DENVER and CAMBRIDGE, Mass., April 21, 2009 (GLOBE NEWSWIRE) -- Infinity Pharmaceuticals, Inc. (Nasdaq:INFI) today presented preclinical data from studies of IPI-926, its oral Hedgehog pathway inhibitor that targets Smoothened, during the 2009 American Association of Cancer Research (AACR) Annual Meeting in Denver, Colo. The data presented further elucidate the promising role of Hedgehog pathway inhibition in addressing a broad range of cancers, including those that are Hedgehog ligand-independent as well as Hedgehog ligand-dependent. IPI-926 is currently in Phase 1 clinical development.
Malignant activation of the Hedgehog signaling pathway is implicated in multiple cancer settings. In certain cancers, the Hedgehog ligand derived from the tumor either signals to the surrounding stroma, such as in pancreatic cancer, or to a subpopulation of Hedgehog-dependent chemo-resistant progenitor cells, as may be found in small cell lung cancer (SCLC), chronic myelogenous leukemia, and multiple myeloma. These cancers, therefore, may be classified as Hedgehog ligand-dependent. In certain other cancers, there is a genetic mutation resulting in activation of the pathway. These cancers thereby function independently of the Hedgehog ligand and include medulloblastoma and basal cell carcinoma.
Infinity presented data during AACR from a primary model of human SCLC showing that Hedgehog ligand is up-regulated in the tumor cells following chemotherapy. In this model, researchers from Johns Hopkins University and Monash Institute of Medical Research demonstrated that following treatment with chemotherapy, Smoothened, the target of IPI-926, localizes to primary cilium in a subpopulation of tumor cells, indicating that the Hedgehog pathway is active in these tumor cells. Data showed that IPI-926 blocks Smoothened localization to the primary cilium, and inhibits the self-renewing capacity of SCLC tumor cells in vitro, suggesting that the self-renewal capacity of SCLC is dependent upon Hedgehog pathway activation. These data support the evaluation of IPI-926 to prolong relapse-free survival following chemotherapy in SCLC.
Infinity reported additional data in a separate presentation showing that Hedgehog ligands are induced following chemotherapy in ovarian and bladder cancer models, as well as in SCLC models. These findings suggest that elevated Hedgehog ligand expression could impart a survival advantage to a subpopulation of tumor cells, promoting their tumorigenic properties following chemotherapy. Taken together, these results provide strong rationale for testing Hedgehog inhibitors in clinical indications such as SCLC, bladder cancer, and ovarian cancer that are initially chemo-responsive, but eventually result in tumor relapse.
In a final presentation, Infinity, in collaboration with researchers from the Fred Hutchinson Cancer Research Center, showed that IPI-926 demonstrated anti-tumor activity in preclinical models of cancers for which there is a genetic mutation resulting in activation of the pathway. In a novel murine model of medulloblastoma, daily administration of IPI-926 relieves the clinical manifestations of the cancer and reduces the size of the tumors leading to prolonged survival. Pharmacodynamic activity of IPI-926 in these tumors was confirmed by analysis of Gli-1 mRNA by RT-PCR, which was down-modulated following administration of IPI-926. Infinity is planning additional studies to determine the potential role of IPI-926 in treating Hedgehog ligand-independent cancers.
Infinity is currently evaluating IPI-926 in a Phase 1 clinical trial in patients with advanced solid tumors. The Phase 1 trial is designed to evaluate the safety, tolerability, and pharmacokinetics of IPI-926 and to determine a recommended dose and schedule for subsequent studies. Additionally, Infinity is evaluating potential anti-tumor activity of IPI-926 and examining pharmacodynamic markers of biological activity.
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 Hedgehog inhibitors, including IPI-926, in treating various types of cancer. 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 IPI-926 will successfully complete necessary preclinical and clinical development phases. 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 and investigational review boards at clinical trial sites; 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.