*Salus Discovery was founded by David Beebe and Scott Berry based on technology developed at UW–Madison and licensed from WARF.
Tuberculosis my not be the epidemic in the United States that it once was, but it’s still one of the leading causes of death and illness in the world. However, thanks to a project currently underway at Salus Discovery, a Madison-based biotech firm, the disease soon could be easier than ever to diagnose in remote settings, allowing for more rapid treatment of those infected with TB and helping to slow the spread of the disease.
According to the National Institutes of Health, it’s estimated that one-third of the world’s population is infected with the TB bacterium and that 16.2 million people currently have TB. The Centers for Disease Control and Prevention note that in 2016, 10.4 million people around the world became sick with TB, and there were 1.7 million TB-related deaths worldwide. TB is also a leading killer of people who are HIV infected.
The picture in the U.S. is better — a total of 9,272 TB cases (a rate of 2.9 cases per 100,000 persons) were reported in the United States in 2016. This is a decrease from the number of cases reported in 2015 and the lowest case count on record in the United States.
Currently, many cases of TB are diagnosed via nucleic acid amplification tests on collected samples of sputum, which is a mixture of saliva and mucus coughed up from the respiratory tract, typically as a result of infection or other disease and often examined microscopically to aid medical diagnosis.
Unfortunately, sputum can be difficult to collect and the tests can require expert personnel to interpret, something that slows down the diagnostic process in remote locations, such as many parts of Africa, where the greatest number of deaths from TB per capita occurs.
While effective TB diagnostics exist, they are limited to locations with clinical laboratories and may be unaffordable to those most at risk to TB-related mortality, notes John Guckenberger, a senior engineer at Salus Discovery. “Our goal is to develop a low-cost assay that can be deployed to locations otherwise unreachable by existing assays.”
Salus was recently awarded a $2.6 million investment from the Bill & Melinda Gates Foundation to advance development of a non-sputum based point-of-care tuberculosis triage test.
In 2014, the World Health Organization identified this test as a specific global need. Salus Discovery, led by co-founders Dr. David Beebe and Dr. Scott Berry, are overseeing the 30-month project, which also involves eight sub-grantees from six different countries.
Salus Discovery, which was started nearly five years ago by researchers from the University of Wisconsin–Madison, currently has seven employees. Its main technology portfolio is geared toward simplified methods to manipulate and analyze biomarkers, including proteins and nucleic acids.
“We’re excited to lead an exceptionally talented group of international collaborators toward a goal that’s incredibly important to global health,” says Beebe. It is estimated that a diagnostic test for tuberculosis with sufficient sensitivity and specificity that is adaptable in areas with limited infrastructure would be used 100 million times per year and save at least 400,000 lives annually.
“We’re extremely grateful to the Bill & Melinda Gates Foundation for this investment, which is very significant for a company of our size,” adds Guckenberger. “Through our work at both Salus and UW–Madison, we’ve developed a reputation for our ability to leverage technology to reduce the cost and complexity of diagnostic tests, and we plan to continue this trend via the development of the next generation of TB diagnostics.”
The simple, low-cost triage test will be designed for use in remote healthcare settings, bringing the test closer to the patients that need it most. The technology will differ from traditional tuberculosis assays by targeting a biomarker in urine versus relying on a difficult-to-collect sputum sample. It will also feature a straightforward, lateral-flow assay readout, provided by U.K.-based Mologic Ltd., that’s similar to a home pregnancy test and will allow for interpretation without an expert. The test aims to accurately detect tuberculosis in both HIV-positive and HIV-negative adults and children, addressing several limitations of current methods. Most importantly, it will bring tuberculosis tests to those without current access.
Field testing in both South Africa and Ethiopia will validate assay functionality with hundreds of “real-world” samples from patients with either confirmed or suspected tuberculosis. Following successful clinical evaluation, Salus intends to seek approval from regulatory agencies and WHO endorsement.
Guckenberger explains the home pregnancy test comparison is an easy one because the two tests will operate in the same manner. “These pregnancy tests — the ones with the +/- lines — are lateral-flow devices. During operation, biomarkers in the urine bind to antibodies and beads (the pink color). These antibody-biomarker-bead complexes then bind to the line(s). One line (-) is a control line to verify the test has run; two lines (+) is a to indicate that the biomarker of interest is present in urine. In our case, we will be using a different biomarker, but the urine will run through the test strip, like a pregnancy test, and the readout will function in the same way (+/- indicators) as a pregnancy test.”
Salus’ technology involves the concentration of disease biomarkers for more sensitive detection, notes Guckenberger. “Assay sensitivity is a core issue within the molecular diagnostic community and we believe that our technologies can be applied to several other diseases including HIV, flu, MRSA, pneumonia, and hepatitis, just to name a few.”
“Technologically, this project aligns perfectly with our long-term vision for Salus as a company, adds Beebe. “It really enables us to grow the business while developing a product with the potential to improve health care for millions. While the focus of this project is tuberculosis in the developing the world, the technology will find utility in a number of other applications in the developed world.”
Guckenberger says Salus is “planning for success” from the outset of this project. This involves not only scientific innovation, but also a significant amount of product development, business development, and regulatory approval planning. “Fortunately, we’ve assembled a very strong network of international collaborators and stakeholders, which have a great deal of expertise in developing and launching TB diagnostics in many different countries. This network will enable us to obtain ‘voice-of-customer’ feedback on several prototypes during the early stages of development.
“We understand the skepticism in this area given the skyrocketing costs within health care these days,” Guckenberger continues. “Our goal is to develop an assay that is low-cost to produce, such that the purchase price of the assay will remain minimal. Salus is committed to ensuring that this test is accessible to those that need it most, and our agreement with the Gates Foundation reflects this commitment to affordable pricing in low-income countries. Further, to create a truly sustainable solution, we are exploring ways to create local value (e.g., jobs, ownership), for example, by moving final product assembly — and eventually manufacturing — to local ownership and control in Africa.”
Guckenberger gives a lot of credit to Madison’s biotech community for Salus’ recent success. “Our close relationship with Middleton-based Gilson Inc. has really accelerated our efforts to bring our technology to market. Our location on Madison’s Capitol Square has provided a welcoming backdrop for interactions with investors, collaborators, and business partners. The critical mass of knowledge within the Madison/UW ecosphere has been invaluable for brainstorming and developing nascent ideas.”