SAN FRANCISCO — At the 43rd annual JP Morgan Healthcare Conference on Wednesday, Natera CEO Steve Chapman provided updates on the firm's new product launches and clinical evidence generation within its cancer business.
First, the firm has launched a new version of Signatera using whole-genome sequencing, rather than its traditional whole-exome sequencing. The test is being offered at scale "right out of the gate" and is now available for both research and clinical use, Chapman said. Natera is leveraging its existing commercial and operational infrastructure to launch the test, so it will maintain its current turnaround times.
Chapman added that Natera expects the whole-genome sequencing-based version of the test to initially be used largely in clinical trials but "if a doctor wants to order it today, they can order it."
Natera is also developing a tumor-naïve minimal residual disease assay, which it expects to launch clinically later this year for colorectal cancer. The company conducted "extensive in-house discovery" to look for methylation targets for the test using the data it has collected from tumor exomes, Chapman said.
Preliminary data for the colorectal cancer test, which is currently available for research use only, will be presented next week at the American Society of Clinical Oncology (ASCO) GI symposium, but Chapman said the data showed "excellent performance that we think is competitive with other tumor-naïve assays in the field." He added that additional data should read out later in 2025.
In the future, Chapman said he expects the whole-exome sequencing-based version of Signatera will make up about 85 percent of MRD volumes, while the whole-genome sequencing and tumor-naïve assays will comprise the remaining 15 percent.
"We're just at the very early stages of MRD," he said. "This is going to be an opportunity that has never been seen before in cancer diagnostics."
Solomon Moshkevich, Natera's president of clinical diagnostics, said that the firm has seen strong growth in MRD testing in 2023 and 2024 that has been driven by both new physician users and existing customers who are comfortable using Signatera in more of their patients and expanding their use to disease indications beyond colorectal cancer.
Chapman also provided initial performance data for its early cancer detection test utilizing DNA methylation signatures. The platform has been built over the past two years and includes data from cancers, premalignant lesions, and other conditions, he said.
The validation strategy for the test includes three studies: CIRCULATE-CRC, PROCEED-CRC, and FIND-CRC. CIRCULATE-CRC is intended to establish the clinical performance of the test in colorectal cancer and includes 5,000 confirmed CRC patients with pre-surgical time points and Signatera ctDNA data. Approximately 30 percent of the cases are asymptomatic patients detected through screening with colonoscopy, and the cohort includes stages I through IV.
The PROCEED-CRC study is intended to establish clinical performance in the screening population and aims to enroll 3,000 patients. Thus far, Natera has enrolled 2,600 patients and expects about 10 CRC patients and 240 advanced adenoma patients once enrollment is completed.
The FIND-CRC study will be used for clinical validation and submission to the US Food and Drug Administration. It aims to include about 17,500 patients with 70 CRC cases and 1,400 advanced adenoma cases.
The preliminary data Chapman shared included 432 prospective samples from CIRCULATE and PROCEED, with 127 confirmed CRC cases. Thirty-four of those 127 cases were screening-detected stage I through III patients, and 80 were symptomatic cases. For the remaining 13 patients, the diagnostic methods used were unknown.
Overall sensitivity was 95 percent, and specificity was 91 percent. Sensitivity for both stage I and stage II patients was 92 percent, while sensitivity for stage III patients was 98 percent and sensitivity for stage IV patients was 100 percent. In asymptomatic patients detected through screening, both sensitivity and specificity were 91 percent.
"We think our data's very good in comparison to some of the other case-controlled studies that we've seen," Chapman said.
In a note to investors, TD Cowen analyst Dan Brennan wrote that other companies such as Exact Sciences, Guardant, and Freenome have seen their early CRC screening performance data "notably degrade to the final pivotal, with the degree of degradation related to how robust and 'real world' applicable the trial and population are for the earlier datasets."
While the headline performance for Natera looks good, "it's early, the trial is heavily enriched (with cancer samples)," advanced adenoma performance remains unknown, and more information is needed about patient backgrounds, Brennan added.
Advanced adenoma data from PROCEED will be shared in the first half of 2025, with the full PROCEED readout later in the year, Chapman noted. FIND-CRC will use the same infrastructure as PROCEED, and if PROCEED's data readout is positive "we can kind of roll directly into" the FIND study, he added.
Financial performance
Chapman also discussed the firm's preliminary Q4 2024 financial results announced on Monday, noting that the company saw revenues grow 52 percent year over year to about $472 million and test volumes grow 26 percent to approximately 793,000. Signatera clinical test volumes increased by 14,500 in the fourth quarter to about 145,000, and Chapman said this was a "record quarter" across all of Natera's flagship products.
CFO Mike Brophy said that the firm saw strong volume growth and incremental improvement of the average selling price of its tests across the board. The average selling price for Signatera increased to about $1,100 in Q4 2024, partially thanks to increased reimbursement from Medicare Advantage plans, he added. The firm has also started to see some initial benefits from reimbursement due to state biomarker laws, as well.
Brophy also said that as Signatera volumes ramp up, Natera's cancer business is becoming competitive with its women's health business when it comes to total revenues.
Chapman added that the firm is looking to increase its share of the women's health market to more than 50 percent and has new product launches for the business planned in 2025. Historically, Natera has been focused on volume growth in its women's health business, but it is now also focusing on improvement in its average selling price, he said.