NEW YORK – Korean cancer diagnostics firm IMBDx is advancing its AlphaLiquid sequencing-based liquid biopsy technology for multiple applications including lung cancer therapy guidance and multi-cancer early detection, with an eye toward clinical guidelines inclusion and regulatory approval in Korea and elsewhere in East Asia.
The Seoul-based company, founded in 2018, develops technologies to address the full continuum of cancer care, including screening and detection, tumor profiling, and recurrence monitoring. The firm's flagship AlphaLiquid platform includes applications for both tissue and plasma-based sample profiling, and includes tests such as the CancerFind multiomic assay for multicancer early detection (MCED), CancerDetect tissue-informed bespoke panel for minimal residual disease detection, AlphaLiquid 100 comprehensive genomic profiling assay, and AlphaLiquid HRR for homologous recombination repair genetic mutations.
AlphaLiquid 100 detects variants across 118 cancer-related genes using ctDNA isolated from plasma samples. According to a publication last year demonstrating its potential clinical utility in non-small cell lung cancer, the assay has been designed to suppress errors by incorporating a proprietary "high-quality unique sequence technology." The company offers the assay through a number of Korean hospitals to patients with advanced solid tumors, according to the company's website.
Although the company has primarily focused on testing blood samples using its technology, it has recently begun exploring other liquid sample types. For instance, IMBDx recently published a study demonstrating the clinical actionability of AlphaLiquid 100 using pleural effusion samples in non-small cell lung cancer (NSCLC).
The study, published earlier this week in the European Journal of Cancer, showed that actionable cancer-related mutations could be reliably found by genotyping cell-free DNA (cfDNA) from pleural effusions in NSCLC patients.
Tae-You Kim, CEO of IMBDx, said that while current NSCLC treatment guidelines –– both in Korea and the US –– recognize the clinical utility of cfDNA assays, they only do so for plasma samples and as a complement to tissue testing for molecular diagnosis in advanced NSCLC.
"If there are not enough circulating [cancer] cells, tumor genotyping may be impossible," Kim said, adding that "pleural effusion is sometimes the only site of [lung cancer] progression."
In their study, which was conducted in Taiwan in collaboration with researchers at the National Taiwan University, researchers conducted comprehensive genomic profiling on 50 newly diagnosed advanced NSCLC using AlphaLiquid 100 on extracted pleural effusion samples, using both Sanger sequencing on reverse-transcribed RNA from pelleted cells and standard clinical genetic testing on patient tissue samples. Of the 50 patients analyzed, 45 had actionable mutations, with AlphaLiquid 100 picking up those mutations in 44 patients, Sanger sequencing in 39, and tissue testing in 33.
In addition, all 50 samples contained sufficient material for analysis with AlphaLiquid 100, which IMBDx highlighted as an important measure of its performance. Comparatively, three samples were insufficient for cell pellet Sanger sequencing and two for tissue testing.
All patients with positive findings were given treatments targeting their specific mutations and all showed either partial response or stable disease. A rare ROS1 fusion variant was detected only by the AlphaLiquid 100 assay in one patient. Although this patient initially showed a partial response to therapy, her tumor progressed after approximately six months.
Kim sees studies like this one as critical for proving the worth of liquid biopsies in clinical settings and for raising awareness of them among physicians. The company also hopes that the evidence generated from this and other ongoing studies eventually proves sufficient to gain inclusion in clinical care guidelines both in Korea and beyond.
"A lot of lung cancer doctors don't know much about the impact of liquid biopsy testing," he said. "With this paper, I think many more doctors may become aware of the clinical utility of liquid biopsies and we expect more doctors [to] use this test to analyze pleural effusions."
Meiling Piao, director of global business development, said that the ability to perform liquid biopsies in samples other than blood provides a way for the firm to expand its services and by extension, its overall business.
