OX2R AGONISTS FOR THE TREATMENT OF
NARCOLEPSY TYPE 1
Deborah Hartman, PhD
Global Program Leader, Neuroscience
Takeda Pharmaceutical Company Limited
New York, NY
November 14, 2019
NARCOLEPSY TYPE 1 IS A RARE, ACQUIRED
CHRONIC NEUROLOGICAL DISORDER
3M ~50% 15Y
Estimated global Estimated
Mean diagnostic
population affected by diagnostic rate for
delay3
NT11 NT1 in US, EU, JP2
When I'm awake, sleep is constantly
• Psychosocially devastating effects intruding on that part of my life. And
when I'm asleep, wakefulness is
• Current treatments are only partially effective constantly intruding on that part of my
life. It's frustrating because no matter
• Polypharmacy is common how well you regulate your narcolepsy,
you're always tired. You're exhausted.
1. Narcolepsy Network. Narcolepsy Fast Facts. Available at: https://narcolepsynetwork.org/about- - Charlie, adviser with NT1
narcolepsy/narcolepsy-fast-facts/. Last Updated June 2015. Last Accessed Sept. 2019
2. Thorpy et al. Sleep Med. 2014 May;15(5):502-7
3. Frauscher B, J Clin Sleep Med 2013;9(8):805-12 120
NARCOLEPSY TYPE 1 IS DISTINGUISHED BY THE PRESENCE OF
CATAPLEXY AND LOW OREXIN LEVELS
Other hypersomnia
disorders
<110 pg/mL
• Idiopathic
Hypersomnia
It’s not just about sleep, it’s • Residual Excessive
about quality of wakefulness Daytime Sleepiness
… it’s really about partnership in Obstructive
with your extended family, Sleep Apnea1
your spouse, taking care of
your children… it limits my
ability to play with my kids.
-Sara, adviser with NT1
121
CSF: Cerebral spinal fluid; Orexin also referred to as hypocretin
1. Individuals with Obstructive Sleep Apnea who are compliant with use of continuous positive airway pressure at night
NARCOLEPSY TYPE I IS CAUSED BY PROFOUND LOSS
OF OREXIN-PRODUCING NEURONS
OREXIN mRNA LABELLING OF ACTIVATION OF OREXIN 2 RECEPTOR (OX2R)
POSTMORTEM HYPOTHALAMIC SECTIONS LEADS TO AROUSAL AND PROMOTES WAKEFULNESS3
Orexin neuropeptides Post-synaptic neurons with Downstream signalling
Healthy control Narcolepsy Type 1 A and B orexin 2 receptors promoting wakefulness
• Individuals with NT1 have >85% less orexin neurons than THE OREXIN HYPOTHESIS IN NARCOLEPSY TYPE I
control, which are located in the hypothalamus1, 2 An orexin 2 receptor agonist may replace the missing endogenous
orexin peptide, addressing the underlying orexin deficiency of
Narcolepsy Type 1 and reduce disease specific symptoms
f: fornix
1. Reprinted by permission from Springer Nature. Peyron C, et al. Nat Med. 2000;6:991-997 122
2. Thannickal TC, et al. Neuron.2000;27:469–474 3. Tsujino N, et al. Pharmacol. Rev. 2009;61(2):162-176
TAK-925, A SELECTIVE OX2R AGONIST, REDUCES NARCOLEPSY-LIKE
SYMPTOMS IN AN OREXIN-DEFICIENT MOUSE MODEL
TAK-925 FULLY RESTORED TAK-925 ELIMINATED SLEEP / TAK-925 ABOLISHED
WAKEFULNESS WAKE TRANSITIONS CATAPLEXY-LIKE EPISODES
Wakefulness time of NT1 mouse model Hypnogram of sleep/wake transitions Cataplexy-like episodes in NT1 mouse
in active phase for one hour in NT1 mouse model model for three hours after chocolate
EEG recordings
* * ** 4
60
50 REM
Vehicle
3
WT
Minutes awake
NREM
40
Count
Wake
30 REM 2
Vehicle
NT1 mouse model
NREM
20 Orexin/ataxin-3 Wake
1 *
10 REM
TAK-925
NREM
**
0 0
Wake
0 1 0 3 0 10 Vehicle 0.3 Vehicle 1
ZT12 ZT13 ZT14
TAK-925 (mg/kg, s.c.) TAK-925 (mg/kg, s.c.)
