Traditional Process

1. TraditionalProcess Japan U.S.A. IND in Japan IND in the U.S. First in Human First in Human Single Ascending Dose Single Ascending Dose Multiple Ascending Dose Multiple Ascending Dose Phase II Phase II Phase III Phase III NDA in Japan NDA in the U.S.

2. Japanese Bridging Strategy Japan U.S.A. West Coast Clinical Trials (as a one stop shop for Phase I studies) • Skip Phase I Studies in Japan • Cost down • Shorten timeline to NDA IND in the U.S. First in Human First in Human Single Ascending Dose Single Ascending Dose Multiple Ascending Dose Multiple Ascending Dose Japanese Bridging Phase IIa Phase IIa Phase III Phase III NDA in Japan NDA in the U.S.

3. Multi-Ethnic Bridging Strategy U.S.A. Japan / Korea / Taiwan China West Coast Clinical Trials IND in the U.S. • Skip Phase I Studies in Japan, Korea, and Taiwan • Cost down • Shorten timeline to NDA in Japan, Korea and Taiwan Include Chinese NDA in your global strategy without delay (After negotiation with SFDA, it is possible to concurrently conduct a required Chinese Phase I and Global Phase III study in China) FIH SAD Japanese PMDA accepts a NDA as long as approximately 15% of entire patient population in the global study is Asian (Chinese, Japanese, Korean, and Taiwanese). MAD Chinese/Japanese/Korean Bridging Study IND in Japan, Korea, and Taiwan Phase II Phase II in Japan, Korea, and Taiwan Phase I in China Global Phase III (1) include Chinese, Japanese, Korean, and Taiwanese patients in the strategy NDA in the U.S. & Europe NDA in Japan NDA in Korea NDA in Taiwan NDA in China