Realizing the Potential of Plasma‐Derived Therapies Investor Relations Day, Covington, GA 15th November 2019 Julie Kim President, Plasma‐Derived Therapies Business Unit (PDT BU)
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Thank you to the Georgia BioScience Training Center Front Entrance Room 139 Room 125 Room 124 Back Entrance 2
Agenda PDT Overview Julie Kim, President, PDT BU Lunch buffet PDT R&D Overview Christopher Morabito, Head, R&D, PDT Covington Site Introduction Carlos Soto, Covington Site Head Q&A Sue Brown, Head, Global BioLife Operations Julie Kim, President, PDT BU Christopher Morabito, Head, R&D, PDT Adrian Murphy, Head of Plasma Operating Unit, Global Manufacturing & Supply Costa Saroukos, Chief Financial Officer Carlos Soto, Covington Site Head Close Julie Kim, President, PDT BU Training Center & Covington Site tour 3
Introducing Takeda’s Plasma‐Derived Therapies Business Julie Kim President, Plasma‐Derived Therapies Business Unit
Plasma‐derived therapies are critical, life‐saving medicines, relied upon by thousands of people worldwide with rare and complex diseases Lynayah’s Family I probably wouldn’t have lived to see six months, which is why my family and I are eternally grateful for you. Your time, and your donation helped save my life. Lynayah & Family Pawel It’s not always easy but, to reach the top, you must go uphill. March 2019 5
Plasma presents a unique opportunity 1 2 3 4 5 Plasma is a durable business with Products have Indication Not subject to Probability of Market lifecycle expansion patent cliffs success for demand compelling growth spanning continues R&D is continues to opportunity… decades generally high grow steadily …AND HAS DISTINCT ASPECTS It can take more than Plasma is collected from 7 months to produce Capital‐intensive human donations ‐ plasma‐derived manufacturing process scarce supply therapies 6
Demand for key plasma‐derived therapies has been continuously increasing and expected to grow Worldwide demand for plasma‐derived therapies is This trend is primarily driven by: expected to increase each year 30 Greater awareness and increasing rates of diagnosis 4 Other 25 +6% 2 Blood Factors 20 3 Albumin 6 Growing access in emerging markets 3 2 15 3 5 3 10 IG New indications in both immune deficiencies 17 and immune‐mediated diseases 11 5 9 0 Innovation in formulations and delivery 2015 2018 2023 systems Global plasma market ($B), 2015‐23 Source: Berman. Plasma Fractionation: The Challenge of Keeping Pace with Global IG Demand / MRB, Evaluate Pharma, PDT Analysis / Chapel H, et al. Front Immunol 2014 Dec 15;5:627. / News release: Shire Launches Paediatric Indication for Immunodeficiency Treatment HyQvia in 7 Europe. 21 July 2016. / News release. Shire Announces FDA Approval for Label Expansion of CINRYZE® for Prevention of Attacks in Pediatric HAE / Jones, et al. Frontiers in Immunology 2018;9:1308.
And plasma still has significant untapped therapeutic potential Multiple factors influence plasma protein By advancing our understanding metabolism and effects in individuals of plasma proteins, we can: • Predict how different patients metabolize plasma proteins, and drive Health individualization of therapy • Investigate strategies that allow the plasma protein to more precisely target Plasma disease or remain in the body longer protein metabolism • Extend the benefits of plasma‐derived & effect therapies across our portfolio Season Age Source: Ignjatovic V, et al. PLoS One. 2011;6:e17213. / Kakisaka T, et al. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;852:257‐267. / Cambras T, et al. Chronobiol Int. 8 2017;34:1248‐1258.