Vehicle or TAK-925 (3 mg/kg) cataplexy-like event
*p<0.05, **p<0.01 vs placebo *p<0.05, **p<0.01 vs placebo
123
TAK-925 SHOWED PROMISING ABILITY TO MAINTAIN WAKEFULNESS
IN AN EARLY PROOF OF CONCEPT STUDY IN NT1 PATIENTS
SLEEP LATENCY IN THE MAINTENANCE OF WAKEFULNESS TEST (MWT): SLEEP LATENCY IN THE MAINTENANCE OF WAKEFULNESS TEST (MWT):
CURRENT TREATMENTS TAK-925 (N=14)
(single dose nine hour continuous IV infusion during the day)6
50 50
***
***
Placebo-adjusted change from baseline
*** P value <0.001
Placebo-adjusted observed value
40 40
36.1 36.7
(minutes, 95% CI)
(minutes, 95% CI)
30 30
***
20 20
18.8
10 10
NR NR
1.9 3.0 3.3 3.8 7.7
0 // // // // 0
pitolisant1 modafinil2 sodium armodafinil4 solriamfetol5 TAK-925 5 mg TAK-925 11.2 mg TAK-925 44.8 mg
oxybate3 (n=6) (n=4) (n=4)
• TAK-925 was well-tolerated; most AEs were mild and no SAEs were observed
• In this TAK-925-1001 study, four 40 minute MWTs were conducted per period
• Direct cross-study comparison can not be made between TAK-925 and treatments due to different studies with different designs
NR: 95% CI rot reported
1. Lancet Neurol. 2017 Mar;16(3):200-207; 2. FDA statistical Review: Page 5, 200 mg; 3. Label/Trial N4; 4. Clinicaltrials.gov (NCT00078377); 5. FDA Statistical Review, Study 14-002, 150 mg 124
6. Evans R, Tanaka S, Tanaka S, et al. 2019. A phase 1 single ascending dose study of a novel orexin 2 receptor agonist, TAK-925, in healthy volunteers (HV) and subjects with narcolepsy type 1 (NT1) to assess safety, tolerability,
pharmacokinetics, and pharmacodynamic outcomes. Abstract presented at World Sleep 2019. Vancouver, Canada. http://www.professionalabstracts.com/ws2019/iPlanner/#/presentation/1832
TAK-925 ALSO REDUCED SUBJECTIVE SLEEPINESS IN THIS EARLY
PROOF OF CONCEPT STUDY IN NT1
KAROLINSKA SLEEPINESS SCALE VALUES DURING AND AFTER ADMINISTRATION OF TAK-925
(single dose nine hour continuous IV infusion during the day)
Mean (SD) Placebo
9
TAK-925 5 mg
8 TAK-925 11.2 mg
Decreasing level of sleepiness
End of infusion TAK-925 44.8 mg
7
6
5 TAK-925 improved
subjective and objective
4
measures of wakefulness
3
2
1
0
1 2 3 4 5 6 7 8 9 10 11
Hours after start of nine hour infusion1
1. TAK-925 effective plasma half-life <2 hours
125
Evans R, Tanaka S, Tanaka S, et al. 2019. A phase 1 single ascending dose study of a novel orexin 2 receptor agonist, TAK-925, in healthy volunteers (HV) and subjects with narcolepsy type 1 (NT1) to assess safety, tolerability,
pharmacokinetics, and pharmacodynamic outcomes. Abstract presented at World Sleep 2019. Vancouver, Canada. http://www.professionalabstracts.com/ws2019/iPlanner/#/presentation/1832
TAK-925 MAINTAINED WAKEFULNESS IN SLEEP-DEPRIVED HEALTHY
ADULTS IN A SECOND PHASE 1 STUDY
SLEEP LATENCY IN THE MAINTENANCE OF WAKEFULNESS TEST (MWT) IN SLEEP-DEPRIVED HEALTHY ADULTS1
***
40
39
(least squares means, 95% CI)
30 ***
Average minutes
25 Results suggest potential
20 therapeutic use of TAK-925 in
other hypersomnia disorders
10
not associated with orexin
deficiency
9
0
Placebo (n=20) TAK-925 44.8mg (n=18) TAK-925 112mg (n=18)
TAK-925 was well-tolerated; most AEs were mild and no SAEs were observed
1. Evans R, Hazel J, Faessel H, et al. 2019. Results of a phase 1b, 4-period crossover, placebo-controlled, randomized, single dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-925, a novel orexin 2
