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Company Presentation May 2025 AIM: POLB
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Disclaimer The contents of this presentation and the information which you are given at the time of the presentation have not been approved by an authorised person within the meaning of the Financial Services and Markets Act 2000 (the “Act”). Reliance on this presentation for the purpose of engaging in investment activity may expose an individual to a significant risk of losing all of the property or other assets invested. This presentation does not constitute or form part of any offer for sale or subscription or solicitation of any offer to buy or subscribe for any securities in Poolbeg Pharma plc (the “Company”) nor shall it form the basis of or be relied on in connection with any contract or commitment whatsoever. No reliance may be placed for any purpose whatsoever on the information contained in this presentation and/or opinions therein. This presentation is exempt from the general restriction (in section 21 of the Act) on the communication of invitations or inducements to engage in investment activity on the grounds that it is made to: (a) persons who have professional experience in matters relating to investments who fall within Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005 (the “Order”); or (b) high net worth entities and other persons to whom it may otherwise lawfully be communicated, falling within Article 49(2)(a) to (d) of the Order (all such persons together being referred to as “relevant persons”). Any person (whether a relevant person or otherwise) is recommended to seek their own independent financial advice from a person authorised for the purposes of the Act before engaging in any investment activity involving the Company’s securities. Any recipient who is not a relevant person should return this presentation to the Company’s registered office and should not act upon it. By accepting this presentation and not immediately returning it, each recipient warrants, represents, acknowledges and agrees that it is a relevant person. This presentation does not constitute or form part of any offer or invitation or inducement to sell, issue, purchase or subscribe for (or any solicitation of any offer to purchase or subscribe for) the Company’s securities in the UK, US or any other jurisdiction and its distribution does not form the basis of, and should not be relied on in connection with, any contract or investment decision in relation thereto nor does it constitute a recommendation regarding the Company’s securities by the Company or its advisers and agents. Nothing in the presentation shall form the basis of any contract or commitment whatsoever. The distribution of this presentation outside the UK may be restricted by law and therefore persons outside the UK into whose possession this presentation comes should inform themselves about and observe any such restrictions as to the distribution of this presentation. The Company has not registered, and does not intend to register, any securities under the US Securities Act of 1933, as amended or to conduct a public offering of any securities in the US. The securities of the Company have not been approved or disapproved by the U.S. Securities and Exchange Commission or by any U.S. state regulatory authority, nor have any of the foregoing passed on the accuracy or adequacy of this presentation. Any representation to the contrary is a criminal offence. This presentation contains "forward-looking" statements, beliefs, estimates, forecasts and opinions, including statements with respect to the business, financial condition, results of operations and plans of the Company and its group (“Group”), which constitute “forward-looking statements” within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements involve known and unknown risks and uncertainties, many of which are beyond the Company’s control and all of which are based on the current beliefs and expectations of the directors about future events. Recipients should note that past performance is not necessarily an indication of future performance and no assurance can be given that they will be attained. Forward-looking statements are sometimes identified by the use of forward-looking terminology such as "believes", "expects", "budgets", "schedules", "forecasts", "may", "might", "will", "will be taken", "occur", "be achieved", "would", "may", "will", "could", "should", "shall", "risk", "intends", "estimates", "aims", "plans", "predicts", "continues", "assumes", "positioned" or "anticipates" or the negative thereof, other variations thereon