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Pancreatic Cancer Liquid Biopsy Test to Be First Product of Harvard Spinout Biomarx Therapeutics

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NEW YORK (GenomeWeb) – 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.

Towia Libermann, a company cofounder and scientific advisor for the Harvard University spinout, said in an interview that Biomarx has raised $200,000 since it was established last year, By the end of 2017, the firm hopes to close a Series A round of about $3.5 million to continue test development.

Should it make good on its promise to develop the test, currently called Bio Pan-Can, Biomarx could be addressing a market size of $2.5 billion as it targets people at a high risk for developing the deadly disease.

US pancreatic cancer statistics are grim. "The overall concept behind the company is that pancreatic cancer is one of the deadliest cancers that exist right now," Libermann said. He noted that in the US, 53,000 people were diagnosed with the disease last year, and the five year survival rate is only about 7 percent. One of the reasons for this high mortality rate is that the disease often remains asymptomatic until it reaches its final, metastatic stage.

"There are no tests available to detect pancreatic cancer early and the patients that are being diagnosed early on are primarily diagnosed due to incidental findings such as various types of imaging or ultrasound," said Libermann.

Even if discovered during a routine ultrasound, pancreatic cancer patients must undergo an endoscopic ultrasound followed by fine needle aspiration to acquire a tissue sample. These are then observed under a microscope by an oncologist.

"Even that test is not accurate," said Libermann.

Biomarx's aim therefore is to shift testing from the metastatic stage to an earlier, localized stage, relying on a panel of internally developed RNA and protein markers. Such a test would improve survival rates and the application of therapies.

"Even by shifting from the metastatic stage to localized stage 2, the survival rate increases by tenfold," said Libermann.

Much of the science behind Biomarx's panel was conducted in Libermann's laboratory. He is an associate professor of medicine at Harvard Medical School and a director of Beth Israel Deaconess Medical Center's Genomics, Proteomics, Bioinformatics, and Systems Biology Center.

Using a number of publicly available gene expression datasets, he and fellow investigators 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.

The predictor also accurately differentiated between pancreatic cancer, benign pancreatic lesions, early-stage pancreatic cancer, and healthy tissue. The study was detailed in the journal Oncotarget last year. The marker panel, including algorithms and methods to either diagnose or determine the stage and severity of pancreatic cancer, is covered by a patent filed with the US Patent and Trademark Office in 2015. The IP, which is assigned to BIDMC and which Biomarx has licensed, also describes potential therapeutic markers, another prospect for Biomarx's business.

While the investigators initially ran their marker set on solid tumor samples to validate the test, they quickly realized the necessity for a blood-based assay instead to reach their target group — those who may not have any symptoms of the disease.

A solid biopsy was "not an attractive proposition because taking biopsies is not something you can routinely use to evaluate if someone develops pancreatic cancer," said Libermann.

Biomarx has thus committed itself to developing an assay that works using liquid biopsies, meaning plasma or serum samples, from patients in high-risk groups, either those with inheritable pancreatic cancer, or those falling into other risk groups, such as patients with pancreatitis or diabetes.

"We don't believe our test will be a routine screening test for everyone, but we think there will be specific guidelines in regard to first calculating the risk and then evaluating if and how frequently such a test should be advised," said Libermann. "Still, the at-risk population will be very high."

The technology underlying the test is still undetermined. Libermann said the firm is courting a number of partners that may be able to develop a sensitive, microfluidic, point-of-care device for it that can measure both protein and RNA markers in a blood sample.

"It's definitely something that could be developed fast and would be a combination of both RNA and protein," said Libermann.

Biomarx includes four other principals in addition to Libermann: CEO Zeid Barakat; CSO and cofounder Roya Khosravi-Far; Manoj Bhasin, another cofounder and codirector of Libermann's center at BIDMC; and Karl Ruping, a cofounder and managing director at IncTank Ventures, a Cambridge, Massachusetts-based company that has invested in Biomarx.

Next month, the firm will move into Pagliuca Harvard Life Lab, a new, 15,000-square-foot facility for life science companies located in nearby Allston, Massachusetts.

Biomarx also has an agreements with SBH Sciences and Woodland Biosciences, two contract research organization that have offered up lab space and other resources to carry out the experiments necessary to get the firm to the "next inflection point," according to Libermann. Biomarx's CRO partner SBH already maintains a CLIA-compliant lab, and could offer its assay once it debuts as a laboratory-developed test.

Libermann explained that the firm's first goal is to develop an LDT because it is easier to get it to the market, and then to obtain an investigational device exemption from the US Food and Drug Administration at a later stage.

Biomarx is also in talks with a number of biobanks in order to refine its assay and marker set. "They know who developed pancreatic cancer and at what point," said Libermann. "If we can get access to these kinds of samples, we should be able to see if our test can be used to diagnose pancreatic cancer three years before it was diagnosed," he said. "We can show value in these kinds of epidemiological studies in cohorts that have been developed and [where it is] just a matter of accessing them."

By running its test on larger cohorts, Biomarx hopes to demonstrate "very high specificity" for its debut test, because it doesn't want to send too many of its potential clients on to follow-up tests unnecessarily after they test positive using Bio Pan-Can.

The company also wants to deliver a highly accurate test to market so that it can compete with other players offering early-stage pancreatic cancer testing. One such competitor is Lund, Sweden-based Immunovia, which has developed a 25-gene microarray panel for diagnosing stage I and stage II pancreatic cancer called Immray PanCan-d. The company announced it commenced a multi-center prospective trial of the assay in December.

Early-stage pancreatic diagnostics, however, are just the first out of Biomarx's pipeline. Libermann noted that the company is also exploring therapeutic targets related to early stages of the disease. One such target is a secreted protein for which Biomarx is developing human monoclonal antibodies that might reduce or prevent the growth of pancreatic cancer.

Biomarx is currently in discussions with companies to determine whether it can develop strategic alliances for therapeutic development, Libermann said. He noted that any funds the firm has raised or intends to raise will go toward developing its first test for early-stage pancreatic cancer.

The application of its panel in other cancers is of interest, too. Libermann said that the firm will likely target aggressive cancers such as glioblastoma, triple negative breast cancer, or gastric cancer next, "cancers where you have limited possibilities to have therapeutic efficacy and where early detection may have an early impact."