On June 30, 2017 Pfizer Inc. (NYSE:PFE) reported that the European Commission has approved BESPONSA (inotuzumab ozogamicin) as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL) (Press release, Pfizer, JUN 30, 2017, View Source [SID1234519739]). This indication includes treatment of adults with Philadelphia chromosome positive (Ph+) as well as Philadelphia chromosome negative (Ph-) relapsed or refractory B-cell precursor ALL. Adults with Ph+ relapsed or refractory CD22-positive B-cell precursor ALL should have failed treatment with at least one tyrosine kinase inhibitor (TKI). With this approval, BESPONSA becomes the first and only antibody drug conjugate (ADC) available for patients with this type of leukemia in the European Union (EU).

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"The European Commission’s approval of BESPONSA represents an important milestone for patients, the oncology community and Pfizer," said Andreas Penk, M.D., regional president, Pfizer Oncology. "This is the first approval for BESPONSA and provides patients in the EU, who are battling an especially hard-to-treat leukemia, with a new treatment option beyond chemotherapy."

ALL is an aggressive type of leukemia that can be fatal within a matter of months if left untreated.1 The goal of treatment in relapsed or refractory (resistant) ALL is to achieve complete remission without excessive toxicity so patients may proceed to additional therapeutic intervention, particularly stem cell transplant, which is the most recognized option to prolong patient survival, maintenance therapy or other therapy.2 In adult patients with relapsed or refractory ALL, median overall survival is just three to six months.3,4,5 The current standard of care is intensive chemotherapy6, which is effective in less than 50 percent of relapsed or refractory patients and associated with poor long-term survival, high toxicities, lengthy inpatient stays and continuous infusions.7

"Acute lymphoblastic leukemia that has recurred or is refractory following first-line therapy is a rare and rapidly progressive disease with poor prognosis," said Professor David Marks, Department of Hematology, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom. "The approval of BESPONSA (inotuzumab ozogamicin) provides a much needed treatment option for physicians and patients alike, that may help improve outcomes for some of the most vulnerable leukemia patients in Europe."

The European Commission’s approval of BESPONSA is supported by results from the Phase 3 INO-VATE ALL trial, in which 326 adult patients with relapsed or refractory B-cell precursor ALL were enrolled and which compared BESPONSA to standard of care chemotherapy. The INO-VATE ALL study had two primary endpoints, complete response with or without hematologic recovery (CR/CRi) and overall survival (OS). Results from the trial were published in The New England Journal of Medicine in June 2016.

In the U.S., BESPONSA received Breakthrough Therapy designation from the Food and Drug Administration (FDA) in October 2015 for ALL. A Biologics License Application (BLA) for BESPONSA for the treatment of adult patients with relapsed or refractory B-cell precursor ALL was accepted for filing and granted Priority Review by the FDA in February 2017. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is August 2017.

With a growing hematology pipeline, Pfizer is committed to extending therapeutic progress in acute and chronic leukemias that leverage select pathways and mechanism of actions (MOAs). Specifically, our investigational products aim to treat some of the hardest to treat leukemias and lymphomas including, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and mantle cell lymphoma (MCL).

Indication for BESPONSA (Inotuzumab Ozogamicin) in the EU

BESPONSA is approved as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor ALL in the EU. Adult patients with Ph+ relapsed or refractory B-cell precursor ALL should have failed treatment with at least one TKI.

Important Safety Information for BESPONSA (Inotuzumab Ozogamicin) in the EU

The most common (≥ 20%) adverse reactions associated with BESPONSA were thrombocytopenia (51%), neutropenia (49%), infection (48%), anaemia (36%), leukopenia (35%), fatigue (35%), haemorrhage (33%), pyrexia (32%), nausea (31%), headache (28%), febrile neutropenia (26%), increased transaminases (26%), abdominal pain (23%), increased gamma-glutamyltransferase (21%), and hyperbilirubinaemia (21%).