agonist, in sleep-deprived healthy adults, utilizing modafinil as an active comparator. Abstract presented at World Sleep 2019. Vancouver, Canada. http://www.professionalabstracts.com/ws2019/iPlanner/#/presentation/2821 126
2. Int J Neurosci. 1990 May;52(1-2):29-37
***: p-value <0.001 relative to placebo
WE ARE COMMITTED TO LEADING INNOVATION IN OREXIN BIOLOGY
AND EXPANDING THERAPEUTIC INDICATIONS FOR OX2R AGONISTS
Rare primary hypersomnia disorders
Top priority
Other hypersomnia disorders
Additional opportunities for expansion
Idiopathic
Hypersomnia
Narcolepsy Residual EDS
Type II in Obstructive • TAK-925-1003 for Narcolepsy Type 2
Sleep Apnea1 (NCT03748979)
Hypersomnia
Shift Work disorders
Narcolepsy Sleep secondary to • SPARKLE 2001 study for Residual EDS
Type I Disorder other in Obstructive Sleep Apnea
REM conditions (NCT04091425)
disorders EDS in other
under neurological • SPARKLE 2002 study for Idiopathic
evaluation & psychiatric Hypersomnia (NCT04091438)
disorders
Metabolic disorders
under evaluation
127
REM: Rapid eye movement
1. Individuals with Obstructive Sleep Apnea who are compliant with use of continuous positive airway pressure at night
TAK-994 IS AN ORAL OX2R AGONIST PROGRESSING TO STUDIES IN
NARCOLEPSY TYPE 1
TAK-994-1501 PROOF OF CONCEPT STUDY IN NARCOLEPSY TYPE 1
• Multi-center, placebo-controlled
trial in North America and Japan
• Enrollment target: 72 adults
• Duration of treatment: 28 days
dosing
• Exploratory outcome measures
include Maintenance of
Wakefulness Test (MWT), Epworth
Sleepiness Scale (ESS), and Weekly
Cataplexy Rate (WCR)
128
Proof of Concept trial: ClinicalTrials.gov Identifier: NCT04096560
DIGITAL TECHNOLOGIES ARE ENHANCING THE DEVELOPMENT OF
OX2R AGONISTS FOR SLEEP DISORDERS
TRADITIONAL CLINICAL INSTRUMENTS DO NOT FULLY MEASURE DIGITAL MEASURES WILL FURTHER CHARACTERIZE SLEEP
SYMPTOMS OF SLEEP DISORDERS ARCHITECTURE AND SUPPORT CLINICAL TRIAL ASSESSMENTS
Hand-scored Automated analysis of NT1 nPSG2
polysomnography (PSG)1
• Real-time data capture to understand disease burden and effects of treatment
• Non-invasive measures to optimize therapy
• Patient stratification using digital fingerprints
nPSG – Night time polysomnography 129
1. Approximately 80% interrater concordance based on Danker-Hopfe et al., J Sleep Res (2009) and Younes & Hanly, J Clin Sleep Med (2016); 2. Analysis shown is based on Stephansen et al., Nature Comm (2018)
WE ASPIRE TO BRING A POTENTIALLY TRANSFORMATIVE OX2R
AGONIST SOLUTION TO INDIVIDUALS WITH NARCOLEPSY TYPE 1
• Achieved early Proof of Concept for NT1
TAK-925 • Awarded Breakthrough Therapy Designation
• Awarded Sakigake Designation
• Launched formulation development activities
TAK-994, first oral OX2R Initiate SPARKLE-1501 Proof of Initiation of NT1 pivotal studies
agonist, entered phase I Concept study in NT1 First approval targeted for 2024
TAK-994
FY19 FY20 FY21
Thank you to all the study participants who have enrolled in these early OX2R agonist clinical trials
130
SUMMARY
1 2 3
TAK-925 has achieved TAK-925 has TAK-994 is an oral
early Proof-of-Concept demonstrated potential OX2R agonist
for OX2R agonists in of OX2R agonists for progressing to studies
Narcolepsy Type 1 treatment of other in Narcolepsy Type 1
sleep-related disorders
131
R&D DAY AGENDA – NEW YORK, NOVEMBER 14, 2019
TIME AGENDA
Welcome and Opening Remarks
12:30 – 12:35
Sheelagh Cawley-Knopf, Head R&D Global Portfolio Strategy