Takeda is now organized – and uniquely positioned ‐ to realize the full potential of plasma‐derived therapies PLASMA‐DERIVED THERAPIES >20 DEDICATED BUSINESS UNIT PLASMA‐DERIVED THERAPIES Top 3 plasma company, investing to grow RARE DISEASE LEADER PLASMA‐ 8 Deep understanding of FOCUSED MANUFACTURING patient’s needs R&D Team SITES GLOBAL PHARMA SCALE & EXPERTISE 140+ PLASMA Capabilities in digital technology, COLLECTION CENTERS data analytics, patient insights 13,000 EMPLOYEES 75+ YEAR worldwide, focused on pioneer legacy in plasma plasma business 9 Source: Evaluate Pharma, PDT Analysis. / Takeda internal data
We are building on a long and successful history of bringing innovative therapies to patients Hyland 1941 1952 1960 1968 1994 1996 2005 2006 2010 2013 2015 2016 2019 Albumin First commercial Albumin Only FVIII facilitated IG with up to 1/month infusions PLASMA‐VAC First commercial FVIII concentrate First time Only plasma allowed SCIG with to be separated First flexible 60ml/60min from whole Albumin First infusions blood for packaging ready‐to‐use storage A1AT 10 Source: Baxter: https://www.baxter.com/our‐story/our‐history / https://www.genengnews.com/news/shire‐baxalta‐complete‐32b‐merger/
We’ve established a dedicated business unit to steer our path, bring focus and harness our end‐to‐end plasma capabilities Donors Plasma Strategy & Operations Commercial Strategy Hospitals & & Sales Patients Plasma Sourcing Manufacturing BioLife RESEARCH & DEVELOPMENT 11
Our PDT BU leadership team draws on, and brings together, Takeda’s extensive plasma experience and broader expertise across our business Julie Kim Ingrid Hofström Emi Psachoulia Sue Brown Christopher Michael Shires Shady Annick Ramy Riad Luana Banu Deborah Hibbett Head of Plasma‐ Executive Chief of Staff Plasma Sourcing Morabito Strategy AbouZahra Deschoolmeester Finance Public Affairs Communications Derived Assistant (BioLife) R&D Operations HR Therapies BU 140 + combined years of plasma experience Adrian Murphy Barbara Thomas Kreil Kasha Witkos Paula Leca Gabriele Ricci Linda Peralta Charlie Manufacturing Glantschnig Pathogen Safety Commercial Legal IT Ethics & Alexander Quality Compliance Business 19 11 Development team members nationalities 60% Female 40% Male 12
Our Ambition Build a respected, We have a singular, dedicated plasma focus and strategy sustainable plasma Responsibility for end‐to‐end plasma business business that reimagines the industry to best serve Dedicated R&D organization and budget patients worldwide We also benefit from the support of a global, values‐based biopharmaceutical company Long‐term view with commitment to invest as plasma is a key growth driver for Takeda Access to Takeda’s broader resources, capabilities and expertise, particularly R&D and manufacturing 13 | Title | DD/MM/YY | Confidential ‐ for internal use only 13
Our strategy and targeted investments extend across the entire value chain PLASMA SOURCING MANUFACTURING COMMERCIALIZATION RESEARCH & DEVELOPMENT 14
PLASMA SOURCING MANUFACTURING COMMERCIALIZATION RESEARCH & DEVELOPMENT 15
BioLife, part of Takeda’s Plasma‐Derived Therapies Business Unit, is an industry leader in the sourcing of high‐quality plasma Broad global footprint Recognized expertise 140+ collection centers across Trained medical staff at each center four countries Dedicated quality, regulatory and Plasma sourced externally from eight medical employees countries Recognized safety and quality Three dedicated screening labs expertise, industry‐leading standards Fully compliant with requirements from: 16 Source: Takeda internal data. / MRB. The plasma protein market in the United States by company, 2018. / Bain & Co. Plasma donor survey 2015. / Takeda. Plasma‐Derived Therapeutics. Pathogen Safety Monograph.
Our BioLife centers offer an exceptional donor experience Efficiency & convenience central to our approach • Repeat donors spend just ~1 hour at the center • Appointment‐based process with digital scheduling Staff committed to the well‐being of our donors Modern, high quality facilities, with free Wi‐Fi and supervised children's playroom in certain centers Facilities designed for donor comfort and regulatory compliance 17
We are accelerating the rate of plasma collection and incrementally increasing overall volume through third parties and acquisition We are building momentum…. Increased plasma volumes by approximately 20% in 2018 Expanded European presence from 7 to 30 collection centers within past 12 months Completed 5 acquisitions in the past 12 months in US, Austria, Hungary and Czechia We are accelerating Plan on opening a total of 19 additional new collection centers in fiscal year 2019 growth with the goal of increasing plasma supply by Leveraging third party supply through long‐term contracts Participating in contract agreements with governments >65% We will continue to focus on operational excellence over the next 5 years Open collection sites faster Increase speed to peak collection volumes Create efficiency via new models and approaches 18 Source: Takeda internal data.
