Aveo strategy ups chances of cancer drug success
strategy can buck high industry failure rates when trying to design
new cancer drugs and it seems to be working after its lead drug has
passed a first-in-man trial with flying colours.
The drug, AV-951, is a vascular endothelial growth factor (VEGF) receptor inhibitor, that blocks all three VEGFRs. Announcing the results of a Phase I trial, Aveo said in a trial of 40 cancer patients, the nine patients with kidney cancer either achieved a partial response or stable disease, with one patient exhibiting a response that lasted for over 30 months. Aveo believes its drug design technique is to thank for the good results and one spokesperson said it provided "the first real opportunity in the industry to substantially increase the probability of success in oncology drugs." In general, Aveo focuses on generating antibody drugs, although AV-951 was in-licensed from Kirin Pharmaceuticals and is a quinoline-urea derivative. It binds to the intracellular tyrosine kinase portion of the VEGF receptors However, for their internal programmes, the first step in the process is identifying a target. To do this, Aveo has created a number of tissue-specific cancer models (i.e. lung, breast, colon etc...) that are genetically engineered to contain certain gene mutations known to increase the likelihood or severity of human cancers (e.g. HER2, EGFR etc...). Once the mouse models have been created, they will also develop common and distinct spontaneous mutations during tumour growth, much like real human cancers. Because the natural cellular interactions and pathways are mimicked, Aveo believes the models provide a better tool to choose targets that drive the growth of tumours. In order to validate the targets, Aveo can use RNA interference to switch certain genes off, check publicly available data in scientific journals and also to see what the intellectual property opportunities are. Antibodies can then be generated against the target both to validate it further and also to look for potential therapies. Perhaps most interesting is the company's Human Response Prediction Platform. Clearly tumours often respond differently to a given drug. However, Aveo can use its mouse models to generate genetic signatures of responsive or non-responsive tumours at the preclinical stage. This is done using microarray analysis. The results can be used in subsequent clinical tests to formulate and test hypotheses and also ensure only those patients most likely to respond are enrolled in trials. "We believe AV-951 has the potential to be best-in-class against a validated target demonstrated to be important in multiple cancer types," said Tuan Ha-Ngoc, CEO at Aveo. "[The drug] has the potential to be effective both as a single-agent and in combination regimens benefiting multiple tumor types." Based on this initial clinical data, Aveo has started a Phase II trial in patients with metastatic renal cell carcinoma. Since the company's lead drug is only just beginning this stage of development, experiments are still underway to correlate these preclinically-derived signatures of responsiveness with human microarray data, with an eye toward the goal of ultimately predicting responsive patient populations and guiding clinical development. Until a significant number of Aveo drugs reach this proof-of-concept stage, the industry won't know if Aveo's confidence is well placed or not.
