ArQule Expands Clinical Program With ARQ 197, c-Met Inhibitor
First patient dosed in new trial in hepatocellular carcinoma
WOBURN, Mass.--(BUSINESS WIRE)--Mar 5, 2009 - ArQule, Inc. (NASDAQ: ARQL) today announced the expansion of its clinical development program for ARQ 197, a proprietary, orally administered small molecule inhibitor of the c-Met receptor tyrosine kinase, with a new target indication, hepatocellular carcinoma (HCC). ArQule and Daiichi Sankyo Co. Ltd. (TSE: 4568) signed a license, co-development and co-commercialization agreement in December 2008 to co-develop ARQ 197.
"Following the recent completion of a strategic review of clinical targets and commercial pathways, as well as discussions with key opinion leaders and our partner, Daiichi Sankyo, we have added HCC as the fourth indication in our clinical trial program for ARQ 197," said Dr. Brian Schwartz, chief medical officer of ArQule. "We have dosed the first HCC patient in a pilot safety study with ARQ 197 as monotherapy. Pending its successful completion, we will move into a Phase 2, single agent trial and also explore a Phase 1-2 combination therapy trial program with sorafenib."
"Over-expression of c-Met and its ligand, hepatocyte growth factor (HGF), is associated with poor prognoses in patients with HCC," said Dr. Jordi Bruix, Head of the Barcelona Clinic Liver Cancer Center at the Hospital Clinic in Barcelona. "We believe that ARQ 197 offers an attractive opportunity for physicians based on its selectivity for c-Met, demonstrated signs of activity in clinical trials to date, and favorable side effect profile, which suggest its utility as monotherapy and its potential value in combination with existing therapies."
Scientific literature related to HCC provides evidence of the aberrant activation of the MET pathway. In addition, the dysregulation of c-Met and HGF has been shown to be common in this disease.1 Cell proliferation is a central mechanism responsible for liver cancer progression, and c-Met is believed to play an important role in this process.
Patients, physicians and other healthcare professionals seeking additional information about these trials may call 1-800-373-7827.
Hepatocellular Carcinoma (HCC)
According to the National Cancer Institute, 21,370 new cases of HCC in the United States were projected in 2008, and 18,410 deaths were projected to be caused by the disease. In the U.S., the increasing incidence of HCC is related primarily to hepatitis C infection and cirrhosis.
The first drug to be approved for patients with unresectable HCC was sorafenib. For patients who experience disease progression following sorafenib treatment or for those patients unable to tolerate sorafenib, no alternative therapy with proven clinical benefit is available. Thus, there is a high unmet medical need for novel treatment approaches in patients with advanced HCC for whom sorafenib treatment is not an option.
About ARQ 197 and c-Met
ARQ 197 is a selective inhibitor of c-Met, a receptor tyrosine kinase. When abnormally activated, c-Met plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. Pre-clinical data have demonstrated that ARQ 197 inhibits c-Met activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical studies to date, treatment with ARQ 197 has been well tolerated and has resulted in tumor responses and prolonged stable disease across broad ranges of tumors and doses.
In addition to HCC, ArQule has ongoing Phase 2 clinical trial programs in the following indications: MiT (Microphthalmia Transcription Factor)-associated tumors, non-small cell lung cancer and pancreatic adenocarcinoma.
About ArQule and Daiichi Sankyo Co., Ltd.
On December 19, 2008, ArQule and Daiichi Sankyo signed a license, co-development and co-commercialization agreement to co-develop ARQ 197 in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan, where Kyowa Hakko Kirin Co., Ltd. (Kyowa) has exclusive rights for development and commercialization.
About ArQule
ArQule is a biotechnology company engaged in the research and development of next-generation, small-molecule cancer therapeutics. The Company's targeted, broad-spectrum products and research programs are focused on key biological processes that are central to cancer. ArQule's lead product, which is in clinical-stage development, is ARQ 197, an inhibitor of the c-Met receptor tyrosine kinase. An additional clinical-stage program includes compounds that activate the cell's DNA damage response mechanism mediated by the E2F-1 transcription factor. The Company's pipeline includes ARQ 621, a compound designed to inhibit the Eg5 kinesin spindle protein for which an IND was filed in December 2008, and a pre-clinical compound designed to inhibit the BRAF kinase. ArQule's current discovery efforts are focused on the identification of novel kinase inhibitors that are potent, selective and do not compete with ATP (adenosine triphosphate), an energy source for cells.
This press release contains forward-looking statements regarding the Company's development of ARQ 197 under the Company's agreement with Daiichi Sankyo Co., Ltd. These statements are based on the Company's current beliefs and expectations, and are subject to risks and uncertainties that could cause actual results to differ materially. Positive information about pre-clinical and early stage clinical trial results does not ensure that later stage or larger scale clinical trials will be successful. For example, ARQ 197 may not demonstrate promising therapeutic effect; in addition, it may not demonstrate an appropriate safety profile in current or later stage or larger scale clinical trials as a result of known or as yet unanticipated side effects. The results achieved in later stage trials may not be sufficient to meet applicable regulatory standards. Problems or delays may arise during clinical trials or in the course of developing, testing or manufacturing these compounds that could lead the Company or Daiichi Sankyo to discontinue development. Even if later stage clinical trials are successful, the risk exists that unexpected concerns may arise from analysis of data or from additional data or that obstacles may arise or issues be identified in connection with review of clinical data with regulatory authorities or that regulatory authorities may disagree with the Company's view of the data or require additional data or information or additional studies. In addition, the planned timing of initiation and completion of clinical trials for ARQ 197 are subject to the ability of the Company and Daiichi Sankyo to enroll patients, enter into agreements with clinical trial sites and investigators, and other technical hurdles and issues that may not be resolved. Drug development involves a high degree of risk. Only a small number of research and development programs result in the commercialization of a product. Positive pre-clinical data may not be supported in later stages of development. Furthermore, ArQule might not have the financial or human resources to meet its obligations or take advantage of its rights under its license, co-development and co-commercialization agreement with Daiichi Sankyo. Also, Daiichi Sankyo has certain rights to unilaterally terminate the ARQ 197 license, co-development and co-commercialization agreement. If it were to do so, the Company might not be able to complete development and commercialization of ARQ 197 on its own. For more detailed information on the risks and uncertainties associated with the Company's drug development and other activities, see the Company's periodic reports filed with the Securities and Exchange Commission. The Company does not undertake any obligation to publicly update any forward-looking statements.
1 Genes and signaling pathways involved in the pathogenesis of HCC, Sem Liv Dis 2007; 27: 55-76 Loss of heptocyte growth factor/c-Met signaling pathway accelerates early stages of N-nitrosodiethylamine induced hepatocarcinogenesis, Cancer Res. 2007; 67: 9844-51