News Releases

Taiho Pharmaceutical Co., Ltd. of Tokyo announced on April 1 results from its Phase III TERRA study on its oral combination anticancer drug TAS-102 (product name in Japan and the US LONSURF^®, nonproprietary names: trifluridine (FTD) and tipiracil (TPI)) in Asian(China, South Korea and Thailand) patients with refractory metastatic colorectal cancer (mCRC). The TERRA study met its primary endpoint of demonstrating improvement in overall survival (OS) in patients with refractory mCRC whose disease had progressed after approved standard therapies. In this study, TAS-102 appeared to be generally well tolerated and its toxicities were consistent with what was previously reported.

More detailed results from this study will be presented at a future international academic conference.

The Taiho team is preparing for the NDAs of TAS-102 in Asian countries.

The TERRA study is a randomized, double-blind, placebo-controlled Phase III comparison study evaluating the efficacy and safety of orally administered TAS-102 in patients with refractory mCRC. The study enrolled 406 patients who received at least two prior regimens of standard chemotherapies for mCRC and were refractory to, or failed, those chemotherapies. The study was conducted in China, South Korea, and Thailand. Patients were randomly assigned to receive either TAS-102 or placebo in order to investigate the efficacy of TAS-102. The primary objective of the TERRA study was improvement in overall survival (OS) versus placebo. The principal researchers are Prof. Jin Li of Shanghai Tianyou Hospital and Fudan University Shanghai Cancer Center (China), Prof. Tae Won Kim of Asan Medical Center (Korea), Prof. Virote Sriuranpong of Chulalongkorn University & the King Chulalongkorn Memorial Hospital (Thailand).

In Asia, the incidence of colorectal cancer is increasing and colorectal cancer is the fourth most common cancer cause of death after lung cancer, hepatic cancer and gastric cancer. In 2012, it is reported that 331,600 people in Asia died from colorectal cancer.¹

LONSURF is currently available in Japan for the treatment of unresectable advanced or recurrent CRC and in the United States for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.^2,3 LONSURF is marketed by Taiho Pharmaceutical in Japan and by Taiho Oncology, Inc., a subsidiary of Taiho Pharmaceutical, in the U.S. In June 2015, Taiho Pharmaceutical entered into an exclusive license agreement with Servier for the co-development and commercialization of LONSURF. Under the terms of the agreement, Servier will commercialize LONSURF in Europe and other regions outside of the United States, Canada, Mexico and Asia. The application is currently under review by the European Commission after the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) where a positive opinion was adopted on February 25, recommending the granting of a marketing authorization for LONSURF^® (trifluridine/tipiracil) for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti EGFR agents.⁴ LONSURF is an oral combination anticancer drug of trifluridine (FTD) and tipiracil (TPI), whose primary mechanism of action differs from fluoropyrimidines. FTD is an antineoplastic nucleoside analog, which is incorporated directly into DNA, thereby interfering with the function of DNA. The blood concentration of FTD is maintained via TPI, which is an inhibitor of the FTD-degrading enzyme, thymidine phosphorylase.

1 http://globocan.iarc.fr/old/summary_table_pop-html.asp?selection=7967&title=Asia&sex=0&type=1&window=1&sort=2&submit=%A0Execute%A0 (analysed March 16th, 2016)

2 FDA News Release. FDA approves new oral medication to treat patients with advanced colorectal cancer. 22 September 2015. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm463650.htm Accessed March 2016

3 Taiho Pharmaceutical News Release. Taiho's Lonsurf® (trifluridine and tipiracil hydrochloride) Tablets Approved in Japan for Treatment in Advanced Metastatic Colorectal Cancer. Available at: http://www.taiho.co.jp/english/news/20140324.html Accessed March 2016

4 Committee for Medicinal Products for Human Use (CHMP) Summary of opinion. http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/003897/WC500202369.pdf