Stemina, a cell-based assay spinout from the University of Wisconsin, Madison, is hoping that by combining two emerging technologies — metabolomics and human embryonic stem cells — it will gain a competitive advantage in the drug discovery-services market.
The company was founded late last year by CEO Elizabeth Donley, who previously served as general counsel and director of business development for the Wisconsin Alumni Research Foundation, and CSO Gabriela Cezar, who heads the Stem Cell Safety Sciences Lab at UW-Madison.
Last week at Cambridge Healthtech Institute’s Molecular Medicine Tri-Conference in San Francisco, Cezar gave a talk on the company’s technical foundation, a metabolomics platform that screens human embryonic stem cells to predict the toxicity of candidate drug molecules.
Cezar noted that animal studies are not only expensive, but they are “limited in their ability to predict human response.” Standard human cell lines, meanwhile, are generally not the same cell type as the target of toxicity and often have a limited life span. Because human embryonic stem cells can differentiate into a variety of cell types, they offer a promising alternative for toxicity screening, she said.
Cezar said that the advantage of metabolomics, which uses mass spectrometry to identify small molecules that are differentially secreted across multiple samples, is that it can identify biomarkers for toxicity that can then be developed into diagnostic tests.
Donley told Cell-Based Assay News in a follow-up interview this week that while the company initially plans to offer drug-screening contract services, “Ultimately, I think the real value of the company will be not just in the service model, but the more interesting piece will be in developing a robust set of biomarkers in a particular area of interest.”
Once the firm identifies biomarkers in stem cell lines, she said, it plans to work on identifying the same metabolites in serum, urine, or other bodily fluids that would enable it to develop a non-invasive test. This approach is expected to work particularly well in biomarker-based tests that monitor how patients respond to drugs over the course of long-term treatment, as in cancer. The stem cell-based approach would enable the firm to identify biomarkers of response in a fully human system “without having to dose a human,” she said.
In her presentation, Cezar described a proof-of-concept study based on the anti-epileptic drug valproate, which is known to cause birth defects such as spina bifida. The goal of the study, she said, was to identify a set of metabolic biomarkers that could be used to predict which women might be at risk.
Cezar and her colleagues first exposed undifferentiated human ESCs to valproate, and later repeated the study using neuronal precursors. After analyzing the mass spec data, the researchers identified a set of differentially secreted metabolites that showed promise as potential diagnostic biomarkers, she said. One of these, kynurenine, a metabolite of tryptophan, was identified as a potential biomarker in a similar study published by Amgen at around the same time, Cezar said.
Leaving the Nest
Stemina is currently operating out of the Stem Cell Safety Sciences Lab at UW-Madison, but plans to rent its own space — and buy its own mass spectrometer — by July 1.
To do so, the firm will need to raise some cash. Donley said the company hopes to do that through a mix of venture capital funding, matching grants from the state of Wisconsin, and contract revenues. Donley and Cezar met with a number of potential investors and customers at last week’s Tri-Conference and Donley said she’s confident that the company will be able to meet its goal of raising $1 million in angel financing and penning two customer contracts by the end of the year.
“Ultimately, I think the real value of the company will be not just in the service model, but the more interesting piece will be in developing a robust set of biomarkers in a particular area of interest.”
Stemina is one of several firms looking to capitalize on the short-term promise of stem cells as drug-discovery tools rather than gambling on the longer-term goal of stem-cell-based therapeutic products. Companies like Stem Cell Sciences and Stem Cell Innovations are both developing human stem cell lines for high-throughput drug screening [CBA News 02-23-07].
The company’s focus on metabolomic biomarkers sets it apart from potential competitors, however, and the firm is hoping to retain its unique position in the marketplace via IP protection. Donley said that Cezar has filed several patents for the technology through the Wisconsin Alumni Research Foundation, one of which is a “broad patent” claiming human embryonic stem cells in combination with metabolomics for drug screening, drug discovery, and diagnostics.
Stemina’s goal is to provide “another layer of confidence for the pharmaceutical industry,” Donley said.
“The idea is to build a system that will allow the pharmaceutical industry to identify drugs that should fail earlier and to identify promising candidates with greater confidence,” she said. “So it’s not to say that you’d do away with doing animal trials. Certainly we can run our metabolomics platform — and probably will — in collaboration with a biotechnology firm that does mouse preclinical work. We can run mouse serum or mouse urine on the mass spec and do metabolomics to cross-tie the results with what they’re seeing in the mice in other tests, as well as what we might see in a human embryonic cellular assay system.”
She added that the metabolomics platform can work with any cell type, “so it’s just a question of getting the right starting material.”