Data Demonstrate Significant Effect On Tumor-Stroma Interaction With Infinity's Hedgehog Pathway Inhibitor IPI-926

Main Category: Cancer / Oncology
Also Included In: Clinical Trials / Drug Trials
Article Date: 24 Oct 2008 - 9:00 PDT

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Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) announced that preclinical studies of IPI-926, Infinity's oral Hedgehog pathway inhibitor currently in Phase 1 clinical development, demonstrate 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. Data reported today also show that in a preclinical model of human pancreatic cancer, daily administration of IPI-926 results in significant tumor growth inhibition when compared to vehicle controls. These data were presented at the 20th EORTC-NCI-AACR Symposium on "Molecular Targets and Cancer Therapeutics" in Geneva, Switzerland.

Data presented demonstrate that a single administration of IPI-926 in a preclinical model of human pancreatic cancer results in rapid and sustained Hedgehog pathway inhibition in the stromal cells, as measured by Gli1 expression, a downstream mediator of Hedgehog signaling. These findings suggest that IPI-926 inhibits tumor growth by down-regulating Hedgehog signaling to tumor associated stroma. The interaction between tumor cells and their supporting stromal cells, mediated by Hedgehog ligand protein expression, is believed to be critical for cell growth in several cancers, including pancreatic, colon, breast and ovarian cancer, suggesting that inhibition of Hedgehog signaling with IPI-926 is an attractive area for clinical study.

"These data not only further our understanding of the tumor-stroma relationship responsible for certain deadly cancers, but demonstrate the impact that novel Hedgehog inhibitor IPI-926 has on those cancer-enabling mechanisms," stated Vito Palombella, Ph.D., vice president of discovery at Infinity. "The anti-tumor activity seen with IPI-926 in a model of human pancreatic cancer is very encouraging, particularly when considering the potential application across several other Hedgehog-reliant cancers."

IPI-926 is a novel, proprietary inhibitor of the Hedgehog signaling pathway currently in Phase 1 development. The Hedgehog pathway is believed to be implicated in at least three cancer settings:

- first, in cancers in which there is aberrant Hedgehog ligand expression driving tumor-stromal interactions, such as in pancreatic cancer;
- second, in cancers in which there is a genetic mutation activating the pathway, such as in medulloblastoma; and
- third, in cancers in which there is a subpopulation of self-renewing progenitor-like cells that are chemo-resistant and Hedgehog dependent, such as in small cell lung cancer.

IPI-926 has demonstrated anti-tumor activity in multiple models across each of these three cancer settings.

During the Annual Meeting of the American Association of Cancer Research (AACR) in April 2008, Infinity presented preclinical data showing that in a novel model of medulloblastoma, IPI-926 demonstrated excellent oral bioavailability, a long plasma half-life and duration of action, and good distribution to tumor tissue. In addition, daily oral administration of IPI-926 in this model led to dose-dependent inhibition of tumor growth, with tumor regression seen at higher doses.

Additional data presented at AACR demonstrated that IPI-926 delayed tumor growth following chemotherapy in a preclinical model of small cell lung cancer (SCLC). In this model, following tumor debulking with a treatment regimen similar to that used clinically in patients with SCLC, once-daily oral administration of IPI-926 led to a statistically significant delay in tumor re-growth as compared to vehicle control.

"The results presented today augment a growing body of preclinical data illustrating the potential for IPI-926 in treating a multitude of deadly cancers and underscore Infinity's expertise and emerging leadership in Hedgehog pathway inhibition," stated Julian Adams, Ph.D., president of research and development and chief scientific officer at Infinity. "Our Hedgehog program is further evidence of Infinity's ongoing commitment to emerging cancer targets, and to those patients in need of better therapies. We look forward to learning more about IPI-926 as we pursue Phase 1 evaluation of this novel anti-cancer compound."

Phase 1 Study of IPI-926

Infinity recently announced that it has initiated a Phase 1 clinical trial evaluating IPI-926 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 will evaluate potential anti-tumor activity of IPI-926 and examine pharmacodynamic markers of its 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 and future clinical trial activity of IPI-926. 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 preclinical data will be replicated in clinical studies. 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 ability to obtain additional funding required to conduct its research, development and commercialization 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 quarterly report on Form 10-Q for the quarter ended June 30, 2008, as filed with the Securities and Exchange Commission on August 6, 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.

Infinity Pharmaceuticals, Inc.