ArQule's tivantinib is a c-MET inhibitor in phase III for relapsed non-small cell lung cancer (NSCLC) patients with a non-squamous histology. While c-MET is a relatively new drug target, the recent approval of Pfizer's Xalkori, which inhibits ALK and c-MET, provides validation for tivantinib. In phase II testing, tivantinib showed evidence of anti-tumor activity when added to Tarceva, particularly among patients with a non-squamous histology. Thus this subset was chosen for further testing in phase III. This report reviews tivantinib’s pre-clinical and clinical evidence of activity, and the likelihood that it will succeed in late stage development. The report also discusses regulatory considerations, competition and differentiation from other c-MET inhibitors, as well as commercial prospects should tivantinib be approved.

Published: November 17th, 2011

Number of pages: 27

Authors: Dr. Drew Applefield and Dr. Ilana Fogelman


TABLE OF CONTENTS
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INTRODUCTION
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1. Non-Small Cell Lung Cancer
- Current treatments – chemotherapy
- Current treatments – targeted therapies
- Current treatments – Pfizer’s Xalkori (crizotinib)

ARQULE’S TIVANTINIB (ARQ-197)
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1. Tivantinib clinical development
- Phase II NSCLC
- Phase III NSCLC
- Tivantinib in other indications

CLINICAL AND REGULATORY DISCUSSION
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1. c-MET as a new drug target for cancer therapy
- c-MET in lung cancer
- c-MET and its relationship with EGFR, another important drug target in NSCLC
- Does Xalkori validate the c-MET pathway in NSCLC?
2. In vitro and in vivo effects on c-MET
3. Is there evidence of clinical activity in NSCLC patients?
4. Is tivantinib safe and well tolerated?
5. Regulatory lessons from the Xalkori approval
6. How will tivantinib fare in phase III?

MARKET ISSUES
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1. The lung cancer market and unmet medical needs
2. The unmet need beyond Xalkori
3. Potential role for tivantinib in treating NSCLC
4. Other indications could expand the market opportunity for tivantinib
5. Several other c-MET inhibitors are in development
6. Tivantinib licensing agreements will impact what revenue comes to ArQule

SUMMARY OPINION
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