FOR IMMEDIATE RELEASE

FOR IMMEDIATE RELEASE FOR UK MEDICAL AND TRADE MEDIA ONLY Takeda Presents Data from TOURMALINE-MM1 Study for Ixazomib, the First and Only Once-Weekly Oral Proteasome Inhibitor Studied in Phase III Clinical Trials in Patients with Relapsed and / or Refractory Multiple Myeloma Data is being presented at the American Society of Hematology (ASH) Annual Meeting in Florida on Monday 7 th December 2015 at 19.45 GMT (Abstract #727) Additional Presentation: Phase 2 Results from an Investigational Study of Ixazomib plus Cyclophosphamide and Low-Dose Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma (Abstract #26) High Wycombe, UK, Sunday 6 th December 2015 Takeda Pharmaceutical Company Limited today announced results from the TOURMALINE-MM1 trial presented at the 57 th Annual Meeting and Exposition of the American Society of Hematology (ASH), showing that treatment with ixazomib capsules is effective in extending progression free survival (PFS) with a manageable tolerability profile in patients with relapsed and / or refractory multiple myeloma. The TOURMALINE-MM1 trial is an international, randomised, double-blind, placebo-controlled Phase III clinical trial designed to evaluate once-weekly oral ixazomib plus lenalidomide and dexamethasone compared to placebo plus lenalidomide and dexamethasone. Ixazomib was recently approved by the U.S. Food and Drug Administration (FDA) in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. The approval was based on the Phase III TOURMALINE-MM1 data, which included 8 clinical trial centres in the UK. Ixazomib is currently under review by the European Medicines Agency (EMA) and was granted an accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP). The TOURMALINE-MM1 data were highlighted at today s ASH press briefing and will be presented in full on the afternoon of Monday 7 th December 2015. Ixazomib data will be featured in 18 presentations at this year s ASH meeting, including an oral presentation of Phase II data from an investigational study evaluating the all-oral combination of ixazomib plus cyclophosphamide and low-dose dexamethasone (ICd) in newly diagnosed multiple myeloma patients. 1

The data presented at ASH this year are the first major output from the comprehensive ixazomib clinical trial program, TOURMALINE, demonstrating Takeda s ongoing commitment to providing effective and convenient treatment options for patients with multiple myeloma, said Andy Plump, M.D., Ph.D, Takeda Chief Medical and Scientific Officer. The breadth and depth of the TOURMALINE program allows us to gather important data across a broad range of patients that live with multiple myeloma and to expand on the efficacy and safety profile of our oral proteasome inhibitor, ixazomib. We will continue this and other important clinical trials and look forward to sharing results over the next few years. The comprehensive Phase III ixazomib clinical development programme, TOURMALINE, includes a total of five pivotal trials four investigating every major multiple myeloma patient population and one in lightchain amyloidosis. Ixazomib, an Investigational Oral Proteasome Inhibitor (PI), in Combination with Lenalidomide and Dexamethasone (IRd), Significantly Extends Progression-Free Survival (PFS) for Patients (Pts) with Relapsed and/or Refractory Multiple Myeloma (RRMM): The Phase 3 Tourmaline-MM1 Study (Abstract #727) TOURMALINE-MM1 (n=722) is the first double-blind, placebo-controlled trial with a proteasome inhibitor and has met the primary endpoint at the first interim analysis. Trial results demonstrate a statistically significant (35%) improvement in PFS, with patients treated in the ixazomib arm living for a significantly longer time without their disease worsening compared to patients in the control arm (20.6 months vs 14.7 months in control group; Hazard Ratio [HR] 0.742; p=0.012). Overall response rate (ORR) was 78.3% in the ixazomib arm and median duration of response was 20.5 months, vs 71.5% and 15 months in the control group. Median PFS in high-risk patients (HR 0.543; HR 0.596 in patients with del(17p)) was similar to that in the overall patient population and in standard-risk patients. Adverse events observed with IRd were consistent with reported safety profiles for the individual agents. The most common gr 3 adverse events included neutropenia, anemia, thrombocytopenia and pneumonia. Gastrointestinal events included diarrhoea, nausea and vomiting. Peripheral neuropathy (PN) rates were 28% in the IRd arm vs 21% in the control arm, 35% vs 21% had rash events, 8% vs 10% had acute renal failure and 4% vs 3% had heart failure. 1 Approximately 4,800 people each year in the UK are diagnosed with Multiple Myeloma (MM) with the disease affecting more men than women. It is the second most common form of blood / bone marrow cancer. 2 2

Treatment advancements over the last decade have meant that 5-year survival rates in MM are increasing at the fastest rate among all cancer types in the UK. 3 However, MM remains an incurable cancer and new and / or improved treatments continued to be needed to extend life expectancy and improve quality of life. Professor Graham Jackson, Consultant Haematologist, Newcastle Hospitals NHS Foundation Trust said: The data from the TOURMALINE-MM1 trial is significant for multiple myeloma patients in the UK, as it shows that ixazomib, a once weekly oral proteasome inhibitor, plus lenalidomide and dexamethasone, is effective in extending progression free survival. In addition, as it is an all-oral triplet regimen, it could reduce the burden of treatment on these patients and be taken at home. The trial itself is particularly interesting as it included a number of patient groups where there are significant unmet needs, for example older patients, patients with moderate renal impairment, light chain disease and high risk cytogenetics. Professor Gordon Cook, Professor of Haematology at the St James's Institute of Oncology, Leeds and Chair of the UK Myeloma Research Alliance commented: The interim analysis of the TOURMALINE MM-1 study has shown a significant advantage in durability of response with the addition of ixazomib to lenalidomide and dexamethasone for patients with previously treated myeloma. In particular, the early analysis shows that patients with high risk disease are offered similar clinical benefits as standard risk disease, which could impact on the clinical care landscape. These results offer significant clinical benefit that we hope to be able to bring to the clinic in the UK soon. Eric Low, Chief Executive of Myeloma UK, said: These results are very exciting for patients. The improvement in progression free survival in this difficult-to-treat stage of myeloma is extremely significant. In addition, its ability to work well in the sub-group of patients with high-risk disease, its relatively low sideeffect profile and its oral administration means that ixazomib will be a very welcomed addition to the treatment armoury for this serious and complex cancer. The TOURMALINE-MM1 trial is currently ongoing. Patients continue to be treated to progression in this trial and will be evaluated for long-term outcomes. Randomized Phase 2 Study of the All-Oral Combination of Investigational Proteasome Inhibitor (PI) Ixazomib Plus Cyclophosphamide and Low-Dose Dexamethasone (ICd) in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) Who Are Transplant-Ineligible (Abstract #26) Takeda also presented preliminary data from an open-label, multi-centre, Phase II study that investigates the all-oral triplet combination of ixazomib plus cyclophosphamide and low-dose dexamethasone (ICd) as 3

