NEW YORK – Liquid biopsy startup Adela is gearing up to bring its whole-methylome sequencing technology into the clinic for both minimal residual disease detection and multi-cancer early detection.
The Toronto-based company launched after licensing a technique called cell-free methylated DNA immunoprecipitation and high-throughput sequencing, or cfMeDIP-seq, developed by Princess Margaret Cancer Center's Daniel De Carvalho.
Over the last two years, Adela has been working to build clinical validity data for the platform in multi-cancer detection.
While Carvalho and others had published studies exploring a number of potential applications for cfMeDIP-seq, Adela needed to lock down wet lab procedures and tune an assay specifically for detection of multiple cancers at once, including those that shed much less tumor DNA into the blood than their counterparts.
The company made the first of this data public last month in a presentation at the annual meeting of the American Association for Cancer Research, demonstrating high accuracy across 12 tumor types.
The retrospective case-control study applied cfMeDIP-seq in a cohort of 4,000 individuals, including patients with newly diagnosed, treatment-naïve cancer and age- and gender-matched non-cancer controls. According to the authors, approximately 50 percent of the cancer cases were stage I and II.
Adela CEO Scott Bratman highlighted that the 12 cancers represented are "very relevant," both for early detection and for cancer management applications.
"We launched the company with a lot of academic data demonstrating high performance in single cancers and in different cancer management applications," added Anne-Renee Hartman, the company's cofounder and chief medical officer. "But this is really the first data looking at 12 cancers collectively and building a classifier that can detect all of them."
In the AACR poster, Park and colleagues reported on a cross-validation using a subset of about 2,000 samples in which they initially trained a machine learning classifier and then tested it in a separate group to assess its ability to distinguish cancer cases from controls.
Overall, the test could detect cancer 94 percent of the time. And notably, performance didn't drop dramatically for early-stage tumors, with stage I cases detected 92 percent of the time.
Performance was also high for tumor types that other studies have found to shed only scant amounts of tumor DNA into the blood. These include bladder, breast, renal, prostate, and endometrial cancer, which, as a group, were detected 91 percent of the time.
According to Hartman, detecting lower-shedding tumors is crucial both for early detection and MRD, where patients are being assessed for the tiniest signal of either lingering cancer or emerging recurrence.
"These cancers represent a high proportion of the incident cancers in the US, and they are also the cancers [for which] early detection and treatment with surgery [conveys] a high likelihood of a durable remission in the future," she said.
The retrospective data aren't enough to support clinical implementation, but the company is already building necessary evidence in a larger multi-cancer study and in various clinical utility efforts focused on specific MRD indications.
For MRD development, Hartman said that the firm has ongoing datasets that it is analyzing to support specific product launches. Alongside this, the firm has an ongoing study called CAMPERR, which launched in May 2022, and is about halfway to full recruitment. The prospective observational trial aims to include at least 5,000 individuals with one of 20 different cancer types, which collectively represent 90 percent of the incident cancers in the US.
"What's very interesting about that study is we have longitudinal monitoring endpoints, for minimal residual disease [in] several cancers including lung, colon, and breast, [and] we are addressing both multi-cancer early detection and also cancer management," she added.
Bratman argued that the nature of the cfMeDIP-seq methodology, which allows sequencing of the whole methylome without the need to sequence the whole genome, will be a boon for Adela in what is anticipated to be a competitive market.
"Our platform is really well poised for developing products across this cancer care continuum," he said, noting that "having a whole methylation enrichment platform that can be deployed across cancer types without the need for tissue is really an important aspect," of the company's commercial strategy.
In MRD, commercial firms have taken two main paths, either developing a system for creating patient-specific tests for circulating tumor DNA based on upfront tissue sequencing, or developing agnostic, fixed assays.
"Because we're looking at the whole methylome, we don't need to create targeted panels for multi-cancer early detection or for MRD," Hartman said. "We are using the same wet lab assay for each application, and all that differs is the classifier development for each application, so it allows us to be very efficient in our product development and to scale more quickly than if we had another technology where we were required to create targeted panels."
An analogous example is Guardant Health, which, like Adela, has tapped genome-wide methylation for both MRD and cancer early detection, although it has initially targeted just a single tumor type, colorectal cancer.
The firm's precedent demonstrates the high bar Adela is attempting to meet with its own technology. Even focusing on the relatively high-shedding CRC, Guardant's most recent prospective sensitivity data fell short of expectations.
According to Hartman, cfMeDIP-seq's demonstrated performance in low-shedding and early-stage tumors gives the firm confidence moving forward. If it can demonstrate similar sensitivity in the CAMPERR trial that Park and colleagues achieved, it would have a strong standing to compete with existing tests on the market.
Bratman said Adela isn't ready to discuss specific commercialization timelines, but the company is in discussions with the National Cancer Institute, which has recently stepped up to spearhead large-scale clinical utility studies intended to bring MCED tests to market.