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Immunovia Early Stage Pancreatic Cancer Test Enters North London Validation Study

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NEW YORK (360Dx) – A multi-antibody platform that simultaneously analyzes information from about 30 biomarker proteins could be what primary care physicians need to detect pancreatic cancer early enough that something can be done to effectively treat it, according to the platform developer and pancreatic cancer researchers familiar with the test.

The test gleans discrete pieces of information from a relatively large number of proteins in a blood sample during a process that enables it to achieve an accuracy of 96 percent in large retrospective clinical studies, Mats Grahn, the CEO of Immunovia, the test developer with headquarters in Lund, Sweden, said in an interview.

Toward the end of next year, the firm plans to launch the assay on its microarray antibody platform in the US and Sweden as a lab-developed test that can be used by primary care physicians, gastroenterologists, and other clinicians when they suspect that their patients could have pancreatic cancer. Longer term, the firm believes that based on the results of clinical studies, patients and healthcare providers using the testing service will be able to receive reimbursements from payors.

Diane Simeone, a surgeon who directs the Pancreatic Cancer Center at NYU Langone Health’s Perlmutter Cancer Center, said in an interview that the Immunovia test is among the most promising in development for a condition that is in critical need of an effective early detection technology.

"A handful of different in vitro diagnostic tests are out there for detecting pancreatic cancer, but the other technologies are not as far along, and they haven't really been tested in early stage pancreatic cancer patients," said Simeone, an unpaid scientific advisor to Immunovia.

Immunovia said on Friday that the Institute for Liver and Digestive Health, University College London has begun collecting 360 blood samples in a project funded by London Cancer Vanguard that aims to assess the utility of the firm's early-stage pancreatic test, the Immray PanCan-d, in patients with abdominal symptoms who attend secondary care centers, including clinics, multidisciplinary diagnostic centers, and gastrointestinal units.

The study, conducted in facilities throughout North London, is expected to run for about one year and has been designed to simultaneously validate the use of a novel early-symptoms digital clinical decision support tool currently used in primary care as a risk assessment tool for pancreatic cancer. 

If the results of the clinical study materialize as expected, the same group of collaborators will begin a large prospective study in 2019, or sooner, Grahn said.

The firm said that in parallel with participating in a future large prospective study, it also has plans to launch its assay as a lab-developed test in the US and Scandinavia, as part of a service for which patients and healthcare providers would pay for testing. "We have been in conversations with the [US Centers for Medicare & Medicaid Services] and commercial payors about reimbursement for the test," but that could only happen after the completion of clinical studies, he added.

The firm's Immray platform uses arrays of human recombinant single-chain fragment variable antibodies. The platform targets immunoregulatory proteins and their cancer-associated antigens. It creates a biological snapshot of a person's immune response by analyzing serum proteins that change as a sign of disease, the firm said.

Grahn said that the company used a discovery version of the platform in developing the early-stage pancreatic cancer test that evaluated around 300 protein targets using its proprietary bioinformatics platform, and narrowed it down to the most suitable 30 biomarker proteins.

The firm maintains its own antibody library, and antibody production and purification systems, and it does its own microarray production.

The decision support tool used in the North London trial, whose development was supported by the UK National Health Service, has already been in use in hundreds of primary care settings in a pilot test area, Grahn said. Between 3 percent and 3.5 percent of people who are screened with the digital tool are shown to have pancreatic cancer after they are referred for further diagnosis and treatment, he added.

In clinical practice, the digital risk assessment tool could be used along with Immunovia's blood test. The digital tool would raise a red flag that a patient could have early-stage pancreatic cancer, and the blood test would confirm whether that is the case in order to rapidly send the patient for imaging and specialist care, Grahn said.

Combining the digital risk assessment tool and the Immunovia test would provide a similar, or better, outcome to providing imagining for every patient suspected of having pancreatic cancer, he said. However, it's a far better solution because providing imagining for that number of patients is not feasible from a health economics perspective, he noted.