or comparable terminology or by discussions of strategy, plans, objectives, goals, future events or intentions. These forward-looking statements may and often do differ materially from actual results. The significant risks related to the Company’s business which could cause the Company’s actual results and developments to differ materially from those forward-looking statements appear in a number of places throughout this presentation and include statements regarding the intentions, beliefs or current expectations of the directors of the Company with respect to future events and are subject to risks relating to future events and other risks, uncertainties and assumptions relating to the Group's business, concerning, amongst other things, the results of operations, financial condition, prospects, growth and strategies of the Group and the industry in which it operates. No one will publicly update or revise any forward-looking statements or any other information contained herein, either as a result of new information, future events or otherwise. In considering the performance information contained herein, recipients should bear in mind that past performance is not necessarily indicative of future results, and there can be no assurance unrealised return projections will be met. Certain of the past performance information presented herein may not be representative of all transactions of a given type. Actual events could differ materially from those projected herein and depend on a number of factors, including the success of the Group’s development strategies, the successful and timely completion of clinical studies, securing satisfactory licensing agreements for products, the ability of the Group to obtain additional financing for its operations and the market conditions affecting the availability and terms of such finances. The forward-looking statements included in this presentation are expressly qualified by the cautionary statements herein. The Company reports under International Financial Reporting Standards as issued by the International Accounting Standards Board. Where foreign currency equivalents have been provided for convenience in this presentation, the exchange rates applied are those used in the relevant financial statements from which the figures have been extracted. This presentation is confidential and is being supplied to each recipient of it solely for its information. While this presentation has been prepared in good faith, no representation, warranty, assurance or undertaking (express or implied) is or will be made, and no responsibility or liability is or will be accepted by the Company or by its officers, employees or agents in relation to the adequacy, accuracy, completeness or reasonableness of this presentation, or of any other information (whether written or oral), notice or document supplied or otherwise made available to any recipient. This presentation has been prepared to assist a recipient in making its own evaluations and does not purport to be all-inclusive or contain all of the information a recipient may desire. Forward Looking Statements This presentation may contain forward-looking statements containing the words "expect", "anticipate", "intends", "plan", "estimate", "aim", "forecast", "project" and similar expressions (or their negative) identify certain of these forward-looking statements. The forward-looking statements in this communication are based on numerous assumptions and Poolbeg’s present and future business strategies and the environment in which Poolbeg expects to operate in the future. Forward-looking statements involve inherent known and unknown risks, uncertainties and contingencies because they relate to events and depend on circumstances that may or may not occur in the future and may cause the actual results, performance or achievements to be materially different from those expressed or implied by such forward-looking statements, and actual results could differ materially from those currently anticipated due to a number of risks and uncertainties. These statements are not guarantees of future performance, cash reach or prospects for market share grow etc. Many of these risks and uncertainties relate to factors that are beyond each of Poolbeg’s ability to control or estimate precisely, such as future market conditions, currency fluctuations, the behaviour of other market participants, the outcome of clinical trials, the actions of regulators and other factors such as Poolbeg’s ability to obtain financing, changes in the political, social and regulatory framework in which Poolbeg operates or in economic, technological or consumer trends or conditions. The