AV-299

AV-299 (formerly SCH 900105), a potent functional anti-hepatocyte growth factor (HGF) antibody, is currently in Phase 2 development and being co-developed by AVEO and Merck (formerly Schering-Plough). Through the use of its Human Response Platform™ (HRP), AVEO scientists identified the HGF/c-Met pathway as a significant driver of tumor growth. HGF is a protein that circulates in the blood and binds to and activates a receptor called c-Met. Activation of c-Met is believed to be important in normal processes in embryonic development and wound healing, but is also believed to trigger many activities involved in cancer development and metastasis. Altered HGF/c-Met signaling is observed in many tumors including bladder, lung, breast, gastric, ovarian, prostate, colorectal, head and neck, certain sarcomas and several other solid tumors and in multiple myeloma and leukemias. There are no approved therapies that target the HGF/c-Met pathway.

 

In preclinical studies of AV-299, AVEO showed that AV-299 has additive efficacy when given in combination with other approved anti-cancer agents such as erlotinib (Tarceva®), cetuximab (Erbitux®) and temozolomide (Temodar®). In additional preclinical studies, AV-299 was more effective at inhibiting tumor growth (at the dose tested) than other anti-HGF antibodies currently in clinical development.

 

AVEO has completed a Phase 1 clinical trial with AV-299. Results of the Phase 1 trial presented at the 2010 ASCO Annual Meeting indicated a favorable tolerability profile with no dose-limiting toxicities up to the highest dose tested (20 mg/kg). In June 2010, AVEO initiated a Phase 2 clinical trial evaluating AV-299 in combination with gefitinib (Iressa™) in patients with non-small cell lung cancer (NSCLC).

 

In March 2007, AVEO entered into a collaboration agreement with Schering-Plough (now Merck), under which Merck was granted worldwide rights to develop and commercialize AV-299. AVEO has primary responsibility for certain U.S.-related development activities through completion of the first Phase 2 proof-of-concept trial, and for conducting translational research to guide the clinical development of AV-299. AVEO retains the option to co-promote AV-299 in the U.S. for certain oncology indications.