NEW YORK (GenomeWeb) – University of Cambridge spinout PredictImmune aims to have a clinical test for the stratification of Crohn's disease and ulcerative colitis patients on the European and US markets next year.
The company this week announced that it received £4.3 million ($5.9 million) from the Wellcome Trust to evaluate the use of its test to guide therapy in 400 patients across the UK. PredictImmune's test relies on a 16-marker gene expression panel run using quantitative PCR to stratify Crohn's disease and ulcerative colitis patients according to the severity of their illnesses.
"When these patients present for diagnosis, you don't know how they are going to fare with the disease," said Andrew Sandham, executive director at PredictImmune. "Some are relatively well treated with steroids and have periodic disease that's not serious," he said. "Others have severe relapses, the disease flares get worse, and they will be put onto more aggressive therapy, typically anti-TNF biologics," Sandham continued. "This test enables you to tell which is which."
Sandham took the helm of PredictImmune in May 2017 when the company raised £4.7 million through a Series A financing round that included investors Parkwalk Opportunities, Cambridge Enterprise, and Wren Capital. That money has enabled the company to set up shop with six employees and a small laboratory on the Babraham Research Campus outside of Cambridge. The company has also worked with external manufacturers and software developers to prepare a kit for the clinical market.
According to Sandham, PredictImmune aims to obtain a CE-IVD mark by the end of this year so that it can sell its kit to the European clinical market. The company is planning to commercialize the test in Europe next year and will seek to make it available to US customers as well through partnering with one or more CLIA-compliant labs. With partners in place, PredictImmune will also run clinical studies, and may eventually submit its test to US regulators for clearance.
"We will probably go with a kit in the US with a proper 510(k), but that won't be our first entrée to the US," said Sandham.
The biology underlying PredictImmune's first test was developed in the laboratory of Kevin Smith, head of the department of medicine at the University of Cambridge, and is described in nearly a dozen papers stretching back a decade. A 2011 Journal of Clinical Investigation paper, for example, discussed the use of  gene expression profiling of CD8+ T cells to differentiate patients with Crohn's disease and ulcerative colitis, as well as to predict disease progression.
As Sandham noted, some patients exhibit T cell exhaustion at the time of their first flare up, while others have an active and amplified T cell component. This distinction, evident in the elevated expression of genes involved in T cell responses, can determine who will go on to suffer a more severe form of the disease. "It's a predictor of outcome," Sandham claimed.
From a master list of 40 markers, the scientists during the process of two studies narrowed in on a set of 16 markers that could be observed in blood. These markers are measured using standard qPCR and the company's software algorithms. Sandham said that PredictImmune is designing its kit to run on Roche's LightCycler instrument, as it is "probably the largest installed PCR platform," but said that it could be run on other PCR systems as well, hypothetically.
That ability, to stratify Crohn's disease and ulcerative colitis patients into two categories — those with a milder form of the disease, and those at risk of severe relapse —  should allow clinicians to personalize therapies for patients, rather than administering the current standard of care, which is "fairly mild immunosuppressive therapy," such as steroids, in the case of Crohn's disease. Patients who are identified as being at risk for severe relapses could proceed directly to anti-TNF biologics, a more aggressive treatment that, if prescribed early, could reduce the severity of their disease over time.
"There is very good reason to believe that if you prescribe anti-TNF biologics to patients first off who will fare worse, they will do better in their life with the disease," noted Sandham.
Sandham maintained that PredictImmune already has the clinical evidence in place to secure a CE-IVD mark for the test later this year. However, the new Wellcome Trust study should add to that body of evidence. The multicenter study, called Predicting Outcomes for Crohn's disease using a Molecular Biomarker (PROFILE), will be run through NHS Cambridge University Hospitals' Cambridge Clinical Trials Unit. The PROFILE trial aims to enroll 400 newly diagnosed adults and will evaluate the ability of the test to guide treatment between standard incremental treatment and first-line use of TNF inhibitors. The primary endpoint of the study is sustained remission from the completion of steroid induction treatment for 48 weeks. A certified clinical lab in the UK will be running PredictImmune's test as part of the study, as the kitted version of the assay is not yet CE-IVD marked, Sandham noted.
PredictImmune expects the results from the PROFILE study in 2020. Sandham said the resulting data should be useful in "getting the health economics of the test and supporting payors and reimbursement." Once PredictImmune's test is CE-IVD marked, the company plans to initiate similar studies across Europe during the course of 2019 that will familiarize clinicians with the test, Sandham noted. "The model is to run these kinds of tests with hospital labs in Europe," he said.
Initial feedback from gastroenterologists familiar with the test has been "very strong," Sandham claimed, adding that there is "high receptivity" to the company's diagnostic as there is no current test to stratify Crohn's disease and ulcerative colitis patients. However, Prometheus Laboratories, a San Diego-based company, does offer a Crohn's stratification service called Monitr that is based on a series of enzyme-linked immunosorbent assays and other tests.
Yet clinical guidelines, both in Europe and in the US, will have to undergo revision before a test such as PredictImmune's becomes a first-line assay used to select treatment for Crohn's disease and ulcerative colitis patients. "We will work with the European, UK, and American authorities to influence guidelines and that will take a number of years," said Sandham. "I think ultimately, that is where the test will lead, [to] the changing of treatment guidelines."
As PredictImmune revs up for commercialization, it also plans to close a round of Series B financing sometime next year to build out its organization, especially in Europe, as well as to support the launch of test services in the US. Sandham did not say how much the company intends to raise, but said that its current activities are still being financed by its Series A. The company is also in the process of expanding its management team, including the appointment of a head of regulatory affairs and quality assurance, he added.
In terms of its test pipeline, Sandham noted that Smith's lab at the University of Cambridge has applied its approach to identify biomarker panels to other inflammatory diseases, including acute vasculitis, lupus, multiple sclerosis, and diabetes. Smith's group published a paper in Current Pharmaceutical Design in 2015, for example, that discussed a CD8+ T-cell gene signature for vasculitis and lupus. The next tests the firm might commercialize will be for those diseases, Sandham said.
"We plan to bring those into the company at around the same point that we brought the present test in," he said, "when they have discovered the signature and had initial clinical validation in a cohort."