Cellular Dynamics International announced this week that it has received a $500,000 Small Business Research Innovation grant from the National Institutes of Health to help it continue developing induced pluripotent stem cell-derived human cardiomyocytes.
The goal of the one-year grant is to develop a predictive in vitro model so that CDI’s pharmaceutical partners can look at more compounds and eventually study animal models more predictively and efficiently, Chris Kendrick-Parker, CDI’s chief commercial officer, told CBA News this week.
The idea is to move fewer compounds into animal models and have a higher degree of confidence in the compounds’ cardiotoxicity profile.
The SBIR grant will also enable CDI to extend its collaboration with Roche, announced last March (see CBA News, 3/4/08), which require Roche to supply CDI with two sets of 25 well-characterized kinase inhibitors to validate CDI’s toxicology products and services. CDI would test those compounds using human cardiomyocytes derived from human embryonic stem cells.
iPS-derived cardiomyocytes could be more predictive than other in vitro models, Kendrick-Parker said. Currently, pharmaceutical researchers must use multiple cell models in order to obtain a profile of a molecule’s potential cardiotoxicity.
“Those [multiple cell models] have been very inefficient and not very predictive,” said Kendrick-Parker.
For example, for electrophysiology, researchers have used the HEK hERG cell line, which was developed for IND filing for ion channels. Kendrick-Parker pointed out that Craig January, a co-founder of CDI, originally developed that cell line.
“Human [iPS-derived] cardiomyocytes have electrophysiological properties. They actually beat, whereas primary cardiomyocytes do not.”
“Moving into human cardiomyocytes was kind of a logical next step for us,” Kendrick-Parker said. He added that CDI will use the funds from the current grant to develop a model that has all of the potential characteristics of a human cardiotoxic event, as opposed to stitching together different animal and human cell lines that do not have the full functionality of a human cardiomyocyte, to try to predict the cardiotoxicity of a compound.
One of the current models in use today is human primary cardiomyocytes from cadavers. These cells do not have the same reproducibility as cell lines, and do not have the electrophysiological properties of iPS-derived cardiomyocytes, said Kendrick-Parker.
“Human [iPS-derived] cardiomyocytes have electrophysiological properties,” he said. “They actually beat, whereas primary cardiomyocytes do not.”
The second model comprises rat myocytes that are manipulated to demonstrate a phenotype similar to that of a human cardiomyocyte. “Still, they are not human cells, [and] they are not cardiomyocytes. They are myocytes that are partially differentiated into h9c2 cells,” said Kendrick-Parker.
Kendrick-Parker said this week that the Roche alliance is ongoing and has been expanded. “The data that we generated in that project, along with this data [generated under the current grant], will be used to produce our product specifications to actually go to market,” he said. CDI anticipates starting to move forward with additional collaborations and full commercialization in the first quarter of 2009.
The worldwide predictive toxicology market is worth several hundred million dollars, Kendrick-Parker said, adding that the in vitro segment of that market is growing at a rate of about 15 to 20 percent per year “because it is becoming so important, especially [for] cardiotoxicity” research.
The size of the iPS-derived cardiomyocyte market is “difficult to predict, because it’s a new paradigm,” but in comparison to cell lines, it is probably a “greater market,” said Kendrick-Parker. It could be worth anywhere between $50 million and $100 million per year worldwide, he said.