In 2009, as a graduate student at the University of Wisconsin-Madison, Chorom Pak was part of a group of researchers working to understand how sensitive patients’ cells were to certain therapies for blood cancers, such as multiple myeloma.
The group, which also included UW-Madison professors Shigeki Miyamoto and David Beebe, and postdoctoral fellow Edmond Young, would receive large numbers of patient samples from hospitals containing cancer cells so that the researchers could analyze them, Pak says.
One major challenge they faced was that some of the samples, which were derived from patient biopsies, did not have large enough counts of cancer cells to be useful to the researchers.
“This was very unfortunate because these patients were volunteering to give us biopsy samples, but we were only able to analyze about half of them,” Pak says. “And on the scientific side, we were potentially biasing our data.”
Given that frustration, they decided they would try to miniaturize the culture system they were working with, so that it would be possible to analyze all of the samples rather than having to throw some of them away, she says.
It took more than three years to finalize a design for a device able to functionally analyze low numbers of blood cancer cells. Soon after, in 2013, Pak formed Lynx Biosciences, a Madison, WI-based startup she continues to lead. The ultimate goal is to be able to test cancer drugs—either alone or in combination with others—on a patient’s own cells, so that people caring for the patient can create an individualized treatment regimen. Lynx is currently in the middle of a second clinical study of the device, and working to secure seed-stage financing (more on those efforts below) to further advance the technology toward FDA approval.
Multiple myeloma occurs due to the accumulation of cancerous plasma cells. The disease can be treated, but there is no cure. The American Cancer Society estimates that this year, there will be 30,280 new cases of multiple myeloma, and 12,590 deaths resulting from the disease.
The assay Lynx is developing is designed to be able to culture both cancerous tumor cells and healthy “normal” cells from the same patient. This “co-culturing” capability allows clinicians to see whether cells live or die in response to a particular drug, Pak says.
Other researchers have tried creating similar tests in the past, she says. However, many of those tests used cancer cells in isolation, and she believes that’s one reason they haven’t worked very well.
“We believe that we’re getting such good results because we’re adding in normal cells from the same biopsy,” Pak says. “We believe [tests that only use cancer cells] are not as representative of what is going on in the patient’s actual cancer microenvironment. We feel that’s the advantage that we have.”
That advantage comes partly from the miniaturized aspect of the technology, Pak says. She gives a large portion of the credit for making the assay so small to Beebe. One of his specialties is microfluidics, a field that involves working with tiny amounts of fluid at the micro scale in medical devices and diagnostics.
Once the research group had a design for a miniaturized culture system, it came up with the idea of making it into an ex vivo model of someone’s own cancer. That term refers to taking a person’s cells outside of the body, but not growing them.
“The reason that we chose to do it that way is so that we can try and maintain these cells to be as close to what they are like inside the person’s body,” Pak explains. “The worry is that if you culture these and if you grow them out or expand them, they can potentially change.”
Lynx’s assay, called MicroC3, falls into a class of tests known as companion diagnostics. Pak says that most of these diagnostics measure a biomarker, such as a gene or a protein, which could show response to a particular drug. However, because the measurement of MicroC3 is whether cells live or die after coming into a contact with a drug, the startup could potentially develop the test as a companion diagnostic to any blood cancer therapy, Pak says.
Other companies, including Seattle-based Presage Biosciences, are developing methods of testing combinations of cancer drugs in live tumors. However, Pak says that as far she knows, most of them are working to create assays that measure the sensitivity or resistance of cells to chemotherapies with treatments for solid tumor cancers in mind.
“Their technology can’t be applied to blood cancers,” Pak says of Presage Biosciences. “We believe that this is an untapped space for us to move into.”
Once Pak and her fellow researchers had created a model of its co-culture system, they began using it to test drugs against samples of patient cells in collaboration with Natalie Callander, a hematologist who directs of the Myeloma Clinical Program at the UW Carbone Cancer Center. The first drug they tested was bortezomib, a common component of multiple myeloma therapies. The group then decided to conduct a small (17 patients), retrospective clinical study involving the drug and its system.
Pak says that the drug responses the researchers found with their test were the same as what was produced in the clinic.
They described some of their findings in a paper, which was published by Integrative Biology in 2015.
Since it was a retrospective study, the researchers proved only that a correlative—but not necessarily causal—relationship between the device and clinical conclusions.
Lynx now wants to prove that more than just a correlation exists, and last March kicked off a prospective study to prove that MicroC3 can actually predict clinical responses. The trial will draw from three sites in Wisconsin, Pak says.
The company hopes to close out the study later this year, and start the next one—Lynx’s pivotal clinical trial—in early 2018, Pak says. It would be the first time MicroC3 would be used to “stratify” patients, or determine which ones receive bortezomib-containing therapy, and which ones don’t, she adds.
Pak says that it would likely take between 12 and 18 months to enroll patients in the pivotal trial. She estimates that about 100 patients would participate, but says the actual total will depend on the results of Lynx’s current prospective clinical study. If the pivotal trial goes as Pak hopes, her company would turn its attention to getting premarket approval from the FDA for the device. The startup would begin to bring in revenue in 2020 if all goes as planned.
Lynx, which in addition to Pak has two part-time employees and counts Young, now an assistant professor at the University of Toronto, as an advisor, has received about $350,000 in grant funding during the four years it has been operating. Most of that came via a Phase 1 Small Business Innovation Research award from the National Institutes of Health and National Cancer Institute to support the prospective clinical trial. Pak says her company is currently seeking between $800,000 and $1 million in seed financing, and is mostly targeting angel investors. After that, her plan is to raise a Series A funding round in late 2018, which would be more likely to involve participation from venture capital groups.
In the long term, the goal is to enter into partnerships with large drug makers that are developing blood cancer drugs, Pak says.
“By using our technology, the pharmaceutical companies can begin to identify patients who are more likely to respond to their drug,” she says. “They can [then] enroll only [those] patients in their clinical trials, which can potentially increase their chances of success and reaching FDA approval.”