Takeda: A Global Values-Based, R&D-Driven Biopharmaceutical Leader
12:35 – 12:45
Christophe Weber, President & CEO Takeda
Translating Science into Highly Innovative, Life-changing Medicines
12:45 – 13:20
Andy Plump, President R&D
Oncology and Cell Therapies with Spotlight on CAR-NK
13:20 – 13:45
Chris Arendt, Head Oncology Drug Discovery Unit
Spotlight on Oncology Opportunities
13:45 – 14:05 • TAK-788 : Rachael Brake, Global Program Lead
• Pevonedistat : Phil Rowlands, Head Oncology Therapeutic Area Unit
14:05 – 14:20 Break
Rare Diseases & Gene Therapy
14:20 – 14:45
Dan Curran, Head Rare Disease Therapeutic Area Unit
Spotlight on Orexin2R agonists
14:45 – 15:00
Deborah Hartman, Global Program Lead
Therapeutic Area Focus in GI with Spotlight on Celiac Disease
15:00 – 15:20
Asit Parikh, Head GI Therapeutic Area Unit
15:20 – 16:00 Panel Q&A Session
16:00 Drinks reception
132
THERAPEUTIC AREA FOCUS IN GI WITH
SPOTLIGHT ON CELIAC DISEASE
Asit Parikh, MD, PhD
Head Gastroenterology Therapeutic Area Unit
Takeda Pharmaceutical Company Limited
New York, NY
November 14, 2019
WE TARGET UNMET NEEDS THAT ALIGN WITH OUR STRENGTHS
AREAS OF FOCUS GI WW RX SALES 2018 (USD BN) TAKEDA GI DISEASE AREAS
Total = $57Bn
High unmet medical need
Other GI inflammation
GI GI
Potential to advance SoC Cancers 3.9
through innovative science – by
being first or best in class 18.2
12.2
GI motility
Fit with internal strengths
0.3 2.9
12.6 Liver fibrosis
Ability to create a commercially 6.5
- viable path Viral hepatitis
Acid related diseases
134
SOURCE: Evaluate Pharma indication specific sales, accessed May 29, 2019. Other GI includes: pancreatic insufficiency, hepatic encephalopathy, diarrhea, bowel clearance, gallstones, hemorrhoids
WE STRENGTHEN ENTYVIO BY CONTINUOUSLY IMPROVING
VALUE FOR PATIENTS
COMPETITIVE POSITIONING EXPANDED PATIENT POPULATIONS GEOGRAPHIC EXPANSION
VARSITY: 1st Head-to-Head study in IBD (UC) Entyvio Subcutaneous Development Entyvio IV
• Vedolizumab was superior to adalimumab on • Positive VISIBLE UC and CD trials • Approved in 68 countries
the primary endpoint of clinical remission at • Subject to regulatory approval, on track to • Launched in Japan (UC: Nov 2018,
wk 52 launch exclusive, digital, needle-free jet- CD: May 2019)
• Onset of action as rapid as anti-TNF injector by 2022
Prefilled syringe Autoinjector pen Portal jet-injector
Gut GvHD prophylaxis
• Could transform SoC for cancer patients
undergoing allo stem-cell transplants
EXPECTED 2019 2020 2021
MILESTONES (FY)
Entyvio (SC UC) US approval Entyvio (SC CD) US, EU approval Entyvio GvHD Ph3 readout
Entyvio (SC UC) EU, JP approval
Entyvio (IV) CN approval
Source: Sands et al. Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis. N Engl J Med 2019; 381:1215-1226
IBD: Inflammatory Bowel Disease; UC: ulcerative colitis; CD: Crohn’s Disease; IV=intravenous; SC=subcutaneous; TNF=tumour necrosis factor; SoC: standard of care; CN: China; JP: Japan; GvHD: graft versus host disease; 135
Clinical remission: Complete Mayo score of ≤2 points and no individual subscore >1 point
WE ARE POSITIONED TO DELIVER NEAR-TERM & SUSTAINED GROWTH
WAVE 11 WAVE 22
TARGET CLINICAL-STAGE NMEs PLATFORMS
APPROVAL FY20 FY21 FY22 FY23 FY24 FY25 AND BEYOND
TAK-7883 TAK-007 TAK-924 TAK-164 TAK-252
2L NSCLC Hematologic AML GI malignancies Solid tumors TARGETED
malignancies CELL THERAPY INNATE NEXT-GEN
ONCOLOGY AND IMMUNE
ENGAGERS IMMUNE
CHECKPOINT
