Of course many diseases could (and eventually will) benefit from the kind of biomarkers becoming common in cancer. Biomarkers are necessary linchpins to enable modern medicine to translate advances in understanding disease biology into practical diagnosis, prognosis, and treatment. One young company, Crescendo Bioscience, has set its sights on developing and commercializing markers for autoimmune diseases. It’s a ripe area and the investing community seems to agree. In September, Crescendo completed a $31 million Series C round and also struck a strategic investment deal with Myriad Genetics for
Crescendo’s first target is rheumatoid arthritis (RA). CEO William Hagstrom says, “It was interesting. You could walk around trade exhibits floors and see all manner of descriptions of RA biology and pathways and mechanisms of how drugs affected them. There wasn’t a single booth or company talking about how they were measuring those things so physicians could better understand what to do with these drugs.”
RA is a solid target on two critical grounds. First, like a great many biomarkers, current RA markers are both coarse and almost entirely subjective.
‘’You don’t cure RA and most autoimmune patients generally. You seek to put them into clinical remission and the standard measures for assessing inflammatory disease activity all had to do with external manipulation of patients joints or digits and doing calculations which were qualitative and subjective as opposed to being based the biology of the disease,” Hagstrom says.
Second, there are around 3,500 office-based rheumatologists in the U.S. alone who treat patients with many different autoimmune diseases, and the typical RA patient has four visits each year. Marketing to that physician community and their patients is a doable task and a sizeable market. The chronic nature of the disease has also created an active patient community seeking to self-manage their disease and receptive to new approaches.
Markers for Disease Biology
The cornerstone of Crescendo’s approach is to develop quantitative markers based on detailed models of disease biology. Its first test—Vectra DA—launched last year at ACR is a blood test that measures 12 key proteins consistently associated with RA disease activity and integrates them into a single objective score for easy interpretation.
The test is intended to provide physicians with a quantitative glimpse into RA activity and was developed much the way modern drugs are. Drawing from the literature and using computational tools such as Ingenuity Systems’ pathway database and analysis software and Entelos’ RA Physiolab platform, Crescendo built a detailed picture of RA biology.
“We were technology agnostic at the front end and chose to screen very large numbers of biomarkers on several different technology platforms (e.g. gene expression) to determine which markers correlated [with] quantitative disease activity,” says Hagstrom. Of an initial list of 390 markers, Crescendo identified a small subset to take into a formal development program.
“We optimized the biomarkers, put them on a single technology platform, and built a cohort of 25 centers across North America called INFORM, which was used as the primary sample set for efforts to develop an algorithm able to deliver a quantitative score on a scale of 1 to 100 to discern a patient’s level of disease activity,” he says. Validation studies in Europe and the U.S. followed. Crescendo has a CLIA lab in San Francisco and is a member of the Batter Up consortium (see, “Batter Up: A Stratified Approach to Rheumatoid Arthritis,” Bio•IT World, March 2011) working on multiple approaches to RA treatment.
Currently, Vectra DA is not linked to any specific therapeutic. “A physician can see in the face of various drug therapies whether the disease activity is declining, stable, or increasing. But we are not measuring drug effect, nor are we seeking to predict a drug response or a drug selection at this point in time. Those are targets of future product development activities,” Hagstrom says. Crescendo already reports the levels of the test’s constituent proteins.
It will be interesting to track Crescendo’s progress and its impact on broader industry efforts to develop and commercialize biomarkers required to deliver personalized medicine.
This article also appeared in the November-December 2011 issue of Bio-IT World magazine. Subscribe today!