“We don’t have a crystal ball for any one patient,” says U-M oncologist Greg Kalemkerian. “That’s what you really want.”
The oncology toolkit has exploded in recent years. Besides chemotherapy, oncologists now have several dozen “precision” drugs to treat specific cancers, and powerful new drugs that unleash the immune system against tumors. But these can be extremely toxic, even fatal, in some patients.
Right now, physicians have no way to accurately predict who will benefit from these drugs. But Dan Rhodes and Scott Tomlins are offering a solution.
Rhodes and Tomlins, who met in 2001 as U-M med students, founded Ann Arbor–based Strata Oncology in 2016. They recently introduced a test that can detect more than 500 DNA mutations and other genetic variants in an individual cancer, along with the expression of certain proteins. The results can guide oncologists to the best drugs to give their patients.
“Strata Select” isn’t a crystal ball—no test can account for all the vagaries of human biology—but if it can take some of the guesswork out of cancer treatment, a huge market awaits it. Investors like the company’s chances, bankrolling it with $128 million in venture capital, including a $90 million funding round in 2021 that set a record for a Michigan biotech company. Merck and Pfizer have also made large investments. Strata’s test, says Arboretum Ventures managing partner and Strata board member Jan Garfinkle, “is going to change the world for cancer patients.”
The study of DNA and its biological role has revolutionized the understanding of cancer. But while scientists have known for decades that mutations and other genetic alterations cause most cancers, only recently has gene sequencing technology become cheap and efficient enough to routinely test across the cancer genome for these mutations.
In some patients, identifying a given gene alteration is enough to virtually ensure that an existing drug will work, and doctors routinely test for these mutations or alterations, at least in advanced cancers. Unfortunately, these are either a minority of cases, or drugs have not yet been invented to treat a given mutation. So oncologists generally choose what drugs to use based on statistical probabilities determined by past clinical trials and hope for the best.
In advanced breast cancer, says U-M oncologist Dan Hayes, “about 20 percent of patients, maybe 15 percent, will have some targetable lesion. And about half of those patients will actually benefit from the therapy we think is going to help them.” That means only about 10 percent will benefit from a genetic test, he says—“But if you’re one of those 10 percent, that’s worth it.”
Kalemkerian treats lung cancer, and more of his advanced patients benefit from targeted therapies and immunotherapy. But he, too, often confronts situations where “there are lots of things that we can do, and the question always is: What should you do?” he says. “We’re always working in an environment where we have incomplete information.”
That’s the knowledge gap that Strata aims to fill. Working with a tiny sample of a patient tumor, the company aspires to give oncologists much more certainty that a given drug will or won’t work for a given patient.
Soon after the company formed, it started a clinical trial in which pathologists at more than forty hospitals around the country send leftover fragments of patient tumors to Ann Arbor—about 70,000 tissue samples to date. Strata lab technicians extract the DNA and RNA and determine the genetic sequence of the tumors’ cells, each of which contains upwards of 20,000 genes. Then Strata scientists look at how well each patient does on a given drug therapy, and, using custom-designed bioinformatics algorithms, compare the outcomes to the cancers’ genetic makeup.
Strata Select also predicts who would respond to immunotherapy, which unleashes the immune system against tumors but attacks normal tissues as well. Adding chemotherapy—which can make immunotherapy work better—increases patient suffering even more. Doctors only want to give these harsh regimens to patients whose tumors will then shrink. But how to know?
Right now oncologists have a single biomarker to help them decide this for most patients, and it’s not very accurate. So a lot of patients end up getting immunotherapy for no purpose, while others who might actually benefit never get it at all. “These are not free and easy drugs to use,” says Hayes. “And so what we need are better markers for these drugs … The stakes are high.”
Strata Select’s five immune-related markers, Strata’s data show, together perform much better than the current marker. The test provides a single “immunotherapy response score” for each patient to help oncologists decide whether they should prescribe immunotherapy only, chemotherapy only, or both together. Tomlins says doctors who treat kidney cancer, for example, are telling him that their patients badly need this test because the current tests are only rarely useful and that “‘this is the treatment decision I’m making every day.’”
So far, Strata is marketing the test mainly to previous customers and to “KOLs”—“key opinion leaders,” as such medical influencers are known. Medicare now reimburses for the test, a huge advantage since roughly half of cancer patients are sixty-five or older. But that doesn’t mean oncologists will order it.
The FDA does not usually review or approve so-called “laboratory-derived tests” like Strata Select. Once Medicare certifies the testing lab for quality, any test can go on the market—but without the FDA’s endorsement, it’s a big hurdle to convince oncologists to order it.
Most follow guidelines set by the National Comprehensive Cancer Network (NCCN), a nonprofit alliance that looks at the evidence and makes recommendations. Strata, says Garfinkle, has not yet submitted its data to the NCCN. “We’re figuring out the process to do that,” she says. “We probably need a special trial to convince them that it makes sense.”
That’s because it’s one thing to look backwards in time at treatment results—Strata’s approach to date—and quite another to design a trial from the ground up.
Such “prospective” trials are much more reliable. Strata recently launched one, the “Strata PATH trial.” Depending on the results, that may be enough to sway NCCN and most oncologists. Until then, Strata faces an uphill battle for acceptance. “They’re well on their way; it’s very exciting stuff,” says Hayes. “But I don’t think they’re quite ready yet to use it routinely … Whether doctors now will vote with their feet or not is not clear to me.”
The test must deliver a score decisive enough to change doctors’ current decisions. Kalemkerian says he’d have to be pretty confident that immunotherapy wasn’t going to work before denying it to a patient. “Our patients don’t have a whole heck of a lot of options, right?” he says. “You hate to take one of them off the table.”