The most common (≥ 2%) serious adverse reactions associated with BESPONSA were infection (23%), febrile neutropenia (11%), haemorrhage (5%), abdominal pain (3%), pyrexia (3%), veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) (2%), and fatigue (2%).

In the Phase 3 INO-VATE ALL trial (N=164 patients treated with BESPONSA), VOD/SOS was reported in 22 (13%) patients including 5 (3%) patients during study therapy or in follow-up without an intervening hematopoietic stem cell transplant (HSCT). Among the 77 patients who proceeded to a subsequent HSCT (6 of whom received additional salvage therapy after treatment with BESPONSA before proceeding to HSCT), VOD/SOS was reported in 17 (22%) patients. Five of the 17 VOD/SOS events that occurred post-HSCT were fatal.

VOD/SOS was reported up to 56 days after the last dose of BESPONSA without an intervening HSCT. The median time from HSCT to onset of VOD/SOS was 15 days (range: 3-57 days). Of the 5 patients who experienced VOD/SOS during treatment with BESPONSA but without an intervening HSCT, 2 patients had also received an HSCT before BESPONSA treatment.

Among patients who proceeded to HSCT after BESPONSA treatment, VOD/SOS was reported in 5/11 (46%) patients who received an HSCT both prior to and after BESPONSA treatment and 12/66 (18%) patients who only received an HSCT after BESPONSA treatment.

The EU Summary of Product Characteristics (SmPC) is available at View Source

About BESPONSA (Inotuzumab Ozogamicin)

BESPONSA is an antibody-drug conjugate (ADC) comprised of a monoclonal antibody (mAb) targeting CD22, a cell surface antigen expressed on cancer cells in almost all B-ALL patients, linked to a cytotoxic agent.8 When BESPONSA binds to the CD22 antigen on B-cells, it is internalized into the cell, where the cytotoxic agent calicheamicin is released to destroy the cell.9

BESPONSA originates from a collaboration between Pfizer and Celltech, now UCB. Under the terms of this agreement, Pfizer has sole responsibility for all manufacturing and clinical development activities for this molecule. Pfizer also collaborated with SFJ Pharmaceuticals Group (SFJ) on the registrational program (INO-VATE ALL) for BESPONSA.

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On June 29, 2017 CANCER RESEARCH TECHNOLOGY (CRT) reported that it has signed a further deal with Merck, a leading science and technology company, to discover new cancer drugs targeting the Hippo pathway, today (Thursday) (Press release, Cancer Research Technology, 29 29, 2017, View Source [SID1234523164]).

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The extension to this alliance follows a successful one-year target validation and drug discovery feasibility partnership between CRT’s Discovery Laboratories (CRT-DL) in London and Cambridge and Merck at Darmstadt in Germany.

In conjunction with Cancer Research UK’s network of key academic scientists, led by Dr Nic Tapon and Dr Barry Thompson, based at the Francis Crick Institute in London, the alliance has developed a better understanding of the role of the Hippo pathway in cancer, and how best to drug key targets.

In healthy cells the Hippo pathway regulates cell size, controlling the growth of tissues during development and regeneration. But, abnormal activation of proteins controlled by the Hippo pathway has been linked to the development of a range of cancers, making it an attractive area for the discovery of novel therapies.

The partnership has now moved into full drug discovery with the aim of eventually identifying molecules to take into preclinical studies and clinical trials. Dr Tapon will remain a key participant in the alliance moving forwards.

CRT will receive royalties and milestone payments from the deal to be invested into Cancer Research UK’s lifesaving research.

Dr Iain Foulkes, Cancer Research Technology’s chief executive, said: "The extension and expansion of this alliance showcases the success of Cancer Research Technology’s Discovery Laboratories drug discovery approach in moving forward exciting new approaches to cancer therapy. We’ve brought together leading academics in the field and industry to build on world-class research, and we’re now focused on developing these early projects for the benefit of cancer patients."

Dr Hamish Ryder, Cancer Research Technology’s director of drug discovery, said: "This important research highlights our expertise in applying translational thinking to novel, very early stage science."

