AVEO Pharmaceuticals' Selective Anti-Notch1 Monoclonal Antibody Exhibits Potent Notch1 Inhibitory Activity
Data Presented at AACR 101st Annual Meeting 2010; Confirm Potential Utility of AVEO's Antibody Pipeline
CAMBRIDGE, Mass., Apr 21, 2010 (BUSINESS WIRE) --AVEO Pharmaceuticals, Inc. (NASDAQ: AVEO), a biopharmaceutical company focused on discovering, developing and commercializing cancer therapeutics, today announced preclinical data which demonstrate that its Notch1-specific monoclonal antibody is a highly potent inhibitor of Notch1 function in both in vitro and in vivo models. These data were presented today at the American Association for Cancer Research (AACR) 101st Annual Meeting 2010 in Washington, D.C.
Effective blockade of Notch signaling has been demonstrated to effectively inhibit tumor angiogenesis, supporting the development of AVEO's Notch1 antibody as an anti-angiogenic agent. Recent data have also suggested an important role for Notch signaling in cancer stem cell maintenance. In the AVEO studies, the expression of Notch pathway-related genes was correlated with Notch pathway dependence in human cancer cell lines to identify tumors that are dependent upon tumor autonomous Notch signaling. Expression of a single Notch target gene, HeyL, was correlated with sensitivity of human cancer cell lines to inhibition of ligand-dependent Notch signal, confirming its role as a predictive biomarker of Notch-dependent tumors. Moreover, elevated HeyL expression identified a significant subset of tumors driven by the mutant Kras oncogene that may be dependent upon Notch signaling. Importantly, the lack of toxicity observed with AVEO's anti-Notch1 antibody in mouse models suggests that the antibody may be combinable with other targeted therapies to enhance anti-angiogenesis effects in the treatment of cancer.
"We believe that the progress we've made in the development of a robust monoclonal antibody pipeline is significant. These data follow on the heels of advances in our partnered antibody programs achieved last year, with our anti-HGF antibody AV-299 and anti-ErbB3 antibody AV-203, and are indicative of the continued potential we envision for our biology-driven oncology antibody pipeline focused on novel targets including RON, Notch and FGFR," said Tuan Ha-Ngoc, president and chief executive officer of AVEO Pharmaceuticals. "We believe that the Notch pathway plays a critical role in the maintenance of tumors. The activity of our Notch1 targeted monoclonal antibody seen in preclinical data to date highlights the potential utility of this therapy."
The Notch receptors are a family of four receptors on the surface of cells, Notch 1-4, whose activity has been shown to play important roles in normal stem cell function and in multiple aspects of tumor biology. Recent data also demonstrated a key role for Notch signaling in tumor angiogenesis.
AVEO generated monoclonal antibodies that inhibit various Notch receptors to assess the therapeutic potential of targeting the Notch pathway in cancer. Biochemical studies demonstrated that the antibody bound to the Notch1 ligand binding domain with high affinity, prevented ligand mediated activation of the receptor, and specifically repressed Notch1-dependent signaling with high potency. Specific inhibition of Notch1 by the antibody did not result in the dose-limiting gut toxicity observed with pan-Notch inhibitors, yet inhibition of functional angiogenesis was observed upon antibody treatment in both in vitro and in vivo models. The lack of toxicity seen with the antibody in mouse models suggests that inhibition of Notch1 could effectively be combined with other therapies to enhance treatment, or to overcome resistances to VEGF/VEGFR inhibition.
Also presented during the course of the meeting were chimeric mouse and Human-in-Mouse (HIM) models in support of AVEO's lead candidate tivozanib, a highly potent and selective inhibitor of VEGF receptors 1, 2 and 3, as well as preclinical data highlighting new targets in cancer, such as Furin. For more information on the data presented at AACR, please visit investor.aveopharma.com.
About AVEO's Notch Program
In vivo genetic screens conducted using AVEO's Human Response Platform(TM) have demonstrated that activation of the Notch signaling pathway is a potent driver of tumor growth and confirmed its important role in tumorigenesis in vivo. AVEO's Notch drug discovery efforts are focused on identifying specific inhibitory antibodies to Notch1, Notch2 and Notch3 that prevent ligand binding and activation of the receptors. To date, the program has generated functional inhibitory antibodies against the Notch1 and Notch3 receptors. To facilitate the in vivo assessment of anti-human Notch1 antibodies, AVEO created mice in which the murine Notch1 gene was replaced with a humanized Notch1 gene.
In June 2009, AVEO was granted a U.S. patent on a method of identifying cancer tissue likely to be sensitive or resistant to treatment with an inhibitor of Notch receptor activation.
About AVEO's Antibody Pipeline
AVEO is discovering and developing a pipeline of targeted therapies that address major unmet needs in oncology. The company utilizes its proprietary in vivo cancer models 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 scheduled to enter a Phase 2 clinical trial in the first half of 2010 and is the subject of a major co-development and co-commercialization partnership with Merck. 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 Fibroblast Growth Factor receptors (FGFR).
About AVEO
AVEO Pharmaceuticals (NASDAQ: AVEO) integrates a proprietary cancer biology platform with drug development and commercial expertise in its efforts to discover and develop targeted cancer therapeutics. The company's lead product, tivozanib, is an oral, triple VEGF receptor inhibitor with potential for a best-in-class profile. Tivozanib is currently being investigated in a global, randomized Phase 3 clinical trial called TIVO-1 comparing tivozanib to sorafenib in advanced kidney cancer, as well as additional clinical studies in other solid tumor types. AVEO's proprietary, integrated cancer biology platform offers the company a unique advantage in oncology drug development that both increases the probability of clinical success and provides a discovery engine for high-value targets. This approach has resulted in a promising pipeline of monoclonal antibodies against novel targets including HGF, ErbB3, RON, Notch and FGFR. For more information, please visit the company's website at www.aveopharma.com.
AVEO's Forward-looking Statements
Any statements in this press release about our future expectations, plans and prospects, including statements about ourantibody program potentially having utility in treating tumors dependent on the Notch pathway or being effectively combined with other targeted therapies to enhance treatment or to overcome resistances to VEGF/VEGFR inhibition, thepotential our biology-driven oncology antibody pipeline,our cancer biology platform increasing the probability of clinical success and providing a discovery engine for high-value targets, and other statements containing the words "believes," "anticipates," "plans," "expects," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks relating to: our ability to successfully research, develop and obtain and maintain regulatory approvals for tivozanib and our other product candidates including the antibodies described in this press release; our inability to obtain and maintain adequate protection for intellectual property rights relating to our product candidates and technologies; unplanned operating expenses and our ability to raise substantial additional funds to achieve our goals; general economic and industry conditions; and other factors discussed in the "Risk Factors" section of the final prospectus relating to our initial public offering filed with the Securities and Exchange Commission, and in other filings that we periodically make with the SEC. In addition, the forward-looking statements included in this press release represent our views as of the date of this press release. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.