A year after introducing its dotLab protein-detection technology, Axela is now fully commercializing the platform, and is currently trying to secure a financing round that would help move the system into the diagnostic market.
While dotLab was launched in North America last year, and in Europe in April, the company’s focus since then has been on evaluating the technology “to understand what’s the value [of it] versus other ways of doing things,” Paul Smith, Axela’s vice president of sales and business planning and research, told ProteoMonitor recently. “Things like complexes, isoforms, multiplexing and dynamic range — that was what was important to people, so we’ve been focused on that.”
To do so, Axela installed dotLab in about 15 facilities where researchers could use the platform and give the company feedback on results obtained on the platform.
For instance, last month the Toronto-based firm announced a collaboration with Jenny Van Eyk at the Johns Hopkins University School of Medicine to use the technology in a clinical trial to evaluate circulating cardiac Troponin complexes.
That followed an announcement in June that the Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center would use the platform to screen high-risk infants for suspected brain injury.
In addition, Axela signed a distribution agreement with VWR International in January for the dotLab technology and reagents covering North America.
Developed by Cynthia Goh, a professor of chemistry at the University of Toronto and founder of Axela, the dotLab system, which retails for $67,900, represents the present and future of Axela as it is the company’s sole product, and has been generating revenues for only the past six months. Smith declined to disclose any figures.
The benchtop system is designed for protein-expression monitoring, routine immunoassay, assay development, and biomolecular interaction applications. Molecules such as antibodies are put on the dotLab Sensor in specific line patterns known to generate diffractive images. After the binding of target molecules, a detectable light diffraction image is generated by a laser, and the image is analyzed quantitatively by the optical reader.
In a paper published in the November 2006 issue of Clinical Chemistry, Axela researchers wrote that the dotLab technology “takes advantage of the inherent properties of diffractive optics to deliver a cost-effective, portable, robust, optical biosensor that detects analytes at picomolar concentrations in complex media.”
The system is meant to address a growing area of concern in biomarker research: verification and validation of biomarkers. Indeed, in numerous talks at proteomics conferences, leading researchers have said that the push should no longer be on discovering new biomarkers but on proving their ability to detect diseases.
The technology, said Smith, addresses several issues that have to date plagued both the biomarker-discovery and -validation phases. First, it allows researchers to develop assays more quickly than ELISAs so that true candidate biomarkers can be verified readily.
“Basically, we said that if we can’t with this technology also satisfy the requirements necessary to make a point-of-care diagnostics platform, then we won’t go ahead with the research platform.”
Also, the platform cuts down on sample costs. Typically, a well-characterized sample will cost about $2,000 and depending on the experiment, multiple samples may be needed for high-sensitivity analysis. The dotLab, however, uses about 60 percent less sample than traditional methods for a single analysis, according to the company.
Another potential advantage of the dotLab system is its reproducibility, which can be difficult with both Western blots and mass spec-based methods.
The model, Smith said, has been to give people a tool “to develop assays, give them a tool to be able to multiplex those into panels a lot simpler than they’ve been able to do before, and then give them a direct pathway without having to change assay formats to a diagnostic platform so if they do make it through that cycle, they’re not redeveloping assays [for] exactly the same thing all the way through.”
While the platform is currently being sold to the research market, it was developed with the diagnostic market in mind.
“Basically, we said that if we can’t with this technology also satisfy the requirements necessary to make a point-of-care diagnostics platform, then we won’t go ahead with the research platform,” Smith said, adding the goal is eventually to make the technology applicable for near-patient point-of-care testing. “The focus is on the commercialization and expansion of sales in the research market as a way of getting a good solid foundation and pipeline for the diagnostics.”
With this in mind, the company standardized the tool’s optics “so that there [are] no adjustments, so that you can put it into a small box, being able to mold optical parts reproducibly,” he said.
Once that was accomplished, Axela moved the platform back into the research market, and, having made inroads there, is now once again concentrating on developing the diagnostic version of dotLab. The company is currently speaking with potential partners for that work, though Smith declined to identify them.
In addition to biomarker verification and validation, the dotLab system is being used by a small handful of undisclosed top-20 drug firms to monitor immunogenecity and immune response to vaccines “so we’ve actually shown that this technology allows you to use the intact virus as a capture agent and we can … truly measure the response to that. We don’t have to break it up into different epitopes … and measure things binding to that,” Smith said.
In the meantime, Axela is collaborating with researchers on projects that it believes will generate novel data and findings and bring additional value to the platform.
In a poster at the recent Human Proteome Organization’s annual conference, Van Eyk and her colleagues said that while it is “accepted dogma” that the Troponin complex subunit cTnI circulates in blood as a cTnI-cTnC complex, “this is based primarily on indirect evidence. There has been no study that has directly characterized the circulating ternary form of these biomarkers, in part, due to a limitation in technology.”
Using the dotLab platform, Van Eyk and her colleagues developed an immunoassay characterizing the circulating form of cTnI. The assay was able to directly probe the integrity of cTnI and determine if the protein is degraded, and to detect circulating cTnI bound to the cTnC and cTnT from serum obtained from a patient with acute myocardial infarction “indicating the dimer or intact Troponin complex is present.”
They added that the dotLab immunoassay is the “first [clinically] applicable and easy-to-use assay that can be used to address the direct interactions of the subunits with the [Troponin] complex,” and “allows the direct measure of protein interactions in complex samples. Real-time binding data allows a more thorough understanding of these complex interactions.”
Detecting cTnI would enable clinicians to stratify the risk of patients to develop acute myocardial infarction and determine who will need more aggressive therapy, Axela said. In the next phase of their work, the Johns Hopkins researchers will use dotLab to evaluate the prognostic value of Troponin complexes and post-translational modifications to cTnI in patients with acute myocardial infarction. The trial will take place in two phases to follow patients over the course of a year to evaluate long-term outcomes of patients.
In addition to the heart disease and brain injury collaborations with Johns Hopkins and Children’s Hospital at UPMC, Axela sees potential for the dotLab system in the area of in vitro fertilization, oncology, and infectious diseases.
Axela is currently trying to secure a financing round that would help it commercialize the current product and to enable it to begin developing the diagnostic pipeline, Smith said. To date, Axela has been primarily funded by Canadian life-sciences venture capital firm VenGrowth.
By next summer, he said, Axela hopes to have filed or be in the process of filing a 510(k) application with the US Food and Drug Administration for a diagnostic platform based on the dotLab technology.