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Last updated on April 18, 2014 at 17:24 EDT

IMC-A12 Plus Temsirolimus Clinical Trial for Advanced Cancer Opens for Patient Enrollment

June 25, 2008

ImClone Systems Incorporated (NASDAQ: IMCL), a global leader in the development and commercialization of novel antibodies to treat cancer, today announced that a Phase 1 clinical trial of IMC-A12, ImClone’s fully human, IgG1 anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody, plus the mTOR inhibitor temsirolimus in patients with advanced solid malignancies and lymphoma has opened for patient enrollment. This study is being carried out at the M.D. Anderson Cancer Center in Houston, Texas and the Barbara Anne Karmanos Cancer Institute/Wayne State University in Detroit, Michigan.

This study is a component of an initial stage of at least 10 Phase 1 and 2 clinical trials of IMC-A12 sponsored by the Cancer Therapy Evaluation Program (CTEP) of the Division of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI), to commence patient enrollment. ImClone announced the selection of these proposals by NCI in September 2007.

“This NCI-sponsored IMC-A12 trial is based on preclinical evidence that the mTOR and IGF-1R growth and survival signaling pathways are intimately linked and, therefore, the combination of IMC-A12 and temsirolimus may be an ideal means to optimize treatment,” said Eric K. Rowinsky, M.D., Chief Medical Officer and Executive Vice President of ImClone. “This is the first study of an IGF-1R inhibitor combined with an mTOR inhibitor and will provide a foundation for future disease-directed trials.”

IMC-A12 is a fully human IgG1 monoclonal antibody. It is designed to specifically target the human IGF-1R, thereby inhibiting certain ligands known as IGFs 1 and 2 from binding to and activating the receptor. This action blocks a signaling pathway that enhances tumor cell proliferation and survival. In 2007, ImClone completed enrollment into two Phase 1 studies of IMC-A12, which demonstrated favorable safety and pharmacokinetic profiles, as well as preliminary evidence of antitumor activity as a single agent when administered either weekly or every two weeks. In addition to this Phase 1 study of IMC-A12 plus temsirolimus, Phase 2 studies of IMC-A12 in patients with advanced prostate, pancreatic, colorectal, liver, and head and neck cancers, as well as a series of Phase 1/2 studies in pediatric malignancies, have begun to enroll patients.

The insulin-like growth factor (IGF) system plays a critical role in the development and progression of many types of solid malignancies, lymphoma, and hematologic cancers. Abnormal activation of the IGF-1R in cancer cells triggers both growth stimulatory and survival signals, thereby conferring an overall growth advantage to cancers. The molecular target of rapamycin, commonly known as mTOR, has been shown to be an important effector of cell-signaling pathways frequently deregulated in cancer. The results of preclinical studies indicate interrelationships between the IGF-1R and mTOR. Treatment of cancer cells with rapamycin analogs has been shown to activate the IGF-1R signaling pathway through a feedback mechanism, which can then potentially confer resistance to the mTOR inhibitors. Combined treatment with the IGF-1R inhibitor, IMC-A12 and the mTOR inhibitor, temsirolimus, is anticipated to be an effective anti-tumor therapeutic strategy and is supported by preclinical results. This Phase 1 study is enrolling up to approximately 40 patients with a wide range of advanced, solid malignancies and lymphoma. The primary study objective is to evaluate the safety profile of IMC-A12 and temsirolimus on a weekly administration schedule and recommend doses for a subsequent Phase 2 study and other disease-directed trials. The study is also designed to ascertain information on biological effects of IMC-A12 and temsirolimus in tumor biopsies performed successively, to characterize the pharmacologic behavior of these agents in combination, and ascertain preliminary efficacy information. Temsirolimus is being provided for these studies under a Cooperative Research and Development Agreement between NCI and Wyeth Pharmaceuticals.

“The growing number of clinical studies of IMC-A12 reflects the considerable preclinical research conducted by our scientists that serves as the foundation of knowledge for these trials,” said John H. Johnson, Chief Executive Officer of ImClone. “The diverse portfolio of IMC-A12 studies is a key component of our comprehensive research program to accelerate the development of ImClone’s proprietary pipeline of fully human IgG1 monoclonal antibodies.”

About ImClone’s NCI-sponsored IMC-A12 Trials

In September 2007, the CTEP of the DCTD, NCI selected 10 proposals for Phase 1 and 2 clinical trials of ImClone’s IMC-A12, and several other proposals have been selected since that time. The selection of the proposed trials followed NCI’s solicitation for specific disease-directed studies among NCI investigators at academic institutions, clinical trial consortia and NCI-sponsored oncology cooperative clinical trial groups in the U.S. The selected trials represent the first stage of clinical evaluations of IMC-A12 sponsored by CTEP, NCI under a Clinical Trials Agreement between ImClone Systems and DCTD, NCI to facilitate the clinical development of IMC-A12. Both randomized and nonrandomized Phase 2 trials sponsored by CTEP will explore the clinical activity, pharmacology and biological effects of IMC-A12 as a single agent or combined with other relevant anticancer agents in a wide range of malignancies including breast, lung, pancreas and liver cancers, as well as both adult and pediatric sarcomas. In addition, Phase 1/2 studies will evaluate the safety, pharmacology, anticancer activity and biological effects of IMC-A12 in children and adolescents with cancer, as well as in combination with other novel targeting agents in which there is a specific rationale for combined use.

About ImClone Systems

ImClone Systems Incorporated is a fully integrated global biopharmaceutical company committed to advancing oncology care by developing and commercializing a portfolio of targeted biologic treatments designed to address the medical needs of patients with a variety of cancers. The Company’s research and development programs include growth factor blockers and angiogenesis inhibitors. ImClone Systems’ headquarters and research operations are located in New York City, with additional administration and manufacturing facilities in Branchburg, New Jersey. For more information about ImClone Systems, please visit the Company’s web site at http://www.imclone.com.

Certain matters discussed in this news release may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and the Federal securities laws. Although the company believes that the expectations reflected in such forward-looking statements are based upon reasonable assumptions it can give no assurance that its expectations will be achieved. Forward-looking information is subject to certain risks, trends and uncertainties that could cause actual results to differ materially from those currently expected. Many of these factors are beyond the company’s ability to control or predict. Important factors that may cause actual results to differ materially and could impact the company and the statements contained in this news release can be found in the company’s filings with the Securities and Exchange Commission, particularly those factors identified as “risk factors” in the Company’s most recent annual report of Form 10-K and in its quarterly reports on Form 10-Q and current reports on Form 8-K. For forward-looking statements in this news release, the company claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. The company assumes no obligation to update or supplement any forward-looking statements whether as a result of new information, future events or otherwise.