DENVER, Colo. and CAMBRIDGE, Mass., April 21, 2009 (GLOBE NEWSWIRE) -- Infinity Pharmaceuticals, Inc. (Nasdaq:INFI) today presented data from its heat shock protein 90 (Hsp90) inhibitor program that supports the scientific rationale for Infinity's recently initiated Phase 2 study in breast cancer, and further enhances Infinity's scientific leadership in the field of Hsp90 inhibition. The data were presented during the 2009 American Association of Cancer Research (AACR) Annual Meeting in Denver. Infinity is developing two Hsp90 inhibitors: IPI-504, which is in Phase 2 clinical development, and its oral Hsp90 inhibitor, IPI-493, which is in Phase 1 clinical development.
Over-expression of the protein HER2 predicts an aggressive type of breast cancer for which Herceptin(r) (trastuzumab) is a primary treatment. Many patients, however, eventually develop resistance to Herceptin. In preclinical experiments, Infinity has shown that administration of IPI-504 results in the rapid degradation of HER2 in vitro, ultimately resulting in tumor cell growth inhibition and cell death. Preclinical data presented at AACR, in collaboration with researchers from Vall d'Hebron Institute of Oncology in Barcelona, Spain, now show that in Herceptin-resistant xenografts, HER2 protein levels were significantly reduced in vivo 12 hours after a single dose of IPI-504, and remained suppressed at 48 hours. Further, dose administration with IPI-504 in this model produced substantial tumor growth inhibition. In March 2009, Infinity initiated an open-label, international, multi-center Phase 2 clinical trial of IPI-504 in combination with Herceptin in patients with advanced or metastatic HER2-positive breast cancer.
Infinity presented additional preclinical data supporting the potential of its Hsp90 inhibitors in multiple cancer indications. In a presentation during AACR, Infinity reported that the in vivo anti-proliferative activity of its Hsp90 inhibitors is independent of the enzyme NQO1. Early work in Hsp90 inhibition had suggested that the presence of the enzyme NQO1 in cancer cells might be required in order for IPI-504 to have potent anti-tumor activity. Infinity showed that in a panel of 30 cancer cell lines, there is a poor correlation between levels of the enzyme NQO1 and the growth inhibitory activity of IPI-504. Furthermore, Infinity showed that cell lines that are not sensitive to IPI-504 in tissue culture are sensitive to IPI-504 when grown as mouse xenograft tumors in vivo. These data support the continued evaluation of Infinity's Hsp90 inhibitors in a broad range of cancers marked by low NQO1 expression.
Infinity researchers also reported on the development of a novel pharmacodynamic activity assay that quantifies Hsp90 inhibition in tumor samples. In preclinical animal models, IPI-504 and IPI-493 are rapidly cleared from the circulation and normal tissue, but accumulate in tumor tissue. Standard pharmacokinetic measurements used to monitor the levels of Hsp90 inhibitors in the clinic may not, therefore, represent an accurate assessment of the level of target inhibition in tumor tissue. Using the novel pharmacodynamic activity assay, tissue culture experiments demonstrated a correlation between the occupancy of Hsp90 and growth inhibition by IPI-504, confirming that IPI-504 affects cell growth through inhibition of Hsp90. Further, results from xenograft tumor samples taken from mice treated with IPI-504 in vivo showed that Hsp90 occupancy was better correlated with Hsp90 client protein degradation and efficacy than either plasma or tumor pharmacokinetics. Infinity plans to use its novel pharmacodynamic assay to directly measure Hsp90 inhibition in tumors and further evaluate the mechanism of action of its proprietary Hsp90 inhibitors, IPI-504 and IPI-493.
Hsp90 Inhibitor Program Clinical Development
Infinity is pursuing clinical development with its Hsp90 inhibitor product candidates, IPI-504 (i.v.) and IPI-493 (oral) in multiple indications. IPI-504 is being evaluated in a Phase 2 trial in combination with Herceptin(r) in patients with HER2-positive breast cancer, in the Phase 2 portion of a trial as a single agent in patients with advanced non-small cell lung cancer (NSCLC), and in a Phase 1 trial in combination with Taxotere(r) (docetaxel) in patients with advanced solid tumors. Infinity expects to report data from the Phase 2 study in patients with NSCLC and preliminary data from the Phase 1 combination study with Taxotere at the 2009 Annual Society of Clinical Oncology (ASCO) Annual Meeting. Infinity is also undertaking a Phase 1 clinical trial with IPI-493, its oral Hsp90 inhibitor, in patients with advanced solid tumors.
About Infinity Pharmaceuticals, Inc.
Infinity is an innovative cancer drug discovery and development company seeking to discover, develop, and deliver to patients best-in-class medicines for the treatment of cancer and related conditions. Infinity combines proven scientific expertise with a passion for developing novel small molecule drugs that target emerging cancer pathways. Infinity's two most advanced programs in Hsp90 inhibition and Hedgehog signaling pathway inhibition are evidence of its innovative approach to oncology drug discovery and development. For more information on Infinity, please refer to the company's website at http://www.infi.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding the utility of its Hsp90 inhibitors in treating various types of cancer and the reporting of data from clinical trials of IPI-504. Such statements are subject to numerous factors, risks and uncertainties that may cause actual events or results to differ materially from the company's current expectations. For example, there can be no guarantee that either IPI-504 or IPI-493 will successfully complete necessary phases of clinical development. In particular, management's expectations could be affected by risks and uncertainties relating to: results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Infinity's ability to enroll patients in its clinical trials; Infinity's reliance on its strategic alliance with Mundipharma International Corporation Ltd. and Mundipharma's ability to meet its agreed-upon funding obligations; unplanned cash requirements and expenditures; and Infinity's ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing. These and other risks which may impact management's expectations are described in greater detail under the caption "Risk Factors" included in Infinity's annual report on Form 10-K filed with the Securities and Exchange Commission on March 13, 2009. Further, any forward-looking statements contained in this press release speak only as of the date hereof, and Infinity expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
Herceptin(r) and Taxotere(r) are registered trademarks of Genentech, Inc. and sonafi-aventis LLC, respectively.