CAMBRIDGE, Mass. and GAITHERSBURG, Md., Feb. 14, 2007 (PRIME NEWSWIRE) -- Infinity Pharmaceuticals, Inc. (Nasdaq:INFI) and MedImmune, Inc. (Nasdaq:MEDI) today announced the initiation of a Phase I/II clinical trial of IPI-504, the companies' development-stage anti-cancer agent and heat shock protein 90 (Hsp90) inhibitor. In this study, which marks the second solid tumor indication in which IPI-504 is being tested, investigators will evaluate IPI-504 in patients with advanced non-small cell lung cancer (NSCLC). This open-label Phase I/II clinical trial of IPI-504 is being conducted at the Massachusetts General Hospital (MGH) and the Dana-Farber Cancer Institute (DFCI) in Boston, Mass.
"Because IPI-504 has an important mechanism of action with the potential to treat patients with resistant disease, we are very excited to initiate this trial in patients with advanced non-small cell lung cancer," said Thomas Lynch, M.D., Chief of Hematology-Oncology at MGH and Director of the Center for Thoracic Cancers at MGH. "Targeted therapies such as erlotinib and gefitinib have improved outcomes in many lung cancer patients, but resistance to these agents remains a challenge."
The goal of the Phase I portion of the multi-center study is to evaluate the safety and the maximum tolerated dose (MTD) of IPI-504 in patients with advanced NSCLC. Once dose-escalation is completed, the Phase II portion of the trial will begin with a goal of determining the potential anti-tumor activity of IPI-504 in NSCLC patients either with or without epidermal growth factor receptor (EGFR) mutations. During this study, IPI-504 will be administered twice weekly by intravenous infusion. Evidence of biological activity in these molecularly defined sub-groups of patients will be evaluated using both CT scans and positron emission tomography, or PET, imaging.
In preclinical models of NSCLC, Infinity researchers have demonstrated that IPI-504 potently inhibits the growth of tumor cells that have a mutated form of EGFR. Mutant EGFR is stabilized and expression enabled by the cellular protein Hsp90; inhibition of Hsp90 leads to the degradation of mutant EGFR and to cancer cell death. Moreover, as demonstrated in preclinical studies, IPI-504 remains effective in inhibiting cell growth and inducing cell death in NSCLC cell lines that have additional mutations that confer resistance to the approved EGFR inhibitors Tarceva(r) (erlotinib) and Iressa(r) (gefitinib).
"The initiation of this Phase I/II trial of IPI-504 is a major milestone for Infinity and underscores the broad potential of IPI-504 in advanced cancer," said David Grayzel, M.D., Vice President of Clinical Development and Medical Affairs, Infinity. "We are delighted to be collaborating with Dr. Lynch, a leader in the treatment of lung cancer, and his colleagues at MGH and the Dana-Farber."
IPI-504 is also being evaluated in an ongoing Phase I trial in patients with refractory gastrointestinal stromal tumors (GIST). Preliminary data from the trial presented at the American Society of Clinical Oncology (ASCO) 2007 Gastrointestinal Cancers Symposium indicate that IPI-504 has demonstrated biological activity in GIST and has been well-tolerated by patients evaluated to date.
About IPI-504
IPI-504 is a small molecule drug candidate being developed jointly by Infinity and MedImmune. IPI-504 has been well-tolerated in its ongoing Phase I studies and has shown promising biological activity in a Phase I clinical trial in patients with relapsed, refractory Gleevec(r)-resistant gastrointestinal stromal tumors (GIST). In preclinical studies, IPI-504 has been shown to inhibit Hsp90 potently and selectively, thereby killing cancer cells. IPI-504 has also demonstrated, in preclinical studies, broad potential to treat certain cancers as both a single agent as well as in combination with existing anti-cancer drugs. The water-based formulation of IPI-504 is delivered as an intravenous infusion; an oral formulation of IPI-504 is currently in preclinical development.
About Hsp90
Hsp90 is an emerging therapeutic target of interest for the treatment of cancer. Proteins are the mainstay of structural and signaling elements of all cells. Hsp90 is a molecule that maintains the conformation and activity of specific proteins in the cell -- these proteins are known as "client proteins" of Hsp90. Many cancers result from specific mutations in, or aberrant expression of, these client proteins. Examples of oncogenic client proteins of Hsp90 include c-Kit in GIST, epidermal growth factor receptor, or EGFR, in NSCLC, and Bcr-Abl in chronic myelogenous leukemia. Hsp90 enables those cancers' survival by maintaining the function of oncogenic client proteins. In preclinical studies, inhibition of Hsp90 has been shown to lead to the degradation of these proteins and cell death, or apoptosis. In addition, oncogenic client proteins that have become resistant to approved targeted therapies have also been shown preclinically to remain sensitive to Hsp90 inhibition. Inhibition of Hsp90 has broad therapeutic potential for the treatment of patients with solid tumors and blood-related cancers, including cancers that are resistant to other drugs.
About Non-Small Cell Lung Cancer
The American Cancer Society (ACS) reports that lung cancer is the leading cause of cancer death for both men and women. The ACS estimates that approximately 214,000 new cases of lung cancer will be diagnosed in the United States in 2007. According to the ACS, non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for about 85% of all lung cancers. In some cases, specific mutations have been identified in a cellular signaling enzyme called epidermal growth factor receptor (EGFR). These mutations allow the survival signal of the mutated cancer cell to be switched "on" all the time. NSCLC patients with mutations in EGFR have been found to benefit from drugs such as Tarceva(r) and Iressa(r) that block EGFR signaling. Over time, however, resistance mutations develop such that patients become resistant to these agents. EGFR is a highly-sensitive client protein of Hsp90, suggesting that inhibition of Hsp90 in NSCLC is an attractive area for clinical study.
About Infinity -- MedImmune Collaboration
In August 2006, Infinity and MedImmune announced that they had entered into an agreement to jointly develop and commercialize novel small molecule cancer drugs targeting heat shock protein 90 (Hsp90) and the Hedgehog cell-signaling pathway. The collaboration is focused on IPI-504, the lead Hsp90 inhibitor in Phase I clinical trials, as well as next-generation oral versions of IPI-504 and a series of molecules targeting the Hedgehog pathway.
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.ipi.com.
About MedImmune, Inc.
MedImmune strives to provide better medicines to patients, new medical options for physicians, rewarding careers to employees, and increased value to shareholders. Dedicated to advancing science and medicine to help people live better lives, the company is focused on the areas of infectious diseases, cancer and inflammatory diseases. With more than 2,500 employees worldwide, MedImmune is headquartered in Maryland. For more information, visit the company's website at http://www.medimmune.com.
Forward-Looking Statements
This announcement contains, in addition to historical information, certain forward-looking statements that involve risks and uncertainties, in particular statements related to the research and development of IPI-504 and other compounds targeting Hsp90. Such statements reflect the current views of MedImmune and/or Infinity management and are based on certain assumptions. Actual results could differ materially from those currently anticipated as a result of a number of factors, including risks and uncertainties discussed in MedImmune's filings with the U.S. Securities and Exchange Commission and in Infinity's quarterly report on Form10-Q for the quarter ended September 30, 2006. There can be no assurance that such development efforts will succeed, that the products will receive required regulatory clearance or, even if such regulatory clearance is received, that the subsequent products will ultimately achieve commercial success. Further, any forward-looking statements contained in this announcement speak only as of the date hereof, and MedImmune and Infinity expressly disclaim any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
Tarceva(r) and Iressa(r) are registered trademarks of OSI Pharmaceuticals, Inc. and AstraZeneca, respectively.