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Plasma-Derived Therapies Basics Plasma‐Derived Therapies Basics July 12, 2019 Tomoko Goto Business Operations Lead /Japan, Plasma‐Derived Therapies Business Unit Takeda Pharmaceutical Company Limited IMAGES COURTESY OF PLASMA PROTEIN THERAPEUTICS ASSOCIATION IMPORTANT NOTICE For the purposes of this notice, “presentation” means this document, any oral presentation, any question and answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (“Takeda”) during the presentation. This presentation (including any oral briefing and any question‐and‐answer in connection with it) is not intended to, and does not constitute, represent or form part of any offer, invitation or solicitation of any offer to purchase, otherwise acquire, subscribe for, exchange, sell or otherwise dispose of, any securities or the solicitation of any vote or approval in any jurisdiction. No shares or other securities are being offered to the public by means of this presentation. No offering of securities shall be made in the United States except pursuant to registration under the U.S. Securities Act of 1933, as amended, or an exemption therefrom. This presentation is being given (together with any further information which may be provided to the recipient) on the condition that it is for use by the recipient for information purposes only (and not for the evaluation of any investment, acquisition, disposal or any other transaction). Any failure to comply with these restrictions may constitute a violation of applicable securities laws. The companies in which Takeda directly and indirectly owns investments are separate entities. In this presentation, “Takeda” is sometimes used for convenience where references are made to Takeda and its subsidiaries in general. Likewise, the words “we”, “us” and “our” are also used to refer to subsidiaries in general or to those who work for them. These expressions are also used where no useful purpose is served by identifying the particular company or companies. Forward‐Looking Statements This presentation and any materials distributed in connection with this presentation may contain forward‐looking statements, beliefs or opinions regarding Takeda’s future business, future position and results of operations, including estimates, forecasts, targets and plans for Takeda. In particular, this presentation contains forecasts and management estimates related to the financial and operational performance of Takeda. Without limitation, forward looking statements often include the words such as “targets”, “plans”, “believes”, “hopes”, “continues”, “expects”, “aims”, “intends”, “will”, “may”, “should”, “would”, “could” “anticipates”, “estimates”, “projects” or words or terms of similar substance or the negative thereof. Any forward‐looking statements in this document are based on the current assumptions and beliefs of Takeda in light of the information currently available to it. Such forward‐looking statements do not represent any guarantee by Takeda or its management of future performance and involve known and unknown risks, uncertainties and other factors, including but not limited to: the economic circumstances surrounding Takeda’s business, including general economic conditions in Japan, the United States and worldwide; competitive pressures and developments; applicable laws and regulations; the success of or failure of product development programs; decisions of regulatory authorities and the timing thereof; changes in exchange rates; claims or concerns regarding the safety or efficacy of marketed products or products candidates; and post‐merger integration with acquired companies, any of which may cause Takeda’s actual results, performance, achievements or financial position to be materially different from any future results, performance, achievements or financial position expressed or implied by such forward‐looking statements. For more information on these and other factors which may affect Takeda’s results, performance, achievements, or financial position, see “Item 3. Key Information—D. Risk Factors” in Takeda’s most recent annual report on Form 20‐F and other documents filed with or furnished to the U.S. Securities and Exchange Commission, available on Takeda’s website at: https://www.takeda.com/investors/reports/sec‐filings/ or at www.sec.gov. Neither Takeda nor its management gives any assurances that the expectations expressed in these forward‐looking statements will turn out to be correct, and actual results, performance or achievements could materially differ from expectations. Persons receiving this presentation should not place undue reliance on forward