May 15, 2011 (Vol. 31, No. 10)

Induced Pluripotent Stem Cells Prove Invaluable in Toxicity and Drug Efficacy Screening

The high failure rate of compounds in clinical development is a major problem for the pharmaceutical industry. Some 90% of compounds fail in clinical trials, mainly due to low efficacy and safety issues—costing the industry hundreds of millions of dollars. The biochemical assays and animal models used in the current drug development process need to be improved—and new tools based on cell lines generated by genetically reprogrammed cells may offer a solution. Promising markets are beginning to form around these new tools, but, as with any technology, companies should be aware of both the risks and benefits.

Induced pluripotent stem cells (iPSC) are somatic cells that have been reprogrammed to have embryonic stem cell-like properties, specifically the ability to differentiate into other cell types. Using iPSC methods, a researcher can harvest a person’s skin cells, induce pluripotency, and then encourage those cells to differentiate into another type of cell, like a neuron or cardiomyocyte. One major benefit of this method is that the induced stem cells are derived from nonembryonic tissue, alleviating many ethical concerns.

Since the introduction of this technique in 2006, researchers have successfully created both iPSC-derived healthy state and disease-specific cell lines that have potential to replace current tools used in toxicity and drug efficacy screening, respectively. Within only a few short years of their invention, a commercial market is forming around the use of iPSC as life science tools.

A number of commercial opportunities exist all along the iPSC value chain, from the reagents used to generate iPSCs to the cell lines that are derived from iPSCs (Figure).

Reagents, Media, Cells, and Tools

The majority of companies playing in the nascent iPSC industry only offer reagents, media, and viral vectors used as tools for iPSC research. While companies in this space tend to be small, the interest of large life science players like Qiagen and Life Technologies indicates the potential for this new industry to take off.

iPSC Lines

Undifferentiated iPSC lines are cells that have been made pluripotent, but have not been differentiated into new cell types. System Biosciences, in collaboration with DV Biologics, has developed both healthy and disease-based iPSC lines for research use. It also offers variations on each cell line, where pluripotency was induced with different methods, e.g., using viral vectors or proteins. System Biosciences also adds value to its offerings by certifying that all its lines maintain pluripotency.

Differentiated Cell Lines

At the end of the iPSC value chain are healthy or disease-based cell lines that have been differentiated for specific applications. Cellular Dynamics International (CDI), the first player to enter this part of the value chain, currently produces cardiomyocytes for pharmaceutical cardiotoxicity testing. Human cardiomyocytes have been proven to be a more accurate model for testing than the traditional animal models, as they increase the screening efficiency in the drug-development process.

This benefit is getting the attention of major pharmaceutical companies like Roche, which recently signed an agreement with CDI to use its iPSC-derived cell lines, and Pfizer, which is developing its own toxicity testing system. Axiogenesis, a German company, is also developing a cardiomyocyte line that will be distributed through Lonza.

The use of disease-based, differentiated cell lines has not yet hit the commercial market, but products are in development. iPieran, a biopharmaceutical company, is developing cell lines from iPSCs for difficult-to-model diseases like Parkinson disease, spinal muscular atrophy, and amyotrophic lateral sclerosis. These lines will be used for internal drug discovery, while additional lines for cardiovascular and metabolic disease will be made with other pharmaceutical industry partners. As the iPS cells are validated against the current drug discovery models, we expect to see their use increase in major pharma company drug discovery processes.

Business Risks

The iPSC space is extremely new, and therefore, rife with business risks. One interesting hurdle involves intellectual property. Because the technology involves manipulating donors’ cells, the issue of ownership and patenting of those cells becomes a pressing question. What is more, a patent license for a method to generate iPSCs today may be obsolete by the time the patent filing is completed. This may be one reason why few companies have yet to commercialize cell lines derived from iPSCs: they are unsure of how to license or protect their intellectual property.

Despite uncertainty, a strong business opportunity exists for companies looking to commercialize iPSCs, due to high demand for iPSC life science tools. In fact, several companies are in or entering the iPSC space, including some major life science and pharmaceutical players. This is in part because of the value added to the pharmaceutical space through improved drug development. However, this is only one example of the commercial opportunities for iPSCs.

Future applications of iPSCs will go far beyond their use as life science tools, ranging from personalized drugs to regenerative cell therapies. Still, the importance of today’s commercial enterprise cannot be discounted, as it offers both a source of revenue and knowledge to leverage when developing iPSC therapies in the future.

Lisa Carey is senior analyst and Michael Tapella ([email protected]) is senior associate at Scientia Advisors.

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