We are further enhancing and digitalizing facilities and services to meet growing needs for the future Improving the donor experience and Attracting new donors in the community improving cost‐per‐liter through omnichannel engagement Reaching new donors Increasing community engagement Mobile Website App Donor Scheduling Information Payment 19 FOR INTERNAL USE ONLY19
PLASMA SOURCING MANUFACTURING COMMERCIALIZATION RESEARCH & DEVELOPMENT 20
We have a world‐leading plasma‐derived therapies manufacturing network in which we continue to significantly invest Covington, GA 8 STRATEGIC LOCATIONS Sanquin, NL Vienna, Austria plus four strategic partners, allowing Round Lake, IL Narita, Japan independent yet inter‐related Lessines, Belgium manufacturing operations Pisa, Italy Halozyme, CA INNOVATION MINDSET Rieti, Italy Los Angeles, CA digitalization and constant drive for Baxter BioPharma, IN excellence to accelerate supply to patients Kamada, Israel CONTINUED CAPACITY EXPANSION to increase production of our portfolio to meet market growth while driving efficiencies CONTINUALLY INVESTING in state‐of‐the‐art facilities that meet the highest quality standards Takeda Mfg. 21 External Mfg.
The global network builds on the strengths of each location while leveraging operational excellence across the sites Mass Capture, Fractionation Los Angeles, USA Rieti, Italy Vienna, Austria Sanquin, NL Covington, USA Downstream Processing Lessines, Belgium Covington, USA Round Lake, USA Pisa, Italy Vienna, Austria 22
We're increasing production capacity by accelerating investment, while further enhancing our quality standards Investing in manufacturing capacity Continually investing in technologies and processes to maximize yield Higher yield, lower cost fractionation techniques We plan to increase our Analytics, automation and digitization to optimize network manufacturing capacity within Optimizing plasma efficiency through the value chain our existing network by Downstream optimization within broader Takeda manufacturing network >65% Capacity Expansion: 2018 – 2023 (projected) over the next 5 years >65% 2018 2023 23
Takeda has world‐class safety capabilities and an unsurpassed reputation in both plasma donation and pathogen safety Donation safety standards Strict donation Donation Strong Plasma screening, criteria and frequency inspection inventory hold and look screening at management record back procedure each visit system Every plasma donation screened for HIV, hepatitis A, B & C, parvo B19 Pathogen safety standards BioSafety Level 3+ Lab Process sciences Virology Publication / Purpose‐built, state‐of‐ Qualified models of all Classical & presentation the‐art biocontainment bioprocessing steps molecular virology Strong track laboratory expertise and record capability Dedicated virology expertise and capabilities 40+ highly >50% with specialized >200 years post‐ trained staff education graduate experience 24
PLASMA SOURCING MANUFACTURING COMMERCIALIZATION RESEARCH & DEVELOPMENT 25
Our broad and differentiated portfolio of plasma‐derived therapies treats rare and complex diseases worldwide ATIII 26 For illustrative purposes only, geographies and products do not correspond
Our two SCIG brands complement each other and address different patient needs • Similar efficacy to IVIG and IV‐like • Well tolerated administration features • Limited volumes (up to 60ml per • High volumes (up to 600ml per site) and site) through frequent infusions monthly infusions (every 3‐4 weeks) • Ease of use/preparation • Improved Bioavailability vs cSCIG • 2 or 4 infusion sites/needles Key Features • 1 or 2 infusion sites/needles • PID, SID* • PID and SID* • CIDP (regulatory approval decision expected in 2023) Indications • Fast, regular infusions • Less frequency, high volume • Daily to biweekly • Monthly to biweekly For patients • Home setting • Home or hospital setting who prefer Source: Borte, et al., Clin Exp Immunol. 2017 Jan;187(1):146‐159. (doi: 10.1111/cei.12866) / Suez, et al., J Clin Immunol. 2016 Oct;36(7):700‐12. (doi: 10.1007/s10875‐016‐0327‐9) / CUVITRU SmPC. / Wasserman RL, et.al, J Allergy Clin Immunol. 2012 Oct;130(4):951‐7. (doi: 10.1016/j.jaci.2012.06.021) / HyQvia SmPC. / Wasserman RL, et al., J Clin Immunol. 2016 Aug;36(6):571‐582. (doi: 10.1007/s10875‐016‐0298‐x) / Clinical trials.gov with published study completion Dec 31 2021 *SID not approved in the US. Only select SIDs are approved for the above‐mentioned products: chronic lymphocytic leukemia, multiple myeloma and hematopoietic stem cell 27 transplantation.
