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AZ, Cellartis Extend Alliance Developing hESC-Derived Liver, Heart Cells


AstraZeneca and Cellartis this week announced that they have extended an existing collaboration to develop toxicology screening assays based on human embryonic stem cell-derived hepatocytes and cardiomyocytes.

The alliance, originally begun in 2006 and extended by two years, calls for the companies to develop assays for target and lead validation, compound screening, drug metabolism studies, and safety assessment.

The companies hope the hESC-derived cells will help researchers predict the human body's response to drugs more effectively than the immortalized human cell lines and animal-derived cell lines and tissues that are currently used by most drug makers, said Aileen Allsop, vice president of R&D science policy for AstraZeneca.

She said the firms began the collaboration as a very speculative, small-scale agreement that AstraZeneca decided to extend because "it is beginning to give us some promising data.

"We are still a long way off from establishing this as a new technology, however," she said.

Financial terms of the collaboration were not disclosed, though the firms said it can be re-extended at the end of the two-year period.

Allsop declined to comment on any milestones within that period, but said: "We do expect significant progress within that timeframe."

Johan Hyllner, chief scientific officer of Cellartis, said the extended deal "will give us enough time, I think, to be able to have these cells ready to be used by AstraZeneca, and by other companies as well."

Allsop said that if scientists can get hESCs to reproducibly differentiate into hepatocytes and cardiomyocytes that can mimic normal human liver and heart cells, the cells will become "fabulous tools for predicting in the lab how new compounds will behave once they get inside a patient."

She added that if such cells become powerful drug-discovery tools, regulatory authorities would need to start taking notice — "but we are a long way off from that stage."

Allsop said an advantage of screening drug candidates with hESC-derived hepatocytes or cardiomyocytes is that, eventually, "you could have a bank of normal liver cells that have been derived from different sources, so that you could better understand how a population might react to compounds," rather than just an individual.

When AstraZeneca began to consider using hESCs in its drug-discovery programs, it developed an internal ethics policy around the use of such cells. "That [policy] then became a factor in our decision to be sure that we could find a company that was happy to accommodate our ethical considerations, and also had the leading science that we were looking for," Allsop said.

She went on to say that AstraZeneca, which is based in the UK, insists that every stem cell line it uses, or that is used on its behalf, is registered through the nation's Stem Cell Bank "so that there is an independent verification, as well as our own investigation."

Allsop added that AstraZeneca only uses stem cell lines that have been derived from embryos surplus to in vitro fertilization, and "only accept[s] stem cell lines that were derived without financial inducement associated with them."

This time last year, Cellartis entered into a similar collaboration with Pfizer (see CBA News, 2/15/08). The goal of that agreement was to generate a predictive developmental screening model for new chemical entities using the Cellartis human embryonic stem cell platform.

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