NEW YORK (360Dx) – Progentec Diagnostics is developing a protein biomarker platform and assay that's showing promise in predicting lupus flares, which are painful for patients and can occur without warning or a clear cause.
The firm's chances of reaching commercialization and achieving adoption have been improved by its signing of strategic investor Mayo Clinic Ventures, an organization with a cadre of physicians that could benefit from use of the test, Scott Meacham, CEO of non-profit investment funding firm i2E and an investor in Progentec, said in an interview.
i2E, which focuses on early-stage technology companies in Oklahoma, where Progentec is based, and has about 40 percent of its portfolio in life sciences, led a $1.25 million first round of investment in the firm that also included funding from OCA Ventures, an early-stage venture capital firm, in addition to Mayo Clinic Ventures.
"From our perspective, it's a great benefit to have a strategic partner like the Mayo Clinic that could help prove the viability and utilization of the test," Meacham said, adding, "If Mayo decides to adopt the test, that's a pretty big stamp of approval. We are still a long way from that, but at least we've reached the first stage."
The biomarker platform and assay being developed for the early detection of lupus flares must undergo additional retrospective and prospective studies, but it could be available as a commercial test from a CLIA-certified lab in about a year and half, Mohan Purushothaman, Progentec's CEO, said in an interview.
"When a patient encounters a flare, there's not much they can currently do except go to an emergency room or a physician and begin a regimen of steroid treatment," Purushothaman said. "We can accurately predict whether the patient is going to get a flare in a window of 8 to 12 weeks prior to the potential onset of a flare," he said, adding that such a biomarker test "could significantly improve" physicians' chances of better managing the disease and the unexpected nature of its flaring.
The platform and assay are based on technology that Progentec licensed from the Oklahoma Medical Research Foundation (OMRF), where lupus researcher Judith James invented the technology.
He noted that the test for lupus, an autoimmune disease that triggers inflammation in body tissues, would address an unmet need in a market that, according to the Lupus Foundation of America, includes up to 1.5 million people in the US and 5 million globally that suffer from systemic lupus erythematosus, or SLE.
SLE is diagnosed by a healthcare provider using symptom assessments, physical examination, X-rays, and lab tests. It could be misdiagnosed if only a blood test is used for diagnosis, and because diagnosis can be challenging, it is important to see a doctor specializing in rheumatology for a final diagnosis, according to the US Centers for Disease Control and Prevention.
SLE may be difficult to diagnose because its signs and symptoms are not specific and can look like signs and symptoms of other diseases.
"We believe that there is a large unmet need in the market for good diagnostics to detect and predict lupus," Purushothaman said. An accurate diagnostic test would create a significant impact for patients as well as how they are managed by physicians, because a single test that effectively predicts the onset of lupus flares doesn't currently exist, he said.Â
The condition is experienced mostly by women between the ages of 15 and 44 who are most often treated with steroids, Purushothaman said. It causes the immune system to attack the body's tissues and organs, and its severity ranges along a continuum from patients who suffer occasionally from flares for unpredictable periods to others whose organs are damaged by the condition.
Patients who experience lupus flares from time to time still end up rushing to emergency rooms in hospitals, and lupus flares can impact their ability to live effectively for days or weeks, he said. About 30 percent of patients with lupus flares sustain organ damage, he noted, and affected organs include the skin, kidneys, lungs, reproductive organs, and the cardiovascular system.
"Unlike rheumatoid arthritis that we know affects joints, lupus affects almost every organ in your body," he said, adding that people tend to be unaware of the extent of its clinical impact and its multifaceted nature.
"If you know that there's a threat of a flare or that a flare is not coming, you manage the patient differently," Purushothaman said, adding, "As we move the test through clinical trials, we are looking to identify what some of those interventions might be and how they can generate an impact from clinical and economic perspectives."
The firm said that it is also developing two additional tests for lupus. One, which the firm believes holds potential as a screening test, focuses on very early-stage detection. "In a small study we have been able to demonstrate the detection of lupus [many] months before symptoms occur," Purushothaman said.
A second test in development for the firm tracks underlying disease activity and its progression and is being designed as a disease activity index. "Many positive patient outcomes can flow from the capability to have an index that detects and evaluates lupus in this way," he said. Patients are managed differently when a clinician knows that a flare-up is imminent, he said.
In small retrospective studies that it has completed thus far, the company has seen sensitivity and specificity levels "in the high 80 percent" range for its protein biomarker test, Purushothaman said.
With the current funding round, Progentec plans to conduct a new retrospective study at OMRF that includes 300 patient samples and is expected to run for eight to 10 months. It's also initiating a prospective study at OMRF and the Mayo Clinic that involves 100 patients and should run for about 18 months, he said.
The studies would help the company further refine the algorithms it uses to evaluate the presence and impact of the "large group" of protein biomarkers that it has identified, he said. The firm did not disclose the specific biomarkers or number of biomarkers in its panel.
A 2014 study published by researchers at OMRF in the journal Arthritis & Rheumatology provides a description of early development work on the test, Purushothaman said.
The researchers evaluated changes in plasma concentrations of soluble mediators that precede clinically defined disease flares. The researchers noted that the evaluated 52 different soluble mediators, including cytokines, chemokines, and soluble receptors, using validated multiplex bead-based or enzyme-linked immunosorbent assays in plasma from 28 patients with SLE who developed disease flare 6 or 12 weeks after a baseline assessment, 28 matched SLE patients without an impending flare, and 28 matched healthy controls.
They found that the levels of proinflammatory adaptive cytokines and shed tumor necrosis factor receptors are elevated prior to disease flare, while the levels of regulatory mediators are elevated during periods of stable disease. Alterations in the balance between inflammatory and regulatory mediators could help identify patients at risk of disease flare and help decipher the pathogenic mechanisms of SLE, the researchers concluded at the time.
Purushothaman noted that the firm's first commercial test will be the key component of a future CLIA-certified central laboratory established by Progentec, to which physicians would ship plasma samples for testing. In about 18 months or so, the firm expects that it will begin offering commercial testing services to academic centers of excellence who are testing their patients for lupus, and it will subsequently open the service to the broader physician community.
The firm is also considering eventually pursuing US Food and Drug Administration clearance, but it has not established a strategy for that yet, though it is closely monitoring the regulatory landscape, Purushothaman said.