NEW YORK (GenomeWeb) – Protein diagnostics firm Protagen has joined the UK-based Maximising Therapeutic Utility for Rheumatoid Arthritis (MATURA) consortium, through which it aims to develop a test for predicting patient response to therapy in RA.
The company hopes via its participation in the consortium to identify a subset of predictive markers from a current panel of 100 proteins it identified as possibly useful through previous studies of RA, Georg Lautscham, the company's chief business officer, told GenomeWeb.
Launched in 2014, the MATURA consortium consists of a group of primarily UK-based academic and industry players that are working to identify predictors of therapy response in RA patients. Currently slated for five years, the effort is funded by organizations including Arthritis Research UK and the Medical Research Council.
RA is commonly treated with TNF-α inhibitors, but, Lautscham noted, in many cases, patients fail to respond to these drugs.
"Basically, all of the currently marketed drugs have a limited response rate," he said. "Certain groups of patients certainly benefit from these drugs, but quite clearly not the majority."
That being the case, the search for predictors of RA therapy response has become a major area of research within the disease. In addition to Protagen, UK-based proteomics firm Avacta is also participating in the consortium, using its aptamer-based technologies for discovery of predictive markers. They are joined by Qiagen and BGI, as well as pharma companies including AbbVie, Genentech, Janssen, and Pfizer.
Protagen has been exploring RA therapy response markers independently of the MATURA consortium and in work done in collaboration with Humboldt University of Berlin researcher Gerd Burmester identified roughly 100 potential markers in a set of 120 patients.
"Based on those results, we got in touch with MATURA and discussed whether we could be part of [the consortium] and get access to the patients that are part of MATURA," Lautscham said. "It is early days, but we are quite pleased that with our approach we were able to find [the roughly 100] response prediction markers. We need further validation, further refinement, but there is a lot of substance in those 100 markers."
Protagen and its collaborators identified the markers using the company's SeroTag platform, which uses bead-based arrays of full-length proteins to screen patient blood samples for autoantibodies characteristic of a given disease. Certain proteins produced by the body can elicit an immune response that can then be detected by measuring antibodies to that protein, and these immune responses can vary between diseased and healthy individuals.
Such immune signatures can also be used to track a patient's response to particular therapies, as in the case of Protagen's RA efforts. While most protein biomarker work focuses on identifying circulating proteins in patient plasma, there are certain potential advantages to an autoantibody-based approach. For one, the body's immune response acts as a natural signal amplifier, meaning that autoantibodies to a protein can be present at significantly higher concentrations than the protein itself, providing a boost to assay sensitivity. Additionally, autoantibodies are in some cases more stable than traditional protein markers.
Firms including HealthTell and Opko Health are similarly pursuing autoantibody-based diagnostics.
According to Protagen, the company has the largest human antigen expression library in the world, a collection of more than 7,000 human proteins that includes more than 95 percent of published, disease-associated autoantigens.
In its collaboration with the HUB researchers, Protagen screened some 8,000 analytes to identify the 100 potential markers. Lautscham said the company hopes ultimately to arrive at a final panel of between five and 15 markers.
The HUB collaboration looked at patients treated with AbbVie's TNF-α inhibitor Humira. Joining the MATURA consortium will allow the company to screen its markers against patients being treated with a variety of RA drugs, Lautscham said, adding that initially the company will run a study using roughly 300 patient samples from the consortium.
The company is participating in one of two research efforts being run by the consortium. In that effort, which is based at the University of Manchester, the researchers are looking for predictive genomic and proteomic markers of drug response. In the other effort, based at Queen Mary University of London, researchers are using biopsies of disease tissue to investigate patient response to three biologic drugs.
Protagen is currently finalizing plans for this trial, which it expects will conclude in Q3 or Q4 of 2016. Lautscham said the company hopes to emerge from its work with the consortium with a finalized panel that it can then take through an independent prospective trial.
Assuming Protagen does ultimately take a test to market, it will likely have a waiting competitor in Crescendo Bioscience's Vectra DA proteomic rheumatoid arthritis test. As GenomeWeb reported last month, academic collaborators of Crescendo, which is a subsidiary of Myriad Genetics, last month presented data at the annual meeting of the American College of Rheumatology that suggested Vectra DA could be useful in identifying patients likely to respond to different second-line RA drugs.
This follows similar data Crescendo presented in 2014 that indicated that Vectra DA, which was originally developed for monitoring RA disease activity, could be useful in predicting response to second-line therapies in patients who did not respond to methotrexate, the first-line therapy for the disease.
In addition to its RA work, Protagen has collaborations in a variety of other disease areas, including a deal it inked earlier this year with Mikrogen to use its platform to develop a diagnostic for Lyme disease and a collaboration with Pfizer on biomarkers for an undisclosed autoimmune disease therapy.
The company also last year signed a deal with Qiagen under which Qiagen is able to provide its pharma partners access to Protagen's SeroTag platform as part of work on protein-based companion diagnostics for autoimmune disorders.