a first line therapy for patients not eligible for transplant. Preliminary data demonstrated comparable activity across treatment arms with a manageable toxicity profile in line with previous ixazomib studies and with manageable myelosuppression. This is the first study to assess ICd for the frontline treatment of multiple myeloma. The Phase II study (n=70) randomized patients receiving ixazomib, low-dose dexamethasone and two different doses of cyclophosphamide 300 mg/m 2 (ICd-300, n=36) or 400 mg/m 2 (ICd-400, n=34), with a mean duration follow-up of 7.0 months in both arms. Preliminary results across treatment arms demonstrated best unconfirmed complete response plus very good partial response (CR+VGPR) of 27% (ICd-300) and 23% (ICd-400), as well as early overall response rates (ORR) of 80% (ICd-300) and 73% (ICd-400). Toxicity was manageable in both the ICd-300 and ICd-400 arms, but toxicity rates appeared higher with ICd-400. Thrombocytopenia events occurred in 5 patients (no gr 3) in the ICd-300 arm and 4 patients (3 gr 3) in the ICd-400 arm. Most common adverse events (>15% all patients) included anemia, neutropenia, nausea, PN, diarrhoea, vomiting, constipation and fatigue. Most common gr 3 adverse events were neutropenia, anemia and pneumonia; no Grade 3 PN was observed. 4 NOTES TO EDITORS About ixazomib capsules Ixazomib is the first and only oral proteasome inhibitor approved by the U.S. Food and Drug Administration (FDA) in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Ixazomib is administered orally, once-weekly on days 1, 8, and 15 of a 28-day treatment cycle. Ixazomib is currently under review by the European Medicines Agency (EMA) and was granted an accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP). Ixazomib also received Breakthrough Therapy status by the U.S. FDA for relapsed or refractory systemic light-chain (AL) amyloidosis, a related ultra-orphan disease, in 2014. About the TOURMALINE clinical development programme The TOURMALINE clinical development programme further reinforces Takeda s ongoing commitment to developing innovative therapies for people living with multiple myeloma worldwide and the healthcare professionals who treat them. Five global Phase III trials are ongoing across a number of UK trial centres: TOURMALINE-MM1, investigating ixazomib vs placebo, in combination with lenalidomide and dexamethasone in relapsed and / or refractory multiple myeloma TOURMALINE-MM2, investigating ixazomib vs placebo, in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma 4

TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed multiple myeloma following induction therapy and autologous stem cell transplant (ASCT) TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed multiple myeloma who have not undergone ASCT TOURMALINE-AL1, investigating ixazomib plus dexamethasone vs physician choice of selected regimens in patients with relapsed or refractory AL amyloidosis In addition to the TOURMALINE programme, a large number of investigator initiated studies are evaluating ixazomib for patients globally. About Multiple Myeloma Multiple myeloma is a cancer of the plasma cells, which are found in the bone marrow. In multiple myeloma, a group of plasma cells, or myeloma cells, becomes cancerous and multiplies, increasing the number of plasma cells to a higher than normal level. Because plasma cells circulate widely in the body, they have the potential to affect many bones in the body, possibly resulting in compression fractures, lytic bone lesions and related pain. Multiple myeloma can cause a number of serious health problems affecting the bones, immune system, kidneys and red blood cell count, with some of the more common symptoms including bone pain and fatigue, a symptom of anaemia. Multiple myeloma is a rare form of cancer, with approximately 4,800 people diagnosed with myeloma every year in the UK. 2 About Takeda Located in Osaka, Japan, Takeda (TSE: 4502) is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for people worldwide through leading innovation in medicine. Additional information about Takeda UK is available through its corporate website, www.takeda.co.uk. Contacts: UK media contacts Cressida Ward Cressida.Ward@takeda.com +44(0)1628 537936 Mark Seymour mark@rmeclipse.com +44 (0)779 158 4373 5

References 1. Abstract #727 Presented at American Haematology Society Annual Meeting. Available at: https://ash.confex.com/ash/2015/webprogram/paper79829.html. Accessed December 2015. 2. Myeloma UK. Facts and Figures. Available at: http://www.myeloma.org.uk/information/what-is-myelomafacts-and-figures/. Accessed December 2015. 3. Cancer Research UK. Myeloma incidence statistics. Available at: http://www.cancerresearchuk.org/health-professional/cancerstatistics/statistics-by-cancer-type/myeloma/incidence#heading-eight. Accessed December 2015. 4. Abstract #26 Presented at American Haematology Society Annual Meeting. Available at: https://ash.confex.com/ash/2015/webprogram/paper80099.html. Accessed December 2015. 6