Shire's Leadership in Rare Hematology
Shire’s Leadership in Rare Hematology
Kim Stratton Head International Commercial International Region has strong expertise in Rare Diseases and a strong focus on Hematology
Old Shire New Shire All countries outside of ~90% USA ~70% Rare Diseases Rare Diseases
Present in 68 countries and Largest Franchise: bringing products Largest Franchise: Hematology to patients in 100+ Genetics (LSD/ HAE) markets > 40% of sales
2 Shire leading Rare Hematology
Shire leads this Shire has 3 key Shire has best in Shire is a dynamic market growth drivers class portfolio serial innovator
. Large global . Drive diagnosis & . ADVATE family . Upgrade current dynamic market with prophylaxis in remains the gold brands growth of 3-5% developing markets standard therapy for . Hemophilia A Drive personalization . Shire is the leader . Drive prophylaxis with Shire medical with longest & personalization . FEIBA and Immune devices & trough heritage, broadest in developed Tolerance Induction studies portfolio & leading markets (ITI) will continue to market share of be the treatment of . Develop . 36% Geographic & choice for vast transformational portfolio expansion majority of inhibitor therapies, e.g. gene with +100 launches patients therapies across +40 countries 3 Globally, the Rare Hematology market is large and growing, led by Hemophilia A
$10B market today continues to grow, expected to reach $13B by 2020
Hemophilia A
Inhibitors
Hemophilia B
von Willebrand disease 0 1,000 2,000 3,000 4,000 5,000 6,000 7,000 ($’000) Global Revenues 4 2015, Shire Proprietary Data on File The Rare Hematology market is heterogeneous, dynamic and increasingly complex
GEOGRAPHY PRODUCT Hemophilia A Hemophilia A CLASS
Inhibitors Inhibitors
International 60% Recombinant 74% Hemophilia B Hemophilia B US 40% Plasma 26% von Willebrand von Willebrand disease disease 0 2,000 4,000 6,000 8,000 0 2,000 4,000 6,000 8,000 Global Revenues ($’000) Global Revenues ($’000)
PATIENT TREATMENT Hemophilia A Hemophilia A REGIMEN
Inhibitors Inhibitors
Adult (18+) 75% Prophylaxis 69% Hemophilia B Hemophilia B Pediatric (0-17) 25% On Demand 31% von Willebrand von Willebrand disease disease 0 2,000 4,000 6,000 8,000 0 2,000 4,000 6,000 8,000 Global Revenues ($’000) ($’000) Global Revenues 5 5
2015, Shire Proprietary Data on File Shire has deep expertise and established leadership with an industry-leading, comprehensive portfolio in Rare Hematology
Annual Global Sales ($B) Global 2015 revenue ($B)* (Constant currency) (Actual rates) 5.0 7% CAGR Other $1.0 Biogen 10% $0.6 Shire Bayer 5% $1.0 $3.6 10% 36% $10B CSL $1.0 10% Pfizer Novo $1.3 Nordisk 13% $1.6 0.0 16% 2011 2012 2013 2014 2015 Hemophilia Inhibitors 3-5% projected CAGR through 2020 despite increasing competition^
*Global market revenues shown at 2015 actual rates, sourced through competitive disclosure. ^Actual rates, previously disclosed by legacy Baxalta 6 Only Shire’s unrivalled, best-in-class portfolio offers personalized care
Octa- Shire Biogen Novo Bayer CSL Pfizer pharma Hemophilia A
Hemophilia w/ Inhibitors
Hemophilia B Indications Acquired Hemophilia A
Von Willebrand disease
Plasma derived factors Recombinant factors
Technologies Extended Half Life (EHL)
Personalized treatment 7 Shire’s global Rare Hematology footprint continues to grow ESTABLISHED
37% Products available US 53% today in RECOMBINATE IMMUNATE 100+ countries HEMOFIL M IMMUNINE
63% 100+ Launches LAUNCHING Int’l 47% (products and new indications) 40+ countries FVIII Sales Inhibitor Sales through 2018
Shire analysis 8 Shire’s world-class leadership in Rare Hematology
PROPEL RECOMBINATE Hemophilia A
Von Hemophilia A Willebrand with Disease inhibitors UNRIVALLED BEST-IN- CLASS PORTFOLIO Acquired Hemophilia B Hemophilia A
