Infinity Reports New Preclinical Data for Saridegib at AACR Supporting Development in Residual Disease Settings

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Apr 1, 2012 - Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) today presented new preclinical data for saridegib (IPI-926), its novel oral molecule that inhibits Smoothened, a key component of the Hedgehog pathway. Data presented showed the anti-tumor activity of saridegib in models of residual disease, in which malignant cells remain present after primary treatment. Importantly, these data show that the ability of saridegib to delay tumor recurrence is time dependent and provide rationale for the development of saridegib in residual disease settings, such as ovarian cancer and small cell lung cancer. These data were presented during a mini symposium session at the American Association for Cancer Research (AACR) 103rd Annual Meeting in Chicago, Illinois (Abstract #979).

“In certain cancers, the activity of the Hedgehog pathway is believed to increase in response to therapy and is thought to play a role in tumor recurrence by promoting the survival of residual cancer cells. Today, we showed for the first time that in preclinical models of residual disease, treatment with saridegib post-therapy delays tumor recurrence, but exhibits a time dependence, or an activity window,” stated Vito Palombella, Infinity's chief scientific officer. “These results are intriguing because they provide insight for the design of clinical trials with Hedgehog pathway inhibitors in a range of residual disease settings and demonstrate the importance of administering saridegib immediately post-therapy.”

Saridegib has been previously shown to delay tumor recurrence following cytoreduction (tumor shrinkage caused by treatment with chemotherapy or targeted therapy) in multiple preclinical models of residual disease, including ovarian, prostate and lung cancer.1,2,3,4 New preclinical data presented today support these findings and show that cytoreduction leads to temporal changes in the tumor microenvironment, as well as upregulation of the Hedgehog ligand and pathway signaling in the tumor cells and surrounding stromal cells, respectively. These new data also suggest that saridegib treatment inhibits the observed Hedgehog pathway activation and may delay tumor recurrence by increasing necrosis, or tumor cell death, post-therapy. Saridegib showed the greatest inhibition of tumor regrowth when administered within 10 days of completing primary therapy, suggesting that there may be a window of activity during which the effects of saridegib are greatest. This presentation, “The anti-tumor activity of the Smoothened inhibitor saridegib (IPI-926) in models of residual disease is time dependent,” may be found in the Publications Archive on Infinity's website, http://www.infi.com/product-candidates-publications.asp.

The window of activity for saridegib in preclinical models was confirmed in a model of ovarian cancer through a collaboration with Bo Rueda, Ph.D., associate director, Vincent Center for Reproductive Biology, Massachusetts General Hospital and associate professor, Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School. A poster highlighting this work, “Hedgehog pathway inhibition delays regrowth of ovarian cancer following paclitaxel and carboplatinum only if initiated immediately after completion of chemotherapy,” will be presented during a poster session on Tuesday, April 3, 2012, from 9:00 a.m. — 1:00 p.m. ET in McCormick Place West, Hall F, Poster Section 11 (Abstract #3285).

About the Hedgehog Pathway and Saridegib

Malignant activation of the Hedgehog pathway occurs in a broad range of cancers through multiple mechanisms, including signaling directly to tumor cells, signaling to tumor progenitor cells and signaling to the tumor microenvironment. Saridegib is a small molecule that inhibits Smoothened, a key component of the Hedgehog pathway. Smoothened inhibition represents a significant anti-cancer opportunity for addressing a number of difficult-to-treat cancers by disrupting malignant activation of the pathway.

Saridegib is currently being evaluated in a randomized, double-blind Phase 2 clinical trial designed to evaluate the safety and efficacy of saridegib compared to placebo in patients with metastatic or locally advanced, inoperable chondrosarcoma, an incurable cancer of the cartilage. In addition, an exploratory Phase 2 trial is under way evaluating saridegib as a single agent in patients with myelofibrosis, a cancer of the bone marrow. In Phase 1 trials, saridegib has been generally well-tolerated and showed evidence of clinical activity. These clinical trials build upon a robust set of supporting data that provide a strong rationale for evaluating the potential of IPI-926 for treatment across a broad range of cancers.

About Infinity Pharmaceuticals, Inc.

Infinity is an innovative drug discovery and development company seeking to discover, develop and deliver to patients best-in-class medicines for difficult-to-treat diseases. Infinity combines proven scientific expertise with a passion for developing novel small molecule drugs that target emerging disease pathways. Infinity's programs focused on the inhibition of the Hedgehog pathway, heat shock protein 90 and phosphoinositide-3-kinase are evidence of its innovative approach to drug discovery and development. For more information on Infinity, please refer to the company's website at 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 those regarding the potential of Hedgehog pathway inhibition for addressing multiple, difficult-to-treat cancers, and the potential of saridegib in residual disease settings such as ovarian cancer and small cell lung 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 Infinity's strategic alliance with Mundipharma will continue for its expected term or that it will fund Infinity's programs as agreed, that any product candidate Infinity is developing will successfully complete necessary preclinical and clinical development phases, or that development of any of Infinity's product candidates will continue. Further, there can be no guarantee that any positive developments in Infinity's product portfolio will result in stock price appreciation. Management's expectations could also be affected by risks and uncertainties relating to: Infinity's 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; unplanned cash requirements and expenditures, including in connection with business development activities; development of agents by Infinity's competitors for diseases in which Infinity is currently developing its product candidates; 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, 2011, filed with the Securities and Exchange Commission on March 13, 2012. 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.

1 McCann CK; Growdon WB; Kulkarni-Datar K; Curley MD; Friel, AM, et al. Inhibition of Hedgehog Signaling Antagonizes Serous Ovarian Cancer Growth in a Primary Xenograft Model. PlosOne 2011; 6(11): 1-9.

2 Mandley E, White K, Faia K, Travaglione V, McGovern K and MacDougall J. The Hh inhibitor IPI-926 delays tumor re-growth of a non-small cell lung cancer xenograft model following treatment with an EGFR targeted tyrosine kinase inhibitor. Poster session presented at American Association for Cancer Research 103rd Annual Meeting; 2010 April 17-21; Washington, D.C.

3 Travaglione V, Peacock C, MacDougall J, McGovern K, Cushing J, et al. A Novel Hh pathway inhibitor, IPI-926, delays recurrence post-chemotherapy in a primary human SCLC xenograft. Poster session presented at American Association for Cancer Research 101st Annual Meeting; 2008 April 12-16; San Diego, CA.

4 Proctor J, Travaglione V, Deyneko I, White K, Read MR, et al. Hedgehog Signaling in Castration Resistant Prostate Cancer. Mini-symposia presented at American Association for Cancer Research 103rd Annual Meeting; 2010 April 17-21; Washington, D.C.

Contact: Infinity Pharmaceuticals, Inc.
Jaren Irene Madden, 617-453-1336
Jaren.Madden@infi.com
http://www.infi.com
or
Media:
Liz Falcone, 617-761-6727
Liz.Falcone@fkhealth.com

 

Posted: April 2012

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