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Old 03-30-2009, 05:51 AM   #1
eric
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Phase 2 Trial of IPI-504 in Combination With Herceptin

I know that there is some excitement about some HSP90 inhibitors at Sloan.
http://www.reuters.com/article/press...09+GNW20090330
Infinity Initiates International Phase 2 Trial of IPI-504 in Combination WithHerceptin(r) in Patients With HER2-Positive Breast CancerCAMBRIDGE, Mass., March 30, 2009 (GLOBE NEWSWIRE) -- Infinity Pharmaceuticals,Inc. (Nasdaq:INFI), an innovative cancer drug discovery and development company,today announced the initiation of a Phase 2 clinical trial of IPI-504(retaspimycin hydrochloride), its lead heat shock protein 90 (Hsp90) inhibitor,in combination with Herceptin(r) (trastuzumab) in patients with human epidermalgrowth factor receptor 2 (HER2)-positive breast cancer. IPI-504 has demonstratedthe potential to disrupt the activity of multiple proteins and cell signalingpathways implicated in tumor growth, including HER2, a key signaling pathway inbreast cancer."This trial will explore the combination of two targeted agents, IPI-504 andtrastuzumab (Herceptin), which should complement each other by disrupting HER2signaling in different ways," said Clifford A. Hudis, M.D., Chief of the BreastCancer Medicine Service and Attending Physician at Memorial Sloan-KetteringCancer Center and an investigator in the trial. "In earlier trials with arelated agent we documented clear evidence of activity when Hsp90 inhibition isadded to trastuzumab in patients with HER2-positive breast cancer. I lookforward to further exploring IPI-504's potential activity in this excitingarea."The goal of this open-label, international, multi-center Phase 2 clinical trialis to evaluate the safety and anti-tumor activity of IPI-504 in combination withHerceptin in patients with pretreated, locally advanced or metastaticHER2-positive breast cancer. IPI-504 is being administered intravenously at 300mg/m2 on a three-week cycle, consisting of twice-weekly treatment for two weeksfollowed by one week off treatment. Herceptin will be administered intravenouslyonce every three weeks. Evidence of anti-tumor activity will be evaluated usingRECIST criteria (Response Evaluation Criteria in Solid Tumors). The Phase 2study will enroll a total of 46 patients and Infinity anticipates presentingpreliminary data in mid-2010."By blocking HER2 signaling through a novel mechanism, IPI-504 may provide a newoption for patients with HER2-positive breast cancer -- one that may overcomeresistance to HER2 targeted agents," said Jose Baselga, M.D., chairman of theMedical Oncology Service and director of the Division of Medical Oncology,Hematology, and Radiation Oncology at the Vall d'Hebron University Hospital inBarcelona, Spain, professor of Medicine at the Universidad Autonoma de Barcelonaand an investigator in the trial.Preclinical data suggest that the HER2 oncoprotein is degraded rapidly whenHsp90 is inhibited by IPI-504, which eliminates HER2 signaling and ultimatelycauses the tumor cell to die. Infinity researchers have demonstrated thatIPI-504 potently inhibits the growth of tumor cells when administered as asingle agent in both Herceptin-sensitive as well as Herceptin-resistant breastcancer xenograft models. Moreover, in these models, the combination of IPI-504and Herceptin results in more robust anti-tumor activity than when either agentwas administered alone."We believe the demonstrated potency and tumor growth inhibition we've seen inpreclinical models of HER2-positive breast cancer with IPI-504 and thesensitivity of the HER2 protein to Hsp90 inhibition could positionanti-chaperone therapy as a key component in the treatment of HER2-positivebreast cancer," said David S. Grayzel, M.D., vice president, clinicaldevelopment and medical affairs at Infinity.Infinity is evaluating the potential of Hsp90 inhibition in a broad range ofcancers, The RING trial is an international Phase 3 registration trial inpatients with refractory gastrointestinal stromal tumors that positions IPI-504as the potential first-in-class Hsp90 inhibitor. IPI-504 is also being evaluatedin a Phase 2 study in patients with advanced non-small cell lung cancer and in aPhase 1b combination study with Taxotere(r) (docetaxel) in patients withadvanced solid tumors. Infinity anticipates presenting data from both of thesestudies in mid-2009. Infinity is also evaluating its oral hsp90 inhibitor,IPI-493, in a Phase 1 study in patients with advanced solid tumors, andanticipates reporting preliminary data from this study by the end of 2009.Targeting Heat Shock Protein 90 (Hsp90) and the Chaperone SystemHsp90 is a central component of the cellular chaperone system -- a system thatsupports and stabilizes a number of cancer-causing proteins such as c-Kit, EGFR,and HER2, enabling multiple forms of cancer to thrive. Inhibition of the Hsp90chaperone knocks out this critical source of support for cancer