TAK-9243 TAK-788 TAK-573 TAK-981 MODULATION MODULATORS
HR-MDS 1L NSCLC R/R MM Multiple cancers
TAK-620 TAK-611 TAK-607 TAK-0794 TAK-754 TAK-755
CMV infect. in MLD (IT) Complications of MG, ITP HemA iTTP, SCD
Immunology
RARE Hematology
transplant prematurity GENE
THERAPY
DISEASES Metabolic
TAK-609 TAK-755 TAK-531
Hunter CNS (IT) cTTP Hunter CNS
TAK-935 Orexin2R-ag TAK-341 Orexin2R-ag TAK-041
DEE (TAK-925/994) Parkinson’s Sleep Disorders CIAS NS OTHER
Narcolepsy T1 Disease GENE PLATFORMS
THERAPY RNA Modulation
NEUROSCIENCE TAK-418 TAK-653 TAK-831 Antibody Transport
Vehicle
Kabuki Syndrome TRD CIAS NS
WVE-120101 WVE-120102
Huntington’s Huntington’s
Disease Disease
TAK-721 Kuma062 TAK-101 TAK-018 TAK-671
EoE Celiac Disease Celiac Disease Crohn’s Disease Acute
GASTRO- (post-op and ileitis) Pancreatitis GENE
MICROBIOME
CELL
THERAPY THERAPY
ENTEROLOGY TAK-954 TAK-906 TAK-951
POGD Gastroparesis Nausea &
vomiting
TAK-003 TAK-214 TAK-426 TAK-021
VACCINES Dengue Vaccine Norovirus Zika Vaccine EV71 vaccine
Vaccine
1. Projected timing of approvals depending on data read-outs; some of these Wave 1 target approval dates assume accelerated approval Orphan potential in at least one indication
2. Some Wave 2 assets could be accelerated into Wave 1 if they have breakthrough data 136
Estimated dates as of November 14, 2019
3. Projected approval date assumes filing on Phase 2 data
4. TAK-079 to be developed in Rare Diseases indications myasthenia gravis (MG) and immune thrombocytopenic purpura (ITP) (FPI projected in each indication in 2H FY19)
TAK-721: ON TRACK TO BE THE FIRST FDA APPROVED
AGENT TO TREAT EOSINOPHILIC ESOPHAGITIS (EOE)
INDUCTION DATA SHOWS SIGNIFICANT
ADDRESSES SIGNIFICANT UNMET NEED HISTOLOGIC AND SYMPTOM RESPONSE
• Chronic, allergic, inflammatory condition of the esophagus Results presented at presidential plenary at ACG, Texas, Oct 2019
that results in swallowing dysfunction
Histologic Response at 12 Weeks (peak ≤ 6 eosinophils/hpf on biopsy)
• Diagnosed prevalence is expected to increase significantly
p < 0.001
60
Proportion of patients
No approved US medication 40
SOC is food elimination, off-label use1
(%)
20
53.1%
53.1%
1.0%
0
TAK-721 granted breakthrough therapy
designation by FDA in 2016
Symptom Response at 12 Weeks (≥ 30% reduction in DSQ score)
60 p = 0.024
Proportion of patients
40
52.6%
52.6%
(%)
EXPECTED 2019 2020 2021 20 39.1%
39.1%
MILESTONES (FY) Q4: Maintenance Q2: NDA filing Q1: Launch
TL results Q4: Approval 0
Placebo (n = 105) 2 mg BID (n=213)
1. Swallowed use of glucocorticoids intended for asthma (e.g., home or compounded thickening of DSQ score: Dysphagia Symptom Questionnaire patient reported outcome score eos/hpf: peak eosinophils per 137
budesonide solution, or swallowing fluticasone aerosol). high-powered field from endoscopic biopsies
Eos/hpf: eosinophils per high-power field; BID: Twice daily; SOC: Standard of care; NDA: new drug application
CELIAC DISEASE IS AN EXAMPLE OF A HIGH UNMET
NEED AREA WITH NO THERAPIES
~1% ~40% ~1M
Estimated
Patients still suffer from
Global population global, eligible
symptoms despite being
affected by celiac1 patient
on a gluten-free diet
population2
• Overlooked disease, growing prevalence
• Chronic symptoms
• Higher risk of certain cancers Some of us are so extremely sensitive that
• High treatment burden affecting the whole family one little crumb will make us extremely sick.
