CAMBRIDGE, Mass., April 15, 2008 (PRIME NEWSWIRE) -- Infinity Pharmaceuticals, Inc. (Nasdaq:INFI) today announced that preclinical data from a model of small cell lung cancer (SCLC) show that following treatment with chemotherapy, once-daily oral administration of IPI-926 leads to a statistically significant delay in tumor re-growth, compared to vehicle control (p=0.01). These results suggest that inhibiting the Hedgehog pathway with IPI-926, Infinity's novel, potent Hedgehog pathway antagonist following chemotherapy delays tumor recurrence in SCLC. These data were presented today during the Annual Meeting of the American Association of Cancer Research (AACR) in San Diego, California.
"These data suggest a subpopulation of 'progenitor-like' cancer cells -- cells that are chemo-resistant and Hedgehog responsive -- are being affected by IPI-926," commented Vito Palombella, Ph.D., vice president of drug discovery at Infinity. "We believe this approach is an exciting opportunity for clinical development of IPI-926, as the data suggest that administration of IPI-926 could lead to increased relapse-free survival for patients living with this aggressive and difficult to treat cancer."
Small cell lung cancer (SCLC) accounts for 10 percent to 15 percent of all lung cancers and is rapidly fatal when untreated. Standard of care is platinum-based chemotherapy, but there have been no new systemic treatments for SCLC in over 20 years and there are no approved targeted therapies for SCLC. While SCLC has a high initial response rate to platinum-based chemotherapy, it almost invariably recurs and is generally fatal within months. One potential explanation for this phenomenon is that while the majority of tumor cells are highly chemo-sensitive, a subset of cells exists within the tumor that is intrinsically resistant to chemotherapy. After chemotherapy, these remaining resistant cells (a potential cancer stem cell population) may lead to tumor recurrence and death. Recent preclinical studies have suggested that Hedgehog pathway signaling may act to maintain cancer 'stem cell' function in multiple myeloma, breast cancer, and glioblastoma; moreover, deregulation of this pathway has been implicated in SCLC.
To test the hypothesis that the Hedgehog pathway is important in maintenance of a chemo-resistant subset of tumor cells within SCLC, a primary human xenograft SCLC model was developed in the laboratory of Neil Watkins, M.B.B.S., Ph.D., assistant professor of oncology at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, with tissue taken directly from a chemo-naive patient. Following tumor debulking with carboplatin and etoposide (a similar regimen to that used clinically in SCLC patients), once-daily oral administration of IPI-926 led to a statistically significant delay in tumor re-growth, compared to vehicle control (p=0.01). Post-chemotherapy, tumor re-growth occurred in all vehicle-treated tumors while once-daily oral administration of IPI-926 led to 82 percent inhibition of tumor growth 35 days post chemotherapy treatment.
"These data suggest that novel inhibitors of the Hedgehog signaling pathway such as IPI-926 may offer much needed new approaches to targeting tumor stem cells and treating life-threatening cancers," stated William H. Matsui, M.D., assistant professor of oncology, Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. "While cancer stem cells are relatively rare, their capacity for self-renewal is likely responsible for the initiation, maintenance and progression of clinical disease through the continual production of new cancer cells. Thus, a better understanding of their biology may lead to the development of treatment strategies with the potential to produce longer-term remissions."
Additional in vitro data presented today also showed that administration of IPI-926 inhibits the growth of acute lymphocytic leukemia (ALL) by targeting a rare progenitor cell population. This subpopulation of tumor cells is believed to have greater self-renewal capacity than the bulk population of tumor cells, and these cells are likely to contribute to drug resistance in this disease. These data suggest that Hedgehog inhibition with IPI-926 may offer a promising new approach to treating ALL.
In a separate poster presented at AACR, data showed that administration of a single oral dose of IPI-926 to adult mice inhibited Hedgehog target gene expression in skin, demonstrating the feasibility of using skin for pharmacodynamic assessment of activity. Skin is a readily accessible tissue that is a convenient marker for biological activity, which may be easily incorporated into early-stage clinical trials.
Steven H. Holtzman, president, chair, and chief executive officer of Infinity, commented, "The data presented this week at AACR on IPI-926, as well as on retaspimycin hydrochloride, our novel Hsp90 inhibitor, highlight Infinity's innovative and fearless approach to oncology drug discovery and development. We believe the Hedgehog pathway and Hsp90 play critical roles in some of the most aggressive cancers for which there are few treatment options, and we look forward to advancing both programs in the months ahead."
About IPI-926
IPI-926 is a novel, proprietary derivative of the natural plant product cyclopamine that binds to the Smoothened receptor to inhibit the Hedgehog Pathway. In preclinical studies, IPI-926 has shown potent and selective inhibition of the Hedgehog pathway and attractive pharmacological properties including oral bioavailability and extended half-life. IPI-926 has demonstrated biological activity in multiple preclinical animal models of cancer. Infinity anticipates commencing clinical trials of IPI-926 in the second half of 2008.
About the Hedgehog Signaling Pathway
The Hedgehog signaling pathway is normally active during embryonic development in regulating tissue and organ formation. When abnormally activated in adults, however, the Hedgehog pathway is believed to play a central role in allowing the proliferation and survival of certain cancer-causing cells, including in certain deadly cancers such as pancreatic cancer, prostate cancer, small cell lung cancer, breast cancer and certain brain cancers. In addition, recent evidence also points to an important potential role for the Hedgehog pathway in cancer stem cells. Cancer stem cells are progenitor cells suspected to be primarily responsible for tumor growth, survival and metastasis, despite treatment with conventional chemotherapeutic agents.
About Infinity Pharmaceuticals, Inc.
Infinity is an innovative cancer drug discovery and development company that is seeking to leverage its strength in small molecule drug technologies to discover, develop, and deliver to patients best-in-class medicines for the treatment of cancer and related conditions. 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 Hsp90 and Hedgehog pathway inhibition to treat various types of cancer and future clinical trial activity for IPI-926 and Infinity's Hsp90 inhibitors. 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 any product candidate Infinity is developing 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 dependence on its collaboration with MedImmune/AstraZeneca; Infinity's ability to obtain additional funding required to conduct its research and development activities; 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 for the year ended December 31, 2007, as filed with the Securities and Exchange Commission on March 14, 2008. 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.
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