On June 29, 2017 Cytovation AS, a privately held biotech company developing CyPep-1 for the treatment of skin disorders, reported that it has raised NOK 20m in a private funding round. The financing was led by a group of private investors in Norway and the Company will use these funds to advance lead product CyPep-1 into a Phase I clinical trial (Press release, Cytovation, JUN 29, 2017, View Source [SID1234561558]).

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Cytovation is developing CyPep-1, a peptide consisting of 27 amino acids that selectively targets cutaneous warts through the destruction of the cell membrane and creating an immune response through the release of antigens. These funds will enable Cytovation to conduct pre-clinical toxicology studies and GMP manufacturing of CyPep-1 as a topical cream for the treatment of warts caused by the human papilloma virus (HPV). This is a completely novel treatment strategy to treat a common disease which has already undergone extensive testing and quality control and also has applications in other dermatological diseases.

Cytovation’s CEO, Kjell Inge Arnevig, commented on the financing: "We have been encouraged by the continuing support of our new and existing investors. These funds will allow us to move through toxicology studies and formulation towards our planned Phase I clinical trial for CyPep-1 with initial results expected during 2018."

June 28, 2017 141 st Ordinary General Meeting of Shareholders Christophe Weber President & CEO 1 Important Notice Forward ‐ Looking Statements This presentation contains forward ‐ looking statements regarding Takeda’s future business, financial position and results of operations, including estimates, forecasts, targets and plans. These forward ‐ looking statements may be identified by the use of forward ‐ looking words such as "aim," "anticipate," "assume," "believe," "continue," "endeavor," "estimate," "expect," "forecast," "initiative," "intend," "may," "outlook," "plan," "potential," "probability," "pro ‐ forma," "project," "risk," "seek," "should," "strive," "target," "will" or similar words, or expressions of the negative thereof, or by discussions of strategy, plans or intentions. Any forward ‐ looking statements in this document are based on the current assumptions and beliefs of Takeda in light of the information currently available to it. Such forward ‐ looking statements do not represent any guarantee by Takeda or its management of future performance and involve known and unknown risks, uncertainties and other factors, including but not limited to: the economic circumstances surrounding Takeda’s business, including general economic conditions in Japan, the United States and worldwide; competitive pressures and developments; applicable laws and regulations; the success or failure of product development programs; decisions of regulatory authorities and the timing thereof; changes in exchange rates; claims or concerns regarding the safety or efficacy of marketed products or product candidates; and post ‐ merger integration with acquired companies, any of which may cause Takeda’s actual results, performance, achievements or financial position to be materially different from any future results, performance, achievements or financial position expressed or implied by such forward ‐ looking statements. Neither Takeda nor its management gives any assurances that the expectations expressed in these forward ‐ looking statements will turn out to be correct, and actual results, performance or achievements could materially differ from expectations. Any forward looking statements herein speak only as of the date of this document, and Takeda and its management undertake no obligation to update or revise any forward ‐ looking statements or other information contained in this presentation, whether as a result of new information, future events or otherwise. Medical Information This presentation contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drug including the ones under development. 