ARQULE INC

ARQULE INC

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Company Overview
ArQule, Inc. is a biotechnology company engaged in the research and development of cancer therapeutics in the United States. The company was founded in 1993 and is headquartered in Woburn, Massachusetts. It operates as a publicly quoted company with shares listed on NASDAQ National Market.
The company’s clinical-stage development programs include ARQ 197, a selective inhibitor of the c-Met receptor, which is in phase I clinical trial to treat patients with metastatic solid tumors; ARQ 501, which is in phase II clinical trials designed to kill cancer cells selectively while sparing normal cells through direct activation of DNA damage response/checkpoint pathways; and ARQ 171, a second-generation E2F-1 compound that is in phase I clinical trial. It also has a preclinical and research pipeline, which includes B-RAF Kinase, HSP90, HDAC, and Eg5 programs.
The company has an alliance with Hoffmann-La Roche to discover and develop drug candidates targeting the E2F biological pathway; and a research agreement with Boston Biomedical, Inc. Further, the mission of the company is to research, develop, and commercialize broadly effective cancer drugs with reduced toxicities compared to conventional cancer chemotherapeutics.
Business Summary
ArQule, Inc. is a clinical-stage biotechnology company engaged in the research and development of cancer therapeutics. The Company employs technologies, such as its ArQule Kinase Inhibitor Platform (AKIP) to design and develop drugs. The Company’s product is ARQ 197, an orally administered inhibitor of the c-Met receptor tyrosine kinase. ARQ 197 is being evaluated as monotherapy and in combination therapy in a Phase II clinical development program that includes trials in Microphthalmia Transcription Factor (MiT) associated tumors, non-small cell lung cancer (NSCLC), pancreatic adenocarcinoma and hepatocellular carcinoma (HCC). The Company has licensed commercial rights to ARQ 197 for human cancer indications to Daiichi Sankyo Co., Ltd. (Daiichi Sankyo) in the United States, Europe, South America and the rest of the world, excluding Japan and certain other Asian countries, where it has licensed commercial rights to Kyowa Hakko Kirin Co., Ltd. (Kyowa Hakko Kirin).
Description and history
ArQule, Inc. is a clinical-stage biotechnology company engaged in the research and development of cancer therapeutics. The Company employs technologies, such as its ArQule Kinase Inhibitor Platform (AKIP) to design and develop drugs. The Company’s product is ARQ 197, an orally administered inhibitor of the c-Met receptor tyrosine kinase. ARQ 197 is being evaluated as monotherapy and in combination therapy in a Phase II clinical development program that includes trials in Microphthalmia Transcription Factor (MiT) associated tumors, non-small cell lung cancer (NSCLC), pancreatic adenocarcinoma and hepatocellular carcinoma (HCC). The Company has licensed commercial rights to ARQ 197 for human cancer indications to Daiichi Sankyo Co., Ltd. (Daiichi Sankyo) in the United States, Europe, South America and the rest of the world, excluding Japan and certain other Asian countries, where it has licensed commercial rights to Kyowa Hakko Kirin Co., Ltd. (Kyowa Hakko Kirin).

The Company’s product pipeline offers multiple therapeutic candidates based on diverse biological targets, mechanisms of action and chemistry. The program is focused on the development of inhibitors of the Eg5 kinesin spindle protein, which include ARQ 621, for which it has filed an Investigational New Drug Application (IND). It has completed Phase II proof-of-principle trials with ARQ 501, an intravenously administered activator of the cell’s deoxyribonucleic acid (DNA), damage response mechanism mediated by the E2F-1 transcription factor. The Company’s drug discovery efforts is focused on the ArQule Kinase Inhibitor Platform (AKIP), which it employs to generate a new class of compounds designed to inhibit a variety of kinases potently, selectively and without competing with adenosine triphosphate (ATP), an energy source for cells.

ARQ 197

ARQ 197 is an orally available, small molecule that inhibits c-Met, the receptor tyrosine kinase of hepatocyte growth factor (HGF). The Company initiated a first Phase I clinical trial with ARQ 197 in late 2005. This open label, dose escalation trial included patients with multiple metastatic tumor types who had disease progression when treated with available therapy or for whom no standard systemic therapy existed. At the 2007 Annual Meeting of the American Society of Clinical Oncology (ASCO) on June 2, 2007, ArQule announced available data from this trial demonstrating that treatment with ARQ 197 was well tolerated over extended dosing periods, with approximately 60% of the evaluable patient population experiencing partial responses, minor responses or stable disease lasting eight weeks or longer. An analysis of tumor image data from this trial was presented at the 2007 AACR-NCI-EORTC International Conference on October 24, 2007.

The Company is conducting Phase II clinical trials with ARQ 197 in four tumor types; MiT-associated tumors, NSCLC, pancreatic adenocarcinoma and HCC. The dose level of ARQ 197 employed in all of these trials is 360 milligram twice daily, reflecting a small increase above the maximum tolerated dose (MTD) of 300 mg twice daily established in the Royal Marsden Hospital trial. The initial clinical trial dose of ARQ 197, 120 milligram, was based on earlier Phase I data related to anti-cancer activity observed with this dose and on plasma exposure data generated before an MTD was identified.

In October 2007, the Company initiated a Phase 2 trial in MiT tumors that employed the original dose of 120 milligram twice daily. The dose was increased to 360 milligram twice daily in October 2008, following the identification of an MTD in the Royal Marsden trial. The primary objective of the trial is to determine the overall response rate in patients treated with ARQ 197. In March 2008, the Company initiated a Phase I/II clinical trial program of ARQ 197 administered in combination with erlotinib in non-small cell lung cancer. The Phase I lead-in trial in this program was designed to determine the safety, tolerability and recommended Phase II dose of ARQ 197 when administered in combination with erlotinib in patients with these tumors.

During the year ended December 31, 2008, the Company successfully completed the Phase I trial, demonstrating that the combination of ARQ 197 and erlotinib was well tolerated at the recommended dose for each drug. It also initiated a Phase I/II clinical trial program of ARQ 197 in HCC in March 2009.

ARQ 501, ARQ 171and ARQ 761: the E2F-1 Program

ARQ 501, ARQ 761 and ARQ 171 are designed to kill cancer cells selectively while sparing normal cells through the direct activation of DNA damage response/checkpoint pathways believed to be regulated by the E2F-1 regulatory protein, thereby restoring the ability of the cell to recognize DNA damage and initiating the process of apoptosis, or programmed cell death, in these cells. ARQ 501 is the first product generated in this program, while ARQ 761 and ARQ 171 are second-generation compounds.

In December 2008, the United States Food and Drug Administration (FDA) accepted an IND for ARQ 621, a product generated from the Company’s advanced clinical program, focused on inhibition of the Eg5 kinesin spindle protein. Eg5 is a member of the kinesin motor protein super family, each member of which is believed to have a specific role in mitosis. ARQ 621 has been shown pre-clinically to inhibit Eg5 potently and selectively and to induce cell death across multiple human cancer cell lines in vitro and in vivo, with low bone marrow toxicity in multiple animal models. The FDA has also accepted an IND for ARQ 761, a second-generation E2F-1 activator.

Business Line
Engaged in the research and development of cancer therapeutics in the United States
Subsidiary
ARQULE BIOTECH DRUG DISCOVERY
Advisor
PRICEWATERHOUSECOOPERS LLP
IPO date
10/1996
US SIC Code
2834
Company Address
19, Presidential Way

City province or state postal code
01801, WOBURN, MA
Phone: +1 781 994 0300
Fax: +1 781 376 6019
Country address: UNITED STATES OF AMERICA
Website url: www.arqule.com