NEW YORK – Chinese molecular diagnostics firm AnchorDx aims to develop a $100 circulating tumor DNA (ctDNA) screening test to detect six major cancer types at an early stage. The goal is to launch the test in the US and Chinese markets once it has been approved by regulatory authorities in those countries. Â
Last week at the second virtual session of the American Association for Cancer Research annual meeting, the company unveiled its Aurora assay, which captures and analyzes methylated ctDNA in blood plasma for multi-cancer screening. The firm has already evaluated the assay in lung, breast, and colorectal cancer and plans to study it further in gastric, esophagus, and liver cancer. These types of cancer account for over 60 percent of newly diagnosed cancer cases and over 70 percent of cancer-related deaths in China, according to a poster presented by the company.
Based on the study results, the AnchorDx team has submitted a patent application in China and plans to file a PCT patent application in the US.
"Aurora is a highly efficient and fully integrated assay, with a manageable cost of [about] $100 per test, which is pivotal for population-based cancer early screening," AnchorDx said on its poster.
The company's goal is to develop practical and accessible tests for cancer diagnosis that include cancer screening, cancer reflex testing, and companion diagnostics, said Kevin Chen, AnchorDx's VP of technology development. Founded in 2015 by CEO Jian-Bing Fan, former senior director of Illumina, AnchorDx is based in Guangzhou in southern China. In June 2019, the company partnered with Ilumina to develop clinical oncology tests for the Chinese market and opened a US branch in Fremont, California.
In 2017, AnchorDx raised $28 million in a Series B funding round and is still using this money, along with the $10 million it received from its A/A+ round. The funding comes from NorthernLight, 6 Dimensions, Jianxin Capital, Marathon, Wuxi AppTec, KingMed, and Arch Venture. AnchorDx is currently looking for a third round of funding of undisclosed amount, Chen said.
The Aurora test uses a small DNA methylation panel that tracks between 100 and 200 methylation biomarkers to identify early stages of six major cancer types — lung, breast, colorectal, gastric, esophagus, and liver cancer. Using only a couple of hundred biomarkers helps to save on assay cost, avoid overfitting, and still maintain good overall performance, said Chen, whereas using 1,000 or even 10,000 different markers makes it very easy to overfit the diagnostic model.
To develop Aurora, the AnchorDx team used public databases, such as The Cancer Genome Atlas (TCGA), but mostly its own in-house database that hosts genome-wide methylation profiling data from more than 2,000 tissue and over 4,000 plasma samples from early-stage cancer patients and normal controls.
To test out Aurora, the team used a total of 246 plasma samples from lung, breast, and colorectal cancer patients as well as 141 normal controls and 19 lung benign nodule samples from six clinical sites in China. To differentiate malignant from normal samples, random forest modeling was utilized to acquire a classifier, which achieved a sensitivity of 55 percent for colorectal cancer, 63 percent for breast cancer, and 82 percent for lung cancer samples of stage I at a predefined specificity of 99 percent.
Chen claimed the Aurora test has better specificity and sensitivity than other cancer screening tests because of the many early-stage cancer samples it has available for biomarker discovery and the new biomarkers AnchorDx has added to its database. "We want to find out the specific markers for early-stage cancer not late-stage cancer, which is very abundant in the public database," he said. "That's why we made our own database."
To run the test, ctDNA is first extracted from blood plasma and then bisulfite-treated. After that, a panel of 100 to 200 DNA methylation biomarkers is captured and converted to a sequence library, followed by sequencing on the Illumina MiSeq system.
"Aurora has a much smaller panel containing many specific markers for early-stage cancers, which facilitate a robust, accurate and low-cost test for multi- or pan-cancer screening," said Chen. "Because [our] panel is condensed and the target size is small, like 100 to 200, we can use pretty low sequencing depth to capture the signal, and then we can use the Illumina MiSeq platform to do the test," he said.
For comparison, Guardant Health's Lunar assay, for example, looks for DNA methylation, among others signals, in ctDNA for early cancer detection. Likewise, Grail has developed a methylation sequencing blood test for early detection of multiple cancers. Nucleix's EpiCheck assay, too, is based on DNA methylation profiles of liquid biopsy samples.
The turnaround time for the Aurora test is a couple days, but with transportation of the samples and sequencing, the entire process can take a week to 10 days, Chen said. Compared to other early cancer detection tests and multi-omics tests that AnchorDx has experience with, the Aurora test is faster, he added.
The test could also be beneficial for in vitro diagnostics (IVD) because the size of the panel is small and the workflow is streamlined, robust, and easy to handle, said Chen. The team is in the process of creating an IVD program using the Aurora test and Illumina MiSeqDx system. AnchorDx hopes to submit the Aurora test for Breakthrough Device application to the US Food and Drug Administration and may start a small trial with collaborators in the US in six to nine months.
To validate the findings presented at AACR, the team will complete model optimization for the remaining three cancer types (gastric, esophagus, and liver), said Chen, and plans to expand the study to a large independent validation cohort in the real-world clinical setting. In the future, the researchers also want the Aurora test to be used on a variety of populations outside of China to see if there is overlap or if they can find new markers to add to their database. After carrying out these studies, Chen said the team will probably publish the information and try to make the test commercially available in China and the US.
As far as how this test will improve other cancer screening tests, the team sees the Aurora test as complementary to standard clinical diagnostics, such as low-dose CT for detecting pulmonary lung nodules. Because low-dose CT often results in unnecessary treatment for benign nodules, Chen said the biomarkers used in the Aurora test could help with differentiating between malignant and benign nodules to prevent overtreatment.
Currently, AnchorDx has two laboratory-developed tests, for bladder cancer and lung nodules, on the Chinese market and plans to get these approved by the FDA for the US market. Overall, the company's main pursuit is to create one diagnostic tool that will recognize multiple cancers in their early stages.Â
"The ultimate goal is to screen different cancers in only one test. In the meantime, we only have specific screening tools for a specific cancer," said Chen. "We think it's very important to integrate our test into downstream clinical practice for each cancer type," which he said differs for each type.