cells, leadingto tumor growth inhibition and cancer cell death. Anti-chaperone therapy viainhibition of Hsp90 may represent a significant yet currently unaddressedstrategy for treating patients with cancer. Infinity is developing twoproprietary anti-chaperone agents, IPI-504 (i.v.) and IPI-493 (oral), which haveshown potent and selective inhibition of Hsp90 in preclinical studies.About HER2-Positive Breast CancerThe American Cancer Society (ACS) reports that among American women, breastcancer is the most common form of cancer. The ACS estimates that approximately182,000 new cases of breast cancer were diagnosed in women in the United Statesin 2008. Statistically, one in eight women will be diagnosed with invasivebreast cancer in her lifetime. Studies show that approximately 25 percent ofbreast cancer patients have an over-expression of a protein called HumanEpidermal Growth Factor Receptor 2, or HER2, and this over-expression isreferred to as HER2-positive. HER2 is a protein that stimulates cancer cells todivide and protects them from cell death. HER2-positive breast cancer is anaggressive subtype of breast cancer. While current therapies targeting HER2 havedemonstrated significant clinical benefit, a substantial number of patients withHER2-positive breast cancer develop recurrent disease, for which novel therapiesare needed.About Infinity Pharmaceuticals, Inc.Infinity is an innovative cancer drug discovery and development company seekingto discover, develop, and deliver to patients best-in-class medicines for thetreatment of cancer and related conditions. Infinity combines proven scientificexpertise with a passion for developing novel small molecule drugs that targetemerging cancer pathways. Infinity's two most advanced programs in Hsp90inhibition and Hedgehog signaling pathway inhibition are evidence of itsinnovative approach to oncology drug discovery and development. For moreinformation on Infinity, please refer to the company's website athttp://www.infi.com.Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of ThePrivate Securities Litigation Reform Act of 1995. These statements involve risksand uncertainties that could cause actual results to be materially differentfrom historical results or from any future results expressed or implied by suchforward-looking statements. Such forward-looking statements include statementsregarding the utility of IPI-504 in HER2-positive breast cancer; future clinicaltrial activity of IPI-504; the potential of IPI-504 to be the first-to-marketHsp90 inhibitor, and the presentation of additional clinical data on IPI-504.Such statements are subject to numerous factors, risks and uncertainties thatmay cause actual events or results to differ materially from the company'scurrent expectations. For example, there can be no guarantee that IPI-504 willsuccessfully complete necessary preclinical and clinical development phases. Inparticular, management's expectations could be affected by risks anduncertainties relating to: results of clinical trials and preclinical studiesfor IPI-504 and competitor Hsp90 inhibitors, including subsequent analysis ofexisting data and new data received from ongoing and future studies; the contentand timing of decisions made by the U.S. Food and Drug Administration and otherregulatory authorities, investigational review boards at clinical trial sites,and publication review bodies; Infinity's ability to enroll patients in itsclinical trials; decisions made by organizations evaluating data forpresentation or publication; Infinity's ability to obtain additional fundingrequired to conduct its research, development and commercialization activities;unplanned cash requirements and expenditures; Infinity's ability to obtain,maintain and enforce patent and other intellectual property protection for anyproduct candidates it is developing; and Infinity's reliance on its strategicalliance partners for financial support. These and other risks which may impactmanagement's expectations are described in greater detail under the caption"Risk Factors" included in Infinity's annual report on Form 10-K filed with theSecurities and Exchange Commission on March 13, 2009. Further, anyforward-looking statements contained in this press release speak only as of thedate hereof, and Infinity expressly disclaims any obligation to update anyforward-looking statements, whether as a result of new information, futureevents or otherwise.Herceptin(r) and Taxotere(r) are registered trademarks of Genentech, Inc. andsanofi-aventis llc, respectively.-0-CONTACT: Infinity Pharmaceuticals, Inc. Monique Allaire 617-453-1105 Monique.Allaire@infi.com http://www.infi.com
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Old 04-05-2009, 03:21 PM   #2
Rich66
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Thanks Eric, in addition to the potential benefits of the studied combination, I am heartened to see the use of a 3 week Herceptin schedule.
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