Plasma derived Hemophilia IMMUNATE Therapies HEMOFIL M IMMUNINE 9 The 3 key unmet medical needs in Hemophilia A
Personalized Early prophylaxis for one Early diagnosis for all for all
• High Annual • Moderate • Everyone is Bleed Rate ABR: 2-103 unique 1 4 (ABR): >40 • Loss of • Low ABR: <2 • Disability work/ school • “Normal life” experience • Life expectancy • Reduced and early teens2 for joint / bone expectancy undiagnosed health patients
Diagnosis from Birth Prophylaxis Personalized Care
1. Hua 2014. 2. Mejia, et al. Jrnl Thromb Haem. 2006. 10 3. Valentino et al. Haemophilia. 2012. 4. Gringeri et al. WFH Poster 2016 Shire, raising global standards of care and minimizing annual bleed rates, driving best patient outcomes
Personalized Early prophylaxis for one Early diagnosis for all for all
only 25% 100% only 8% 60% <3% 100% of patients are diagnosed1 of patients receive of prophylaxis patients prophylaxis1 receive personalized care2
On Treatment Prophylaxis Personalized Care
e.g. India, China, Vietnam e.g. Russia, Brazil, Argentina e.g. US*, Japan, Europe
HEMOFIL M IMMUNATE RECOMBINATE PROPEL
1. World Federation of Hemophilia Annual survey 11 2. Shire analysis * myPKFiT is not approved in the United States Parents and patients are loyal to established treatments and not willing to compromise efficacy and safety
Decisions largely driven by efficacy, safety and personalization
49% of patients have never switched treatment or have switched only once1
Patients prefer product enhancements within a trusted portfolio rather than switch to an entirely new product
1. Shire analysis 12 ADVATE is the proven gold standard Factor VIII therapy
Worldwide leader More than 13 years approved in 50+ of real world Proven bleed prevention countries experience 42% of patients on ADVATE prophylaxis bleed free Clinicians rate ADVATE as the Trusted Standard of Care1 Proven effectiveness in the real world 1.66 solid clinical data Annual Bleed Rate (ABR)
effective prophylaxis Proven safety in the real world
0.15% Inhibitor rate in severe previously trusted by patients treated patients
1 1. Shire analysis 13 ADVATE + myPKFiT: the only registered software based medical device for personalized Hemophilia dosing
Considering the Personalized prophylaxis uniqueness of each patient tailored for each patient
Trough levels >1% = more patients reach ZERO bleeds
Filed in the US
Physicians more likely to prescribe ~3X ADVATE after using myPKFiT 14 ADYNOVATE: expanding personalization of care, building on the success of ADVATE
STRONG COMMERCIAL MOMENTUM
Launched European Pediatric in US in Q4 Launch and Surgery PROVEN ADVATE 2015 and in 2017 indications BLEED PREVENTION Japan in Q2 2017 2016 (US, JP)
SIMPLE, TWICE-WEEKLY Momentum with new patients from across portfolio and competition INFUSION Launch on track
15 ADYNOVATE + PROPEL: Continuing research to optimize outcomes with personalized approach
40% of patients achieve PROPEL Study zero bleeds on prophylaxis1,2
100% Can a threshold of FVIII trough level of 10-12% further reduce annual 80% 3
bleed rate to zero ? 60% Peaks: important for trauma or Patients 40% activity-induced bleed prevention4
20% FVIII Troughs may be important for 5 level spontaneous bleed prevention 0% No bleeds No joint bleeds No spontaneous bleeds ADYNOVATE Clinical Data Per-protocol Analysis Set (PPAS): N=101. Time
1. Konkle, EAHAD 2015 Poster 2. Konkle, Blood. 2015. 3. Den Uijl Haemophilia, 2011. 4. Valentino WFH 2014. 5. Collins PW. J Thromb and Haemost. 2012 16 Shire’s Hemophilia A portfolio: Leadership based on proven factor therapy & serial innovation
