Infinity and MedImmune Provide Update On Phase I GIST Trial for IPI-504, a Novel Hsp90 Inhibitor
Phase I Trial Expanded to Test Multiple Administration Schedules
ORLANDO, Fla., Jan. 22, 2007 (PRIME NEWSWIRE) -- Infinity Pharmaceuticals, Inc. (Nasdaq:INFI) and MedImmune, Inc. (Nasdaq:MEDI) today announced updated preliminary data from an open-label Phase I study of IPI-504, a small molecule inhibitor of heat shock protein 90 (Hsp90), in patients with Gleevec-resistant metastatic gastrointestinal stromal tumors (GIST). The data, which included further evidence of biological activity of IPI-504, were presented at the American Society of Clinical Oncology (ASCO) 2007 Gastrointestinal Cancers Symposium. Additionally, the companies announced that they have begun dose administration on a second schedule for this Phase I trial of IPI-504.
The updated data were presented on January 19 by George Demetri, M.D., Director of the Ludwig Center at Dana-Farber/Harvard and Director of Dana-Farber's Center for Sarcoma and Bone Oncology. Accompanying Dr. Demetri's oral presentation was a poster entitled, "Inhibition of the heat shock protein 90 (Hsp90) chaperone with the novel agent IPI-504 to overcome resistance to small molecule kinase inhibitors (SMKIs) in metastatic GIST: Updated results of a Phase I trial."
As reported, in eight of 18 evaluated patients (44%), positron emission tomography (PET) imaging revealed a decrease in tumor uptake of 18-fluorodeoxyglucose, an imaging agent used to measure metabolic activity, in response to IPI-504 administration (referred to as a "PET response"). This update of previously reported results includes an additional PET response at 400 mg/m2. (See below for additional information about PET imaging.) In addition to the observed PET responses, stable disease has allowed seven of 20 evaluated patients (35%) to receive five or more cycles of therapy with IPI-504. IPI-504 has been well-tolerated at all dose levels tested, and a maximum tolerated dose has not been reached.
The goal of this Phase I study of IPI-504 is to evaluate the safety and maximum tolerated dose, pharmacokinetics, and biological activity of IPI-504, and to recommend a dose for further studies. To date, 21 patients have received IPI-504 on its original schedule ("Schedule A") at dose levels ranging from 90 to 400 mg/m2. Schedule A entailed a 21-day cycle with patients treated with IPI-504 on days 1, 4, 8, and 11, followed by 10 days off treatment (referred to as a "drug holiday"). Patients were eligible to receive multiple cycles of therapy if clinical benefit was observed.
Based on the observed evidence of biological activity and IPI-504's observed tolerability to date, Infinity and MedImmune have expanded the Phase I trial as previously announced to add a second schedule of administration ("Schedule B"). On the new schedule, patients are treated with IPI-504 twice weekly without a drug holiday in a 21-day cycle. The first patient on Schedule B was enrolled in December.
Preliminary data from the trial were initially announced in November 2006 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Prague, Czech Republic.
IPI-504 is Infinity's proprietary small molecule drug candidate being developed jointly by Infinity and MedImmune. In preclinical studies, IPI-504 has been shown to potently and selectively inhibit Hsp90, thereby killing cancer cells. 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 GIST. In preclinical studies, IPI-504 has demonstrated 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.
Heat shock protein 90 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, also called "client proteins" of Hsp90. Many cancers result from specific mutations in such client proteins; Hsp90 enables those cancers' survival by maintaining the function of their mutated client proteins. Therefore, 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 Gastrointestinal Stromal Tumors (GIST) and Hsp90
The American Cancer Society (ACS) reports that GIST is the most frequent form of gastrointestinal sarcoma, a life-threatening disease highly resistant to traditional cytotoxic chemotherapy or radiation treatment. The ACS estimates that between 4,500 and 6,000 Americans develop GIST each year. In the majority of GIST cases, specific mutations in cellular signaling enzymes ("kinases") called KIT or PDGFRA cause the growth and survival signal of the cell to become permanently active, leading to cancer. Both KIT and PDGFRA are client proteins of Hsp90, suggesting that inhibition of Hsp90 in GIST is an attractive area for clinical study.
About Positron Emission Tomography (PET) Imaging
Positron emission tomography, also called PET, is an imaging technology that measures functional processes in the body. A radioactive isotope is attached to a metabolically active molecule related to glucose; the combined tracer molecule is then injected into the human body where it is taken up and trapped within the tumor cells. The most common tracer used in oncology for PET imaging is 18-fluorodeoxyglucose, or 18-FDG. Different colors or degrees of brightness on a PET image represent different levels of tissue or organ metabolic activity. PET imaging in oncology takes advantage of the fact that cancer cells exhibit higher-than-normal levels of glucose uptake and, therefore, show up clearly as bright spots on PET images. Oncologists often use PET scans to detect tumors, or to examine the effects of a cancer therapy by measuring the metabolic activity of the cancer cell before and after treatment. To date, 18-FDG PET imaging results have correlated very well with clinical outcomes in GIST patients treated with molecular targeted therapies.
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, Infinity's lead Hsp90 inhibitor in Phase I clinical trials, as well as next-generation oral versions of IPI-504 and a series of preclinical 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. INFI-G
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 www.medimmune.com.
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.
Gleevec(r) is a registered trademark of Novartis Pharmaceuticals Corporation.
-0- CONTACT: Infinity Pharmaceuticals, Inc. Media: Monique Allaire 617-453-1105 Investors: John Evans 617-453-1254
MedImmune, Inc. Media: Kate Barrett 301-398-4320 Investors: Peter Vozzo 301-398-4358 http://www.medimmune.com
Posted: January 2007