. Importantly, the submission included the draft protocol of the pivotal phase 3 clinical trial for evidence of efficacy and safety with the selected dose. This submission is a significant step forward, as it sets the stage for the continued progression of the phase 3 program, with Paradigm eagerly awaiting the FDA’s feedback to expedite the path to bringing iPPS to market. 08 Annual Report 2024 Outlook for 2024 As we continue to navigate the regulatory landscape, our focus remains on delivering iPPS to the market as swiftly and safely as possible. The data generated thus far provide a compelling case for iPPS as a transformative treatment for OA, offering hope to millions of patients who currently lack satisfactory therapeutic options. We are confident that our ongoing phase 3 program will further validate the efficacy and safety of iPPS, paving the way for regulatory approvals and commercial success. I sincerely thank the Board for their steadfast support this year, and I’m deeply grateful to the Paradigm team for their relentless effort in delivering exceptional results. Our commitment to improving patient outcomes drives every step we take, and we look forward to achieving more milestones in the year ahead. Dr Donna Skerrett Chief Medical Officer New York City, New York 30 August 2024 Paradigm Biopharmaceuticals Limited Paradigm Biopharmaceuticals Limited Annual Report 2024 09 iPPS: EFFECT SIZE DETERMINES PHASE 3 POTENTIAL Effect size is a key metric in clinical trial research that measures the difference in outcomes between groups subjected to different interventions. It’s an extremely useful analysis that cuts through dense data to tease out the magnitude of an intervention’s effect on trial participants, providing valuable insights into clinical efficacy. Following is an exploration and interpretation of effect size analysis of Paradigm’s clinical trials. Paradigm’s Experience of iPPS for Knee OA Paradigm has conducted four highquality clinical trials investigating the effects of injectable pentosan polysulfide sodium (iPPS) on participant pain and impaired function caused by knee osteoarthritis (with or without associated bone marrow lesions – BML) or due to anterior cruciate ligament (ACL) injury, and which included a total of 11 participants. In three studies Paradigm investigated 2 mg/kg total body weight iPPS – the highest dose evaluated over the clinical program – with dosing twice weekly 10 Annual Report 2024 over six weeks. All three studies demonstrated reduced pain and improved function and established an iPPS safety profile. In addition, Paradigm has collected real-world iPPS usage data from iPPS supplied under the Therapeutic Goods Administration Special Access Scheme (TGA SAS) in patients with knee OA and other similar conditions (hip, foot, or hand OA), as well as patients with knee OA in an Expanded Access compassionate use program in the US. Altogether, over 1000 trial participants and patients have been treated with Paradigm’s iPPS. Paradigm Biopharmaceuticals Limited Understanding Clinical Trial Analysis Models and Effect Size In two phase 2 clinical trials evaluating the efficacy of iPPS versus placebo, the statistical analysis model MixedModel Repeated Measures (MMRM) was employed to calculate the effect size of the treatment over time. The effect size is the magnitude of difference between groups and provides a meaningful relationship between variables or the differences between groups. Importantly, effect sizes are independent of the sample size and are categorised as either small (0.20–0.49), medium (0.50–0