Getting a blood test to screen for cancer in the earliest stages might seem like a pipe dream. But a group of biotech entrepreneurs say they're close to making it a reality.
If Gabriel Otte's start-up, Freenome, is successful, millions of people could get a blood test to screen for early-stage colorectal cancer. Freenome looks for two major biomarkers in the blood. It's simultaneously hunting for tiny fragments of DNA that are shed into the bloodstream from a tumor, as well as early signals that the patient's immune system is starting to respond.
The medical industry has known for years that that blood-based "liquid biopsies" can find signatures of cancer. But the tests on the market today focus on monitoring the progression of the disease once a patient has been diagnosed with cancer, including how it's responding to treatment.
The next generation of companies want to detect cancer while it's early and often easier to treat.
These companies have connections to some of tech's giants. Freenome has funding and close ties to Alphabet's Verily, while Grail, another company in the space, is backed by Amazon. Thrive, the new kid on the block, is financed by former Google Ventures chief Bill Maris' new fund, Section 32, and a slew of other health investors.
All three of them say they're starting to see results that could someday help their technologies save millions of lives.
Otte, who started the company in 2014 with his co-founder Riley Ennis, wasn't always intending to focus on colorectal cancer. In the company's early days, he used a nascent version of Freenome test to diagnose his dad with prostate cancer after a screening test came back negative. For a while, the company looked at prostate cancer as a first focus for its test and Otte is still hoping to bring that to market at some point.
But Freenome, which is backed by more than $230 million in venture capital, honed in on colorectal cancer because so many patients avoid getting colonoscopies and providing stool samples for analysis. It's also a common cancer type, with the American Cancer Society estimating that there will be more than 150,000 new cases of the condition in the United States alone this year, and it's the second deadliest cancer after lung cancer.
There are some promising signs the approach is working. This month, Freenome started releasing data from its prospective study of 3,000 participants.
For the study, it recruited healthy patients undergoing a routine colonoscopy and those who were recently diagnosed with colorectal cancer. It asked the group for both fecal and blood samples.
The company said it analyzed a "statistically significant" sub-cohort of 574 of the 3,000 patients. Otte shared in an interview that the test picked up on 32 people with cancer and missed a few cases.
The company demonstrated a sensitivity of 94 percent, and specificity of 94 percent for early-stage colorectal cancer overall. In other words, it provided some false positive results, meaning it alerted someone to cancer that did not show up in further tests 6 percent of the time, and it missed several of the patients that did in fact have cancer.
Otte said that Freenome's test performed better than the stool test in a side-by-side comparison, and that far fewer people returned the fecal samples than blood. The company's next study, which represents a step towards FDA approval, will involve more than 10,000 patients.
"Within three years from now, we will hopefully see this test FDA approved and out so it can begin to save lives," Otte explained.
Public market investors are keeping a close eye on Freenome, and the results from its prospective study caused major fluctuations to the stock price for its competitor Exact Sciences, which also provides a DNA based approach to colon cancer screening called Cologuard. Exact requires a stool sample that can be collected from home.
While Freenome is focused on colorectal cancer, Thrive and Grail are working on tests that can sniff out multiple types.
Thrive, the new kid on the block, is looking to commercialize a cancer-detecting blood test developed by researchers out of Johns Hopkins including oncology professor Dr. Bert Vogelstein. The company says it's already identified pancreatic and ovarian cancers, two of the deadliest types, for its screening test.
Biomedical experts say both the different approaches can work, if doctors understand both their benefits and drawbacks.
"I'm certain the FDA (U.S. Food and Drug Administration) and the medical system will ensure these companies are very clear about what they're designed to do or not do," said Michael Pellini, a partner at Section 32, who previously ran the cancer-focused diagnostics company Foundation Medicine.
But for all the companies in the space, there are bio-ethical considerations as no test is accurate 100 percent of the time.
While Freenome is focused on mitigating false negative results for its test -- the number of patients that are given false reassurance -- Thrive is working to bring down its rates of false positives.
Thrive CEO David Daly explained that false positives could add huge costs to the already overburdened health care system.
Or as Thrive founder Dr. Vogelstein put it, a lot of false positives could do "more harm than good."
"That's has long been the conceptual and the technical obstacle," he said by phone.
Daly says Thrive's multi-cancer blood test is not intended to replace the standard of care, meaning that patients given false reassurance would still be recommended the traditional screening tests, like mammographies or pap smears. Through those tests, it's highly likely that the patients would be alerted to the disease.
Ultimately, the buyer of these tests will be insurance companies. They won't reimburse for the tests if they're also footing the bill for a lot of additional testing, says Daly.
Freenome's Otte takes the exact opposite approach, and asks the question: Would patients rather have false reassurance, or some undue anxiety ahead of a follow-up test? He believes that most people would opt for the latter as it means they're not walking around without cancer without knowing it.
But there are also practical reasons for Otte to take that approach. The follow-up for his colorectal test will be routine screening that a patient would do anyway, like a colonoscopy. For Thrive, it would likely begin with a full body imaging test called a PET scan to locate the tumor, which can cost thousands of dollars and comes with a risk of radiation exposure. And from there, yet more testing. So it's essential that the company keeps its false positive rates extremely low.
Where all of these companies and their investors seem to agree is that patients have a better chance of survival if any of their tests come to market.
"Accurate, low-cost liquid biopsy can transform how we diagnose and manage cancer," said Nina Kjellson, a biotech investor with Canaan, a venture capital firm. Kjellson notes that it will take technical advances, large sample sets and collaboration with the pharmaceutical world to make it happen, but that investors believe that the prize is "well worth chasing."
"I do believe this is the current decade will be known as the decade that we brought cancer screening into the mainstream," adds Section 32's Pellini.