Kyowa Hakko Kirin Co : Kyowa Hakko Kirin Announces Temporary Suspension of Patient Enrollment for Phase 3 Clinical Study of ARQ 197 (Tivantinib) in Combination with Erlotinib in Non-Small-Cell Lung Cancer Patients

August 30, 2012

Tokyo, Japan, August 30, 2012--- Kyowa Hakko Kirin Co., Ltd., ("Kyowa Hakko Kirin")
announced the temporary suspension of patient enrollment in an international phase 3 clinical
(ATTENTION) study evaluating the combination of ARQ 197 (tivantinib) and erlotinib in
patients with advanced or metastatic non-small-cell lung cancer in Asia (Japan, Korea, and
Taiwan) according to the recommendations by Safety Review Committee
This study is a randomized, double-blinded trial comparing ARQ197 and erlotinib to placebo and erlotinib. Patient enrollment has been suspended based on the higher frequency of
interstitial lung disease cases in the study as one of drug-related adverse reactions.
Non-small-cell lung cancer is a disease that new drugs with remarkable efficacy and safety
are expected and Kyowa Hakko Kirin will make further investigations to find out a possibility to resume the study.
Kyowa Hakko Kirin signed a license agreement with ArQule for the exclusive rights to the development and sales of ARQ 197 in Japan and some parts of Asia (China, Korea, and Taiwan) on April 27th, 2007.

ATTENTION is an abbreviation of Asian Trial of Tivantinib plus Erlotinib vs. Erlotinib for

NSCLC without EGFR Mutation. Please see below for details.

< http://www.kyowa-kirin.co.jp/english/news/2011/e20110809_01.html>

ARQ 197 is an orally administered low molecular weight compound discovered by ArQule, which selectively inhibits c-Met (receptor tyrosine kinase). c-Met is a hepatocyte growth factor receptor with a high level of expression and activity in a wide variety of solid cancers. The expression of c-Met is reported as being related to the infiltration and metastasis of cancer and correlated with the malignancy of cancer.

Erlotinib is an orally administered molecularly targeted drug that selectively inhibits tyrosine kinase in epidermal growth factor receptors. It is indicated for non-small-cell lung cancer and
marketed under the brand name Tarceva®.

Lung cancer can be categorized into two major categories: small cell lung cancer and non-small-cell lung cancer. Non-small-cell lung cancer can be further categorized into squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. This clinical study is conducted with non-small-cell carcinoma, excluding squamous cell carcinoma, as the indication.

Safety Review Committee is established to evaluate the safety data of the study. The committee will investigate the safety data independent of the sponsor and give an advice(s) to the sponsor.

Interstitial lung disease is a disease which belongs to a diffuse lung disease and its primary lesions are of a pathological change in alveolus interstitium (alveolus wall) or peribronchial interstitium. It causes
It causes inflammation, increase of collagen etc. leading to thickened wall.
Interstitial pneumonia causes a symptom of breathing difficulty, fever, and dry cough. When the disease progresses, lung will become fibrotic, be small and hardened. If this fibrosis takes place extensively, dyspnea may occur leading to the death.

ArQule is a biotechn ology company in th e United Stat es eng a ged in the research and devel opme nt of next-g eneratio n, small molecule cancer ther ape utics.
URL: http://www.arqule.com/

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