News Release

December 24, 2014
Taiho Pharmaceutical Co., Ltd.

Taiho Pharmaceutical Completes Submission of TAS-102 New Drug Application to the US Food and Drug Administration for the Treatment of Refractory Metastatic Colorectal Cancer

Taiho Pharmaceutical Co., Ltd. (HQ: Tokyo, President and Representative Director: Masayuki Kobayashi) announced that it has completed on December 19, 2014 its rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) for TAS-102 (nonproprietary names: trifluridine and tipiracil hydrochloride, brand name in Japan: "Lonsurf_® combination tablet T15, T20"), an oral combination anticancer drug under investigation for the treatment of refractory metastatic colorectal cancer (mCRC).

TAS-102 was granted Fast Track Designation on September 12, 2014, with the first sections of the rolling submission accepted by the FDA on October 16, 2014. Taiho Oncology's NDA submission is supported by the results from the Phase III RECOURSE trial of TAS-102 in 800 mCRC patients, whose disease had progressed after or who were intolerant to standard therapies. The TAS-102 RECOURSE trial met the primary efficacy endpoint of statistically significant improvement in overall survival versus placebo (HR = 0.68, p < />
About TAS-102
TAS-102 is an oral combination anticancer drug of trifluridine (FTD) and tipiracil hydrochloride (TPI). 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. TAS-102 was approved initially in Japan in March this year for the indications of "unresectable advanced or recurrent colorectal cancer (only if refractory to standard therapies)," based on the results of the Phase II clinical trial conducted in Japan, and launched in Japan in May under the brand name "Lonsurf_® combination tablet T15, T20".

About Metastatic Colorectal Cancer
Colorectal cancer is the third most common cancer worldwide. In 2014, it is estimated that 136,830 patients (71,830 men and 65,000 women) will be diagnosed with, and 50,310 patients will die from, cancer of the colon or rectum in the United States.ⁱ Colorectal cancer was the second most common cancer in Europe in 2012. In addition, it was estimated that 447,000 patients (242,000 men and 205,000 women) were diagnosed with and 215,000 patients died of colorectal cancer in Europe during 2012.ⁱⁱ
There are no definitive data on the number of patients who are refractory to standard metastatic colorectal cancer treatments.

i Cancer facts & figures 2014. American Cancer Society.
ii Ferlay, J. et. al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. European Journal of Cancer. 49; 1374-1403.