Four-year-old liquid biopsy company Inivata, based in Cambridge, U.K., with a testing laboratory in Research Triangle Park, NC, is now making its presence felt in the growing circulating tumor DNA (ctDNA) analysis arena. The company’s positive momentum is exemplified by two roughly concurrent developments this year. In late March, the company closed its Series B funding round that raised £39.8 million ($52.6 million), money that will be used primarily to support the continued commercial roll-out of its InVisionFirst-Lung liquid biopsy test for non-small cell lung cancer (NSCLC). A couple of weeks later, it received a final local coverage determination for the test from Medicare administrative contractor Palmetto GBA, a decision that effectively provides nationwide Medicare reimbursement for the test. In early June, on the heels of these developments, company CEO Clive Morris sat down with Clinical OMICs Editor in Chief Chris Anderson at the American Society for Clinical Oncology (ASCO) Annual Meeting in Chicago to discuss the company’s progress and its vision for the future.
How was Inivata founded?
Morris: We are a spinout from the University of Cambridge in the U.K. Our testing platform was specifically developed for circulating tumor DNA and the challenges of it. Because the levels of circulating tumor DNA are very low in some patients, you need an exquisitely sensitive, specific test. Rather than adapting technologies that have been used somewhere else that are less than ideal, what (Nitzan Rosenfeld) our scientific founder did was create technology that is designed to be and is, we have shown, as sensitive as digital droplet PCR, which is considered the gold standard on a single gene test—but with the benefits of testing a broad panel.
What does the company see as the advantages of this technology?
Morris: If you think about PCR, or digital droplet PCR, it is very, very sensitive and very, very specific. There is a reason nature has been using PCR effectively to replicate DNA since the beginning of time, so we take exactly that and then we apply that to circulating tumor DNA. The challenge with PCR is how do you scale it? Doing individual PCR reactions isn’t tenable across many genes. How do you look at these complex changes in gene translocation, gene fusions, and things that wouldn’t naturally be done by PCR? We found a way to do that, to multiplex across many hundreds of different areas. We also cover things like single nucleotide variants, insertions, deletions, and copy number gene translocations. We’ve adapted the technology—called Tam-Seq—to be able to do that and that is our InVision platform.
Earlier this year the InVisionFirst-Lung liquid biopsy test received a local coverage decision from Palmetto GBA, assuring reimbursement from Medicare in the U.S. What about efforts in the rest of the world?
Morris: Like many companies, we will start in the U.S. and try to be successful here. At our lab in Cambridge [U.K.], we can service across the European Union and beyond. The way we have built our workflows are for them to be modular. We can do two things with that: One, as our volumes go up in our current labs, we can add modules, and that just scales out. Two, we can also transplant different modules into different labs, so it should be relatively straightforward for us to set up new labs in different geographies as we need to. We will look to partner overseas and certainly in Asia. In Europe we will probably do a little bit of both—some commercialization ourselves, but also look for local partners as well.
Where do you see the sweet spot in the market for Inivata and how do you compete with the larger, more established players?
Morris: There is a range of different places we can apply this technology, never mind additional technologies we may access and develop. The first one is this lung cancer patient stratification tool and getting that all the way through to reimbursement. We are one of only two tests that are reimbursed—the other one is the Guardant360. But there will be others. So the differential is: We think we have a best-in-class test—sensitivity, specificity and also turnaround time. We think we are leading the market in all of those.
Also, the field is evolving so rapidly it’s not a case of build a test and commercialize one test. It is more of a pipeline story of how do you develop technologies and, indeed, branch into other technologies to provide these solutions to patients. Different technologies will work better in different settings and that is what we want to do—to determine where they can solve areas of unmet needs. Our current technology is appropriate in some settings, but not all. We will bring additional technologies from other areas. What we want to do is build, over time, a portfolio of liquid biopsy products that address multiple area of unmet need.
What is your turnaround time?
Morris: We offer seven days from the time of taking the blood sample. The reason that is important is it fits in with the weekly clinical cycle—clinicians tend to work on a weekly basis. They want to see the patient today, draw the blood, and bring the patient back into the clinic next week to start whatever treatment is appropriate.
Do you see your technology being used as an early cancer screening tool?