Currently, global supply is not keeping up with demand for IG therapies STRONG & CONTINUED IG DEMAND The Global Polyvalent IG Market (IVIG/SCIG) IG is increasingly recognized for its diverse from 2000 to 2016, with Projected Global Demand Through 2024 therapeutic value, and is expected to grow in Millions of grams approved indications for a range of diseases 300 Actual 250 Estimate MARKED BY SCIG GROWTH RATE 200 SCIG market continues to drive IG growth at CAGR of 20% 150 100 15% 30% 50 $12B $20B 0 (2019) (2025) 2000 2003 2005 2008 2010 2012 2014 2016 2018 2020 2022 2024 Source: The Marketing Research Bureau, Inc. (Orange, CT) 85% 70% IVIG SCIG Source: 2016 WW MRB Report, 2017 US MRB Report / Berman. Plasma Fractionation: The Challenge of Keeping Pace with Global IG Demand / Chapel H, et al. Front Immunol 2014 Dec 15;5:627. / Jones G, et al. Front Immunol. 2018 Jul 2;9:1308. / PPTA. The PPTA vision on the 28 plasma protein therapies sector for the next decade in Europe. 10 April 2014
Takeda’s commitment during times of supply‐demand imbalance is to focus on sustainable patient care Consider the global Support for those Focus on existing Partner to explore community with highest need to patients first and and implement gain treatment responsibly pursue policies and practices new opportunities that enable sustainable supply 29
Our goal is to continue to bring personalized, innovative, lifelong care to as many people as possible throughout the patient journey Diagnosis Access Partnership with large hospital Sustainable pricing systems in the US to leverage Dedicated access support electronic medical records Patient assistance programs Co‐chairing the Global Commission to End the Diagnostic Odyssey for Broad portfolio of products Children with Rare Disease Awareness campaigns Diagnostic test kits Personalized Care & Support Enhanced patient services Nurse training to support new patients Devices and delivery systems 30
We anticipate significant growth opportunities across our portfolio Global plasma Takeda revenue market size Example Takeda products (OY, 2018) (OY, 2018) Immunoglobulin ~2,870 ~12,500 Last Liter Albumin ~580 ~5,000 Hemophilia ~890 ~2,800 products First Liter Other products ~660 ~3,700 Antithrombin III *2018 revenue is a pro‐forma which adds Legacy Shireʼs 9 month (April – December 2018) revenue previously reported under US GAAP and conformed to IFRS without material differences and converted to JPY using FY2018 actual rate for the period. 2018 revenue also includes product sales of Nihon Pharmaceutical products, Takedaʼs consolidated subsidiary. Total ~5,000* ~24,000 31 Source: MRB; EvaluatePharma; Takeda internal data
And we are embarking on a trajectory to improve overall Plasma‐ Derived Therapies business performance Key Growth & Margin Drivers for PDT Key Financial Aspiration for PDT* • Focused sustainable, value‐based commercial Annual revenues strategies, including tenders (CAGR) Mid to high single digit • Process efficiencies across the network • Capacity increase across collections and manufacturing CAPEX (% of Revenue) • R&D investments across portfolio Mid single digit * The “Key Financial Aspirations” listed above represent Takeda’s goals in the long‐term for the PDT business as of the date hereof and are based on certain assumptions. Actual Amounts/results may differ materially and are subject to a number of risks and 32 uncertainties. See “Note Regarding Forward Looking Statements” on Page 1 of this presentation.