delivery of this presentation shall not give rise to any implication that there have been no changes to the information and opinions contained in this presentation since the time specified. Subject to obligations under the London AIM Market (“AIM”) and Securities and Exchange Commission (“SEC”) (as applicable and as amended from time to time), none of the Company, the Group, their affiliates and advisers and their respective directors, officers, partners, representatives, employees and agents, undertakes to publicly update or revise any such information or opinions, including without limitation, any forward-looking statement or any other statements contained in this presentation, whether as a result of new information, future events or otherwise. In giving this presentation none of the Company, the Group, their affiliates and advisers and their respective directors, officers, partners, representatives, employees and agents, undertakes any obligation to provide the recipient with access to any additional information or to update any additional information or to correct any inaccuracies in any such information which may become apparent. Certain industry and market data contained in this presentation has been obtained from third party sources. Third party industry publications, studies and surveys generally state that the data contained therein have been obtained from sources believed to be reliable, but that there is no guarantee of the accuracy or completeness of such data. While the Company believes that each of these publications, studies or surveys has been prepared by a reputable source, the Company has not independently verified the data contained therein. In addition, certain of the industry, scientific and market data contained in this presentation comes from the Company’s own internal case studies, research and estimates based on the knowledge and experience of the Company’s management in the market in which it operates. While the Company believes that such research, estimates and results from its case studies are reasonable and reliable, they, and their underlying methodology and assumptions, have not been verified by any independent source for accuracy or completeness unless otherwise stated and are subject to change without notice. Risks and uncertainties affecting the Company are outlined further in the Company AIM filings. 2
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Focused on Partnering to Minimise Cost & Accelerate Development Pipeline Investment Highlights 3 Strong financial position: Debt free with c.£6.2M cash (March 2025) AIM: POLB Multiple Near-Term Value Inflection Points High Value Programmes Targeting Critical Unmet Medical Needs Highly Experienced Team with Proven Track Record 1. Unaudited management accounts as at 31 March 2025
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Product Modality Indication Preclinical Phase 1 Phase 2 Phase 3 Upcoming Expected Clinical Milestones POLB 001 p38 MAPK inhibitor Cancer Immunotherapy- induced CRS* 1st patient dosed in Phase 2a trial expected H2 2025 Phase 2a interim analysis expected H1 2026 Phase 2a topline data expected H2 2026 Oral Encapsulated GLP-1 GLP-1R agonist Obesity and diabetes POC trial expected to start within the coming months Topline POC data expected H1 2026 AI Programmes Novel drug discovery Influenza Potential partnership RSV Potential partnership High Value Pipeline Programmes Multiple near-term clinical value inflection points – positioned well for partnering 4 Phase 2 ready *Further life cycle opportunities, including severe influenza AI: Artificial Intelligence; CRS: Cytokine release Syndrome; GLP-1: Glucagon-like Receptor-1; MAPK: Mitogen Activated protein Kinase; POC: proof of concept
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POLB 001 Potentially breakthrough orally delivered p38 MAPK inhibitor to prevent cancer immunotherapy-induced CRS 5
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Cancer Immunotherapy-induced CRS is a High Unmet Need 6 1. Average rate from Summary of Product Characteristics (SmPCs) for Yescarta, Tecartus, Abecma, Kymriah, Carvykti, Breyanzi, Elrexfio, Columvi, Epkinly, Tecvayli and Talvey; 2. Datamonitor Healthcare. Forecast: Diffuse Large B-Cell Lymphoma and Multiple Myeloma, 2023; 3. Abramson JS et al. Blood Adv. 2021 Mar 23;5(6):1695-1705. *In this context, adequately is defined as both not completely preventing grade 2+ CRS and potentially sufficient to support active clinical development towards a regulatory approval of a medicine. Grade 2 CRS is defined as described by Lee et al, Biol Blood Marrow Transplant . 