Xoma Ltd. and Aveo Pharmaceuticals, Inc. announced a $6 million agreement for Xoma to manufacture and supply AV-299, Aveo's novel anti-HGF antibody, in support of early clinical trials.
The companies also announced that Xoma has successfully completed the Human Engineering (HE) of AV-299. This agreement further strengthens the collaboration between the companies that began with the humanization of AV-299.
Under the supply agreement, Xoma will create AV-299 production cell lines, and conduct process and assay development, as well as cGMP manufacturing activities in support of Aveo's IND filing and early clinical trials.
On April 27, 2006, Xoma and Aveo announced an agreement under which Xoma would use its HE technology to humanize AV-299. Xoma created four Human Engineered™ versions of the original AV-299, all of which met design goals and were delivered ahead of schedule. From these four versions, Aveo selected one as its lead development candidate. For work conducted and licenses granted, Xoma received an up-front license fee and is eligible for development milestones and royalty payments on sales of AV-299. Aveo retains all development and commercialization rights to AV-299.
"The Human Engineered AV-299 product candidate has fully retained its specificity and functionality in vitro and in vivo," said Tuan Ha-Ngoc, Aveo's president and chief executive officer. "Accessing Xoma's biologicals manufacturing capabilities allows Aveo to continue its accelerated product development timelines for the AV-299 programme, increasing the potential for its clinical and commercial success."
"This success is another demonstration of the robustness and speed advantages of Xoma's HE technology," said Jack Castello, chairman of the board, president, and chief executive officer of Xoma. "We expect this to be the first of many HE™ relationships that evolve into broader arrangements and allow us to leverage Xoma's innovations, expertise and antibody development infrastructure."
AV-299 is a highly potent antagonist of hepatocyte growth factor/scatter factor (HGF/SF), which has demonstrated excellent efficacy in preclinical models of human cancer. The HGF/c-Met pathway is frequently deregulated in different types of human cancers and is thought to play an important role in regulating tumour growth, invasion and metastasis. Utilizing its proprietary technology platform, AVEO has developed substantial evidence of the importance of the HGF pathway in tumour maintenance. The diverse biological roles of the HGF/c-Met pathway make the selection of patients most likely to respond to anti-HGF therapies especially difficult. To guide the clinical development of AV-299, AVEO is using its proprietary preclinical models of human cancer to identify specific populations of tumours in which the HGF/c-Met pathway plays a critical role in tumour maintenance, as opposed to those in which the pathway is activated but not essential. AVEO's Human Response Prediction™ platform provides AVEO with unique insight into the biology of anti-HGF therapies, and uniquely positions it to move AV-299 forward into clinical development.
AVEO's AV-299 programme exemplifies the progress AVEO has made in discovering drugs that target functionally relevant tumour maintenance genes identified and validated by AVEO in its proprietary in vivo cancer models.
HE technology is a patented, clinically tested humanization technology for modifying non-human antibodies to make them suitable for medical purposes in humans. HE technology is distinct from other humanization techniques and is independent of CDR grafting. Xoma's HE technology is based on the conserved structure-function relationships among antibodies and defines which amino acid residues in a non-human antibody variable region are candidates for substitution. The result is a 93 per cent 95 per cent human antibody generated in approximately 3 months with preserved antigen binding, structure, and function.