Beyond blood and pleural effusion, Piao said that IMBDx is also working on applying its assays to cerebrospinal fluid (CSF). Earlier this year, IMBDx and National Taiwan University published a separate study exploring the use of AlphaLiquid 100 in NSCLC patients with leptomeningeal metastasis, a condition wherein cancer cells spread to thin membranes called leptomeninges that cover the brain and spinal cord.
Meanwhile, IMBDx is also stepping into the MCED field with its plasma-based CancerFind, which combines epigenomics, fragmentomics, and genomics to screen for eight cancer types — colorectal, stomach, liver, pancreas, lung, breast, ovarian, and prostate cancer — and potentially identify a tumor's tissue of origin.
IMBDx was recently selected to lead a multi-company MCED development and commercialization project within Korea by the Korean Advanced Research Projects Agency – Health (ARPA-H), which provided approximately $55 million in funding.
"The goal of this project is to develop an MCED test for the most common types of cancer at an affordable price," Kim said, adding that IMBDx is targeting a final price of not more than $200.
As part of that effort, the company is scaling up its CancerFind MCED assay to detect 15 cancer types over the next two to three years and 30 cancer types by 2029, when the ARPA-H project is scheduled to end..
Piao said that CancerFind currently shows a cancer detection sensitivity of approximately 88 percent, specificity of 96 percent, and tissue-of-origin accuracy of 84 percent. Piao said that through the ARPA-H initiative, the company hopes to further improve the test's accuracy to 90 percent sensitivity and 95 percent specificity.
One way in which this is happening is through an expanded repertoire of biomarkers. Along with epigenomics and fragmentomics, IMBDx is working to incorporate genomic biomarkers that include copy number variations, end motif analysis, nucleosomes, and virus DNA, as well as gene variant analysis.
IMBDx also hopes that the ARPA-H project will help the company expand the assay's geographical reach.
"By 2029," Piao said, "we aim to achieve Korean FDA approval [for] CancerFind." This, she said, is part of the company's long-term strategy to commercialize CancerFind globally. The company is already working with various academic and commercial entities to market its tests abroad, with distributors in over 30 countries, Piao said. Last year, for example, the company partnered with San Diego-based Inocras to introduce its tests to the US market.
IMBDx is also collaborating with global pharmaceutical firm AstraZeneca in applying its liquid biopsy platforms to guide the use of targeted therapies in prostate cancer. The companies have been working together, for example, to use AlphaLiquid HRR as a companion diagnostic for olaparib, a PARP inhibitor developed by AstraZeneca used to treat several types of cancer and marketed as Lynparza.
"Our partnership with AstraZeneca began with [homologous recombination repair] testing for prostate cancer and has now expanded into multi-tumor solutions [using the] AlphaLiquid 100," Piao said.
Kim noted that liquid biopsy solutions are especially important in cases such as prostate cancer, in which acquiring tissue samples can be complicated.
"And most prostate cancer metastasizes to the bone," Kim added, "[from which] it is very difficult to get tissue."
IMBDx recently showed data from a study done with AstraZeneca that Kim said showed strong evidence that plasma-based HRR testing provides a viable alternative solution to tissue testing.
That study, presented last month at the annual conference of the American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, demonstrated that a customizable NGS-based AlphaLiquid HRR assay successfully identified numerous HRR mutations in patients with metastatic, castration-resistant prostate cancer who were ineligible for evaluation by tissue-based biopsy methods.
The AlphaLiquid HRR assay has also been tested in several other cancers, including gastric, liver, and lung cancers, although Kim said that it is important to continue generating data to support broad guideline inclusion of MCED testing. He added that he expects the ARPA-H program to provide a significant assist in that effort.
"In our ARPA-H project, we are going to include more than 5,000 patients in a clinical trial," Kim said. "[With] this data, I think MCED testing can begin to be incorporated into standard screening programs."
"Hopefully we can help more and more cancer patients," Piao added, "or even healthy but high-risk individuals to lead better lives throughout their cancer journey."