2019 Apr;25(4):625-638. janssenscience.com & doi.org/10.1182/blood-2022-159381; 4. Independent research by Decisive Consulting Limited. https://teamdecisive.com/meet-the-team. CAR T: Chimeric Antigen receptor T cell; CRS: Cytokine release Syndrome Effective preventative therapy represents a >US$10B market opportunity No approved therapies for prevention Approved options for CRS management (tocilizumab) have not adequately* prevented Grade 2+ CRS in clinical trials >70%1 of patients experience CRS on certain bispecific antibody / CAR T therapies and are restricted to specialist cancer centres Effective preventative therapy represents a >US$10B market opportunity4 May enable broader, safer delivery of cancer immunotherapies in outpatient setting Cytokine Release Syndrome (CRS) A severe, potentially life-threatening side effect of cancer immunotherapies
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7 * There was no significant or meaningful difference between POLB 001 High dose group and no CRS control group at all timepoints. CRS clinical score is a symptomatic measurement of animal behaviour and appearance CRS: Cytokine release Syndrome; MAPK: Mitogen Activated Protein Kinase; TNF: Tumour necrosis factor; IL-6: Interleukin-6 • Potent and selective p38 MAPK inhibitor • Oral drug • Excellent safety and tolerability profile • Selectively targets excessive inflammation without immunosuppression • Strong patent portfolio • Potential for Orphan Drug Designation • Key opinion leaders have positively endorsed the programme • Phase 2 ready • Effectively prevented CRS in humanised mouse model* • 97 subjects dosed across a first in human study and LPS challenge clinical trial • Potent TNF-α and IL-6 inhibition shown in preclinical and clinical trials • Potent reduction of a range of other inflammatory mediators POLB 001 Overview Strong Preclinical & Clinical Data Potential to Make Cancer Immunotherapies Safer & More Accessible
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• Strategic expansion of POLB 001 into oncology as a CRS preventative therapy, a significantly larger market than severe influenza, with significant interest from Big Pharma to supply drug • Patent applications filed • LPS data generated & presented at the premier clinical conference in haematology (ASH) POLB 001 has Progressed Rapidly into Oncology From concept to validated preclinical data in c.12 months; Phase 2 ready in just c.24 months 8 • >US$10B market opportunity confirmed • Independent KOLs endorse clinical potential • Preclinical CRS data generated & presented at ASH 2023 2024 Today • Phase 2 ready • First patient dosed in Phase 2a trial expected H2 2025 • Strong indications that Big Pharma will provide the necessary bispecific antibody, free of charge, for the Company’s proposed Phase 2a trial which is a significant validation as to industry interest in POLB 001 and its potential ASH: American Society H ematology Annual Meeting; CRS: Cytokine Release Syndrome; LPS: Lipopolysaccharide, an inflammatory stimulus
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POLB 001 Prevented CRS in Humanised Mouse Model Highly effective and superior to a TNF-α antibody in a gold standard model of CRS 9 Study Day 10 Day 10 CRS Scores IL-6 TNF-α CRS Scores CRS Biomarkers Study Day Study Day Study Design 0 1 432 5 6 7 8 9 10 Humanization & tumour induction BID POLB 001 dosing Day No CRS Control CRS Control POLB 001 Low POLB 001 Medium POLB 001 High Anti-TNF Antibody αCD28CRS induction Study outcomes Study Groups ASH ‘24 POLB 001 prevented CRS symptoms* POLB 001 decreased all key CRS biomarkers tested The experimental model is a previously validated CD28 superagonist induced CRS model in humanized tumour bearing mice performed by The Jackson laboratory. A TNF antibody was included as a robu st comparator as these have been found empirically to be the most potent preventors of CRS in mice despite limited utility in humans. * Statistically significant reduction of CRS scores compared to untreated controls. CRS scores had no significant difference to No CRS Control group. BID: twice daily; CRS: Cytokine Release Syndrome; TNF: Tumour necrosis factor; IL -6: Interleukin -6; IL-8: Interleukin -8