To facilitate the test's adoption, the firm has established a US subsidiary in Boston that will house a CLIA reference lab and commercialization operations for the firm. Grahn said that the Boson-based laboratory complements the Oregon Health & Science University Knight Diagnostic Laboratories facility in Portland, with whom Immunovia has a research-based collaboration, and which will serve as its reference laboratory for the firm in the Western part of the US.

As is normal, the test's potential is tied directly to the results of clinical trials. Grahn, Simeone, and Stephen Pereira, who is leading the UCL team of clinicians using the test in the London-based clinical trial, are encouraged by the results they've seen so far.

Pereira, a professor of hepatology and gastroenterology at UCL Institute for Liver and Digestive Health, said in a statement that the Immunovia test "has already demonstrated encouraging results for accurate detection of early stages of pancreatic cancer, and this pilot study will provide the first opportunity to evaluate if the test could be used for diagnosing high-risk, symptomatic patients at a treatable stage."

He noted that almost half of the patients with pancreatic adenocarcinoma are diagnosed with the cancer when they are admitted to a hospital during an emergency. The patients are unlikely to survive for one year after being diagnosed, he said, adding that there are many reasons for this, such as patients having vague symptoms, physicians not considering the possible diagnosis of cancer, or hospitals not having clear pathways to investigate such patients, he noted.

Pancreatic cancer is not prevalent enough for it to be deployed in an economical way as a screening tool for an entire population, Grahn said. However, there are three clinical categories in which high-risk patients should be tested, he noted.

For the first group — those with a family history of pancreatic cancer — the firm initiated a prospective clinical study late last year, with partners in Europe and the US, to validate its test in 1,000 patients.

The longitudinal clinical study, called Panfam-1, uses the company's blood test to analyze people at high risk for FPC over a period of three years. The subjects are being recruited at sites in the US and in Europe that offer FPC screening programs.

Ramon y Cajal Institute for Health Research in Spain, Mount Sinai in New York, the Knight Cancer Institute, and the University of Liverpool have begun collecting samples, and Immunovia is in discussions with several other pancreatic cancer surveillance programs in Europe and the US about their participation in the study.

The study follows a retrospective clinical validation study of Immray PanCan-d that the company completed last year.

The number of pancreatic cancer cases that fall within this group is about 10 percent of the total number of pancreatic cancer cases, Grahn said.

Therefore, 90 percent of cases are "sporadic," and to address these, there are two remaining categories of high-risk patients that should be tested, he said. One of those categories, consisting of patients 50 and older who have contracted new-onset diabetes, is coming into focus for many leading cancer agencies, including the National Cancer Institute, the National Institutes of Health, and others, he noted. These patients have an eight- to tenfold increased potential for developing pancreatic cancer, he said, adding that testing these patients for the potential of having early-stage pancreatic cancer "is a large opportunity to address the sporadic segment" of the pancreatic cancer patient population.

"The third high-risk group, consisting of patients with vague symptoms, are being tested as part of the North London study. When people develop pancreatic cancer, they exhibit symptoms such as abnormal back pain, indigestion, sudden weight loss, and others, but primary care [doctors] and other physicians are not likely to routinely test these patient for pancreatic cancer," Grahn said. "They test patients first for almost all other suspected conditions, and the time from a first visit to the actual pancreatic cancer diagnosis can be devastating; it can frequently take six to nine months, and in that time, many of the patients move from treatable to non-treatable."

Simeone said, "About 85 percent of patients present with advanced disease that's at a stage that is not amenable to surgical resection, our only curative approach." Pancreatic cancer re-emerges in about 70 percent of those 15 percent of patients who receive surgeries, she said.

To move the needle on this disease, clinicians need to be able to detect it earlier, she noted. But the pancreas sits in the back of the upper abdomen, and "it's not easily assessed by a physical exam or a standard endoscopy test, so it is has been difficult to develop an early detection test," Simeone added.

In a quest to achieve early detection, multiple groups are developing different types of platforms, she said. "They vary from using circulating tumor DNA to exosomes to abnormal circulating pancreas cells — which is a platform on which we've done some work — and on to using different kinds of protein assays," she noted.