Key takeaways 132 At Takeda, plasma is a Our goal is to Our broad and long‐term strategic accelerate growth in differentiated portfolio focus, led by a capacity by >65% over brings personalized, dedicated business the next 5 years to innovative, lifelong unit investing to grow bring additional and care and underlines our across the value chain improved therapies to credentials for and leveraging Takeda more people around reimagining the capabilities the world industry 33
A New Dedicated Focus on Innovative, Sustainable Solutions for Plasma‐Derived Therapies Christopher Morabito, M.D. Head of R&D, Plasma‐Derived Therapies
PDT R&D’s credentials and infrastructure are well‐established Partobulin Albumin (Austria, Health Ministry Approval) 1941 1952 1968 1968 1986 1994 1998 1999 2001 2002 2005 2006 2008 2010 2013 2016 Tetabulin Antithrombin III (Canada, Health Ministry Endobulin S/D Approval) Partobulin S/D Pathogen Pharmaceutical Pilot Labs Safety Science Global Center of Strong team Within Vienna, Los Excellence for connected across Angeles, Georgia and Pathogen Safety the value chain Lessines sites 35
Our independence brings focus on plasma and is bolstered by access to broader R&D capabilities and resources Focused entirely on plasma‐derived therapies Lean and agile team PDT Based in Cambridge, MA and Vienna, Austria R&D Separate R&D prioritization Dedicated budget Global R&D Common Takeda values, patient‐focused vision Common governance Shared resources (e.g. Medical Affairs, Safety, Quality) These links strengthen Takeda R&D’s modality mix, now the broadest among the Top 10 global biopharmaceutical companies 36
The PDT R&D Leadership Team is well‐integrated and brings deep and diverse functional expertise Christopher Morabito MD R&D Head Boston, MA Catherine Parham MD Rory Bukofzer Leman Yel MD Chris Tremblay Bagirath Gangadharan PhD Andreas Liebminger PhD Sascha Haverfield DPhil Program Leadership Program Leadership Clinical Medicine R&D Operations Translational Research Pharmaceutical Sciences Regulatory Affairs & Boston, MA Boston, MA Boston, MA Boston, MA Vienna, Austria & Devices Development Operations Vienna, Austria/Boston, MA Boston, MA Geoffrey Pot PhD Gabriele Ricci William Standaert Cara Laurello Ambreen Landa Pritesh Patel Julia Ellwanger Global Manufacturing Digital Technologies Legal Ethics and Compliance Human Resources Finance Communications External Supply & Plasma Boston, MA Zurich, Switzerland Boston, MA Boston, MA Boston, MA Bannockburn, IL Innovation Lessines, Belgium 37 Flag = country of origin
We are driving a culture of innovation through two R&D engines Research/Early Development Late Development Translational Integrated Pharmaceutical Care Solutions Sciences Translational Research Pharm Sci and Devices Early Development Innovation Engine Late Development Innovation Engine Generate new and improved therapeutics by: Improve health outcomes by: Investigational new drug candidates Diagnostic efficiencies Mechanisms of action Expanded data and devices to support effectiveness Responder populations Point of Care services and drug delivery services New process development Data‐driven guidelines for acute and chronic management 38
PDT R&D Strategy Maximize the therapeutic Realize full potential of in‐line First and Last Liter products value of plasma‐derived Expanded indications and benefit‐risk datasets therapies for patients with Device‐driven solutions for diagnosis, management, rare and complex diseases and long‐term follow‐up through innovation across Global expansion the product life cycle New formulations Optimize efficiencies of plasma‐derived therapy production Pharmaceutical science support for manufacturing Identify and develop new plasma‐derived therapies New targeted therapies for diverse therapeutic areas 39