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LPS Human Challenge – Potent Inhibition of Excessive Inflammation Positive data supports the potential of POLB 001 to effectively prevent CRS 10 73.5% and 56.2% reduction for 70 mg and 150 mg doses respectively (p = 0.0003) LPS IV 57.4% and 63.5% for 70 mg and 150 mg doses respectively (p = 0.0002) Placebo 30 mg POLB 001 70 mg POLB 001 150 mg POLB 001 Results - TNF-α Results - IL-6Trial design Trial design: Single site, randomized placebo controlled LPS challenge trial. Healthy males administered BID oral POLB 001 or vehicle only control & challenged with local dermal LPS on day 4 and systemic IV LPS on day 6 to evaluate effect of POLB 001 on local and systemic inflammatory responses respectively. n=9 per group, all endpoints were exploratory. Clinically meaningful parameters such as temperature, heart rate, C-reactive protein and blood pressure were monitored, along with target inhibition and a range of exploratory biomarkers. CRS: Cytokine release Syndrome; ID: Intradermal; IV: Intravenous; TNF: Tumour necrosis factor; IL-6: Interleukin-6. ASH ‘23 1 2 3 4 5 6 7 8 9 10 11 12 13 140 POLB 001 Dosing Day 4 Single ID dose LPS Day 6 Single IV dose LPS D1 to D7 Day Potential to effectively prevent CRS while preserving key immune system functionality
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Proposed POLB 001 Phase 2a Trial Prevention of CRS in relapsed refractory multiple myeloma patients receiving bispecific antibody 11 2x Daily Oral BsAb: Bispecific antibody; CRS: Cytokine release Syndrome; KOL: Key Opinion Leader *Bispecific antibody dosing days estimated for demonstrative purposes only and may vary. Single Arm Approved BsAb N = ~30 Open Label • Incidence of Grade 2+ CRS • Incidence of CRS all grades • Confirm safety and pharmacokinetics • Tocilizumab usage … 1 2 3 4 5 6 7 … 14 …-4 BsAb Step Up Dose 1 POLB 001 Day* Step Up Dose 2 First Tx Dose Weekly dosing Dose Key Objectives/EndpointsTrial Design • Proposed POLB 001 Phase 2a trial expected to start in H2 2025, with interim analysis expected H1 2026 and topline data expected H2 2026. Potential for partnering on positive data • Strong indications that Big Pharma will provide the bispecific antibody, free of charge, for the Company’s proposed Phase 2a trial which is a significant validation as to industry interest in POLB 001 and its potential • Leading myeloma clinicians are enthusiastic to participate in the trial • KOLs Martin Kaiser (Royal Marsden), Gareth Morgan (NYU Langone) and others have positively endorsed the programme
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Significant Market Opportunity in a Rapidly Growing Field CRS is a major issue and rate limiting in delivering cancer immunotherapies 12 1. Grand View Research. CAR T-Cell Therapy Market Analysis 2023-2030. 2. Grand View Research. Bispecific Antibodies Market Size, Share & Trends Analysis Report. 3. Datamonitor Healthcare. Forecast: Diffuse Large B-Cell Lymphoma and Multiple Myeloma, 2023. CAR T: Chimeric antigen receptor T cell Bispecific Antibodies & CAR T Therapies1,2,3 $30bn $60bn $90bn $120bn 2022 2023 2024 2025 2026 2027 2028 2029 2030 c. US$120B Growth Sales • No approved therapy for CRS prevention & few approved for CRS management • The need for effective CRS management is being driven by rapid growth of CRS-inducing immunotherapies • Bispecific antibody and CAR T therapy market expected to grow exponentially POLB 001 – potential first approved preventative therapy for cancer immunotherapy-induced CRS
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CRS Preventative Therapy: >US$10B US Market Opportunity Significant opportunity exists for POLB 001 as CRS preventative for BsAb and CAR T treatment3 13 1st, 2nd and 3rd line+ MM and DLBCL patients in the US and EU5, receive CAR T and bispecific antibody therapy1 An effective preventative therapy for CRS could enable outpatient administration and broader uptake of immunotherapies2 Potential across additional haematological malignancies, solid tumours and new areas like severe influenza n = ~500,000 patients1 71% 29% Multiple myeloma Diffuse large B- cell lymphoma Addressable MM and DLBCL population by 2030 in the US and EU5 Estimate encompasses solely MM & DLBCL due to rapid advancements in bispecific antibody & CAR T treatment for these indications. Conservative price estimate versus market peers BsAb: Bispecific antibody; CAR T: Chimeric Antigen Receptor T cell therapy; CRS: Cytokine release Syndrome; MM: Multiple Myeloma; DLBCL: Diffuse Large B-Cell Lymphoma; 1. Datamonitor Healthcare. Forecast: Diffuse Large B-Cell Lymphoma and Multiple Myeloma, 2023. 2. Hansen DK et al., Cancers (Basel). 2023. 7;15(24):5746. 3. Independent research by Decisive Consulting Limited. https://teamdecisive.com/meet-the-team
