AVEO Pharmaceuticals presented a novel human hepatocyte growth factor (HGF) knock-in model and announced data demonstrating strong preclinical activity of SCH 900105 (AV-299), a highly potent antagonist of hepatocyte growth factor/scatter factor (HGF/SF)
DENVER, CO, USA | APRIL 20, 2009 | AVEO Pharmaceuticals, Inc., a biopharmaceutical company leveraging breakthrough discoveries in cancer biology to discover, develop and commercialize targeted oncology therapies, today presented a novel human hepatocyte growth factor (HGF) knock-in model and announced data demonstrating strong preclinical activity of SCH 900105 (AV-299), a highly potent antagonist of hepatocyte growth factor/scatter factor (HGF/SF). Additionally, data assessing Fibroblast Growth Factor Receptor-2 (FGFR-2) response to an FGFR antagonist in a novel FGFR-2 driven model were also highlighted. These data were presented today at the American Association for Cancer Research (AACR) 100th Annual Meeting in Denver, Colorado.
“Preclinical data presented at AACR underscore the unique capability of our proprietary Human Response Platform to guide drug development strategies for our lead antibody candidate SCH 900105 (AV-299), currently in Phase 1 clinical development, and reinforce the broad potential of our rapidly maturing proprietary antibody pipeline,” stated Tuan Ha-Ngoc, president and chief executive officer of AVEO Pharmaceuticals. “Through internal antibody discovery efforts and selective in-licensing of targeted small molecule therapeutics, AVEO is building a diversified product pipeline and rapidly advancing toward its vision of becoming a fully integrated oncology company.”
The HGF/c-Met pathway in human cancer is frequently activated by stromal derived HGF. In order to faithfully recreate the tumor-stromal-endothelial interactions of HGF/c-Met axis in preclinical efficacy models, AVEO created a human HGF “knock-in” host strain, replacing the murine HGF gene with human HGF gene. Multiple paracrine models were established in this host strain, allowing the testing of SCH 900105 (AV-299) in a setting more relevant to human disease.
Preclinical data presented at AACR demonstrated that SCH 900105 (AV-299) is efficacious in glioblastoma multiforme, non-small cell lung cancer (NSCLC), and pancreatic cancer models. In the U87 GBM model, SCH 900105 (AV-299) administration resulted in complete regressions even after withdrawal of treatment. In addition, several combination studies performed with SCH 900105 (AV-299) and other targeted therapeutics, chemotherapies and anti-angiogenic agents demonstrated additive efficacy in vivo.
AVEO Genetic Screen Identifies Fibroblast Growth Factor Receptor-2 (FGFR-2) As Promising Target
AVEO identified FGFR-2 as an important tumor maintenance gene utilizing its proprietary in vivo genetic screen technology. To further validate the target, and to create a unique FGFR-2 driven tumor model, AVEO applied its directed complementation technology to develop a novel FGFR-2 driven breast tumor model. Drug efficacy studies using a non-selective FGFR inhibitor resulted in pharmacodynamic inhibition of the introduced human FGFR2 protein and led to significant tumor growth inhibition.
Consistent with this effort at AVEO, recent data from human correlative and mutational studies has implicated FGFR2 as a potentially important target in human breast cancer.
“We are pleased that the data we’ve generated using our in vivo genetic screen technology is aligning with emerging data from human studies,” stated Murray O. Robinson, Ph.D., senior vice president, oncology, at AVEO. “The FGFR-2-driven models may serve as a critical tool in developing new therapies that target FGFR-2, and given the activity seen by non-selective FGFR-2 antagonists in this model, we believe that an antibody specific to FGFR-2 may be a promising therapeutic agent.”