We are prioritizing near‐term late development… RESEARCH / NON‐CLINICAL DEVELOPMENT LATE DEVELOPMENT CUVITRU HYQVIA HYQVIA Halozyme Halozyme Wearable Device US ‐ Pediatric PID EU ‐ Pediatric PID HYQVIA HYQVIA ‐ HyHub Halozyme Flextronics Chronic inflammatory demyelinating Delivery Device polyneuropathy (CIDP) HYQVIA CINRYZE Geographic expansion Geographic expansion IMMUNOLOGY CUVITRU GLASSIA Kamada Immunogenicity/ bronchioalveolar Geographic expansion lavage FEIBA Volume reduction HEMATOLOGY 40
… while enabling discovery of next generation therapeutics RESEARCH / NON‐CLINICAL DEVELOPMENT LATE DEVELOPMENT TAK 881 CUVITRU HYQVIA HYQVIA Facilitated 20% SC IgG Halozyme Halozyme Wearable Device Halozyme US ‐ Pediatric PID EU ‐ Pediatric PID Primary Immunodeficiency (PID) TAK 880 Alpha‐1 Antitrypsin HYQVIA HYQVIA ‐ HyHub Halozyme Low IgA‐IgG (IV) Flextronics (A1AT) Chronic inflammatory demyelinating Next generation formulations Delivery Device Primary Immunodeficiency polyneuropathy (CIDP) Hyper‐Immune IG HYQVIA CINRYZE Infectious disease Geographic expansion Geographic expansion IMMUNOLOGY CINRYZE CUVITRU GLASSIA Kamada Immunogenicity/ bronchioalveolar Ex‐HAE indications TBD Geographic expansion lavage GLASSIA CUVITRU Kamada A1ATD‐emphysema* Japan ‐ PID (FPI Q4 2019) PROTHROMPLEX TOTAL Butyryl Cholinesterase PROTHROMPLEX TOTAL FEIBA Device and formulation Organophosphate poisoning US ‐ Drug‐induced bleeding** Volume reduction CEPROTIN Geographic expansion HEMATOLOGY 41 *Subject to regulatory approval **Pending FDA Pre‐IND consultation and future acceptance of an IND Programs and projects added since Day 1
Over the next 3 years, we plan to allocate resources to research and early development Estimated % of PDT R&D spend for FY2023 Distribution of PDT R&D spend for FY2019 60% ~70% of resources will be allocated to improving in‐line products and production efficiencies 95% 10% Optimizing value of in‐line products 30% Plasma production efficiencies 5% 0% New plasma‐derived therapies 42
Our goal is to realize the full potential of in‐line first and last liter products Estimated % of PDT R&D spend for FY2023 Expanded indications and benefit‐risk datasets 60% Device‐driven solutions for diagnosis, management, and long‐term follow‐up Global expansion New formulations 10% Optimizing value of in‐line products 30% Plasma production efficiencies New plasma‐derived therapies 43
Immunoglobulins provide the scaffold for PDT innovation Current State US & EU IgG use by indication* Exploring efficacy and safety of HYQVIA in patients with PID and other neuro‐immune diseases (e.g. CIDP) immunology Ongoing delivery device development SID Other SID 4% PID 15% Opportunities 26% Indications: New neuro‐immunology and secondary immunodeficiencies (SID) programs** ITP Geographic expansion: CUVITRU‐Japan first patient to be enrolled 9% in Q4 FY 2019 Other Integrated care solutions: Immuno Advance point of care diagnosis of primary Other 8% Neuro immunodeficiency (PID) 13% New delivery and eHealth devices CIDP Develop f‐20% SCIG 19% GBS 2% MMN Autoimmune 4% Diseases Source: Bain Study (US&EU), Volumes, Estimates based on internal calculations on EU Country Data *Not all indications are approved for a Takeda product 44 **Subject to regulatory approval
Facilitated 20% SCIG has the potential to provide further value to patients who require higher volume administrations Pig model, sequentially administered recombinant human hyaluronidase (rHuPH20) and 20% IgG (CUVITRU)* Pre Injection Post Injection Next Day 400 Control + Ig rHuPH20 + Ig 300 Control + Ig ****p = <0.0001 200 (mmHg ± SEM) 100 Mean In‐Line Pressure rHuPH20 + Ig 0 0 500 1000 1500 2000 Time (Sec) Significantly decreased induration and infusion pressure and induration, and improved cutaneous blood flow * In collaboration with Halozyme 45 Sequentially administered rHuPH20 and CUVITRU is for investigational use only