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~500,000 Patients Bottleneck Eligible bispecific antibody / CAR T patients in US & EU for DLBCL and MM alone far exceeds treatment capacity1 CRS An effective CRS preventative therapy may remove the bottleneck >US$10B1 Market opportunity Potential to Greatly Enhance Uptake of BsAb and CAR T Therapies Effective prevention of CRS by POLB 001 may enable broader access to cancer immunotherapies 14 “Bispecific antibodies will only be delivered in specialist cancer centres until there is a way to make them safer. POLB 001 could make treatment safe enough to extend them to a much wider patient population” Prof Gareth Morgan, myeloma specialist, US “If there was a therapy that was orally delivered, a whole lot of infrastructure requirement falls away” Prof Martin Kaiser, myeloma specialist, UK KOL: Key opinion leader; 1. Datamonitor Healthcare. Forecast: Diffuse Large B-Cell Lymphoma and Multiple Myeloma, 2023. 2. Abramson JS et al. Blood Adv. 2021 Mar 23;5(6):1695-1705. 3. Independent research by Decisive Consulting Limited. https://teamdecisive.com/meet-the-team. * CRS prevention may contribute to bottleneck removal. Other issues, such as manufacturing, supply and other adverse events, may also present barriers to wider uptake. *
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GLP-1 Programme 15 Oral encapsulated GLP-1R agonist targeting the obesity market
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Oral GLP-1R Agonist Targeting the Obesity Market Proof of concept trial with topline data expected H1 2026 161. poolbegpharma.com/pipeline/glp-1r-agonist-2/. GLP-1: Glucagon like-peptide-1; R&D: research and development; PI: Principal Investigator Oral • Proprietary delivery technology with leading expert in obesity and metabolic medicine, Prof le Roux, to conduct proof of concept trial • Microencapsulated GLP-1 with targeted gut delivery with potential to improve convenience and bioavailability • Potential to overcome oral delivery challenges of peptide- based biologicals1 • Proof of concept trial to start within the coming months with topline data expected H1 2026, with the potential for partnering on positive data • Potential for further partnerships beyond GLP-1 “This trial is designed to generate impactful data that demonstrates our ability to safely and efficiently deliver an oral GLP-1R agonist using a validated technology” Prof Carel le RouxPotential to partner the programme and the technology – multiple opportunities for value creation Trial Investigator: Prof Carel le Roux Site: University of Ulster Objective: Demonstrate GLP-1 uptake Endpoints: Safety, tolerability & PK Design: An adaptive proof of concept study of safety, tolerability and pharmacokinetics of administration of an oral encapsulated GLP-1R agonist in people with obesity N = Up to 20 Population: Obese subjects
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Significant Potential for Differentiated Products to Gain Market Share 17 1. Global Data, Assessing the Economic Impact of Obesity and Overweight on Employers, Feb 2024. 2. The Economist, March 2023. 3. Stierman B, Afful J, Carroll MD, et al. National Health and Nutrition Examination Survey 2017–March 2020 prepandemic data files development of files and prevalence estimates for selected health outcomes. Natl Health Stat Report. 2021;158. 4. PMID: 26921819 5. PMID: 35101924. 6. PMID: 29033597. API: Active Pharmaceutical Ingredient; GLP-1: Glucagon like-peptide-1 Economic impact of obesity on US businesses & employees 2023 1 US$347B GLP-1R agonist market projection by 2031 2 US population effected by Obesity 3 AnaBio’s Encapsulation Centre of Excellence • 2,000m2 state of the art manufacturing facility • FFSC2200, FDA accredited • Commercialises fragile bioactives in food and beverage applications Large Growing Market Shortcomings of Existing Options US$150B 42% Major shortcomings within currently approved treatment options c.99% API wasted in current oral options4 56% Discontinuations would prefer oral alternatives6 Patients discontinue GLP-1s within 1 year5 >45% Patients cite vomiting for discontinuation6 45%64% Patients cite nausea for discontinuation6
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AI Programmes Transforming unique human challenge trial data into potential clinical assets 18
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Transforming Unique Human Challenge Trial Data into Potential Clinical Assets 191. poolbegpharma.com/pipeline/artificial-intelligence/ AI: Artificial Intelligence; RSV: Respiratory Syncytial Virus • A number of potential targets and clinical- stage repurposing candidates have been identified • Discoveries represent potential new classes of therapy for Influenza and RSV – large market opportunities • Potential partnering opportunities for further AI programmes & drug discovery 1 • Discussions ongoing in respect to potential collaborations Unique Human Challenge Data AI-Led Programmes Novel treatment modalities • Unique multi-omic datasets • RSV, Influenza and other respiratory viral infections • Faster, lower-cost discovery with potential to reduce risk and increase potential for success • Outputs from successful programmes • Targeting host response Human Challenge Trial Data – Exceptional Granularity and Quality 1 2 3
