This story has been updated to include additional information from Adela.
NEW YORK – Adela, a spinout from Canada's University Health Network, is commercializing a DNA methylation-based liquid biopsy technology that may have applications across the spectrum of cancer testing applications, especially multi-cancer early detection.
The Toronto-based company has licensed cell-free methylated DNA immunoprecipitation and high-throughput sequencing, or cfMeDIP-seq, a genome-wide approach to detecting methylation developed by Daniel De Carvalho, a cofounder and the firm's chief scientific officer, and other researchers. Last week, Adela closed a $60 million Series A financing round, led by F-Prime Capital.
"Because of technical advantages, we believe we can hit the requirement for an early cancer detection screening test for high sensitivity" and specificity, said Anne-Renee Hartman, Adela's chief medical officer. The method does not rely on bisulfite conversion to detect methylation, a sample preparation process that destroys cell-free DNA. In addition to detecting cancer at an early stage, the firm believes its technology can provide information about tissue of origin and even histological subtype. "We believe we can be best in class," she said.
Company officials declined to discuss specific metrics of the assay's performance. Instead, they pointed to data in nine peer-reviewed publications from De Carvalho, collaborators, and even a few independent researchers. None of those data were generated by the company, CEO Scott Bratman said.
These studies have suggested cfMeDIP-seq can provide early detection of at least 10 different cancer types. Building on a 2018 study published in Nature, which demonstrated that the method could differentiate between seven different tumor types, De Carvalho has led studies showing the ability to detect cancers not easily found by other blood-based tests, such as brain cancers and renal cell cancer, and particularly deadly cancers, such as pancreatic cancer.
"This is all beautiful data, but it's in the research space. They have not yet done a definitive clinical trial in order to support the approach in early clinical detection," said Elaine Mardis, coexecutive director of the Institute for Genomic Medicine at Nationwide Children's Hospital and a brain cancer researcher. "How they design that trial and how long it takes will be an important next step."
The company is currently planning studies to train its classifier algorithm and clinically validate its test, Hartman said, noting that the firm will provide more information when those studies are launched "in the near future." The company hopes to have data from them sometime in 2022, she added.
Founded in 2020 as DNAMx, the company changed its name to Adela because it found that people had difficulty pronouncing the original one. The company is in "building mode," Bratman said, and has about a dozen employees but is adding to its headcount "every couple weeks" and will likely triple in size by the end of the year.
Adela enters a market that is still nascent but already dominated by earlier entrants. Grail, an Illumina spinoff that the sequencing giant is trying to reacquire despite resistance from the US Federal Trade Commission, launched its Galleri cancer early detection test last month, backed by data from its PATHFINDER study. Like Adela's test, Galleri is also based on methylation sequencing across the genome.
Thrive Earlier Detection, based in Cambridge, Massachusetts, has already raised approximately $367 million between its 2019 Series A and 2020 Series B financing rounds, is in the process of finalizing its test design, and is in talks with the US Food and Drug Administration to plan a multisite trial.
But Adela officials believe that ultimately their assay will have technical advantages that will allow it to "change the way we detect, diagnose, and treat disease," Hartman said.
In a one-page flyer for potential investors from 2018, the firm said that out of 189 plasma samples from patients with seven cancer types and healthy controls, cfMeDIP-seq correctly classified 171. In a comparison of 200 early-stage pancreatic cancer patients and 200 healthy donors, cfMeDIP-seq detected cancer with 0.94 specificity and 0.82 sensitivity in a blinded test.
Those plasma samples were included in the 2018 Nature paper as part of the assay classifier training set. There, the results were presented as an area under the ROC curve, Adela officials said. "The statement regarding pancreatic cancer detection performance is based on unpublished data. Multiple papers have been published since then further describing the performance of the platform for cancer detection," Adela officials said in an email.
While the firm has plans to eventually offer testing for patients after diagnosis, as well, the focus is on early detection. "This is not a single cancer blood test," Hartman stressed. While the company doesn't know yet how many cancers it will be able to detect, "we are focusing on detecting cancer with high incidence and mortality," she said. "That number adds up rapidly."
In already completed studies, cfMeDIP-seq has shown promise for detecting acute myeloid leukemia, pancreatic, colorectal, breast, lung, renal, bladder, prostate, ovarian, head and neck, and intracranial brain cancers.
"The brain cancer detection aspect is incredibly interesting in the context of potential for best in class," Mardis said. Brain cancers, while rare, often have a very poor outcome. "There may be an advantage to early detection of high-grade brain cancers, because treatment in early-stage disease is likely to be more effective," she said.
"A number of studies just using cell-free DNA from blood have demonstrated that if you're trying to detect brain cancer mutations, say from a patient with a diagnosed cancer, that's extraordinarily difficult to accomplish with any precision," Mardis said. Based on work done with methylation arrays, researchers have found clear patterns in many brain cancers allowing precise typing or even subtyping.
In general, detecting cancer earlier raises the chances of successfully treating it, which is a driving rationale for the entire early detection field. "Not only is there a higher chance of successfully treating it, but you could also avoid future hospitalization, treatment and death from metastatic disease," Mardis said. Brain cancers are also very difficult to get biopsies for.
"This approach is promising but not there yet in terms of bona fide proof of clinical benefit," she said. "The argument for early detection by these genomic approaches is more intuitive argument at this time but is supported by data on survival rates in early versus late-stage cancer."
Adela officials also believe their tests can be used for minimal residual disease monitoring and patient response to therapy. It may even have applications outside of oncology.
"Cell-free DNA in circulation can contain signals derived from other tissues that are not malignant," Bratman said. "We can envision using this to detect organ damage and disease involving a variety of tissue distinguished within the methylome, but it's too early to say at this point what those would be."