PROTHROMPLEX TOTAL can be developed to treat a variety of bleeding disorders Changing Treatment Paradigm (EU Total Prescriptions) 37% 31% 53% 45% Current State 70% 62% Many different mechanisms used for prophylactic and surgical anti‐ coagulant therapy 63% 69% 47% 55% PROTHROMPLEX TOTAL use is limited to Vitamin K antagonists 30% 38% associated bleeding ex‐US 2014 2015 2016 2017 2018 2019 Vitamin K Antagonists Source: IMS/IQVIA (Q12019) Opportunities Direct Inhibitors (FX & FII) Geographic expansion into the US* Broaden indication to include treatment of multiple types of drug‐ induced bleeding Improved use via new formulations and device 46 *Pending FDA Pre‐IND consultation and future acceptance of an IND; Investigational use, subject to regulatory approval
ARALAST & GLASSIA provide opportunities to improve outcomes in patients with alpha‐1 antitrypsin deficiency (A1ATD) Healthcare Resource Utilization in A1ATD‐Emphysema 15 Current State Current standard of care does not adequately treat A1ATD 10 10.12 8.48 Opportunities Mean Number 5 5.57 Of Events Per Year 4.56 New clinical study to assess the efficacy of a higher dose of GLASSIA in 3.93 2.0 2.19 1.24 0.70 0.37 patient with emphysema related to A1ATD 0 Emphysema Chronic COPD Bronchiectasis Exacerbations Next generation A1AT*: formulation, delivery and management devices Bronchitis Explore A1AT as acute phase reactant Severe A1ATD Non‐severe A1ATD Source: Herrera et al (2019) Chest annual meeting 47 *Investigational use, subject to regulatory approval
Investigational A1AT‐replacement formulations may offer additional value to patients* Short term Mid term In Vivo Model Highly purified post‐ Protein Modification PK parameters for a modified A1AT fractionations site‐specific modification leading to have been assessed in vivo Statistically significant improvement of pdA1AT‐precursor an extended t1/2 PK parameters for modified A1AT compared to Aralast Concentration Purification of A1AT by ultra filtration potentially by ion‐exchange chromatography leading to an extended t1/2 Formulation Development Evaluate SC administration Device Development Potential to add incremental value for patients 48 *Subject to regulatory approval
We are optimizing efficiencies of plasma‐derived therapy production Estimated % of PDT R&D spend for FY2023 Optimizing value of in‐line products Plasma production efficiencies 60% New plasma‐derived therapies 10% Pharmaceutical science support for manufacturing 30% 49
We are further improving manufacturing efficiencies to increase yield High yield high throughput initiatives will improve delivery of last liter products to patients globally A new high yield & high throughput process: Process development to shorten IgG upstream and total albumin cycle times Capture of purification waste to isolate proteins for possible new development Potential Significantly benefit of reduced higher yield COGS with and increased positive ROI capacity 50
We are identifying and developing new plasma‐derived therapies Estimated % of PDT R&D spend for FY2023 Optimizing value of in‐line products Plasma production efficiencies 60% New plasma‐derived therapies 10% 30% New targeted therapies for diverse therapeutic areas 51
We believe there is a tremendous amount of untapped potential in plasma proteins Homeostasis >3000 plasma proteins control balance, some with health promoting effects and other with disease associated effects Disease Generally, PDTs have been developed to replace functional deficiencies in health promoting proteins Treatment strategies Biopharmaceuticals We believe PDTs, alone or Plasma Combination derived therapies in combination, can be developed to therapies Recombinant (PDTs) proteins, gene mAB, siRNA PDTs mAB, siRNA address acute and chronic diseases therapy 52