Among them, Varleigh Dx and Cancer Research Technology has launched a protein biomarker test for pancreatic cancer, with hopes of translating the marker for diagnostics in several other cancers.

Their test, which measures the concentration of antibodies bound to the MCM5 protein, has been CE marked and is available for diagnostic use across the UK.

Supporting the test launch, researchers from University College London published a study in January in the British Journal of Cancer demonstrating that the test can help improve diagnosis of patients with unclear results from standard cytology methods.

Researchers at Harvard Medical School and Massachusetts General Hospital are developing an exosome-based nanoplasmonic assay to fit into clinical workflows that's taking aim at high-throughput detection of pancreatic ductal adenocarcinoma.

The assay leverages low blood volumes and the clinical potential of exosomes — tiny vesicles shed by all kinds of cells, including tumor cells. Exosome Diagnostics has licensed the technology and is exploring integrating the test with its own portfolio of exosome tests to explore the potential for doing concurrent testing of exosome-based proteins and mRNA.

 A Harvard University spinout Biomarx Therapeutics is preparing a blood-based test for early-stage pancreatic cancer that it hopes to have on the market by the first quarter of 2019.

Using a number of publicly available gene expression datasets, the firm has developed a panel of genes — including TMPRSS4, AHNAK2, POSTN, ECT2, and SERPINB5 — for differentiating pancreatic cancer and healthy pancreas tissue, applying the resulting predictor to other datasets for independent validation to confirm its accuracy. In 2016, researchers described the test in the journal Oncotarget.

"What's happened so far in this space is that you have small studies thatare not very well powered, and do not really cater to the very early stage of the disease," Simeone noted, "so we have to assemble ourselves in a very different way to tackle this problem, to develop a large collaborative network. Some of those efforts are starting to happen."

Immunovia, she said, is engaging with different centers around the world to collaborate in an attempt to move a successful early pancreatic cancer test toward commercialization. "The goal is to test the platform in a high-risk population that's followed over time, and I think that this is an important study to do," she said. NYU Langone itself is coordinating the collaboration of healthcare centers around the US to support the clinical testing of early-stage pancreatic cancer diagnostic tests in high-risk populations, she noted. Adding

"I would like for us to have a bake off where we would test multiple promising technologies head to head, and then learn some things — do certain technologies outperform others; is there a complementary nature to any of the technologies, meaning they could be combined; and if you have a positive test with a new technology what is the lead time between the presentation of a patient with pancreatic cancer and receiving a positive test result?"

Data are emerging, she said, that show that early detection "can change outcomes and increase survival for pancreatic cancer, so we need to change the nihilistic thinking that's out there in the community about this disease. There are lot of significant scientific advances that are happening that can change early detection in this patient cohort."

Immunovia was founded in 2007 by investigators from the Department of Immunotechnology at Lund University and CREATE Health, the Center for Translational Cancer Research in Lund, Sweden.

In October, Immunovia said it had received a SEK4.9 million ($585,000) follow-on grant to support development studies for its Immray pancreatic cancer test. The grant is from the Swelife Accelerator Innovation Program, which is designed to support Sweden's small-to-medium-sized enterprises. The Create Health Translational Cancer Center at Lund University will collaborate with Immunovia on its studies.

Since 2015, Immunovia’s shares have been listed on Nasdaq First North in Stockholm, an investment marketplace designed for small and growing companies.

Grahn said that the company is "well financed," and that it is moving to the Nasdaq main listing in Stockholm, a marketplace for small-, mid-, and large-cap companies, around the beginning of next year. He noted that the company has obtained $25 million in investments to finance its pancreatic cancer business, and it has also received EU grants of €4 million.

Its largest investor to date is Sweden's Handelsbanken Funds, he said.

The firm is also using its platform to develop a test that it can distinguish patients suffering from systemic lupus erythematosus from those with other autoimmune diseases using its antibody array platform.