Protein biomarker-discovery firm Predictive Biosciences earlier this month announced it has raised $21.75 million in a Series B funding round that it will use to validate and perform multi-site clinical trials of protein biomarkers for bladder cancer.
Founded in 2006, the company developed a technology that is based on matrix metalloproteinases, a family of zinc-dependent endopeptidases that have been associated with certain cancers. Predictive has licensed the rights to two biomarkers, MMP2 and MMP9, from Children’s Hospital Boston that its researchers have identified as being especially correlative with bladder cancer.
While Inverness Medical Innovations offers a protein-based diagnostic for bladder cancer that was originally developed by Matritech, unlike that test, which is designed to help diagnose patients with the cancer, Predictive’s assays are designed to sort out patients who may be at risk for developing the cancer but who don’t have it.
“What we want to do is rule patients out of the system who would not necessarily have to undergo diagnostic procedures to confirm whether or not they have cancer,” company CEO and President Peter Klemm told ProteoMonitor recently.
In particular, he said, the company’s urine-based tests, called Intervention Diagnostics, are aimed at two patient populations: those who may be at risk for recurrence of bladder cancer, and those who have hematuria, or blood in their urine, which is a possible symptom of an existing malignancy.
Those who have had the disease and surgery to remove it must continue monitoring for recurrence afterward. That means cystoscopy, an invasive procedure in which a cystoscope is inserted through the urethra to view the bladder.
During the first two years after surgery, the procedure is done every three months, followed by another two years in which it is done every six months. After that the test is performed annually.
“What we want to do is offer this urine-based test at those monitoring intervals initially [concurrent with them] but over time replace more and more of the cystoscopies as we get an increase in clinical data and robustness,” Klemm said.
For hematuria, cystoscopy is again often employed to rule out cancer.
“What our test would do is to be able to help those patients and their urologist understand that that patient absolutely does not have bladder cancer without having to undergo that invasive procedure,” said Eugene Chiu, a co-founder and vice-president of business development of Predictive.
“What we want to do is offer this urine-based test at those monitoring intervals initially [concurrent with cystoscopies] but over time replace more and more of the cystoscopies as we get an increase in clinical data and robustness.”
“The reason that we’re targeting [these two populations] is that our test individualizes the diagnostic intervention such that the patients or the physician can determine whether or not … cystoscopy is needed,” he said.
According to the National Cancer Institute, this year nearly 69,000 people in the US will be newly diagnosed with bladder cancer and more than 14,000 will die from the disease. Worldwide, the diagnostic market for the disease is $1.2 billion, Klemm said, adding that Predictive’s share of that market could be “sizeable.”
“It’s a very attractive market segment [and] we felt this was a good starting point for us,” he said. Predictive’s focus at the moment is on epithelial cancers. In addition to MMP2 and MMP9, the company is conducting clinical work on a disintegrin and metalloproteinase, ADAM12, as a potential biomarker for breast cancer. While mammograms have proven to be a powerful tool in the diagnosis of breast cancer, about 80 percent of mammograms result in false-positives, according to Klemm.
Chiu declined to say how many biomarkers the company has in its portfolio but said that Predictive has 26 issued and pending patents covering the portfolio, “and some of those are for one or more biomarkers, so it’s a large portfolio.” The biomarkers are mainly for cancer and tissue remodeling diseases.
The company’s diagnostic tests under development are ELISA-based but use a “clinical algorithm” to determine a negative predictive value that assesses the presence of cancer in a patient. The assays are optimized to provide an “almost 100 percent” negative predictive value “by which you can say [that] any concentration at that level or lower is almost 100 percent sure that you are not suffering from any cancer,” Klemm said.
To be sure, the field of protein biomarker research has been defined by failure, and biomarkers have had virtually no clinical utility. So why would Predictive believe it can succeed where others have failed?
“Part of the problem with biomarkers is that a lot of companies look at them and end up with, let’s say, 75-, 80-percent specificity and sensitivity, so you more or less are delivering an answer to the physician which is informative but not actionable,” Klemm said. “What we are trying to do now [is] optimize the assays toward a very clear actionable result …so the physician can really act upon this.”
As part of that process, the Lexington, Mass.-based company will be using part of the $21 million raised in its Series B round to validate its technology and conduct clinical trials. The money adds to a $10 million Series A round it raised two years ago shortly after it was launched.
“Needless to say market adoption is a slow-moving animal … so what we want to do is have enough substantiated clinical data with collaborators and really do our homework well in clinical work and [have] scientific evidence for this,” Klemm said. “We are in the final stages of validation and we want to plan and move this forward into clinical trials over the course of the next year and increase the amount of clinical verification of those indications.”
Predictive is in the process of designing its validation studies and clinical trials. Company officials declined to comment on specifics about either, though Chiu said that the validation studies are being done in collaboration with “major academic clinical sites.” He declined to identify them.
One of the investors in the Series B round is Kaiser Permanente Ventures, an investment arm of Kaiser Permanente, which operates an HMO as well as its own hospitals and clinics. There has been no promise that Kaiser Permanente will use any assays developed by Predictive, but given the significant amount of patients in its network, “we would expect at least some beta sites out of it, if not access to certain samples we couldn’t get otherwise and ultimately potentially customers,” Klemm said.
The company declined to disclose any timeline for the commercialization of its diagnostic tests.
The company also will use the funds to open a Clinical Laboratory Improvement Amendment-compliant laboratory. Klemm said he expects CLIA certification to happen by the beginning of the year. The bladder cancer diagnostic will be offered initially as a CLIA-based test to be administered by urologists, he added.
Other participants in the Series B financing were new investor New Enterprise Associates, a healthcare and technology venture capital firm. Existing investors Flybridge Capital Partners and Highland Capital Partners also participated.