2 Our mission is to strive towards Better Health and a Brighter Future for people worldwide through leading innovation in medicine Vision 2025 • We serve the needs of our patients, wherever they are. • We earn the trust of society and customers through Takeda ‐ ism. • We are recognized as best in class because of agility and innovation, qualities that help us build a steady pipeline and deliver growth, year on year. Mission Major trends shaping our business environment 3 Society Pharma industry Science & technologies advancing Unmet medical needs Demand for access to medicine Aging population Healthcare system under significant financial pressure Digital More scientific innovation Growth driven by innovation in the U.S. and by innovation and demand in EM More access to medicine in EM Pressure on drug prices and reimbursements Pharma industry’s reputation EM=Emerging markets 4 Value Driven: Takeda ‐ ism • Pa Ɵ ent → Trust → Reputa Ɵ on → Business Global, Agile, and Committed to Innovation • Created global organization and capabilities • Driving patient ‐ centricity and local empowerment • Therapeutic area focus: Oncology, GI, CNS, plus Vaccines World ‐ class Governance & Diverse Leadership • BOD with majority of external directors, and with Audit & Supervisory committee • Diverse & seasoned Takeda Executive Team • Comprehensive talent development programs Grow Portfolio Rebuild Pipeline Boost Profitability Transformation momentum is backed by Takeda’s values and culture GI=Gastrointestinal, CNS=Central Nervous System, BOD=Board of Directors Takeda’s Corporate Philosophy 5 Takeda ‐ ism will guide us to reach our Vision We take action and make decisions by focusing on our four priorities, in order of: Putting the patient at the center 1234 Building trust with society Reinforcing our reputation Developing the business Values Continue to commit to CSR, Access to Medicine and R&D initiatives for patients & people CSR programs Access to Medicines R&D initiatives Recent progress Global CSR programs 2017: Voted by employees Access to Medicine Our focus e.g.-Employee volunteer opportunities-Disaster Relief-x-z CSR=Corporate Social Responsibility 6 Environment, Health and Safety e.g.-Patient Assistance Programs-Access Accelerated e.g. Proposed Board of Directors for a best ‐ in ‐ class governance 7 Christophe Weber Representative Director President & CEO Masato Iwasaki Director, JPBU President Andrew Plump Director, Chief Medical & Scientific Officer Yasuhiko Yamanaka Director, A&SC member Shiro Kuniya External Director, Chair A&SC Koji Hatsukawa External Director, A&SC member Jean ‐ Luc Butel External Director, A&SC member Masahiro Sakane External Director Chair of the Board meeting Yoshiaki Fujimori External Director Toshiyuki Shiga External Director Emiko Higashi External Director Michel Orsinger External Director James Kehoe Director, Chief Financial Officer Internal directors External directors Audit & Supervisory Committee (A&SC) directors Compensation committee Chair Compensation committee Nomination committee Chair Nomination committee C C C C Developing our global workforce with around 30,000 employees in 74 countries 8 Takeda’s employee distribution Emerging markets 35% Japan 27% EUCAN 21% US 17% Note: March 2017 data excluding Wako Pure Chemical Industries (Europe + Canada) Global, Diverse and Experienced Takeda Executive Team (TET) 9 Giles Platford President EUCAN BU Thomas Wozniewski Global Manufacturing and Supply Officer Ramona Sequeira President US BU Gerard Greco Global Quality Officer Andrew Plump Chief Medical and Scientific Officer Christophe Bianchi President Global Oncology BU Rajeev Venkayya President Global Vaccine BU Christophe Weber President & CEO Masato Iwasaki President Japan Pharma BU James Kehoe Chief Financial Officer Haruhiko Hirate Corporate Communications and Public Affairs Officer Yoshihiro Nakagawa Global General Counsel David Osborne Global Human Resources Officer Ricardo Marek President EM BU U.S. JAPAN SINGAPORE SWITZERLAND BU=Business Unit 10 Transforming R&D: Therapeutic