looking statements. Takeda undertakes no obligation to update any of the forward‐ looking statements contained in this presentation or any other forward‐looking statements it may make. Past performance is not an indicator of future results and the results of Takeda in this presentation may not be indicative of, and are not an estimate, forecast or projection of Takeda’s future results. Medical information This presentation contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. Financial information Takeda’s financial statements are prepared in accordance with International Financial Reporting Standards (“IFRS”). The financial statements of Shire plc (“Shire”) are presented in accordance with accounting principles generally accepted in the United States (“U.S. GAAP”). Therefore, the respective financial information of Takeda and Shire are not directly comparable. The Shire acquisition closed on January 8, 2019, and our consolidated results for the fiscal year ended March 31, 2019 include Shire’s results from January 8, 2019 to March 31, 2019. References to “Legacy Takeda” businesses are to our businesses held prior to our acquisition of Shire. References to “Legacy Shire” businesses are to those businesses acquired through the Shire acquisition. AGENDA: 1 2 3 What are plasma‐ What is the PDT What is Takeda’s PDT derived therapies market? business? (PDT)? 11 What are plasma‐derived therapies (PDT)? What is Plasma? Blood contains… 55% 44% 1% Plasma Red blood White blood cells cells & platelets Definition of Plasma : Plasma is the clear, straw‐colored liquid portion of blood that remains after red blood cells, white blood cells, and platelets are removed. Plasma has multiple components with different clinical uses and it cannot be manufactured in a laboratory. Source: B Positive Plasma website https://www.bpositivetoday.com/#iLightbox[gallery_image_1]/0 4 What are blood products? What are plasma‐derived products? Blood Products Market in Japan Blood Products Blood Products for Transfusion Plasma‐Derived Products • Whole Blood Products • Immunoglobulin • Blood Component Products • Albumin ‐ Red Blood Cell Products • Coagulation Factors ‐ Platelet Products • Other Replacement Therapies ‐ Fresh Frozen Plasma Products (or I.c.‐hospital blood collection) + Other Fractionators Source: MHLW. Blood Business Report (2018) 5 Clinical uses of plasma products span four primary categories Description Uses ▪ IVIG/SCIG – congenital antibody deficiencies, ▪ Assists in the destruction of foreign molecules Immuno‐ neurologic, hematology – 200+ diseases ▪ Main function of the humoral immune system globulin (IG) ▪ Hyperimmune –target antigens of specific conditions ▪ Maintains intravascular colloid osmotic pressure ▪ Albumin – Fluid loss, sepsis/septic shock, plasma exchange, ▪ Can compete with non‐protein based volume burn therapy, renal dialysis Albumin replacement solutions such as starches, Ringer’s Lactate, or saline ▪ Replaces missing factors in the clotting ▪ Factor VIII/IX – Hemophilia A/B Coagulation cascade due to deficiencies or dysfunctions ▪ vWF –Von Willebrand Disease Factors ▪ Factor II, V, VII, X, XI, XIII & fibrogen –deficiencies for blood loss or congenital Plasma proteins used to treat extremely rare ▪ AT‐III – excessive clotting Other ▪ diseases Replacement ▪ AAT/A1PI –COPD, cirrhosis, jaundice Therapies ▪ C1‐INH – Hereditary Angioedema IVIG: Intravenous Immunoglobulin, SCIG: Subcutaneous Immunoglobulin, vWF: Von Willebrand Factor, AT‐III: Antithrombin III, AAT/A1P1: Alpha‐1 Antitrypsin/Apha‐1 Proteinase Inhibitor, COPD: Chronic Obstructive Pulmonary Disease , C1‐INH: C‐ 1 Inhibitor Source: PPTA (Plasma Protein Therapeutics Association) 6 It can take 1000+ donations to derive a 1‐year‐therapy for 1 patient and, for some patients, plasma products are the only treatment they can rely on Estimated donations needed Availability of non‐Plasma Products for one patient for one year Immunoglobulin None globally Primary Albumin Recombinant albumin* immunodeficiency 130: disease FVIII/FIX/FXIII Recombinant FVIII, Recombinant FIX, Bi‐specific Antibody Inhibitor Products Recombinant FVII, Bi‐specific Antibody Alpha 1 antitrypsin Anti Thrombin III Recombinant Anti Thrombin III 900: deficiency Prothrombin None globally C1 inactivator Icatibant acetate 1200: Hemophilia Protein C None globally Fibrin Sealant None globally *: Recombinant albumin product was approved but not available Source: PPTA (Plasma Protein Therapeutics Association) , MHLW 7 Plasma can be collected either as recovered plasma or as source plasma via a process called apheresis Recovered plasma is
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