About SCH 900105 (AV-299) and AVEO/Schering-Plough Global Partnership
SCH 900105 (AV-299) is a highly potent humanized neutralizing antibody against hepatocyte growth factor/scatter factor (HGF/SF), which has demonstrated excellent activity in preclinical models of human cancer. AVEO’s SCH 900105 (AV-299) program exemplifies the progress AVEO has made in discovering drugs that target functionally-relevant tumor maintenance genes identified and validated by AVEO in its proprietary in vivo cancer models. To guide the clinical development of SCH 900105 (AV-299), AVEO is using its proprietary, genetically engineered models of human cancer to identify molecular signatures that define subpopulations of cancer that are more likely to respond to SCH 900105 (AV-299).
On April 4th, 2007, AVEO announced that it had entered an exclusive worldwide license and development agreement with Schering-Plough for SCH 900105 (AV-299). AVEO will have primary responsibility for clinical development of SCH 900105 (AV-299) through proof-of-concept in man and will apply its HRP™ during a multi-year translational research program designed to discover biomarker profiles of patients most likely to benefit from treatment with SCH 900105 (AV-299). AVEO retains the option to co-promote SCH 900105 (AV-299) in the United States for certain oncology indications. Under the terms of the deal, AVEO received a $7.5 million upfront payment and a $10 million equity investment from Schering-Plough. Schering-Plough will fund all research and development expenses. Milestone payments for the successful development and commercialization of AV-299, if all approvals in multiple indications and all sales milestones are achieved, could exceed $460 million. Upon commercialization, AVEO is eligible to receive royalties on net sales.
About AVEO
AVEO is a late-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 and therapies. This approach has resulted in a balanced pipeline of novel cancer therapies focused on well-validated targets (VEGFR, EGFR) and promising novel targets (HGF, FGFR, ErbB3 and NOTCH), as well as collaborations with Eli Lilly, Merck, OSI Pharmaceuticals, Schering-Plough and Biogen Idec. The company’s lead product, AV-951, a potential best-in-class triple VEGF receptor inhibitor, is completing Phase 2 clinical development in patients with metastatic renal cell cancer and is expected to enter Phase 3 development in 2009. 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 www.aveopharma.com.
SOURCE: AVEO Pharmaceuticals, Inc.
Post Views: 131
AVEO Pharmaceuticals presented a novel human hepatocyte growth factor (HGF) knock-in model and announced data demonstrating strong preclinical activity of SCH 900105 (AV-299), a highly potent antagonist of hepatocyte growth factor/scatter factor (HGF/SF)
DENVER, CO, USA | APRIL 20, 2009 | AVEO Pharmaceuticals, Inc., a biopharmaceutical company leveraging breakthrough discoveries in cancer biology to discover, develop and commercialize targeted oncology therapies, today presented a novel human hepatocyte growth factor (HGF) knock-in model and announced data demonstrating strong preclinical activity of SCH 900105 (AV-299), a highly potent antagonist of hepatocyte growth factor/scatter factor (HGF/SF). Additionally, data assessing Fibroblast Growth Factor Receptor-2 (FGFR-2) response to an FGFR antagonist in a novel FGFR-2 driven model were also highlighted. These data were presented today at the American Association for Cancer Research (AACR) 100th Annual Meeting in Denver, Colorado.
“Preclinical data presented at AACR underscore the unique capability of our proprietary Human Response Platform to guide drug development strategies for our lead antibody candidate SCH 900105 (AV-299), currently in Phase 1 clinical development, and reinforce the broad potential of our rapidly maturing proprietary antibody pipeline,” stated Tuan Ha-Ngoc, president and chief executive officer of AVEO Pharmaceuticals. “Through internal antibody discovery efforts and selective in-licensing of targeted small molecule therapeutics, AVEO is building a diversified product pipeline and rapidly advancing toward its vision of becoming a fully integrated oncology company.”
The HGF/c-Met pathway in human cancer is frequently activated by stromal derived HGF. In order to faithfully recreate the tumor-stromal-endothelial interactions of HGF/c-Met axis in preclinical efficacy models, AVEO created a human HGF “knock-in” host strain, replacing the murine HGF gene with human HGF gene. Multiple paracrine models were established in this host strain, allowing the testing of SCH 900105 (AV-299) in a setting more relevant to human disease.