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20 CytoReason’s Partners Novel influenza drug targets successfully identified and prioritised Successfully identified drugs with potential to combat RSV with existing clinical data in other indications OneThree Biotech’s Partners Actively discussing the exciting outputs from our AI-led programmes with prospective partners “Human challenge data is extremely rare, and the number of such datasets is limited. None of them have the same richness as this dataset” Prof Shai Shen-Orr, Co-Founder & Chief Scientist “One thing I was excited about was the uniqueness and quality of the data. AI is only as powerful as the data you bring in” Neel Madhukar, PhD, CEO AI: Artificial Intelligence; RSV: respiratory Syncytial Virus Human Challenge Data has Attracted Expert AI Collaborators
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Focused on Partnering to Minimise Cost & Accelerate Development Pipeline Investment Highlights 21 Strong financial position: Debt free with c.£6.2M cash (March 2025) AIM: POLB Multiple Near-Term Value Inflection Points High Value Programmes Targeting Critical Unmet Medical Needs Highly Experienced Team with Proven Track Record 1. Unaudited management accounts as at 31 March 2025
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Appendix
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Leadership Team with Record of Delivering Value Track record of building successful life-science companies 23 Cathal Friel Executive Chairman Ian O’Connell Chief Financial Officer Jeremy Skillington PhD Chief Executive Officer
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Board Includes Leading Non-Executive Directors A long history of success in the life sciences industry Prof Luke O’Neill Non-Executive Director Eddie Gibson Non-Executive Director Prof Brendan Buckley Non-Executive Director Market access expert Supported numerous drug companies secure pricing and reimbursement Co-Founder Inflazome which was acquired by Roche in 2020 for €380M + milestones Previously scientific advisory board member of GSK & Pfizer Former Chief Medical Officer at ICON plc Former member of Committee for Orphan Medicinal Products & Scientific Advisory Group for Diabetes and Endocrinology at the EMA 24
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25 An Oral p38 MAPK Inhibitor That Selectively Targets Key Inflammatory Path Without Broad Immunosuppression Phase 2 ready asset with a comprehensive pre-clinical and clinical data package Favourable Safety and Tolerability Profile 97 subjects dosed during Phase I FIH and LPS Challenge studies No SAEs or discontinuations due to AEs, all were of mild intensity No clinically meaningful findings in clinical laboratory test results, vital signs or ECG Favourable safety & tolerability profile Designed to Prevent Immunotherapy-Induced CRS Suitable for at-home dosing (used in LPS Challenge Trial) Hepatic metabolism and biliary excretion profile favourable for multiple myeloma and renally impaired populations BID oral regimen designed to provide targeted protection during CRS risk period Half-life of 7-14 hours provides adequate exposure and avoids excessive exposure beyond periods of CRS risk POLB 001 AE: adverse event; FIH: First in human; SAE: Serious adverse events; ECG: Electrocardiogram, BID: twice daily
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Potent and Selective Inhibition of p38 MAPK Signalling Effective target engagement demonstrated in LPS human challenge trial 26 Blood samples were taken before and after administration of intravenous LPS. Peripheral blood samples were analysed by flow cytometry. Monocytes were gated by FSC, SSC and CD14+. Data is presented as mean MFI values of phospho-p38 +/- SEM • POLB 001 was widely distributed • POLB 001 inhibited p38 MAPK activation, direct measurement of activation • POLB 001 inhibited in vivo and ex vivo responses to LPS-induced TNF-α, indirect measurement of p38 MAPK inhibition Levels of Phosphorylated p38 MAPK in Circulating Monocytes 30 mg POLB 001 70 mg POLB 001 150 mg POLB 001Placebo POLB 001