I'm one of those people, and there is really
• No current pharmacologic therapies
nothing I can do about it
– Delisi, Celiac disease patient
1. Pooled global prevalence; Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-836 138
2. Estimated number of patients projected eligible for treatment, in markets where the product is anticipated to be commercialized, subject to regulatory approval
WE ARE FOCUSING ON THE NARROWEST
POPULATION WITH HIGH UNMET NEED
20% Moderate Our focus:
• Niche patient segment
with the highest unmet
40% Uncontrolled* on GFD need
• Severe symptoms with
villous atrophy
18% Severe • Continue to suffer
60% despite the GFD and are
highly likely to take a
Controlled on Gluten therapy
2% Refractory
Free Diet (GFD)
*Uncontrolled defined as ongoing chronic moderate to severe symptoms with villous atrophy 139
OUR APPROACH TO TREATING CELIAC DISEASE
TREATMENT OPPORTUNITIES FOR CELIAC DISEASE
1
1 Enzymatic digestion of gluten Kuma062 promises greatly increased
3 Microbiome Modulation enzymatic efficiency and improved
2 Reduce intestinal permeability formulation over predecessors
2
3 Microbiome modulation
4 Cytokine inhibition
4
5 Transglutaminase inhibition
5
6 Promote Immune tolerance TAK-101 (TIMP-GLIA) has the
6 potential to be a first in class,
tolerizing immune therapy for celiac
disease
Source: Green and Cellier, 2007
140
KUMA062: A HIGHLY POTENT ORAL GLUTENASE THAT COULD CHANGE
THE STANDARD OF CARE IN CELIAC DISEASE
CLINICAL DATA SHOWS KUMA062 CAN DEGRADE
ABOUT KUMA062 >95% OF INGESTED GLUTEN
• Kuma062 is an oral, computationally-engineered super glutenase
• Enhanced catalytic activity compared to other glutenases Gluten recovery in gastric contents aspirated 30mins after
meal containing 3g of gluten
Optimal activity at
Resistance to common
the pH range of the 800
digestive proteases p = 0.001
stomach after a meal 700
Gluten (mg)
600
500 >95% gluten
400 degradation
300
200
100
0
Placebo (n=13) 900mg Kuma062 900mg Kuma062 +
Specificity for peptides Eliminates ex vivo T cell (n=12) Nexium (n=13)
with immunogenic response to all 3 major
regions of gliadin gliadin families • Kuma well-tolerated, no identified safety concern
• Decision to acquire PVP Biologics expected Q3 FY2019
141
TAK-101: POTENTIAL BEST-IN-CLASS, INTRAVENOUS THERAPY FOR
CELIAC DISEASE DESIGNED TO MODIFY T CELL RESPONSE
ABOUT TAK-101* TAK-101 REDUCES IMMUNE ACTIVATION AFTER GLUTEN EXPOSURE
Interferon-gamma ELISPOT measurement of gluten-responsive T cells
• Biodegradable polymer encapsulating antigen
• Designed to induce tolerance to gluten, reduce T cell 30
Increase in gluten-responsive T
responses to gliadin 25 p = 0.0056
cells (spot-forming units)
20
Treatment with TAK-101
15 reduced immune
activation by >85%
10
5
0
Placebo TIMP-GLIA
n=16 n=13
PROPRIETARY PARTICLE SURFACE
PARTICLE CORE PROGRAMMED WITH
TAKEDA ACQUIRED EXCLUSIVE GLOBAL LICENSE TO TAK-101
GLIADIN TO INDUCE TOLERANCE
• Expected to provide durable (3 months or longer) down
regulation of T cell responses to immunogenic gliadin peptides
*Formerly TIMP-GLIA 142
Source: https://www.courpharma.com/our-technology/
WE ARE LEADING THE SCIENCE IN CELIAC DISEASE
WITH A NEW AI - BASED TOOL AND INGESTIBLE DEVICE
PIONEERING AT BOUNDARIES INNOVATIVE USE PRECISION
