-- Infinity Advances Hedgehog Pathway Inhibitor Into Later Clinical Development --
-- New Preclinical Data in Several Cancer Indications Further Support Broad Therapeutic Potential of IPI-926 --
CAMBRIDGE, Mass., April 21, 2010 (GLOBE NEWSWIRE) -- Infinity Pharmaceuticals, Inc. (Nasdaq:INFI), an innovative drug discovery and development company, today announced that it has initiated a randomized Phase 1b/2 clinical trial evaluating IPI-926, its novel, oral Hedgehog pathway inhibitor, in combination with gemcitabine in patients with pancreatic cancer. In addition, Infinity reported new preclinical data on IPI-926 during the 2010 American Association of Cancer Research (AACR) Annual Meeting demonstrating that IPI-926 delays tumor re-growth after regression of the tumors by chemotherapy and by targeted therapy, further supporting the potential for Hedgehog pathway inhibition by IPI-926 in a broad range of difficult to treat cancers.
"We are excited to evaluate IPI-926 in a clinical study that builds upon the encouraging preclinical data we have generated in which Hedgehog pathway inhibition may improve access of chemotherapeutics to tumors by altering the tumor microenvironment," said Vito Palombella, Ph.D., vice president of drug discovery, Infinity. "Pancreatic cancer is an aggressive disease with few meaningful therapeutic options. We believe the administration of IPI-926 in combination with chemotherapy may represent a new approach to improving outcomes in patients with this disease."
Pancreatic Cancer Clinical Trial and Preclinical Rationale
The Phase 1b/2 clinical trial evaluates patients with previously untreated, metastatic pancreatic cancer. The Phase 1b portion of the study is a dose-escalation evaluating once-daily oral administration of IPI-926 and weekly intravenous administration of gemcitabine. The Phase 2 portion of this trial is set to commence once the recommended Phase 2 doses for IPI-926 and gemcitabine have been established. The Phase 2 is an international, multi-center, randomized, double-blind study evaluating approximately 120 patients. The primary endpoint of the Phase 2 portion of the study is overall survival. Secondary endpoints include progression free survival, time to progression, and overall response rate.
"There is a critical need for new therapies for patients with pancreatic cancer, particularly therapies that could be used in combination with current standards of care," said Charles Fuchs, M.D., disease center leader, Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute, associate professor of medicine at Harvard Medical School, and an investigator in the trial. "Inhibiting the malignant activation of the Hedgehog pathway with IPI-926 represents an innovative approach to addressing a number of difficult to treat cancers, and I look forward to exploring the potential activity of IPI-926 in this important area in cancer research."
A paper published in Science last year by Cancer Research UK's Cambridge Research Institute in collaboration with Infinity reported that in a transgenic mouse model of chemotherapy-resistant pancreatic cancer, the administration of IPI-926 in combination with gemcitabine improved drug delivery, and resulted in induction of apoptosis in the tumor, decreased metastases, and a doubling of median survival as compared to control.
Further, Infinity presented new preclinical data at AACR building upon the rationale for combining IPI-926 with a variety of chemotherapies in pancreatic cancer. Data reported show that in a xenograft model of pancreatic cancer, the combination of IPI-926 and nab-paclitaxel resulted in 77% tumor growth inhibition compared to control (p=0.0048). These data, along with data showing an increase in tumor perfusion by IPI-926, demonstrated that IPI-926 may increase the activity of nab-paclitaxel through increased drug delivery.
Information regarding the clinical trial, including participating clinical trial sites, is available at www.clinicaltrials.gov.
Preclinical Data in Minimal Residual Disease Setting Presented at AACR
At AACR, Infinity reported new preclinical data demonstrating that IPI-926 delays tumor re-growth after regression of the tumor by either chemotherapy or targeted therapy. In an oral presentation, Infinity reported data showing that administration of IPI-926 in combination with docetaxel, a chemotherapy, led to a statistically significant delay in tumor re-growth compared to vehicle control (p=0.004) in a xenograft model of castration resistant prostate cancer. Post-chemotherapy, tumor re-growth occurred in all vehicle-treated tumors while co-administration of IPI-926 led to 70 percent inhibition of tumor growth 55 days post chemotherapy treatment.
In a poster presentation, Infinity showed that IPI-926, when administered after treatment with a targeted therapy, gefitinib, significantly delayed tumor re-growth in EGFR-mutated non-small cell lung cancer (NSCLC) xenograft models. Data showed that treatment with gefitinib resulted in an up-regulation of Hedgehog ligands that signal to the surrounding tumor stroma. Infinity has demonstrated that IPI-926 significantly down-regulates Hedgehog signaling in tumor stroma, leading to tumor growth inhibition in xenografts. Data presented showed that in models of NSCLC, tumors treated with IPI-926 after regression following treatment with gefitinib, led to a 65% decrease (p=0.0104) in tumor volume compared to vehicle-treated mice, suggesting an important role for Hedgehog pathway inhibition in delaying tumor re-growth in NSCLC. Further, Infinity has previously shown data demonstrating that IPI-926 was active in delaying tumor re-growth after cytoreduction by chemotherapy in xenograft models of small cell lung and ovarian cancers.
Together, these preclinical data suggest that inhibition of the Hedgehog pathway might be an important strategy in minimal residual disease where the tumor initially responds to therapy, but later relapses – a paradigm that is applicable to multiple cancer types and treatment modalities.
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 in the inhibition of the Hsp90 chaperone system, the Hedgehog pathway and fatty acid amide hydrolase are evidence of its innovative approach to 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 those regarding the utility of Hedgehog pathway inhibition and the therapeutic potential 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 Infinity's strategic alliance with Mundipharma International Corporation Ltd. will continue for its expected term or that it will fund Infinity's programs as agreed. Management's expectations could also 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; unplanned cash requirements and expenditures, including in connection with business development activities; 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 12, 2010. 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.