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Reduced Key Indicators of LPS-Induced Systemic Inflammation The reduction of systemic cytokines align with improvement in clinically meaningful endpoints 27 No significant effect on body temperature with a trend towards reduction compared to placebo Suppressed increase in heart rate following IV LPS administration CRP level reduction of 33.1% and 33.3% seen for 70 mg and 150 mg doses respectively Mean Body Temperature Heart Rate Rise (bpm) C-Reactive Protein (CRP) 30 mg POLB 001 70 mg POLB 001 150 mg POLB 001Placebo POLB 001
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1. Ayuketang FA, Jäger U. Management of Cytokine Release Syndrome (CRS) and HLH. 2022. The EBMT/EHA CAR T Cell Handbook. Chapter 26. Grades & Severity of CRS CRS is a common adverse event following CAR T and bispecific antibody treatment 28 CRS Parameter1 Grade 1 Grade 2 Grade 3 Grade 4 Fever Fever ≥ 38°C (not attributable to any other cause). In patients who have CRS then receive antipyretics or anti- cytokine therapy such as tocilizumab or steroids, fever is no longer required to grade subsequent CRS severity. In this case, CRS grading is driven by hypotension and/or hypoxia Hypotension* None Not requiring vasopressors Requiring a vasopressor ± vasopressin Requiring multiple vasopressors (excluding vasopressin) Hypoxia* None Requiring low-flow oxygen (≤6 L/min) Requiring high-flow oxygen (>6 L/min) Requiring oxygen by positive pressure POLB 001 *CRS severity is determined if either hypotension or hypoxia criteria is achieved for a given grade
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POLB 001: Oncology CRS - Regulatory Exclusivity / Patent Timeline 29 POLB 001 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 2039 2040 2041 2042 2043 2044 2045 Europe US Orphan exclusivity – 10 years* Orphan exclusivity – 7 years* Medical use protection for class of p38 inhibitors – patent application pending Method of treatment protection for class of p38 inhibitors – patent application pending ** Future IP Formulation QC/CMC Clinical findings/indications/patient populations SPC TBC Method of treatment protection for class of p38 inhibitors – patent granted† ** †Portfolio includes a patent covering use of POLB 001 for hypercytokinemia/CRS that was granted by the US Patent Office in April 2024, with a latest expiry date in Dec 2038 excl. extensions. *Orphan exclusivity subject to grant of Orphan Drug designation and Orphan Designation by FDA and EMA respectively ** Subject to any extensions: patent term adjustment (PTA) and/or patent term extension (PTE) Note: Commencement date for market exclusivity and Orphan exclusivity is for demonstrational purposes only and is not intended to reflect actual, anticipated or proposed dates by the Company
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POLB 001: Flu & Hypercytokinemia - Regulatory Exclusivity / Patent Timeline 30 POLB 001 Future IP Formulation QC/CMC Clinical findings/indications/patient populations †Portfolio includes a patent covering use of POLB 001 for hypercytokinemia/CRS that was granted by the US Patent Office in April 2024, with a latest expiry date in Dec 2038 excl. extensions. *Orphan exclusivity subject to grant of Orphan Drug designation and Orphan Designation by FDA and EMA respectively ** Subject to any extensions: patent term adjustment (PTA) and/or patent term extension (PTE) Note: Commencement date for market exclusivity and Orphan exclusivity is for demonstrational purposes only and is not intended to reflect actual, anticipated or proposed dates by the Company 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 Europe US Orphan exclusivity* – 10 years Orphan Exclusivity* – 7 years Medical use protection for class of p38 inhibitors – patent granted, further application pending Medical use protection for class of p38 inhibitors – patents granted†, further patent applications pending** Market Exclusivity – 5 years Market Exclusivity – 11 years
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Oral Encapsulated GLP-1 - Regulatory Exclusivity / Patent Timeline 31 Oral Encapsulated GLP-1 Future IP Formulation QC/CMC Clinical findings/indications/patient populations *Subject to any extensions, such as US patent term adjustment (PTA). **Unfiled; filing date TBC. † Extent of coverage of specific products in development is TBC. 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 2039 2040 2041 2042 2043 2044 2045 Europe US Exclusively in-licensed rights – patents granted and further applications pending †* Potential for new patent applications to extend term** Exclusively in-licensed rights – patent granted and further applications pending †* Potential for new patent applications to extend term**
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Listed on the London Stock Exchange, AIM ticker: POLB Stay in touch