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Millennium: The Takeda Oncology Company with its parent company Takeda Pharmaceutical Company Limited (TSE:4502) today announced results from two arms of a phase I clinical trial of ADCETRIS (brentuximab vedotin) in combination with chemotherapy for the treatment of newly diagnosed mature T-cell lymphoma (MTCL) patients, including patients with systemic anaplastic large cell lymphoma (sALCL). These data were presented at the 54^th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012 in Atlanta, GA. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30. ADCETRIS is not approved for use in the front-line treatment of MTCL.

This three arm phase I, open-label, multicenter study was designed to determine the safety and activity of sequential and combination treatment approaches of ADCETRIS with CHOP¹ or CH-P chemotherapy in newly diagnosed patients with CD30-positive mature T- and NK- cell lymphomas. Data evaluating ADCETRIS in sequence with CHOP in patients with newly diagnosed sALCL were previously presented at the ESMO 2012 Congress (European Society for Medical Oncology).

In arms two and three of the trial, newly diagnosed patients received up to six cycles of ADCETRIS every three weeks in combination with CH-P. Patients who achieved at least a partial remission (PR) after completing the six cycles of combination therapy were eligible to receive continued single-agent ADCETRIS for up to a total of sixteen 3-week cycles. The primary endpoints of the trial included defining maximum tolerated dose of ADCETRIS in combination with CH-P and evaluating safety. The secondary endpoints were investigator assessment of response, progression-free survival (PFS) and overall survival (OS).

“We are encouraged by the results of this trial investigating ADCETRIS in patients diagnosed with these aggressive types of lymphoma, including systemic anaplastic large cell lymphoma,” said Tim Illidge, M.D., Professor of Targeted Therapy and Oncology, University of Manchester, UK. “These data are sufficiently compelling to support evaluating the ADCETRIS-containing regimen in a large randomized trial against the standard of care.”

Brentuximab Vedotin Administered Concurrently with Multi-Agent Chemotherapy as Front-line Treatment of ALCL and Other CD30-Positive Mature T-Cell and NK-Cell Lymphomas (Abstract #60)

Data were reported on 26 previously untreated patients who received ADCETRIS concurrently with CHP. Nineteen patients had sALCL, and seven patients had a diagnosis of another subtype of mature T- or NK-cell lymphoma. Patients received 1.8 milligrams per kilogram (mg/kg) of ADCETRIS every three weeks concomitantly with standard-dose CHP. The median age of patients across all treatment arms was 55.5 years. Key findings, which were highlighted in an oral presentation at ASH by Michelle Fanale, M.D., Assistant Professor in the Department of Lymphoma/Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, include:

• At the time of presentation, 16 of 26 patients (61 percent) were continuing therapy with single-agent ADCETRIS and two patients (8 percent) experienced disease progression. The remaining eight patients (31 percent) discontinued therapy.
• The maximum tolerated dose of ADCETRIS in combination with CHP was not exceeded at 1.8 mg/kg.
• The most common treatment-emergent adverse events occurring in more than 30 percent of patients were nausea (62 percent), peripheral sensory neuropathy (62 percent), diarrhea (58 percent), fatigue (54 percent), alopecia (46 percent) dyspnea (38 percent), constipation (35 percent) cough (35 percent) and febrile neutropenia (31 percent).
• Adverse events with a severity of Grade 3 or higher occurred in more than 5 percent of patients and included febrile neutropenia (23 percent), nausea (8 percent) neutropenia (8 percent), peripheral sensory neuropathy (8 percent), pulmonary embolism (8 percent), hyperglycemia (8 percent), and respiratory failure (8 percent). Five patients discontinued therapy due to an adverse event.
• All 26 patients (100 percent) achieved an objective response after either completing six cycles of combination therapy or at the latest assessment for three patients who discontinued treatment prior to cycle six. Twenty-three patients (88 percent) achieved a CR and three patients (12 percent) achieved a PR.
• Among the seven non-sALCL patients, 100 percent achieved a CR with combination therapy, including two patients with PTCL – not otherwise specified (PTCL-NOS), two patients with angioimmunoblastic T-cell lymphoma, two patients with adult T-cell leukemia/lymphoma and one patient with enteropathy-associated T-cell lymphoma.

A phase III clinical trial of ADCETRIS in CD30-positive MTCL patients is planned to compare PFS in patients receiving ADCETRIS in combination with CHP to patients receiving CHOP alone. The trial is expected to begin by late 2012 or early 2013.

About ADCETRIS

ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL):

1. following autologous stem cell transplant (ASCT) or

2. following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option.

ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).

ADCETRIS was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in August 2011 for two indications: (1) the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS. ADCETRIS has not been approved for use in any front-line setting.

Seattle Genetics and Millennium are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where the Takeda Group is solely responsible for development costs.

About T-Cell Lymphomas

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphomas are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes. The World Health Organization identifies 22 subtypes of mature T- and NK-cell neoplasms, including systemic ALCL which is an aggressive type of T-cell non-Hodgkin lymphoma that expresses CD30. Other mature T-cell lymphomas include PTCL, angioimmunoblastic T-cell lymphoma and adult T-cell lymphoma.

About Millennium

Millennium: The Takeda Oncology Company , a leading biopharmaceutical company based in Cambridge, Mass., markets a first-in-class proteasome inhibitor in the US, and has a robust clinical development pipeline of global product candidates. Millennium Pharmaceuticals, Inc. was acquired by Takeda Pharmaceutical Company Ltd. in May, 2008. The Company’s research, development and commercialization activities are focused in oncology. Additional information about Millennium and Takeda are available through their respective websites, http://www.millennium.com and http://www.takeda.com.

About Takeda Pharmaceutical Company Limited

Located in Osaka, Japan, Takeda 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 patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate Website, www.takeda.com.

¹ cyclophosphamide, doxorubicin, oncovin, prednisone

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