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ArQule Inc. Message Board

  • carylindsay1443 Apr 26, 2012 10:03 AM Flag

    ShareHolder Letter--4/24/12

    Letter to Shareholders(4/24/12)


    We completed a transformational year for ArQule in 2011 marked by noteworthy progress in the development of tivantinib (ARQ 197), our lead product candidate. Tivantinib is an orally administered, small-molecule inhibitor of the c-Met receptor tyrosine kinase, a molecular target that is over-expressed in a number of tumor types, associated with poor prognosis and involved in resistance to other anti-cancer therapies.

    At the heart of the clinical development strategy for tivantinib is data generation from randomized, double-blind, controlled Phase 2 trials. These data provide the basis for advancement into Phase 3 trials with what we believe is a significantly greater probability of clinical and regulatory success.

    During 2011, tivantinib became the focus of a worldwide clinical development effort that includes two ongoing Phase 3 trials of tivantinib in combination with erlotinib in non-small cell lung cancer (NSCLC) of non-squamous cell histology. In the first quarter of the year, we and our partner, Daiichi Sankyo, initiated the first of these trials, named MARQUEE. We are enrolling approximately 1,000 patients at over 200 clinical sites in the U.S., Canada, Eastern and Western Europe, Australia and Latin America. The primary endpoint of this trial is overall survival.

    MARQUEE is being conducted under a Special Protocol Assessment, or SPA, agreed upon with the FDA. The SPA provides us with a defined clinical and regulatory pathway for tivantinib. Patient enrollment during the past 14 months puts us on track to meet our projected milestone events for the MARQUEE trial. These include full enrollment of the trial mid-year, an interim analysis planned in the second half of 2012 after approximately 50 percent of survival events have occurred, and final data read-out expected in mid-2013.

    Following the enrollment of the first patient in MARQUEE, our partner for tivantinib in Asian territories, Kyowa Hakko Kirin (KHK), initiated its own Phase 3 trial with tivantinib and erlotinib in NSCLC in August 2011. KHK’s commitment to this trial, named ATTENTION, underscores the therapeutic and commercial potential of tivantinib in this important part of the world. The ATTENTION trial is expected to enroll approximately 460 patients with non-squamous NSCLC and wild-type EGFR at clinical sites in Japan, South Korea and Taiwan. The primary endpoint of this trial is overall survival.

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    • carylindsay1443 Apr 26, 2012 10:05 AM Flag

      Part 3:
      Our proprietary early-stage product pipeline is directed toward other molecular targets with roles in the development of human cancers. These include ARQ 621, an inhibitor of the Eg5 kinesin motor protein that has completed Phase 1 testing, and ARQ 736, an inhibitor of the RAF kinases that is in the later stages of a Phase 1 trial. Our pre-clinical pipeline includes ARQ 087, an inhibitor of fibroblast growth factor receptor (FGFR) for which we may file an Investigational New Drug application in 2012. Our strategy with these product candidates remains to generate pre-clinical and early clinical data that will inform decisions about further development independently or on a partnered basis.

      Our partnered early-stage product pipeline includes ARQ 092, an AKT inhibitor discovered through our ArQule Kinase Inhibitor Platform (AKIP™) collaboration with Daiichi Sankyo. This is the first AKIP™ compound to enter the clinic under this collaboration, and we are utilizing the capabilities of AKIP™ technology along with Daiichi Sankyo to discover compounds that inhibit additional kinase targets in the field of oncology. We are also seeking to expand the applications of AKIP™ technology through additional collaborative research programs, as well as through our own internal discovery and development activities.

      During 2011, we received non-dilutive financing payments from our partners totaling $45 million. These included a $25 million milestone payment from Daiichi Sankyo triggered by the dosing of the first patient in the MARQUEE trial, a $10 million payment from KHK triggered by dosing of the first patient in the ATTENTION trial, and a $10 million payment from Daiichi Sankyo for the licensing of ARQ 092. We ended the year with approximately $109 million in cash and marketable securities. In April 2012, we strengthened our finances through an offering of shares resulting in net proceeds of approximately $56 million. We believe that these financial resources will be sufficient to finance our operations through 2014 and the read-out of data from our Phase 3 trials and consummation of other important milestones.

      We have begun 2012 having demonstrated that tivantinib has conferred clinical benefit in randomized, Phase 2 settings in combination and as a single agent. Further, we have demonstrated the therapeutic impact of this lead compound in two important tumor types, NSCLC and HCC. We have also shown that tivantinib is readily combinable with other targeted compounds and chemotherapeutic agents. Finally, patient enrollment is proceeding as planned in two Phase 3 trials with tivantinib that span worldwide geographies. We believe that these impressive and encouraging achievements set the stage for another transformation at ArQule that will take place over the next two years.


    • carylindsay1443 Apr 26, 2012 10:04 AM Flag

      Part 2:
      The most recently added study in the NSCLC program for tivantinib is an open-label, Phase 2 trial targeting patients with KRAS mutations treated with tivantinib plus erlotinib or chemotherapy, with the primary objective of progression-free survival. We initiated this trial based on a particularly robust clinical benefit in these patients observed in our randomized, double-blind Phase 2 trial that was also the basis for our two ongoing Phase 3 trials.

      We read the most recent set of promising randomized Phase 2 data with tivantinib in early 2012 in hepatocellular carcinoma (HCC). In this trial, tivantinib as a single agent therapy produced a statistically significant improvement in time to progression in the intent-to-treat population. Patients with higher levels of c-Met who were treated with tivantinib experienced pronounced benefit in this population. These exciting findings represent the first randomized data reported with a c-Met inhibitor administered as a single agent in this disease. Second line therapy in HCC remains a high unmet need, lacking an approved treatment. We look forward to presenting complete data from this trial, including secondary endpoint, sub-group and biomarker analyses, at the Annual Meeting of the American Society of Clinical Oncology on June 2.

      A third randomized Phase 2 trial is ongoing in colorectal cancer, evaluating the combination of tivantinib, irinotecan and cetuximab, with the primary objective of progression free survival. Daiichi Sankyo is conducting this trial in approximately 130 patients, and the results are expected to be read toward the end of this year or early next year.

      The National Cancer Institute has selected tivantinib for study under a Cooperative Research and Development Agreement (CRADA). The CRADA provides financial support for independent investigator-sponsored clinical trials with promising compounds. Patient enrollment is ongoing with tivantinib as a single agent and in combinations with other anti-cancer therapies in a number of CRADA-sponsored trials. These include Phase 2 single agent trials in prostate cancer (randomized), multiple myeloma and breast cancer, with trial protocols in other indications under review. In addition, trials with tivantinib are ongoing or planned in combination with other agents.

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