AVEO Pharmaceuticals’ Novel Triple VEGF Receptor Inhibitor Shows Tumor Regression in Patients with Advanced Renal Cancer; Clinical Activity and Tolerability in other Solid Tumors including Colon and Lung Cancers

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AVEO Pharmaceuticals’ Novel Triple VEGF Receptor Inhibitor Shows Tumor Regression in Patients with Advanced Renal Cancer; Clinical Activity and Tolerability in other Solid Tumors including Colon and Lung Cancers

Proprietary Human Response Platform Data Reveal Distinct Biomarkers Potentially
Critical to Determining Treatment Success
   

SAN DIEGO, Calif and CAMBRIDGE, Mass, April 14, 2008 – AVEO Pharmaceuticals, Inc., a biotechnology company leveraging breakthrough discoveries in cancer biology to discover, develop and commercialize targeted oncology therapies, today announced that their novel oral triple VEGF receptor inhibitor AV-951 shows clinical activity in multiple advanced solid tumor types including renal, colon and lung cancers and is well tolerated according to new data from the expanded Phase 1 clinical trial of the company’s lead product candidate.  Partial response or stable disease was observed across all patients with renal cell carcinoma, and overall, one-third of patients across all tumor types achieved tumor shrinkage during treatment with AV-951.  These data, along with results from a new pre-clinical study utilizing AVEO’s Human Response Platform (HRP™) to evaluate potential biomarkers for AV-951 sensitivity and resistance in proprietary models of breast cancer, were presented today at the American Association for Cancer Research (AACR) annual meeting.

“Despite the availability of a number of therapies targeting the VEGF receptor kinase, off-target toxicities associated with these drugs have led to poor combinability with other targeted agents and chemotherapy,” stated Robert Figlin, MD, chair, Division of Medical Oncology and Therapeutics Research, and Arthur and Rosalie Kaplan Professor of Medical Oncology at the City of Hope Comprehensive Cancer Center in Duarte, CA.  “The clinical activity and good tolerability observed in the complete Phase 1 trial of AV-951 further highlight the potential role of this agent in the treatment of numerous cancers, as a single agent or in combination with other anti-cancer agents and is encouraging for us in the medical community.” 

In the Phase 1 dose-escalation study presented at an AACR oral session evaluating 41 patients with advanced solid tumors taking 1.0 mg, 1.5 mg and 2.0 mg per day of orally administered AV-951, clinical benefit (i.e., partial response or stable disease lasting for three months or longer) was achieved across multiple tumor types.  Strong anti-tumor activity was seen in nine patients with advanced renal cancer, with two patients achieving partial responses and seven achieving stable disease.  In addition, clinical benefit was observed in patients with colon and lung cancers.  Overall, tumor shrinkage was observed in 33 percent of all patients during treatment with AV-951.  Study results also indicated that the maximum tolerated dose of oral AV-951 is 1.5 mg/day when given for 28 consecutive days followed by two weeks off treatment.  Hypertension, a biomarker of VEGF inhibition, was the most frequently observed side effect observed with AV-951; hypertension was dose-dependent and manageable with standard anti-hypertensive drugs. 

“Results from Phase 1 research of our novel, oral triple VEGFR inhibitor have not only indicated highly selective, potent activity in some of the most difficult-to-treat cancers, but these new data showcase the promising efficacy, safety and tolerability of AV-951 at doses lower than other approved targeted therapies,” said Tuan Ha-Ngoc, president and chief executive officer of AVEO.  “We look forward to obtaining initial results from our ongoing 200-patient single agent Phase 2 trial and our Phase 1b Torisel combination trial, both in patients with metastatic renal cell cancer, later this year.”     

Additional data presented today at a separate AACR oral session provided new information regarding AV-951 drug sensitivity in vivo and specific molecular signatures to help identify responsive patient populations.  Leveraging AVEO’s proprietary HRP™ to support further development of AV-951, AVEO created an alternate approach for preclinical antiangiogenic response prediction and biomarker discovery.  A large, proprietary population of more than 100 genetically engineered murine breast tumors were generated, in which defined genetic alterations, such as HER2 overexpression, were allowed to be combined with spontaneous genetic alterations to more accurately model human cancer populations. Characterization of this tumor population revealed a surprising degree of variation in key parameters such as angiogenesis, microvasculature, VEGF expression, microarray gene expression and chromosomal gain/loss by array Comparative Genomic Hybridization.

Based on this work, AVEO has conducted drug efficacy studies of AV-951 across multiple tumors in this novel preclinical model. These efforts have revealed potential molecular signatures that may serve as biomarkers for clinical responsiveness to AV-951.

“These data showcase our ability to clearly isolate tumor response to AV-951 across a more human-like population of genetically engineered tumors,” stated Murray Robinson, PhD, senior vice president of oncology at AVEO.  “We believe our novel, integrated cancer biology platform and cutting-edge translational research effort, predicting potential human response to specific anti-cancer therapies, truly differentiates AVEO and will ultimately increase the probability of our clinical, regulatory and commercial success as we further develop our pipeline.”

About AV-951

AV-951 is a novel, highly potent and specific inhibitor of VEGF receptors 1, 2 and 3. Angiogenesis inhibition has demonstrated benefit for patients with a wide range of cancer types, including renal cell carcinoma, metastatic breast cancer, colorectal cancer, and non-small cell lung cancer.  Due to its specificity, AVEO believes AV-951 may be more readily combined with standard chemotherapy as well as other targeted therapies, potentially increasing the breadth of its clinical utility.  AVEO’s translational research effort, comprising its Human Response Platform, offers an opportunity to exploit AV-951’s unique characteristics and will provide further insight into potential clinical settings, combinability with other anti-cancer agents, tumor subtypes and responsive patient populations.

AVEO has initiated a Phase 2 trial of AV-951 in approximately 200 patients with metastatic renal cell carcinoma (mRCC) as well as a Phase 1b trial in combination with temsirolimus, an approved mTOR inhibitor, in patients with mRCC.

About AVEO

AVEO is a clinical-stage biopharmaceutical company focused on the discovery and development of novel, targeted cancer therapeutics.  AVEO’s proprietary, integrated cancer biology platform enables the company to pursue highly efficient drug development strategies in oncology that increase the probability of clinical success and provides a discovery engine for high-value targets.  This approach has resulted in a balanced pipeline of novel cancer therapies focused on well-validated targets (VEGFR, EGFR) and promising novel targets (HGF), as well as collaborations with Eli Lilly, Merck, OSI Pharmaceuticals and Schering-Plough.  Through a combination of internal drug discovery and selective in-licensing of targeted therapeutics, AVEO is building a diversified product pipeline and moving toward its vision of becoming a fully integrated biopharmaceutical company. For more information, please visit the company's website at http://www.aveopharma.com/.