Area focus and footprint concentrated in Japan & U.S. Oncology GI Vaccine CNS Regenerative Medicine Vaccine U.S. Bushu Pharmaceuticals SCOHIA Partnership Research Engine Functional partnership Asset externalization Research site location Health Innovation Park at Shonan Japan CNS=Central Nervous System, GI=Gastroenterology All trademarks and registered trademarks are the property of their respective owners 11 Pipeline as of May 10, 2017 Investing heavily in our early pipeline, while maximizing the value of our marketed portfolio Phase 1 Phase 2 Phase 3 /Filed Life cycle management Oncology GI CNS Other Vaccines TAK ‐ 659 Hematologic malignancies TAK ‐ 931 Solid Tumors TAK ‐ 058 CIAS TAK ‐ 831 Schizophrenia, Ataxia TAK ‐ 020 RA TAK ‐ 906 Gastroparesis TAK ‐ 202 Solid Tumors TAK ‐ 243 Solid Tumors TAK ‐ 580 Solid Tumors TAK ‐ 954 Enteral Feeding Intolerance TAK ‐ 041 CIAS, Neg. symptoms TAK ‐ 653 TRD TAK ‐ 021 EV71 Vaccine TAK ‐ 079 RA CX601 Perianal Fistulas in CD AD ‐ 4833/ TOMM40 Delay of MCI TAK ‐ 003 Dengue Vaccine Relugolix Uterine Fibroids (JP), Endometriosis, Prostate Cancer NINLARO FL MM, Amyloidosis, Maint MM post ‐ SCT, Maint MM w/o SCT ALUNBRIG ALK+ NSCLC (EU), FL ALK+ NSCLC ICLUSIG CML, SL CML, Ph+ ALL ENTYVIO UC/CD, SubQ, GvHD, IO Colitis, H2H, PSC TRINTELLIX TM Cognition in MDD, MDD (JP), ADHD ADCETRIS FL HL, MTCL, CTCL Cabozantinib Solid Tumors (JP) TAKECAB ARD (Asia), NERD (JP) Rasagiline Parkinson’s disease (JP) AMITIZA Ped Constipation, New Formulation TAK ‐ 788 (AP32788) NSCLC TAK ‐ 071 LBD ‐ AD TAK ‐ 935 Epilepsy XMT ‐ 1522 HER2 positive Solid Tumors pevonedistat HR MDS sapanisertib RCC, Breast, Endometrial TAK ‐ 214 Norovirus Vaccine namilumab RA Late ‐ stage / Life cycle management 12 Enhance pipeline through collaborations and external innovation mainly focused on early stage Oncology GI CNS Value Creation Discovery / Preclinical Phase 1 Vaccines XMT ‐ 1522 TAK ‐ 788 (AP32788) TAK ‐ 906 TAK ‐ 954 TAK ‐ 094 TAK ‐ 792 TAK ‐ 233 TAK ‐ 935 Undisclosed TAK ‐ 272 Relugolix Cx ‐ 601 ALUNBRIG, ICLUSIG Cabozantinib Not all ‐ inclusive. All trademarks and registered trademarks are the property of their respective owners BARDA 13 Grow Portfolio • Underlying Revenue +6.9%, every region growing • Growth Drivers +14.7%, Entyvio 146.5 Bn yen Rebuild Pipeline • Significant progress in R&D transformation • Over 50 collaborations in 18 months Boost Profitability • Underlying CE growth: +24.2% • Underlying CE margin: +180 bps • ROE is recovering: 6.0% in FY16 (+2.1pp from FY15) FY2016 results reflect transformation success Note: • "Underlying growth" compares two periods of financial results on a common basis, showing the ongoing performance of the business excluding the impact of foreign exchange and divestitures from both periods • CE="Core Earnings" is calculated by taking reported Gross Profit and deducting SG&A expenses and R&D expenses. In addition, certain other items that are non ‐ core in nature and significant in value may also be adjusted • bps=basis point: one hundredth of a percent • ROE=Return on equity 14 ROE performance is recovering (%) Takeda’s historical ROE evolution 15.1 10.9 14.4 11.8 6.1 6.3 4.5-6.3 3.9 6.0 0% Actos settlement FY07 08 09 10 11 12 13 14 15 16 15 FY2017 and future outlook 16 Projecting strong underlying performance in FY2017 Underlying Revenue Underlying Core EPS Underlying Core Earnings FY2017 guidance (growth %) Low single digit Mid ‐ to ‐ high teen Low ‐ to ‐ mid teen Annual dividend per share 180 yen 17 +100 ‐ 200bps Underlying Core Earnings margin improvement every year driven by: Gross profit for ~50% Global Opex Initiative • Pay less • Buy less • Work better OPEX for ~50% R&D transformation + + + + ‐ Inflation and Investments ‐ Price pressure COGS improvement Product mix 18 Capital allocation priorities Internal investment in R&D and product launches Dividend as key component of shareholder returns Maintain investment grade credit rating Disciplined and focused M&A 1 2 3 4 19 Thank you

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