CAMBRIDGE, Mass., May 29, 2009 (GLOBE NEWSWIRE) -- Infinity Pharmaceuticals, Inc. (Nasdaq:INFI), an innovative cancer drug discovery and development company, announced the recent publication of a new scientific paper further supporting Hedgehog signaling pathway inhibition as a promising new approach to treat cancer. The data featured in the paper show that IPI-926, when administered in combination with gemcitabine in a preclinical mouse model of treatment-resistant pancreatic cancer, increased tumor cell death, resulting in a reduction of tumor size and increased survival. These data suggest that IPI-926 may enable chemotherapeutic agents to successfully access and kill tumor cells. Infinity is currently evaluating IPI-926 in a Phase 1 clinical trial in patients with advanced solid tumors.
The paper, lead-authored by Kenneth P. Olive, Ph.D., is titled "Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer" and was published in the online edition of the journal Science on May 21, 2009.
"It is promising to see these preclinical results, particularly in a disease setting as clinically challenging as pancreatic cancer," said Dr. David Tuveson, senior author and group leader in tumor modeling and experimental medicine at Cancer Research UK's Cambridge Research Institute. "For patients with pancreatic cancer, the need for new treatments -- especially those that could be used in combination to improve the activity of the current standards of care -- is critical."
Malignant activation of the Hedgehog pathway plays a key role in multiple cancer settings. This pathway involves two cell-membrane proteins, Patched and Smoothened, and is regulated by the absence or presence of Hedgehog ligand. Smoothened has a critical role in the malignant activation of the Hedgehog pathway because it initiates a signal transduction cascade that can result in cell differentiation, migration, and proliferation. Smoothened can promote growth of certain cancers via three modes of malignant activation of the Hedgehog pathway: ligand-independent signaling activated by genetic mutation, and ligand-dependent signaling either to the tumor cell itself or from the tumor to cells in the microenvironment.
In pancreatic cancer, the Hedgehog ligand derived from the tumor signals to the surrounding stroma. This results in support for tumor growth and survival through mechanisms originating in the stromal cells.
IPI-926 is a novel, potent, orally-available small molecule that inhibits the Hedgehog pathway by targeting Smoothened. Preclinical data with IPI-926 demonstrates that the compound significantly down-regulates Hedgehog signaling in tumor stroma, thereby disrupting the communication process between tumor and stroma, ultimately leading to tumor growth inhibition.
Scientists at Cancer Research UK's Cambridge Research Institute, who were co-funded by The Lustgarten Foundation and the National Institutes of Health, led an international team of scientists who found that a genetically modified mouse model of pancreatic cancer that closely resembles human cancer was also largely resistant to gemcitabine treatment. The lack of responsiveness was due to high stroma content and deficient vasculature in the tumors, which leads to inefficient delivery of therapeutic agents. In this model, inhibition of the Hedgehog pathway by IPI-926 administration resulted in depletion of tumor stroma and increased the number of blood vessels in the tumor, thereby improving delivery of therapeutic agents. Further, the combination of IPI-926 with gemcitabine resulted in induction of apoptosis in the tumor, decreased metastases, and a statistically significant extension of survival.
"Unlocking the therapeutic potential of existing chemotherapeutic agents by inhibiting the Hedgehog pathway could prove to be a critical step in developing treatment for some of the most difficult cancers," said Vito Palombella, Ph.D., vice president of drug discovery, Infinity. "We are very encouraged by these early, but key, data with IPI-926. We are advancing IPI-926 through clinical development and continue to explore the biology of hedgehog pathway inhibition."
About the Hedgehog Signaling Pathway
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.
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, or that the preclinical data described in this press release will be replicated in clinical trials. 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 quarterly report on Form 10-Q filed with the Securities and Exchange Commission on May 6, 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.