CAMBRIDGE, Mass.—AVEO Pharmaceuticals, Inc. and CentocorOrtho Biotech Inc. have entered into an exclusive license agreement for theworldwide development and commercialization of AVEO's internally discoveredantibodies, which target the RON (Recepteur d'Origine Nantais) receptor.
"We are delighted to enter into this strategic alliance,"said Elan Ezickson, executive vice president and chief business officer ofAVEO, in a statement regarding the agreement.
AVEO will initially receive $15 million, half of which willbe paid as an upfront payment from Centocor and the second half of which willbe paid through the sale of newly issued shares of AVEO common stock to Johnson& Johnson Development Corporation, an affiliate of Centocor. The secondhalf of the payment falls under a separate equity private placement and stockpurchase agreement. Under the terms of the license agreement, AVEO couldpotentially receive up to $540 million in milestone payments if certaindevelopment, regulatory and commercialization goals are achieved, and will alsobe entitiled to a tiered, double-digit royalty on net sales worldwide uponcommercialization.
For their part, Centocor is responsible for handling allclinical development, manufacturing and commercialization activities and costs.Centocor will also provide funding for certain areas of AVEO's research,including translational research studies using its Human Response Platform toidentify biomarkers for patients that would most likely benefit from beingtreated with RON-targeted antibodies.
"This license agreement highlights the broad potential ofour unique monoclonal antibody R&D capabilities and further supports AVEO'sstrategy to maximize our proprietary cancer biology platform to build asustainable cancer therapeutics company," said Ezickson.
RON, or MST1R, receptor tyrosine kinase is part of the c-METRTK family, and over-expression of the kinase has been found in several solidtumor types, including breast, non-small cell lung, prostate, glioblastomamultiforme (GBM), colorectal, ovarian, pancreatic and bladder cancers. Thekinase is associated with disease progression as well as metastasis. The RONpathway is suspected to play a part in several aspects of cancer development,including regulation of tumor growth, survival and metastasis, as well as bonedisruption.
In AVEO's proprietary in-vivomodels, both wild-type RON and ROND160 have proven to drivetumor growth. Additionally, the company's anti-RON antibodies have demonstratedstrong anti-tumor activity. Through use of its bioinformatics tools, AVEO hasalso generated a RON pathway gene index, which is capable of quantifying thelevel of TON pathway activation. This index has made it possible for AVEO toidentify human tumor cell lines that display high RON-pathway activity, and thecompany has also been able to demonstrate that inhibiting RON function by useof anti-RON antibodies can potently inhibit tumor cell growth and survival.
Last November, at the EORTC-NCI-AACR Symposium in Berlin,Germany, AVEO presented preclinical data from its anti-RON antibody programthat demonstrated the inhibition of both RON and ROND160'sfunction, in addition to a possible biomarker to identify tumors that are mostlikely to respond to anti-RON antibody treatment.
"We believe that the RON pathway is a promising novel targetfor combating cancer growth and progression," said Ezickson in a statementregarding the agreement.