Washington Editor

The cancer firm AVEO Pharmaceuticals Inc. padded its portfolio through a licensing deal for a multiple kinase inhibitor, MP-412, which might have use in a range of oncology applications.

"This is the successful execution of a strategy we have at the company," said President and CEO Tuan Ha-Ngoc, noting that AVEO already has built a platform and its internal scientific base, but now is turning toward product development. That includes looking for externally developed, near-clinic compounds for which the company can "provide unique insight into how to develop it, to identify the right tumor types and the right patient populations, so that we can increase the probabilities of success," he said.

To that end, the Cambridge, Mass.-based company gained an exclusive license to develop and commercialize the targeted therapy product from Mitsubishi Pharma Corp. in all territories outside Asia. Specific financial terms were not disclosed, although Ha-Ngoc told BioWorld Today that the deal includes "fair and reasonable" up-front, milestone and royalty payments for Tokyo-based Mitsubishi, which will have access to AVEO's data for its own Asian development plans.

"It's very important not just to come in with money," he said, "but to come in with unique insight and expertise to shed light on how to best optimize clinical development and therefore bring the product to the market with the right label and the right indication."

AVEO expects to file an investigational new drug application and begin clinical studies by the middle of this year. Initial plans call for developing MP-412, renamed AV-412 by AVEO, for solid tumors, with AVEO's human response prediction platform to be used for identifying patients likely to respond to the treatment.

The technology is based on genetically defined mouse models of human cancer, each of which is engineered to contain signature genetic mutations that are present in human disease. At last month's San Antonio Breast Cancer Symposium, the company detailed its creation of a human tumor, with all phenotypic and genotypic characteristics, in an animal model. The platform is the basis of a relationship between AVEO and Merck & Co. Inc., of New York, to pinpoint patients most likely to respond to certain investigational cancer drugs, and the companies signed a second partnership just two months ago. (See BioWorld Today, Nov. 3, 2005.)

Already, AVEO has a good idea about the potential of AV-412, courtesy of a material transfer agreement by which Mitsubishi allowed AVEO to conduct early studies last summer. The drug, which inhibits the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2), generated "very exciting" data in a traditional experiment, confirming its dual mechanism, Ha-Ngoc said. A subsequent study demonstrated success in a model with an EGFR mutant that might be responsible for resistance to Tarceva (erlotinib, OSI Pharmaceuticals Inc. and Genentech Inc.). "So that created a lot of excitement for us," he added, "and also for Mitsubishi."

Although there are targeted cancer therapies on the market, Ha-Ngoc said there still are patients "very much in medical need." The dual mechanism of action of AV-412, classified as a second-generation multiple kinase inhibitor, has the potential to benefit those with non-small-cell lung, metastatic breast, pancreatic, head and neck and hormone-refractory prostate cancers. Also, he said AVEO plans to pair it with chemotherapy to create a combination treatment.

The oral drug has a toxicity profile similar to other molecules in its class, and Mitsubishi's research to date has it positioned well for AVEO's near-term IND plans "so we can hit the ground running," Ha-Ngoc said. In final preparations for early clinical studies, AVEO is overseeing fill and finish work on AV-412's active pharmaceutical ingredient through a U.S. contractor.

Privately held AVEO is using its predictive platform models to identify and validate new cancer targets, around which it has begun to build a pipeline. With AV-412 now its lead product, the company plans to identify another clinical candidate for tumors later this year and file its IND next year. At the same time, additional in-licensing opportunities are being explored to locate compounds synergistic with the human response prediction platform.

In the long term, Ha-Ngoc said AVEO expects to internally commercialize its oncology products, including AV-412, but it could partner that product, or any others, should the right circumstances arise.

AVEO changed its name earlier this year from GenPath Pharmaceuticals Inc. With more than $70 million raised since its 2002 inception, Ha-Ngoc said its present funding is sufficient to finance activities at least through AV-412's proof-of-concept studies.