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CHICAGO & OSAKA, Japan

Takeda Pharmaceutical Company Limited (TSE:4502) today reported results from a Phase 1 study evaluating the safety, tolerability, and maximum tolerated dose (MTD) of MLN9708, the first investigational oral proteasome inhibitor in clinical trials. The study evaluated once a week oral dosing of single agent MLN9708 in patients with relapsed and/or refractory multiple myeloma (MM). These data were reported in an oral presentation during the annual meeting of the American Society of Clinical Oncology (ASCO), held May 31st to June 4th in Chicago, Illinois.

“Single agent MLN9708 showed promising responses in heavily pretreated patients with relapsed and/or refractory multiple myeloma. Responses were observed regardless of prior therapies, which included various proteasome inhibitors and immunomodulatory agents,” said Karen Ferrante, M.D., Head of the Takeda Oncology Therapeutic Area Unit. “These data further support the study of once a week oral MLN9708 in the three on-going global Phase 3 TOURMALINE trials of MLN9708.”

Weekly MLN9708, an investigational oral proteasome inhibitor, in relapsed/refractory multiple myeloma: Results from a phase I study after full enrollment (Abstract #8514)

This ongoing study evaluated MLN9708 in 60 MM patients who had received two or more prior therapies. The primary objectives were to determine the safety, tolerability and MTD of once a week MLN9708. Results from the dose-escalation and expansion cohorts presented by Shaji Kumar, M.D., included:

• Patients had received a median of four prior therapies;
  • 85 percent, 97 percent, 53 percent and 15 percent of patients had received prior VELCADE^®(bortezomib), lenalidomide, thalidomide and carfilzomib/marizomib respectively
  • 72 percent of patients were refractory to their last therapy
• The MTD has been determined at 2.97 mg/m² on a once a week dosing schedule
• Three patients experienced dose limiting toxicities (DLT)
  • One patient at 3.95 mg/m² experienced grade 3 nausea, vomiting and diarrhea and one patient experienced grade 3 erythema multiforme rash
  • One patient at 2.97 mg/ m² experienced grade 3 nausea, vomiting and diarrhea
  • All three patients continued on study at a lower dose
• Among 50 evaluable patients, an overall response rate (ORR) of 18 percent was observed, including one very good partial response (VGPR) and eight partial responses (PR)
• In the 31 response evaluable patients at the MTD, an ORR of 26 percent was achieved
• Across all cohorts, the most common drug-related adverse events of any grade were thrombocytopenia (43 percent), diarrhea and nausea (38 percent), fatigue (37 percent), vomiting (35 percent), decreased appetite (25 percent) neutropenia (22 percent) and peripheral neuropathy (20 percent)
• The most common drug-related adverse events of grade 3 or higher were thrombocytopenia (33 percent), neutropenia (18 percent), diarrhea (17 percent), lymphopenia and fatigue (8 percent), anemia, decreased appetite, and nausea (7 percent) leucopenia and vomiting (5 percent)
• Two patients died due to progressive disease
• Patients received a median of 2 cycles of therapy

Patients aged 18 years or older received MLN9708 on days 1, 8, and 15 of 28-day cycles. In the dose-escalation phase, patients were required to have ≥2 prior therapies (including bortezomib, thalidomide/lenalidomide, and corticosteroids).

About MLN9708

MLN9708 is an investigational oral, proteasome inhibitor, which is being studied in multiple myeloma and other malignancies. It is the first oral proteasome inhibitor to enter clinical trials. Three global Phase 3 trials are on-going; TOURMALINE-MM1, investigating MLN9708 in combination with lenalidomide and dexamethasone in relapsed and/or refractory MM, TOURMALINE-MM2, investigating MLN9708 in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM who are not eligible for transplantation, and TOURMALINE-AL1, investigating MLN9708 plus dexamethasone in patients with relapsed or refractory light chain amyloidosis (AL). For additional information on the ongoing Phase 3 studies please visit www.tourmalinetrialal1.com and www.tourmalinetrialmm1.com and http://clinicaltrials.gov/show/NCT01850524.

Editor’s Note: This press release is also available under the Media section of the Company’s website at: www.millennium.com/InTheNews.aspx.

About Takeda

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 people worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.