Preclinical data presented at AACR demonstrated that SCH 900105 (AV-299) is efficacious in glioblastoma multiforme, non-small cell lung cancer (NSCLC), and pancreatic cancer models. In the U87 GBM model, SCH 900105 (AV-299) administration resulted in complete regressions even after withdrawal of treatment. In addition, several combination studies performed with SCH 900105 (AV-299) and other targeted therapeutics, chemotherapies and anti-angiogenic agents demonstrated additive efficacy in vivo.
AVEO Genetic Screen Identifies Fibroblast Growth Factor Receptor-2 (FGFR-2) As Promising Target
AVEO identified FGFR-2 as an important tumor maintenance gene utilizing its proprietary in vivo genetic screen technology. To further validate the target, and to create a unique FGFR-2 driven tumor model, AVEO applied its directed complementation technology to develop a novel FGFR-2 driven breast tumor model. Drug efficacy studies using a non-selective FGFR inhibitor resulted in pharmacodynamic inhibition of the introduced human FGFR2 protein and led to significant tumor growth inhibition.
Consistent with this effort at AVEO, recent data from human correlative and mutational studies has implicated FGFR2 as a potentially important target in human breast cancer.
“We are pleased that the data we’ve generated using our in vivo genetic screen technology is aligning with emerging data from human studies,” stated Murray O. Robinson, Ph.D., senior vice president, oncology, at AVEO. “The FGFR-2-driven models may serve as a critical tool in developing new therapies that target FGFR-2, and given the activity seen by non-selective FGFR-2 antagonists in this model, we believe that an antibody specific to FGFR-2 may be a promising therapeutic agent.”
About SCH 900105 (AV-299) and AVEO/Schering-Plough Global Partnership
SCH 900105 (AV-299) is a highly potent humanized neutralizing antibody against hepatocyte growth factor/scatter factor (HGF/SF), which has demonstrated excellent activity in preclinical models of human cancer. AVEO’s SCH 900105 (AV-299) program exemplifies the progress AVEO has made in discovering drugs that target functionally-relevant tumor maintenance genes identified and validated by AVEO in its proprietary in vivo cancer models. To guide the clinical development of SCH 900105 (AV-299), AVEO is using its proprietary, genetically engineered models of human cancer to identify molecular signatures that define subpopulations of cancer that are more likely to respond to SCH 900105 (AV-299).
On April 4th, 2007, AVEO announced that it had entered an exclusive worldwide license and development agreement with Schering-Plough for SCH 900105 (AV-299). AVEO will have primary responsibility for clinical development of SCH 900105 (AV-299) through proof-of-concept in man and will apply its HRP™ during a multi-year translational research program designed to discover biomarker profiles of patients most likely to benefit from treatment with SCH 900105 (AV-299). AVEO retains the option to co-promote SCH 900105 (AV-299) in the United States for certain oncology indications. Under the terms of the deal, AVEO received a $7.5 million upfront payment and a $10 million equity investment from Schering-Plough. Schering-Plough will fund all research and development expenses. Milestone payments for the successful development and commercialization of AV-299, if all approvals in multiple indications and all sales milestones are achieved, could exceed $460 million. Upon commercialization, AVEO is eligible to receive royalties on net sales.
About AVEO
AVEO is a late-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 and therapies. This approach has resulted in a balanced pipeline of novel cancer therapies focused on well-validated targets (VEGFR, EGFR) and promising novel targets (HGF, FGFR, ErbB3 and NOTCH), as well as collaborations with Eli Lilly, Merck, OSI Pharmaceuticals, Schering-Plough and Biogen Idec. The company’s lead product, AV-951, a potential best-in-class triple VEGF receptor inhibitor, is completing Phase 2 clinical development in patients with metastatic renal cell cancer and is expected to enter Phase 3 development in 2009. 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 www.aveopharma.com.
SOURCE: AVEO Pharmaceuticals, Inc.
Post Views: 131
