Triple VEGF Receptor Inhibitor

Highlights :

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Monday, 27 April 2009 13:17

AVEO Pharmaceuticals, Inc., a biopharmaceutical company leveraging breakthrough discoveries in cancer biology to discover, develop and commercialize targeted oncology therapies, today announced data from its proprietary preclinical models which demonstrates that the company's potent and selective triple VEGF receptor inhibitor, AV-951, exhibits robust inhibitory activity in its novel, genetically engineered model of hepatocellular carcinoma (HCC), the most common form of liver cancer. These data were presented at the American Association for Cancer Research (AACR) 100th Annual Meeting in Denver, Colorado.

"By utilizing the unique capability of our proprietary cancer biology platform to guide drug development strategies for AV-951, which is currently completing Phase 2 clinical development in advanced renal cell carcinoma, we are able to create more relevant models of human cancer in which to evaluate efficacy," stated Tuan Ha-Ngoc, president and chief executive officer of AVEO Pharmaceuticals. "The activity of AV-951 in AVEO-engineered models of hepatocellular carcinoma highlights the potential role of our novel, triple VEGF receptor inhibitor in the treatment of this deadly cancer."

AVEO generated primary HCC tumors in mice using a previously established tissue reconstitution approach. Mice reconstituted with KRAS/p53- and myc/p53- developed tumors in the liver with a latency of two to five months and penetrance of 30 to 50 percent. Histological examination demonstrated that these tumors resemble the features of human HCCs.

Preclinical data presented at AACR showed variation in vessel histology among primary HCC tumors, and a subset of HCC tumors exhibited microvessels consistent with VEGF driven angiogenesis. AVEO observed activity of its potent, triple VEGF inhibitor AV-951 in these HCC models, suggesting that AV-951 may be an efficacious single-agent treatment for human HCC.

"Recently, one multi-targeted tyrosine kinase inhibitor was able to demonstrate survival benefit in this type of liver cancer. To evaluate whether AVEO's selective VEGF receptor inhibitor may be efficacious in liver cancer, we created and evaluated these engineered HCC models," stated Murray O. Robinson, Ph.D., senior vice president of oncology at AVEO. "We are encouraged by the activity of AV-951 in this model."

About Liver Cancer

Liver cancer is the fifth most common cancer type and the third leading cause of cancer related death worldwide. In the U.S., the number of new cases continues to rise. The most common causes of liver cancer include hepatitis B/C infection, consumption of Aflatoxin B1 contaminated food, and alcohol abuse. The prognosis for most liver cancer patients is extremely poor due to late diagnosis and the five-year overall survival is less than 10 percent. Current treatment options are limited and include surgery, radiation therapy and chemotherapy. Liver cancer can be divided into two subtypes: hepatocellular carcinoma (HCC), which originates from hepatocytes and accounts for 80 to 90 percent of the cases; and adenocarcinoma, which originates from ductal epithelial cells and accounts for the other 10 to 20 percent.

About AV-951

AV-951 is a novel, highly potent and selective inhibitor of VEGF receptors 1, 2 and 3, exhibiting picomolar inhibitory activity against all three receptors. 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 potency and specificity, AVEO believes AV-951 may enable maximal inhibition of the VEGF pathway, while avoiding side effects associated with off-target activity. Such a profile may enable AV-951 to be more readily combined with standard chemotherapy as well as other targeted therapies, potentially increasing the breadth of its clinical utility. In addition, AVEO has evaluated AV-951 using its Human Response Platform (HRP™), a unique set of engineered tumor models that provide further insight into potential clinical settings, combinability with other anti-cancer agents, tumor subtypes and responsive patient populations.

AVEO is conducting a Phase 2 placebo-controlled, randomized discontinuation trial assessing the efficacy and safety of once-daily, oral AV-951 in renal cell carcinoma (RCC) as well as ongoing Phase 1b trials of AV-951 in combination with temsirolimus, an approved mTOR inhibitor, in patients with mRCC; in combination with the FOLFOX6 chemotherapy regimen in patients with advanced colorectal cancer and other gastrointestinal cancers; in combination with paclitaxel in patients with metastatic breast cancer; and as monotherapy in patients with non-small cell lung cancer.

Source
AVEO Pharmaceuticals, Inc.

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