OF CLINICAL MEDICINE OF TECHNOLOGY MEASUREMENT USING AI
• Innovative, non-invasive, patented • Ingestible high resolution camera pill • Pioneering Automated Image
method of measuring total burden • Modern machine-learning/ AI based assessment quantifies disease burden
of intestinal disease image processing
143
TAKEDA IS THE BEST COMPANY TO BRING
CELIAC THERAPIES TO PATIENTS
World-class, fully connected GI commercial infrastructure
across 65+ countries that supports $6bn+ revenues • Extensive GI clinical footprint
• Strong reputation for scientific
excellence
• Lauded for calculated risk-taking by
the GI community
• Experience with redefining
guidelines and treatment paths
144
NME MILESTONES ACHIEVED IN FY19 AND LOOKING AHEAD TO
OTHER POTENTIAL MILESTONES1 THROUGH FY20
PIVOTAL STUDY STARTS, APPROVALS
MLD PEVONEDISTAT AML EoE
TAK-611
Ph 2 start2 TAK-924 Ph 3 start
TAK-721
Approval
cTTP 1L NSCLC Huntington’s Disease
TAK-755
Ph 3 start
TAK-788
Ph 3 start
mHTT ASO
Pivotal start
1H FY 2019 2H FY 2019 1H FY 2020 2H FY 2020
Narcolepsy PEVONEDISTAT HR-MDS 2L NSCLC
TAK-925
POC TAK-924 Ph 2 Overall Survival
TAK-788
Ph 2 Pivotal
TAK-620
R/R CMV SOT & HSCT
Ph 3 data
TAK-721
EoE
Ph 3 data (induction) TAK-007
Hem. Malignancies
POC
TAK-573
R/R MM, Solid Tumor
POC
TAK-755
iTTP
POC
Celiac Disease Hunter (IT) DEE
TAK-101
POC
TAK-609
Ph 3 data 2yr extension
TAK-935
POC
Huntington’s Disease Gastroparesis
mHTT ASO TAK-906
POC POC
EoE Nausea & Vomiting
TAK-721 TAK-951
Ph 3 data (maintenance) POC
Oncology
Rare Disease
Neuroscience
Gastroenterology
Denotes milestones that have been achieved.
KEY DATA READOUTS
145
1. Potential key milestone dates as of November 14, 2019. The dates included herein are estimates based on current data and are subject to change
2. Potentially registration enabling
SUMMARY
1 2 3
We have built an We are well We have multiple
industry-leading positioned to bring milestones, including
portfolio rooted in the first therapies to expected key approvals
unparalleled scientific celiac patients that in the next 2 years that
excellence and could change the will be transformative
outstanding global standard of care for patients
commercial strength
146
R&D DAY AGENDA – NEW YORK, NOVEMBER 14, 2019
TIME AGENDA
Welcome and Opening Remarks
12:30 – 12:35
Sheelagh Cawley-Knopf, Head R&D Global Portfolio Strategy
Takeda: A Global Values-Based, R&D-Driven Biopharmaceutical Leader
12:35 – 12:45
Christophe Weber, President & CEO Takeda
Translating Science into Highly Innovative, Life-changing Medicines
12:45 – 13:20
Andy Plump, President R&D
Oncology and Cell Therapies with Spotlight on CAR-NK
13:20 – 13:45
Chris Arendt, Head Oncology Drug Discovery Unit
Spotlight on Oncology Opportunities
13:45 – 14:05 • TAK-788 : Rachael Brake, Global Program Lead
• Pevonedistat : Phil Rowlands, Head Oncology Therapeutic Area Unit
14:05 – 14:20 Break
Rare Diseases & Gene Therapy
14:20 – 14:45
Dan Curran, Head Rare Disease Therapeutic Area Unit
Spotlight on Orexin2R agonists
14:45 – 15:00
Deborah Hartman, Global Program Lead
Therapeutic Area Focus in GI with Spotlight on Celiac Disease
15:00 – 15:20
Asit Parikh, Head GI Therapeutic Area Unit
15:20 – 16:00 Panel Q&A Session
16:00 Drinks reception
147
Panel Q&A Session
© 2019 Takeda Pharmaceutical Company Limited. All rights reserved