NEW YORK – Within less than a year, diagnostics firm Oncocyte has transformed from a pre-commercial company with a single test in development to a commercially operating diagnostics provider with three tests in its pipeline, the two newest of which have now beat its original DetermaVu in the race to the clinic.
The dramatic turn is the result of a pair of back to back acquisitions, first of Razor Genomics last September and then of Insight Genetics this January. Oncocyte launched the lung cancer prognostic assay DetermaRx, the fruit of the Razor acquisition, at the beginning of the year. It then made what it now calls DetermaIO, formerly Insight's Immune Modulation, or IM Score, available last week as a research-use-only tool.
During a call discussing the company's Q4 2019 earnings on Wednesday, Oncocyte CEO Ron Andrews said that Oncocyte is hoping that providing research-use availability for the new immune-oncology test will help the company build relationships with biopharma partners that can begin to generate near-term revenue as well as evidence to support clinical implementation of the assay, either as a more generalized clinical decision-making tool, or ideally, as a companion to choose patients eligible for treatment with specific IO drugs.
DetermaIO is a gene expression test, performed on tumor tissue, that evaluates molecular signals from the immune microenvironment to identify individuals that are more or less likely to respond to checkpoint immune therapies.
"Checkpoint inhibitors have transformed the treatment paradigm in late-stage lung cancer. But as an industry, we still have a lot of work to do on how to best use them," Andrews said during the call.
Oncocyte believes its test could be a better predictor of patient response than both currently used PD-L1 biomarker assays and much heralded, but still experimental tumor mutational burden, or TMB.
The firm highlighted data presented at last year's annual meeting of the Society for Immunotherapy of Cancer, for example, which showed a stronger association between the IM score and response to IO treatment in lung cancer patients than seen with PD-L1 IHC staining and TMB.
"There are widely recognized challenges with both of these biomarkers and plenty of room for improvement, [which] is why we're so excited about our opportunity," Andrews said during the call. That said, he added, the evidence so far is still very preliminary and will need to be proven in a larger sample set.
"Work is already underway to extend this into larger, more diverse populations across multiple types of solid tumors," he said.
Various companies have developed or are exploring assays that detect gene expression changes associated with the body's tumor-immune response and the tumor microenvironment, hoping to capture signals that mark a cancer as being immunologically "hot" or "cold." So far, none have achieved significant progress into the clinic, but such approaches seem to be readily being taken up for retrospective analysis of drug trial cohorts, according to reports from companies like NanoString Technologies, Cofactor Genomics, and others.
Andrews said this is also an area that Oncocyte aims to address with DetermaIO.
"Being able to accurately predict which patients will benefit from treatment … could also have a real impact on the speed at which new therapies are brought to market," he said. "There are close to 3,000 PD-1 and PDL-1 clinical trials ongoing designed to recruit over half a million patients."
"Being able to outperform [other] tests … to improve the identification and qualification of potential patients for clinical trials and appropriate treatments may be truly transformative, [and] owning the pharma compliant lab that we acquired with Insight Genetics leaves us well positioned," Andrews said.
While the company believes it can begin attracting biopharma interest with its current in-house testing set up, Andrews also said that Oncocyte plans to simultaneously pursue a CE Mark kit strategy for DetermaIO in Europe, recognizing that decentralized capabilities are a priority for potential pharma partners outside the US.
According to Andrews, some discussions with partners for drug studies using DetermaIO have already begun but may be stymied by the current pandemic crisis. "We had been in very close contact with a couple of key investigators that had some trials that had failed in Italy, and we were very hopeful to be able to bring that to closure."
"As you might imagine, that has now been put on the back burner for all the obvious reasons. But, our strategy remains intact," he said.
Doug Ross, Oncocyte's chief medical officer, said that despite this, there remain opportunities both in lung cancer and in breast cancer that the company is pursuing, with "conversations with multiple different pharma partners" ongoing.
Andrews also said that the company has planned to release new data on the test at the American Society of Clinical Oncology meeting this May. Though the physical conference has been cancelled amid restrictions around the COVID-19 pandemic, ASCO has said that the meeting will still take place digitally in some form.
To bring the assay forward as a clinical test, the company will need to replicate and expand on the initial IM Score data to develop a sufficient evidence base for seeking payor coverage, but Andrews expressed confidence, saying that the firm hopes to begin discussions with the Centers for Medicare and Medicaid Services later this year.