Morris: Our strategy is, at the moment, to focus on those patients who have already been diagnosed with cancer, not to do the early detection or screening. Our view is, with the technology we have, let’s maximize the value of what this can do for patients right now: residual disease, disease monitoring, recurrence, disease stratification, and advanced disease monitoring.
There is a big unmet need around lung cancer and getting patients to therapy. A study published in 2017 on community oncology in the U.S. showed less than 10% of patients were profiled for all of the FDA-approved drugs, never mind the investigational drugs. That’s just criminal. People are dying of lung cancer who just aren’t getting these therapies. A big part of that is the difficulties with tissue in lung cancer and we can overcome that. ctDNA technologies are here to stay, they are not just hype and hope and then something that disappears. They are actually cementing in clinical practice. Once you do that, then you branch out and find additional uses.
How can you get people to adopt your tests?
Morris: The first part is having good data, doing the right clinical work, and having the right clinical trials. We have clinical validation data published that shows the performance of the test. There are also two transitions that need to be made: transition people from reliance on just tissue to considering blood. Then, having made that first leap, providing education on which is the best blood test to do.
Is there opportunity for Inivata to engage with pharma for co-development and the creation of companion diagnostics?
Morris: That is absolutely the intent. If you think about what you need for a companion diagnostic, you need something that is ideally freely available and that is one of the advantages of a broad platform. You are not doing a single-gene test. It is not a test for a single cancer drug, but potentially many on one panel. But you want great performance. You want high sensitivity and high specificity to be able to get the most patients.
Now that InVisionFirst-Lung will be reimbursed by Medicare, how will you get private payers on board?
Morris: One of the reasons we have reimbursement coverage from Medicare is we put together the full clinical program and demonstrated the value of that test in practice. You have to show your analytical validation, your clinical validation, and your clinical utility.
As we think about this for our first product, what we see is the chronic under testing of patients and (because of that) not making the most of the therapies that are approved. Also, patients may have already been tissue biopsied, and it has failed. Is that patient going to go through another tissue biopsy that costs about $15,000 under Medicare, and is higher under private payers? Tissue biopsy for lung cancer has a significant complication rate and you still run the risk that it will fail again. Why not run a liquid biopsy that is probably, on average, going to be more informative, you are not going to have complications, and you save money every time you do it?
So there is a strong value argument there for private payers. We have to make those arguments, and that is part of making it on the case-by-case basis, which over time can become a coverage decision. There is a sense that payers are becoming more aware of this. They do see the value.
What are the future opportunities for Inivata?
Morris: We are already moving into monitoring situations—patients with advanced cancer for whom we can tell whether they are responding to therapies or relapsing. We can also find some of the mechanisms of resistance, why are patients becoming resistant. That is one avenue.
The other is into earlier stage cancer and detecting residual disease. When a patient has been diagnosed with early-stage cancer, they may undergo surgery that is potentially curative. Because circulating tumor DNA is cleared from the blood pretty quickly, you can use these tests a week to a month following surgery. If you can detect ctDNA at that point, you know the patient hasn’t been cured and you can then guide additional therapy. In the future, these tests could become the companion diagnostics for adjuvant therapy.
Finally, because these tests are noninvasive, we think we can produce a cost-effective test that you can use for monitoring patients. Today, generally for five years following surgery, patients will go back to see their surgeon or their oncologist and have CT scans, PET scans, bone scans, or other sorts of investigations to try to find evidence of recurrence. After five years, if it looks like it is all clear, the patient has been cured.
Imagine if that can be done noninvasively with a blood test out in the community, much as a patient may have their cholesterol checked. They would go have a simple blood test, and if that looks clear, come back in six months and have another blood test done. The patient is only referred to the specialist center when there is evidence of recurrence. It is better for patients, less invasive, and a better quality of life not exposing them to radiation and a whole host of other things. And, of course, you are using the healthcare resources in a more efficient way.
What is your model for providing this type of treatment monitoring?
Morris: The strategy around the early-stage cancer, residual disease, and recurrence monitoring is to create patient-specific panels. We inform them via knowledge of that patient’s genotype and make a patient-specific panel. This has two advantages: one is they become coupled with our platform sensitivity and specificity—they become exquisitely sensitive assays for detection—and they have a relatively low cost of goods. We can actually think about how to move these into a monitoring setting, where the price point can be lower for reimbursement.