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
Other 8%
Advance point of care diagnosis of primary Neuro
immunodeficiency (PID) 13%
New delivery and eHealth devices CIDP
Develop f-20% SCIG 19%
GBS
2%
MMN Autoimmune
Diseases
4%
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
Mean In-Line Pressure
Control
(mmHg ± SEM)
+ Ig ****p = <0.0001
200
100
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%
45%
Current State 70% 62% 53%
Many different mechanisms used for prophylactic and surgical anti-
coagulant therapy 55% 63% 69%
47%
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
Of Events Per Year
Mean Number
10
10.12
8.48
Opportunities 5
5.57
New clinical study to assess the efficacy of a higher dose of GLASSIA in
4.56
3.93
2.0 2.19
patient with emphysema related to A1ATD 0
1.24 0.70 0.37
Next generation A1AT*: formulation, delivery and management devices Emphysema Chronic
Bronchitis
COPD Bronchiectasis Exacerbations
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
pdA1AT-precursor an extended t1/2 Statistically significant improvement of
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
derived
Combination
therapies
in combination, can be developed to Recombinant
therapies
(PDTs)
mAB, siRNA mAB, siRNA
address acute and chronic diseases proteins, gene
therapy
PDTs
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
IMMUNOLOGY
Immunogenicity/bronchioalveolar EU Pediatric PID Ex-HAE indications TBD
lavage
TAK 880 CINRYZE NEUROIMMUNOLOGY/OTHER
HYQVIA - HyHub Low IgA-IgG (IV) AUTOIMMUNE
Flextronics Primary Immunodeficiency Geographic expansion
Delivery Device
HYQVIA Hyper-Immune IG PLASMA-DRUG
HYQVIA Halozyme COMBINATIONS
US Pediatric PID Infectious disease
Geographic expansion
CUVITRU Alpha-1 Antitrypsin (A1AT) INTEGRATED CARE: DEVICES
CUVITRU 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
HEMATOLOGY
CEPROTIN PROTHROMPLEX TOTAL PROTHROMPLEX TOTAL
Geographic expansion Device and formulation US - Drug-induced bleeding **
FEIBA Butyryl Cholinesterase
Volume reduction Organophosphate poisoning
*Subject to regulatory approval
53
**Pending FDA Pre-IND consultation and future acceptance of an IND
Clinical-stage assets Platforms
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
1 2 3
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