The Niche

VCs consider routes to make reprogrammed cells into products

Posted by Monya Baker on behalf of Natalie DeWitt

What do the top venture capitalists interested in investing in iPS cells consider the major hurdles on the road to viable clinical products? Today stem-cell scientists Deepak Srivastava and Shinya Yamanaka of the Gladstone Institute in San Francisco were joined by Beth Seidenberg of venture-capital firm Kleiner Perkins Caufield and Byers to answer that question for an audience consisting mainly of investors.

Yamanaka was reluctant to give a timetable for clinical application. Alternatives to viral integration as a means to make iPS cells are clearly on the way, he said, but the similarity of reprogrammed cells to cancer cells presents another serious hurdle. Srivastava added that expansion of cells is another major focus—how to generate the large quantities of cells needed for human therapy.

As someone who is mainly preoccupied by the science, I found it fascinating to hear Siedenberg, a drug development expert for a venture capital firm, break the road to clinical development into the following seven steps, two scientific feats to be established, plus a series of questions that clinicians and regulators must figure out how to answer. (My own observations are in parentheses.)

• A way around viral transduction to reprogramming must be developed. (This is a hot area of research and already small molecules are being screened and developed to do this).

• Differentiate iPS cells into any cell type. (Many papers report differentiation of ES cells to useful cell types such as neurons or cardiomyocytes—but only in rare cases do these procedures achieve robust efficiency. It is proving to similarly be a challenge for iPS cells).

• What is the best way to administer the cells? Will novel biomaterials to form scaffolds be needed?

• What safety and regulatory process must be in place before using cell transplantation in humans?

• What dose will be required and how often?

• How do you gauge the efficacy of the cells destined for transplantation? How do you know if they are working?

• And a major hurdle, how to handle the manufacturing of cells to control costs and reproducibility?

The first two goals are well underway in scientific labs. But the next five are key for developing therapies, and are the questions investors and drug developers ask about any product in their pipeline. However, using cells for transplantation instead of small molecules raises serious challenges in terms of bringing a cost effective product to market. Do companies developing hES cell therapies like Geron have the answers? By now, the FDA has likely told them what experiments are necessary to move their cell product for spinal cord injury into clinical trials, but so far they’ve been silent.

See also FDA places Geron’s clinical trial on hold. This can get you to Monya Baker’s overview of the FDA’s meeting on how to assess whether embryonic-stem cell derived products were ready for human trials as well as transcripts of that meeting.

Seidenberg pointed out that the nearest term application of iPS cells is testing for drug toxicity. At present, 63% of drugs are withdrawn because of toxicity, usually to the heart and liver. Individuals are susceptible to varying degrees depending to some extent on their genotypes so iPS cells provide a great opportunity for testing toxicities in cells with a wide array of genotypes. And these investigations may, in turn, help answer some of the questions necessary to bring these cells to the clinic.

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