ADYNOVATE: Personalized care with PROPEL Study: proven ADVATE bleed Can a threshold of FVIII prevention with twice- trough level of 10-12% further weekly infusion reduce annual bleed rate to zero? ADVATE+myPKFiT: Personalized PROPEL SHP656: Weekly EHL* PK-based dosing based on ADVATE SERIAL • PSA technology INNOVATION IN ADVATE: Proven FACTOR • Phase 1 trial underway efficacy and safety REPLACEMENT • Phase 3 could start in profile with +13 years of SHP656 Weekly 2017 real world experience rFVIII Broader impact of Factor VIII Broader beyond coagulation cascade impact of • Bone and joint health Factor VIII • Quality of the clot formation • “Feel good factor” 17 * Extended Half Life
Shire’s global leadership in Rare Hematology
RECOMBINATE Hemophilia A
Von Hemophilia A Willebrand with disease inhibitors UNRIVALLED BEST-IN- CLASS PORTFOLIO Acquired Hemophilia B Hemophilia A
Plasma derived Hemophilia IMMUNATE Therapies HEMOFIL M 18 IMMUNINE Global inhibitor market is driven by international growth
~$2B Global Market Distinct Patient Segments (percent of patients)
Adults Shire 44% 56% Novo Nordisk Pediatric
Shire Sales
US Prophylaxis 37% 43% 63% 57% International On-Demand
19 Shire analysis Eradicating the inhibitor and returning to factor replacement therapy through ITI is the primary goal for inhibitor patients
Hemophilia A 20 - 30% develop inhibitors Immune Tolerance Induction (ITI) Therapy
Current ITI Failure (30%1) Current ITI Success (70%1)
Bypassing Agents Potential future ITI Success (96%2) FEIBA, NovoSeven Aggressive ITI plus bypass
Return to factor
1. Hay, DiMichele. Blood. 2012 replacement therapy 2. Nakar et al, Hemophilia 2014 20 70% of physicians report being satisfied with on-demand or prophylactic bypassing therapy
Hemophilia A 20 - 30% develop inhibitors Immune Tolerance Induction (ITI) Therapy
Potentially related to: Reported current ITI Failure (30%1) May consider 2 Unsatisfied 15% new options Non-optimal outcomes 12% Bypassing Agents Treatment burden FEIBA, NovoSeven Satisfied 42% 31%
On-Demand Prophylaxis (57%) (43%)
1. Hay, DiMichele. Blood. 2012. 21 2. Shire Data on File. FEIBA offers a unique mechanism with 40+ years of global real world experience of bypassing therapy
Only bypass widely Only FEIBA acts on approved for both all three pathways prophylaxis and on-demand
FEIBA’s unique multi- Continued factor mechanism investments to regulates coagulation upgrade FEIBA cascade • Patient support Enables a clot to form as programs close as possible to the • Upgraded infusion body’s natural process in a experience self-regulated manner
22 Future innovation for inhibitor patients will be driven by : eradication, prediction and prevention
ERADICATE PREDICT PREVENT Primary Treatment Predict high risk Prevent inhibitor Goal patients development • Standard of care is early • Predictive modelling, • Increase early ITI +/- bypassing agent algorithms and prophylaxis • Drive up eradication biomarkers to identify • Critical first 20 exposure from 70% to 96% high-risk patients days1
1. Gouw et al. Blood. 2007. 23 Future innovation in Rare Hematology
Non-factor Based Therapies Gene Therapy
• Shire non-factor R&D commenced in late • Potential for transformative care as a 1990s, e.g. bi-specific and anti-TFPI programs multi-year treatment for certain patient segments • 15 years of know-how and extensive IP with dozens of patents • SHP654: 2017 Phase 1 clinical studies commence for Hemophilia A • Understanding impact of non-factor/factor co- administration on patient safety • SHP648: Pre-clinical for Hemophilia B • Continuing internal and external programs with bi-specific and other non-factor treatments Other Therapies
• SHP655: Phase 1 recombinant ADAMTS13 for hereditary TTP (thrombotic thrombocytopenic purpura)
24 Shire leading in Rare Hematology
LIFE PK MOMENT CURVE
SHP656 Non- RECOMBINATE Weekly factor rFVIII approaches CARE BLEEDS