We are well‐positioned to create near‐term and sustainable growth NEAR TERM CATALYSTS SUSTAINED GROWTH TARGET FY19 – FY22 FY23 – FY24 FY25 AND BEYOND APPROVAL FY HYQVIA CUVITRU GLASSIA Halozyme HYPERIMMUNE IGx Kamada GENERATION Chronic inflammatory demyelinating Japan PID (FPI Q4 2019) A1ATD‐emphysema* polyneuropahty (CIDP) GLASSIA HYQVIA CINRYZE Kamada Halozyme ACUTE PHASE REACTANTS Immunogenicity/bronchioalveolar EU Pediatric PID Ex‐HAE indications TBD lavage TAK 880 CINRYZE HYQVIA ‐ HyHub NEUROIMMUNOLOGY/OTHER Low IgA‐IgG (IV) AUTOIMMUNE Flextronics Primary Immunodeficiency Geographic expansion Delivery Device HYQVIA Hyper‐Immune IG PLASMA‐DRUG HYQVIA Halozyme IMMUNOLOGY COMBINATIONS US Pediatric PID Infectious disease Geographic expansion CUVITRU Alpha‐1 Antitrypsin (A1AT) CUVITRU INTEGRATED CARE: DEVICES AND DIAGNOSTICS Wearable Device Next generation formulations Geographic expansion TAK 881 Facilitated 20% SC IgG PLASMA PROTEOMICS for Halozyme BIOMARKERS and NEW DRUG Primary Immunodeficiency (PID) DISCOVERY CEPROTIN PROTHROMPLEX TOTAL PROTHROMPLEX TOTAL Geographic expansion Device and formulation US ‐ Drug‐induced bleeding ** FEIBA Butyryl Cholinesterase Volume reduction Organophosphate poisoning HEMATOLOGY 53 *Subject to regulatory approval Clinical‐stage assets Platforms **Pending FDA Pre‐IND consultation and future acceptance of an IND
Treatment paradigms of rare and complex diseases are dynamic and we are innovating continuously Uncertainties PDT Innovation Deepening understanding of underlying Directed most appropriate uses of PDTs mechanisms of diseases and co‐morbidities With Takeda Global R&D, investigate plasma‐drug combinations Evolution of Fc‐ and Fc‐Receptor approaches Focus on primary and secondary immunodeficiencies (including anti‐FcRn) Identify IG responders in specific auto‐immune Gene therapies and RNAi for specific diseases diseases Develop PDTs in conjunction with gene therapies and RNAi (e.g. A1ATD‐liver disease) Perception of lack of plasma product Integrated care solutions will help to expand differentiation therapeutic values and differentiate Takeda products New formulations may offer new approaches for patients 54
Key takeaways for Plasma‐Derived Therapies R&D 132 Dedicated PDT R&D Poised to deliver near‐ Committed to creating organization focused on term value by long‐term value by – and investing in – optimizing our in‐line unlocking the full reimagining plasma, portfolio and potential of plasma to while leveraging improving efficiencies develop innovative, Takeda’s broader R&D throughout the value integrated solutions resources and chain that meaningfully capabilities benefit patients globally 55
Introducing our Covington Manufacturing Facility Carlos Soto Covington Site Head 56
This was our starting place in October 2012 57
Our vision and plans for Covington enable us to serve more patients as we continue to ramp up our operations Increases capacity for Investment of Manufacturing Takeda will employ $1 BILLION+ campus covers ~1,500 EMPLOYEES PLASMA‐DERIVED 2 THERAPIES 1 MILLION+ FT in Georgia at full ramp up 2012 2014 2016 2018 2020 Commissioning, FDA license & Ramp up to full Construction Qualification & commercial production Validation production start 58
This is how our site looks today ‐ November 2019 59
Our current footprint allows for further expansion
Today, we manufacture these therapies from plasma proteins GAMMAGARD Liquid FLEXBUMIN 61
Our facility is vertically integrated Fully integrated end-to-end production site • ~1000 employees today Plasma testing Fractionation Purification Filling Packaging / ramp up plan in place • Site includes already approved BioLife testing and storage facility Flexible design for future expansion Fractionation capacity, million liters Original design basis ~3 Current “optimized” capacity >4 Expansion potential with added investment 10+ 62
Video of Covington Manufacturing Facility 63
Creating impact together Through a dedicated plasma business unit, we will reimagine the plasma industry and uncover the full potential of plasma‐ derived therapies to benefit patients worldwide 64
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Sue Brown Julie Kim Christopher Adrian Murphy Costa Saroukos Carlos Soto Head, Global President, PDT BU Morabito Head of Plasma Chief Financial Officer Covington Site Head BioLife Operations Head R&D, PDT Operating Unit, Global Manufacturing & Supply 66