NEW YORK – Natera's plans for the future involve expanding its existing diagnostic capabilities to cover additional markets, and doing it in a very big way.
On a conference call to discuss the company's third quarter earnings this week, CEO Steve Chapman highlighted the progress Natera is making in expanding its transplant diagnostic test to additional organs beyond kidney, and revealed new initiatives for developing a multicancer early detection screening platform.
Natera recently added quantification to its Prospera transplant rejection test, a new technique that improves performance over earlier methods that reported donor-derived cell-free DNA fraction alone.
With the addition of quantification, Chapman said, Prospera is now the only commercially available cell-free DNA test for kidney rejection that provides the quantity and fraction of donor-derived cell-free DNA, as well as the total amount of cell-free DNA. Other tests, which only report on the fraction of donor-derived cell-free DNA, may result in false negatives, he said.
In testing the utility of the quantification method, the company found that it improved Prospera's performance in 41 total kidney transplant recipients, nine of whom were experiencing rejection, he added. Whereas the baseline Prospera test detected rejection in seven of the nine patients, the enhanced version of the test was able to detect rejection in all nine patients.
This enhanced effect was most prominently seen in the company's Trifecta study, which Chapman called the largest prospective, multisite, fully biopsy-matched study ever performed in the kidney transplant space. The study included more than 300 biopsy-matched blood samples and more than 100 biopsy-confirmed rejections.
"The initial results exceeded our expectations and we believe can eliminate the need for costly multi-modality approaches to bolster test performance," he added, seemingly calling out Natera competitor CareDx's emphasis on multi-modal transplant diagnostics.
Chapman also highlighted Natera's recent expansion of Prospera to heart and lung transplant rejection monitoring, both of which are supported by prospective datasets that the company believes can "redefine these fields," he said.
Notably, he added, it's been "relatively easy" and cost effective for the company to expand beyond kidney monitoring to other organs because all the tests rely on the same core technology, and the commercial rollouts have proved fairly efficient because Natera was able to use a lot of the same infrastructure, including nurse coordinators and customer support.
Further, he said, Prospera Heart offers compelling advantages over competitors' tests because its validation study was a multisite study that included more than 250 prospective samples and another 100 samples from a biopsy match biobank.
"The initial results were impressive, but then further improved with quantification where we were able to achieve an area under the curve of 0.88," Chapman added. "These are really exceptional AUCs in the heart transplant monitoring space, further underscoring the power of our technology. What's critical about these results is that the Prospera Heart test is delivering this exceptional AUC by performing cell-free DNA [analysis] alone, and therefore, we believe there is no need for cumbersome and costly multi-modality approaches to bolster test performance."
In an additional ding to competitor CareDx, Chapman also noted that its competitor's test charges Medicare twice for every multi-modality patient, since separate DNA and RNA tests are being performed. "Because we are delivering excellent performance on a cell-free DNA-based test alone, Prospera Heart reduces the cost to the system and is less than half the price of the expensive multi-modality approaches," he said.
Some of the same advantages and performance metrics hold true for the company's Prospera lung test, he said. The company plans to submit dossiers for Medicare reimbursement under the existing local coverage decision and anticipates receiving coverage in 2022 for Prospera Heart and Lung.
Besides transplant testing, Natera continues its initiatives in the oncology space. It recently published a colorectal cancer study that introduced Signatera velocity as a clinically useful metric. The study demonstrated the value of calculating circulating tumor DNA growth rate over time, or velocity, suggesting that patients with fast-growing tumors may have worse outcomes than patients with slow-growing tumors.
Natera believes this will be an advantage for recurrence monitoring.
Notably, Chapman disclosed that the company has signed a partnership deal with Aarhus University, giving Natera access to a prospective 40,000-sample biobank of patients screened for colorectal cancer, more than half of which have stage I or II cancers. In addition, under the terms of the deal, Natera has access to and has an exclusive option to license Aarhus' methylation signature for colorectal cancer, which it plans to combine with its own methylation and ctDNA technology, Chapman said.
Aarhus' methylation signature alone reported an average sensitivity of 85 percent for detecting colorectal cancer, with a specificity of 99 percent for stage I through IV, he added. The performance was also very strong for early-stage cancers, with an 80 percent sensitivity in stage I cancers and 85 percent sensitivity in stage II cancers.
"Our strategy [in early cancer detection] is to pursue a capital-efficient development program that is not distracting from the work we are doing with Signatera, but instead leverages the technology we are already developing, along with the data we are generating with our growing base of clinical volumes in oncology," he said. "That last item is critical because we run an upfront exome on every Signatera sample. We're accumulating a dataset of tens of thousands of early-stage cancer exomes that has never existed before. We can now interrogate that dataset to assist in the design of a DNA-based signature that maximizes test performance."
According to Chapman, Natera has already completed the initial design of the colorectal cancer early screening DNA component of the test and is now moving on to validate and expand on that effort with Aarhus University.
To begin, the company aims to replicate the results of Aarhus' methylation signature. Chapman said he believes Natera can improve on the signature by incorporating it into its own methylation workflow and adding its own DNA technology.
The company will start with a colorectal cancer assay and may add more cancer types in the future, he said, and it plans to generate data on the performance of DNA and methylation analysis sometime in 2022. "There's still a lot of work to do, so we're not putting out any timelines right now, but we do think we can generate some data during that time frame," he said.
"[W]hile our initial focus is on generating a proof of concept and then validation data for colorectal moving towards the commercial launch, our longer-term plan is to have a pan-cancer assay."
More broadly, Chapman compared the company's quantitative approaches in both oncology and transplant diagnostics to its launch of the fetal fraction metric for its Panorama NIPT test in 2013. At that time, no other NIPT reported fetal fraction, but physicians gravitated to Natera's diagnostic because of that result, he said. Now, fetal fraction has become the gold standard in the field.
"These new oncology and transplant metrics provide a window into a patient's underlying biology, which can offer a physician crucial context [for] clinical decision-making," he said. "Our technology lends itself to these types of metrics, further differentiating the clinical utility of our products across all areas of our business."