Oct 17, 2005 | Before breast cancer patients can receive Genentech’s Herceptin, their tissues are screened for the HER2 protein. To gauge HER2 levels, pathologists score slides under a microscope on a crude four-point scale. But as pathologists at Yale University have discovered, a computer can score the tissues more accurately and detect lower levels of clinically relevant HER2 expression than the human eye.
Now the Yale team has scaled up its technology and formed HistoRx, a company to supply proteomic services for drug discovery. The company offers a platform called Aqua, which can perform automated, in situ analysis of protein expression levels on tissue microarrays in less than an hour.
Location: New Haven, Conn.
Funding: $2 million (Series A)
Founders: Robert A. Curtis,
David Rimm, and Robert Camp
CEO: Robert A. Curtis
“Looking at tissue and proteins and pathways in specimens is the best way to go,” says Emanuel Petricoin, co-director of the Center for Applied Proteomics and Molecular Medicine at George Mason University
. “Proteomics is not just about measuring. It’s about location.” For some projects, Petricoin says, the HistoRx approach may be superior to his own center’s protein microarrays: “We can look at 100 to 200 things at once. But we lose the spatial orientation.”
Aqua can stratify patients in clinical trials or help decide which subgroups of affected patients will benefit from a drug once approved. “It’s our opinion that that is the future,” says David Rimm, a pathologist at Yale and cofounder of HistoRx. “That is the essence of personalized medicine. How do you find which patients will respond to which drugs?”
The HistoRx platform only works with small quantities of biopsied tissue. Generally, for now, that will mean the company is working on cancer. But it hopes to work with intestinal, skin, kidney, and other tissues.
In humans, of course, biopsies will be harder to obtain than a simple blood draw. But such samples will also be more accurate, pinpointing that a cancer drug is affecting a cell’s nucleus, cytoplasm, or membrane. Says Rimm: “You need to see the level of expression in the context of the tissue. You can’t grind it up and measure it. People have tried that, and it doesn’t always work.”
The company’s technology includes proprietary image-analysis algorithms that depend on special dyes and tissue preparation techniques. Through its access to medical records at Yale, the company also offers access to eight microarray databases with 3 million tissue blocks from 1 million patients. The company has promising projects in melanoma and breast cancer, Rimm says. But he notes that the mere publication of a biomarker almost never leads to an immediate change in clinical practice.
Without a biomarker that predicts response to therapy (or lack of response) under a particular drug, research is hard to justify; clinicians ignore the biomarker. “Most biomarkers haven’t changed the way you manage the patient,” says Rimm. “We’re not out there finding biomarkers. It’s going to be the drug company that drives the demand for the biomarker.”
In their research, Rimm and Yale colleague Robert Camp have shown their proprietary image-analysis algorithms can score tissues better than subjective human interpreters. “The ability to accurately distinguish between HER2-normal and HER2-intermediate tumors by automated analysis not only has prognostic value but may help in the development and evaluation of new therapeutics targeted to treat this subpopulation,” Rimm, Camp, and colleagues wrote in Cancer Research in 2003.
Two new techniques — putting seven biomarkers on one slide and using ratios of nuclear to cytoplasmic protein levels — allow HistoRx to detect classifications of tumors that are impossible for humans to see.
In some cases, Rimm says, unnamed customers in industry have volunteered to supply tissue. In other cases, Yale may tap its own leftovers from clinical practice or purchase what is needed. “We are not limited to where we can get the tissues from,” says Rimm.
Rimm says HistoRx’s long-term goal is to license home-brew-style tests to major diagnostic concerns such as LabCorp and Quest Diagnostics. At that point, HistoRx might not have the capacity to handle a national volume of tests for a major drug. “The money is made on the reagents,” Rimm explains. With luck, HistoRx would seek approval for a new diagnostic test just as a customer filed its paperwork for a new drug.