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. 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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