While antibody microarrays are viewed as a promising tool to measure disease-related protein biomarkers, Molecular Staging (MSI), of New Haven, Conn., is proposing to use them at a much earlier stage — in biomarker discovery. Big pharma is buying into it: Last week, MSI announced a research collaboration with Eli Lilly to identify biomarkers in serum samples from patients with sepsis.
“There is a need for a simple diagnostic test that will identify sepsis in much the same way that today you can identify a heart attack,” said Stephen Kingsmore, COO of Molecular Staging. At present, he said, diagnosis of sepsis is based on non-specific symptoms, and early sepsis in particular is difficult to identify. In the US alone, 200,000 people die from sepsis every year.
MSI will study samples from patients with moderate or severe sepsis from a 1,700-person clinical trial that Lilly conducted on its recently approved sepsis drug, Xigris.
MSI will use its antibody chips, which employ a signal amplification technology licensed from Yale called “rolling circle amplification,” to measure 130 different cytokines in the samples. It will then analyze the data to identify biomarker classifier sets for different clinical endpoints, according to Kingsmore. The aim of the study is to understand the different stages of sepsis better, and to find markers that indicate a treatment effect from Xigris. If the study is successful, Lilly might develop a diagnostic kit from these markers.
Financial terms of the agreement were not disclosed, but Kingsmore said MSI will receive upfront payments, milestones for the discovery of biomarkers, and share intellectual property with Lilly.
To convince Lilly of the capabilities of its platform, MSI performed a pilot study, the results of which “passed our internal specifications,” said Brian Edmonds, group leader in cell systems at Lilly. “What sets them apart from others is the comprehensive package that they present,” he said. This package consists of a diversity of antibodies to proteins of relevance in inflammation, as well as bioinformatics and expertise in a number of disease areas, including “many of the therapeutic areas that Lilly is currently working in.”
At least one other company, Zyomyx of Hayward, Calif., has also been developing a cytokine antibody chip, but Edmonds believes that, at least for now, it lags behind MSI’s technology. “They don’t have the same diversity of content on their chips: They are not offering the same kind of statistical packages to analyze the data,” he said. The two companies also differ in that Zyomyx is planning to sell its protein biochip system and chips directly, starting later this quarter, while MSI has adopted a service-based business model.
MSI’s approach restricts study to a limited number of defined analytes. However, it allows for quantitative comparisons, while most unbiased discovery approaches do not, said Edmonds. Also, many of the analytes “are already understood to be somehow involved in the progression of inflammatory disease,” he added, making them likely to go up or down during sepsis.
The agreement with Lilly is not Molecular Staging’s first pharma deal: According to Kingsmore, the company is collaborating with two more “of the top five pharmas” as well as three biopharmaceutical companies. He said the company has validated a number of biomarkers in a second cohort of patients, and has submitted several papers for publication to scientific journals, including one on cerebral palsy biomarkers. “A high priority for us is this year to publish two or three papers in well-respected journals showing that you can indeed use protein chips to identify valuable biomarkers in clinical conditions,” he said.
Eventually, MSI will need to establish partnerships for sales and distribution, but “until we have biomarkers that are ripe for market development, it’s somewhat premature,” Kingsmore said. MSI’s inflammatory bowel disease biomarkers might be the first the company will move forward, he added.