Preclinical Data Also Support Evaluation of Retaspimycin in HER2-Positive Breast Cancer and Metastatic Melanoma
SAN DIEGO, Calif., April 15, 2008 – Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) and MedImmune today announced that preclinical studies evaluating lead drug candidate retaspimycin hydrochloride ("retaspimycin," also known as IPI-504) suggest that retaspimycin represents a novel strategy for the potential treatment of patients with non-small cell lung cancer (NSCLC) who exhibit resistance to Iressa® (gefitinib) or Tarceva® (erlotinib). Data were presented today during the Annual Meeting of the American Association of Cancer Research (AACR) in San Diego, California. Retaspimycin, a selective small molecule inhibitor of heat shock protein 90 (Hsp90), is currently being evaluated in the Phase 2 portion of an ongoing Phase 1/2 clinical trial in patients with advanced non-small cell lung cancer.
Multiple mechanisms have been identified that are believed to mediate acquired resistance to tyrosine kinase inhibitors in NSCLC, including epidermal growth factor receptor (EGFR) secondary mutations and MET amplification. These resistance mechanisms can occur concurrently in the same tumor. The data reported today at AACR suggest that irrespective of the resistance mechanism, these cancer cells remain sensitive to Hsp90 inhibition, and retaspimycin potently induces apoptosis (cell death) in these preclinical experiments. In xenograft models of Iressa-resistant lung cancer, administration of retaspimycin resulted in significant anti-tumor activity. In addition, enhanced anti-tumor activity was reported in these models when retaspimycin was administered in combination with Iressa even though the cells had acquired resistance to Iressa as a single agent.
"Existing therapies in many types of cancer are not adequate because they are either not comprehensive enough or resistance develops and therapies are no longer effective," stated Pasi A. Janne, M.D., Ph.D., assistant professor of medicine at the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute and lead investigator on this preclinical study. "Hsp90 inhibition functions regardless of the mutation in the cancerous protein that confers resistance, providing us with a novel approach to address the growing challenge of acquired drug resistance. Furthermore, Hsp90 inhibition provides the ability for a single agent to inhibit multiple different simultaneous resistance mechanisms."
In two additional AACR abstracts, data were presented that show the activity of retaspimycin in preclinical models of both melanoma and breast cancer. In melanoma, the main genetic lesions identified in patients are activating mutations in B-Raf. These mutations make the activity of the B-Raf protein dependent upon Hsp90, and administration of retaspimycin has been shown preclinically to potently inhibit B-Raf signaling and to induce apoptosis. In xenograft models of human melanoma, tumor growth was significantly inhibited following administration of retaspimycin alone and in combination with Taxol® (paclitaxel).
In breast cancer, over-expression of the protein HER2 predicts an aggressive disease for which there are few treatment options available. Preclinical data suggest that HER2 is very sensitive to Hsp90 inhibition, and retaspimycin demonstrated significant biological activity when administered as a single agent in both Herceptin® (trastuzumab)-sensitive as well as Herceptin-resistant breast cancer xenograft models. In addition, in these models the combination of retaspimycin and Herceptin resulted in tumor regression as well as more robust anti-tumor activity than when either agent was administered alone. Regression was also observed in preclinical models when retaspimycin was administered in combination with Tykerb® (lapatinib). These studies support the clinical development of retaspimycin in patients with HER2 positive breast cancer and metastatic melanoma.
"We are very pleased with the growing preclinical and clinical evidence supporting the potential of retaspimycin in a broad range of cancers – both as a single agent and in combination with other anti-cancer treatments," stated Steven H. Holtzman, president, chair, and chief executive officer at Infinity. "The promising results presented at AACR further support the clinical development path we have created for our Hsp90 program."
About Retaspimycin Hydrochloride
Retaspimycin hydrochloride, also known as IPI-504, is a small molecule drug candidate being developed jointly by MedImmune and Infinity. Retaspimycin has shown evidence of biological activity in a Phase 1 clinical trial in patients with metastatic and/or unresectable gastrointestinal stromal tumors (GIST) and in the Phase 1 portion of a Phase 1/2 study in patients with advanced non-small cell lung cancer (NSCLC). Retaspimycin is also being evaluated in Phase 2 studies in patients with NSCLC and patients with hormone-refractory prostate cancer, as well as in a Phase 1b trial in combination with Taxotere® (docetaxel).
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.infi.com.
MedImmune strives to provide better medicines to patients, new medical options for physicians and rewarding careers to employees. Dedicated to advancing science and medicine to help people live better lives, the company is focused on cardiovascular/gastrointestinal disease, neuroscience, oncology, infection, respiratory disease and inflammation. With approximately 3,000 employees worldwide and headquarters in Maryland, MedImmune is wholly owned by AstraZeneca plc (LSE: AZN.L, NYSE: AZN). For more information, visit MedImmune'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 retaspimycin hydrochloride. Such statements reflect the current views of Infinity and/or MedImmune and are based on certain assumptions. MedImmune is a member of the AstraZeneca Group of companies. Actual results could differ materially from those currently anticipated as a result of a number of factors, including risks and uncertainties discussed in the reports and other documents filed by Infinity and AstraZeneca with the Securities and Exchange Commission and in Infinity's annual report on Form 10-K for the year ended December 31, 2007 filed with the Securities and Exchange Commission on March 14, 2008. 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 Infinity and AstraZeneca expressly disclaim any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as otherwise may be required by applicable law or regulation.
Iressa®, Tarceva®, Taxol®, Herceptin®, Tykerb®, and Taxotere® are registered trademarks of AstraZeneca plc, OSI Pharmaceuticals, Inc.,Bristol-Myers Squibb, Hoffman-La Roche Ltd., GlaxoSmithKline, and sanofi-aventis llc, respectively. INFI-G