AVEO's RON antibody shows anti-tumor activity in human cancer xenografts

Nov 19 2010

AVEO Pharmaceuticals, Inc. (NASDAQ: AVEO), a biopharmaceutical company focused on discovering, developing and commercializing cancer therapeutics, today announced preclinical data from AVEO's anti-RON antibody program which demonstrated the successful identification of antibodies with potent anti-tumor activity that demonstrated inhibition of the function of both wild type RON and the RONΔ160 variant, as well as a potential biomarker to identify tumors likely to respond to treatment with the anti-RON antibody. These data were presented yesterday in a late-breaker plenary presentation during the 22^nd Annual Symposium of the European Organization for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research (EORTC-NCI-AACR) in Berlin, Germany. The lead antibodies from this program have been humanized for planned therapeutic development.

“Essential role of fibroblast growth factor receptor 2 (FGFR2) in tumorigenesis of human cancers harboring FGFR2 amplification demonstrated by a functional blocking antibody.”

"We are very pleased with these preclinical results and the promise of our lead antagonistic RON antibody, which demonstrated anti-tumor activity in a panel of human cancer xenografts," stated Jeno Gyuris, Ph.D., senior vice president, head of research at AVEO. "We believe RON is a promising novel biological target for combating cancer growth and progression. These data, and the biomarker we have discovered, may help us identify responsive patient populations for clinical investigation of our anti-RON antibody."

RON (Recepteur d'Origine Nanatais, or MST1R) receptor tyrosine kinase is a member of the c-Met RTK family. The RON pathway is involved in several aspects of cancer development including regulation of tumor growth, survival and metastasis, and bone disruption. Research has shown that over-expression of RON has been observed in multiple solid tumor types including breast, colorectal, non-small cell lung, glioblastoma multiforme (GBM), prostate, pancreatic, ovarian and bladder cancers, and is associated with disease progression and metastasis.

AVEO's research of RON biology has been aided by its novel, genetically defined, in vivo murine tumor models and related bioinformatics tools. In AVEO's proprietary in vivo models, both wild-type RON and RONΔ160 have been shown to potently drive tumor growth, with AVEO's anti-RON antibodies demonstrating strong anti-tumor activity. AVEO has also utilized its unique bioinformatics tools for biomarker research and to generate a RON pathway gene index that quantifies the level of RON pathway activation. AVEO has used this index to identify human tumor cell lines with high RON pathway activity, and has demonstrated in preclinical models that the inhibition of RON function by the anti-RON antibody potently inhibited tumor cell growth and survival. These studies provided preclinical evidence of the potential benefits of RON inhibition and identified a genetic context in which RON inhibition may have therapeutic benefit.

"We believe that the preclinical data from our RON program are promising and that these data, as well as the findings in our FGF program, are indicative of the continued potential we envision for our biology-driven oncology antibody pipeline," said Elan Ezickson, executive vice president and chief business officer of AVEO. "We believe that the progress we've made in the development of a robust and diverse monoclonal antibody pipeline is significant and provides us with strategic options. With AV-299 in Phase 2 clinical development, AV-203 in IND-enabling studies and preclinical work continuing in our Notch pathway program, and with our lead small molecule program - tivozanib - rapidly advancing in Phase 3 clinical development, we believe we are in a unique position with a strong portfolio of oncology product candidates."

FGFR Preclinical Findings Also Highlighted at EORTC

Findings from AVEO's work on the FGFR pathway, which strongly support the belief that FGFR2 plays an essential role in the initiation and/or maintenance of human cancers harboring FGFR2 amplification, were highlighted in a poster presentation earlier this week titled, "Essential role of fibroblast growth factor receptor 2 (FGFR2) in tumorigenesis of human cancers harboring FGFR2 amplification demonstrated by a functional blocking antibody."

Fibroblast growth factors, or FGFs, and their receptors, FGFR1-4, represent a signaling network that may play an important role in the regulation of cell growth, survival, differentiation and angiogenesis. Through its Human Response Platform™ (HRP), AVEO has identified FGF ligands and receptors as potential drivers of tumor growth in a variety of tumor models and observed the activation of the pathway in tumor development. In this study, AVEO generated monoclonal antibodies (mAbs) against the extracellular ligand binding domain of FGFR2 to address the role of FGFR2 in tumorigenesis and to explore the potential of FGFR2 as a novel therapeutic target. AVEO scientists used an FGFR2-IIIb specific antibody to investigate the importance of FGFR2 signaling in gastric and breast cancer cell lines in vitro and in vivo. This antibody specifically and potently inhibited the growth of FGFR2-amplified human cancer xenografts. These findings suggest that cancer patients with activated/amplified FGFR2 signaling could potentially benefit from therapeutic intervention with FGFR2-targeting antibodies.

AVEO's Antibody Discovery and Development Capabilities

AVEO is actively pursuing a pipeline of 10 antibody programs designed to produce inhibitory antibodies against four important cancer target classes/pathways that have been identified using AVEO's proprietary genetic screens. In addition to leveraging AVEO's technology for target identification and validation, AVEO has also developed a unique array of discovery capabilities and tools to facilitate generation and selection of optimized antibody therapeutics. The company utilizes its proprietary in vivo cancer models in its efforts to identify and validate pathways and targets whose dysregulation drives tumor growth and maintenance.

The company's drug discovery efforts are focused on functional antibodies that inhibit the activity of these targets. AVEO's most advanced antibody program, AV-299, a potent functional anti-HGF antibody, is in Phase 2 clinical development. AVEO's second most advanced antibody program targets the ErbB3 (HER3) receptor, and is partnered with Biogen Idec. AVEO has additional unpartnered preclinical antibody discovery programs underway focusing on other important cancer targets, including the RON, Notch, and FGFR pathways.

Source: AVEO Pharmaceuticals, Inc.