In 2005, Rhodes and Tomlins were lead authors of an article in the journal Science that created a sensation among cancer researchers. As PhD students in U-M medical prof Arul Chinnaiyan’s lab, they had discovered a genetic mutation that drives about half of all prostate cancers.
After completing his degree, Tomlins joined the U-M faculty. Though he developed a diagnostic test based on the prostate gene, the university did little to actively market it. (See “The Headlong Growth of LynxDx,” September 2020 Observer.)
Rhodes, meanwhile, went into business. He and Chinnaiyan started a company to market cancer databases and software they’d developed to other researchers. In 2012, they sold it for $50 million. “I kind of overnight became one of the few people in our sort of Midwest ecosystem who had founded, built, and exited a biotech or health care technology company,” Rhodes says by Zoom from the company’s offices off Jackson Rd.
Tomlins, meanwhile, won tenure as a genitourinary pathologist and cancer researcher. But in 2015, Rhodes contacted him to suggest they reunite to make cancer genetic testing more widely available.
U-M and other academic centers already did such testing for research purposes, but Tomlins thought many more cancer patients could benefit. “‘Hey, everybody should be doing this,’” he recalls thinking.
So he signed on with Rhodes and Harvard oncologist Keith Flaherty to found Strata Inc. In 2017, he left his faculty position to join the company full-time. “In terms of my academic career, that was easily the most difficult decision I’ve ever made,” he says.
Strata’s long-term goal has always been to find new cancer biomarkers. But it started out as a kind of patient recruiter for drug companies.
The companies needed to identify patients with rare mutations who could be enrolled in clinical trials for their experimental targeted drugs. Strata did that by offering free gene sequencing results to participating hospitals; the companies then paid Strata for finding patients who might benefit from their drugs.
But as the FDA approved more mutation-targeted drugs, Medicare started to reimburse hospitals for such testing, and private insurers followed suit. Hospitals no longer needed Strata’s free testing, and drug companies no longer needed its help finding patients.
Initially, the company pivoted and started charging for its DNA and RNA results. Then, facing fierce competition in the genetic testing market, Strata again changed direction. “Everyone’s getting reimbursed [for testing] now,” says Garfinkle. “Dan Rhodes and Scott Tomlins were thinking, ‘What else can we do to differentiate ourselves from everyone else?’” That’s when they landed on Strata Select.
Given the enormous stakes, both medical and financial, a lot of companies are going after the same problem. What sets Strata apart is its testing system, which analyzes much smaller tumor samples than its competitors can. That’s important, because many tumor biopsies contain barely enough tissue to determine how advanced the tumor is, much less look at several hundred individual biomarkers.
This technical feat, which took several years for Strata to accomplish, is one of the reasons they’ve received such support from venture capitalists prepared to spend over a hundred million dollars on the chance of a big payoff later. At some point, though, Strata will have to deliver for its investors.
One oncologist who’s sold on Strata Select is Adam Forman, whose private-practice group is affiliated with Ascension Providence hospitals in Novi, Southfield, and Rochester. “We’re getting results in eight days, compared to three or four weeks from the other companies,” he says. The company’s immunotherapy response score especially has made a difference. Forman, on the day he spoke to the Observer by phone, prescribed a targeted therapy over immunotherapy for a young woman with advanced breast cancer, based on the relative strength of those two scores. “Both were reasonable options,” he says. “The Strata test showed me that she was less likely to respond to immune therapy.”
At a list price of $6,500, few patients can afford to pay for the test out of pocket, so more insurers must get on board. (Rhodes says Strata offers financial assistance to those who aren’t covered.) Medicare approval was a good start, but then “you have to go to every private payer to also approve it,” Garfinkle says. “It’s a big undertaking.” Forman says he was able, with Strata’s help, to get his patient’s private insurer to cover her test.
Strata, meanwhile, is setting its sights on an even bigger goal: bringing targeted drug therapy to many more patients. The Strata PATH trial doesn’t just select patients for immunotherapy. It also includes a variety of other drugs from Merck, Pfizer, and Gilead Sciences that are approved for individual tumor types—lung, say, or breast—but which any patients who score well on Strata’s test, no matter where their cancers originate, can take. Some of these are “antibody-drug conjugates,” a form of targeted therapy where an antibody guides a chemotherapy molecule to cancer cells and then kills them. (That’s what Forman selected for his breast cancer patient after her Strata test.) But there were no good biomarkers for these drugs, and so no way to predict whose tumors will respond.
Strata recently discovered such a biomarker. The hope is that it identifies many more patients who can benefit from these powerful but toxic drugs—patients the pharmaceutical companies themselves often ignore.
“It’s sort of an astounding dynamic that we have right now,” Rhodes says, “where pharma will bring a drug to the [most common] tumor type that they believe it has success at” to the FDA for approval—then, once it’s granted, “just kind of sit out then in that one tumor type, for years. It’s our belief that, with the biomarker, there may be three or five or ten times more patients that [could be] benefitting.”
Rhodes, who deals with statistical models and algorithms, is by nature an optimist. “I’m always trying to push the limits,” he says. Tomlins, on the other hand, is more grounded in the frustrating reality of human biology. “Scott sort of reins in my thinking,” Rhodes says. “Together we’ve been able to do a number of incredible things, going back to the PhD work we did together.”
Changing the way cancer is treated is even harder than finding new cancer genes. But “they’re working on a great angle,” says Kalemkerian. “This is what we want to do in oncology, right? We want to get the right drug to the right person at the right time.”