SHP654 BEST IN SHP648 z SERIAL PERSONALIZED CLASS + Gene Tx PROPEL INNOVATION CARE PORTFOLIO
Broader impact of IMMUNATE FVIII HEMOFIL M ACTIVITY PHENOTYPES LEVELS
LIFESTYLE
25 Michael D. Tarantino, MD
Medical Director and President, Bleeding & Clotting Disorders Institute, Peoria, Illinois Professor of Pediatrics and Medicine, University of Illinois College of Medicine at Peoria The Physician’s Perspective on Personalized Care for Hemophilia
Michael Tarantino, MD Treating hemophilia means understanding the distinct needs of the patient community
Hemophilia Proper diagnosis and treatment planning Complex decision care is making warrants a Clinical characteristics and patient-related factors multifactorial personalized approach 1 Variability throughout life stages to optimize outcomes
1. National Hemophilia Foundation-McMaster University Guideline on Care Models for Hemophilia Management. Haemophilia 2016. 28 Each patient is unique and requires a highly individualized approach
Inter-patient variability warrants an individualized approach that addresses patient activity, lifestyle, and potential acute events to properly protect against bleeds1,2
160 ADVATE 100 PK Care Activity BAX 855 60 Parameters Goals Levels 40 dL ]
20 Bleed Age Lifestyle Phenotype 3 Factor VIII Activity [IU/ Joint Status
0 6 12 24 32 48 56 72 96 Time [h]
1. Valentino LA, et al. Haemophilia. 2014 29 2. Konkle et al. Blood 2015. Clinicians need options that build on proven concepts, can be trusted and reliable
Factor therapy, use of prophylaxis1 have revolutionized the Considerations for treatment of hemophilia2 future care: Patients have benefited from improved quality of life, decreased morbidity, and increased life expectancy2 1 Opportunities remain to improve care and address 45 Comparison of annualized bleeding rates persistent unmet needs 3 40 (ABRs) between treatment regimens 35 2 Innovation is important
30 On-Demand and requires reliable, 25 Prophylaxis sustainable solutions
20
15 3 Safety and efficacy must 10 not be compromised by 5 convenience or 0 All Joint Non-Joint All Joint Non-Joint All Joint Non-Joint non-outcomes-related All Etiologies Spontaneous Etiologies Traumatic Etiologies attributes
1. Srivastava A et al. Haemophilia. 2013. 2. Franchini M, Mannucci PM. Semin Thromb Hemost. 2014. 30 3. Valentino et al. J Thromb Haemost . 2012 New generations of care for hemophilia are reaching zero bleeds with a personalized approach
Significant strides have been made with safe, effective regimens, but the community seeks new options that build on success of factor replacement therapy
Hemophilia treatment parameters are complex and evolve over the course of the patient’s life
New options should build on the success of the treatment paradigm of factor replacement
31 Shire’s Leadership in Rare Hematology
Kim Stratton Head International Commercial Shire leading Rare Hematology
Shire leads this Shire has 3 key Shire has best in Shire is a dynamic market growth drivers class portfolio serial innovator
. Large global . Drive diagnosis & . ADVATE family will . Upgrade current brands dynamic market with prophylaxis in remain the gold growth of 3-5% developing markets standard therapy for . Drive personalization Hemophilia A with Shire medical . Shire is the leader . Drive prophylaxis devices & trough studies with longest & personalization . FEIBA and Immune heritage, broadest in developed Tolerance Induction . Develop portfolio & leading markets (ITI) will continue to transformational market share of be the treatment of therapies, e.g. gene . 36% Geographic & choice for vast therapies portfolio expansion majority of inhibitor with +100 launches patients across +40 countries 33 Thank you
34 Thank you
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