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Antibodies are the first wave of IGF-1R antagonists for cancer therapy

Posted on: 06 Mar 06

Summary

At least six fully human or humanized antibodies against insulin-like growth factor-1 receptor (IGF-1R) are in early clinical development or close to phase I
BARCELONA, Spain | March 6, 2006 | The Business Intelligence firm La Merie S.L. reported today that antibodies are at the forefront of novel cancer therapeutics targeting the insulin-like growth factor-1 receptor (IGF-1R). Pfizer is leading the field with the fully human IgG2 antibody CP-751,871 under investigation for multiple myeloma and advanced non-small cell lung cancer. Five other companies are closely following with antibody projects. Only six companies are currently visible with small molecule inhibitors targeting the IGF-1R tyrosine kinase which are not always selective for IGF-1R. INSM-18 from Insmed and the University of California San Francisco is a dual inhibitor of IGF-1R and Her2/neu and is the only clinical stage IGF-1R small molecule antagonist (phase I/II in prostate cancer). These results and more were found in a search conducted by La Merie Business Intelligence published in the March 6 issue of R&D Pipeline News, edited by La Merie. The competitor analysis of CB1 antagonists can be acquired at www.pipelinereview.com, La Merie’s News Center and Online Store.

Although the IGF-1 receptor was first cloned in 1986, it was the success of targeted drugs such as trastuzumab and imatinib that tyrosine kinase inhibitors and growth factor receptor blockers became hot targets. Now companies are aggressively pursuing compounds that target IGF-1R. Other reasons for the long delay in bringing compounds against IGF-1R into the clinic may be: 1) the fear that blocking IGF-1R in cancer therapy would also block the insulin receptor and signaling (70 % homology with IGF-1R) and, thus might be diabetogenic; and 2) the expression of IGF-1R in normal tissue throughout the body. Aventis selected an antibody which does not bind to the closely related insulin receptor. However, preclinical data indicate a limited spectrum of tumor cell lines against which the antibody was effective.

While antibodies are exquisitely selective inhibitors of the IGF-1R function by inducing rapid internalization and down regulation of the receptor, small molecule tyrosine kinase inhibitors suffer from a lack of selectivity because of binding to a well conserved site. In fact, several of the IGF-1R tyrosine kinase inhibitors in development are dual inhibitors, and in general do not lead to internalization and downregulation. Nevertheless, small molecule IGF-1R inhibitors offer the advantage of the ability to control the duration of drug exposure in contrast to long-acting antibodies.

Apart from antibodies and small molecules, there are individual approaches using peptides, proteins or antisense oligonucleotides to antagonize IGF-1R. The latter one has been evaluated as a topical cream to treat patients with psoriasis, but needs further dose optimization.

About R&D Pipeline News

R&D Pipeline News is a premier information source about research and development projects in the pipeline of the biopharmaceutical industry. The periodical is directed to all stakeholders in R&D. The weekly publication comes in a rapid- and easy-to-screen tabular format and provides access to the original information source via hyperlinks. R&D Pipeline News covers all relevant treatment modalities and is directly delivered to the desktop via e-mail. More information about the journal, a free trial and subscriptions are available via La Merie’s Business Intelligence Center www.pipelinereview.com.

About PipelineReview.com

PipelineReview.com is the News Center and Online Store of La Merie Business Intelligence focused on R&D in the Biopharmaceutical Industry. Visitors of PipelineReview.com will find R&D relevant press releases and can receive selected R&D news from one or more of the site’s News Channels. A free R&D Newsletter conveniently brings via e-mail a daily selection of the most interesting news from biopharmaceutical R&D. For more information visit www.pipelinereview.com.

About La Merie

La Merie S.L. is a Business Intelligence enterprise fully dedicated to provide high quality R&D information to the biopharmaceutical industry. La Merie offers individual consultancy services and publishes reports and periodicals. For more information visit www.lamerie.com.

SOURCE: La Merie Business Intelligence

La Merie Business Intelligence

Last updated on: 27/08/2010 11:40:18

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