"I'm a little shy to give exact [projections]," Ross added, "but we're going to get some guidance from them on how to advance that forward, whether it be with one of the drugs that are trying to penetrate the market or to provide the right sort of information that would give oncologists more information for the judicious use of checkpoint inhibitors."
As it walks the path it has laid out for DetermaIO, Oncocyte is also negotiating its first months of clinical test provision with DetermaRx, formerly the Razor Genomics test, which is performed on tumor tissue samples to predict chemotherapy benefit in patients with non-squamous non-small cell lung cancer.
Previous research performed by Razor Genomics showed that high-risk patients identified by DetermaRx who were treated with adjuvant chemotherapy had a significant improvement in survival rates compared to high-risk patients that did not receive chemotherapy.
"This is a remarkable result and the reason we've been pushing hard to get this test in the market for patients," Andrews said this week.
Oncocyte announced the commercial launch of DetermaRx with two early-access sites — in Orange County, California and Florida — this January.
On the call this week, Andrews said that now, about seven weeks into commercial operations, all seven of the firm's early-access targets are active and a total of 13 sites have been onboarded. "We continue our efforts to strategically bring on more customers and believe we'll have a rapidly growing list over the next several months," he added.
He also said that Oncocyte has so-far returned high-risk results for seven clinical cases, and all of the physicians for those patients made a treatment change based on that information.
Despite that momentum, the company is likely to face a struggle with the emerging pandemic situation. Speaking to early-access physicians, Andrews said, the message has been that urgent cases are largely still receiving surgery, and thus become potentially eligible for tissue testing, in most areas of the US, though not the hardest hit cities.
"While we are expecting a slowing of our sample volume growth trajectory over the next 30 to 45 days … the reality is these tumors must be removed, and thus these surgeries will happen," he argued. "We know these patients are in need of life-saving procedures, and we will be ready to serve our early-access sites and bring on new customers when the current situation eases."
DetermaRx had already received a positive draft local coverage determination prior to Razor and its test being acquired by Oncocyte, and the company had previously anticipated this being finalized by the end of this month. But now it is projecting for some time before the end of the first half of the year.
"We've been in direct dialogue with our contact at CMS, and they have confirmed we are currently in the queue awaiting [finalization] … and the subsequent pricing that will come with it."
Padma Sundar, Oncocyte's senior vice president of marketing, said that the company has developed evidence to support two different possible pricing outcomes for DetermaRx: first, if CMS decides to perform what is known as crosswalking, where it sets a price based on the test's similarity to an existing priced assay, and second, if the payor decides to set a new price, known as a gapfill.
According to Sundar, the firm submitted a "very comprehensive pricing dossier to CMS" that makes a case for a crosswalk based on the Oncotype DX breast cancer test, which "uses a very similar methodology in terms of RT-PCR and a proprietary algorithm."
Oncocyte also performed a "pretty comprehensive house economic analysis, which demonstrates that at a price comparable to Oncotype DX (between about $3,500 and $3,800) this test delivers significant savings to the healthcare system."
"Based on those two analyses, we feel pretty confident at getting a pricing that's comparable to other tests in this space using a similar methodology ,[the] obviously example being [Exact Science's] Oncotype DX for breast cancer," Sundar said.
As with DetermaIO, Andrews said that Oncocyte now plans to develop a kit version of DetermaRx.
"We are working with a couple of potential partners," Andrews explained on the call. "The good news … is there's quite a few manufacturers of instruments today that have saturated the clinical market. The bad news for us right now is all the momentum we had, as you might imagine, is now being absorbed by these manufacturers trying to get COVID," he added.
The company initially thought that it might be able to see progress on this front by the end of this year, but that timeline may no longer be predictable. That said, Andrews added, DetermaRx "is a 14-gene [panel] and … can be run on any multiplex [real-time] PCR platform."
"I think we're in good place … We just need to see some light at the end of tunnel on the current situation, so we can get some bandwidth from these potential manufacturers," he said.
With both DetermaRX and the new DetermaIO now commercially available to some extent, it is Oncocyte's original assay, DetermaDx (originally DetermaVu), that has faced the greatest challenges in reaching the clinic.
But, during the call this week, Andrews announced that the company has finished its CLIA lab validation of the blood-based test and begun a clinical validation that should support a publication in the scientific literature and a bid for CMS coverage.
"Since we have collected all of the necessary patient samples prior to the current COVID pandemic, and our lab personnel qualify as essential workers under the current stay at home orders in California, we remain on track to complete [the validation] by the end of Q2," Andrews said.