2009-11-17 18:38:03 -

AVEO Pharmaceuticals, Inc., a biopharmaceutical company focused on discovering, developing and commercializing cancer therapeutics, today announced preliminary results from a Phase 1 clinical study evaluating its oral, triple VEGF receptor inhibitor tivozanib in combination with the mTOR inhibitor temsirolimus (Torisel ® ), a rapamycin pro-drug, in patients with advanced kidney cancer. Torisel is approved in the United States and European Union for

the treatment of advanced kidney cancer. Preliminary results of this ongoing study show tumor shrinkage in 12 out of 16 patients evaluated, and two partial responses as assessed by RECIST criteria; the combination was well-tolerated with no dose limiting toxicities (DLT). These data were presented today at the International Conference, “Molecular Targets and Cancer Therapeutics,” hosted by the American Association for Cancer Research (AACR), National Cancer Institute (NCI), and European Organization for Research and Treatment of Cancer (EORTC) in Boston, Mass.

“While efficacy and tolerability of targeted cancer therapies are paramount, safe combinations of novel drugs are also critical to ensuring optimal treatment for patients with difficult-to-treat cancers such as advanced kidney cancer; toxicities associated with many currently available TKIs limit the opportunity for a combination approach,” commented Fairooz Kabbinavar, M.D., professor of medicine and urologic oncology, Henry Alvin and Carrie L. Meinhardt chair in Kidney Cancer Research, director, Hematology-Oncology Fellowship Program, medical director, Thoracic Oncology and Kidney Cancer Programs, David Geffen School of Medicine, University of California, Los Angeles and a co-investigator in the study. “The results observed in the tivozanib Phase 1 combination study with temsirolimus indicate anti-tumor activity with a favorable tolerability profile; this is the first positive combination data we've seen for a VEGF TKI with an mTOR inhibitor.”

The Phase 1 study assessed once-daily, oral tivozanib (three weeks on, one week off) and IV temsirolimus (IV once weekly) in 16 patients with advanced kidney cancer with clear cell component, who had failed up to one prior VEGF-targeted therapy. Median duration of treatment was 16.8 weeks, with a range of 0.7 to 51.4 weeks. Following are preliminary results from this ongoing study.



- Tumor shrinkage was observed in 12 patients with two partial responses, as evaluated using RECIST criteria
- Maximum tolerated dose was tivozanib 1.5 mg and temsirolimus 25 mg; there were no dose limiting toxicities and no grade 4 toxicities in the study
- Treatment related adverse events seen in ≥ 20% of patients include mucositis/stomatitis, thrombocytopenia, diarrhea, fatigue, hypertension, rash, nausea and vomiting

Preclinical Combination Data in Breast Cancer Model

Results from a preclinical study evaluating the activity of tivozanib and mTOR inhibitor rapamycin, as single agents and in combination, in a genetically engineered HER2 driven breast adenocarcinoma model were also presented at the meeting. Data indicate that tivozanib and rapamycin each exhibited distinct inhibition profiles as single agents, and that evidence of resistance began to emerge after six weeks of treatment with either drug alone. However, when combined, no evidence of drug resistance was observed with the tivozanib/rapamycin combination over the course of the study.



About AVEO

AVEO is a biopharmaceutical company focused on discovering, developing and commercializing cancer therapeutics. Its product candidates are targeted against important mechanisms known or believed to be involved in cancer. AVEO has recently completed a 272-patient phase 2 clinical trial of tivozanib, its lead product candidate, in renal cell cancer, or RCC. AVEO is also conducting phase 1b trials of tivozanib in various combinations and dosing regimens in RCC and additional solid tumor indications, including breast cancer, colorectal cancer and lung cancer.
In addition to tivozanib, AVEO has a pipeline of monoclonal antibodies derived from its Human Response Platform technology, or HRP™, a novel method of building preclinical models of human cancer which is intended to more accurately represent cancer in patients. For more information, please visit the company’s website at www.aveopharma.com : .

AVEO Pharmaceuticals, Inc.David Johnston, Chief Financial

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