With a new CEO at the helm, the Laboratory for Advanced Medicine (LAM) is preparing for the launch of its first liquid biopsy—a blood test designed to detect early-stage liver cancer, expected to win approvals starting in China this year.

LAM is preparing a submission to Chinese regulators for approval to market the IvyGene® Liver Cancer Test, following completion of a clinical trial. The test is designed to detect and measure DNA methylation patterns that are consistent with actual cancer presence.

“We anticipate getting full registration status in China probably at the end of the first half of this year, or the beginning of the second half of this year,” Kenneth Chahine, PhD, JD, told GEN Edge.

As for U.S. approval, LAM anticipates FDA approval around the end of 2020 or early 2021, depending on how soon it can complete a U.S. clinical trial (CLiMB, NCT03694600). The CLiMB trial is designed to assess the test alone and in combination with ultrasound for the detection of hepatocellular carcinoma (HCC) within a high-risk population due to liver cirrhosis.

Liver cancer is one of several cancers for which LAM is developing early detection tests; others include colon cancer and breast cancer. The company estimates a potential market in those three indications alone of more than 200 million people.

Chahine was appointed to lead the company last November, succeeding founding CEO Shu Li, PhD, who continues to serve as Chairman of LAM’s Board of Directors. Chahine joined LAM from Ancestry.com’s AncestryDNA division, which he commercialized and scaled into one of the world’s largest consumer genomic businesses as executive vice president and general manager.

At AncestryDNA, he oversaw the launch of AncestryHealth®, a physician-ordered laboratory-developed test (LDT) designed to report genetic predisposition to conditions such as breast, ovarian, and colon cancer, as well as cardiac and blood clotting disorders on a next-generation sequencing (NGS) platform.

Minding the mundane

“As we grow, I think the thing we need to strengthen is going from basic research to commercialization,” Chahine said. “That’s the key—making sure that the test is robust and the supply chain is in good working order. It’s a bit mundane that people don’t think about. But to be successful commercially, that’s super critical.”

LAM’s test is designed to measure the methylation status of cell-free DNA at target gene sites. The results are reported as a quantitative IvyGene™ Score (calculated as a composite average of cell-free DNA that is methylated at the target sites as a fraction of the total cell-free DNA present). The test is intended for use with other diagnostic and confirmatory tests, including mammograms, PET scans, and biopsies.

The liver cancer test was granted the FDA’s Breakthrough Device designation in September 2019. Two months later at The Liver Meeting 2019, hosted in Boston by the American Association for the Study of Liver Diseases (AASLD), LAM presented an analysis of blood samples from 450 subjects using its DNA methylation technology. The technology correctly detected HCC in patients for an overall sensitivity of 88% (n=218/249) and correctly identified 96% of healthy donors (n= 80/83) and 98% of patients with benign disease (n=116/118) with a combined specificity of 97%.

In a paper, “Circulating tumor DNA methylation profiles enable early diagnosis, prognosis prediction, and screening for colorectal cancer,” published on New Year’s Day in Science Translational Medicine, a team of Chinese researchers presented positive results for one of LAM’s ctDNA methylation markers in the diagnosis, surveillance, and prognosis of colorectal cancer. cg10673833 yielded high sensitivity (89.7%) and specificity (86.8%) for detection of colorectal cancer and precancerous lesions in a high-risk population of 1493 participants, according to the prospective cohort study.

“What that showed was a really great proof of concept,” Chahine said. “If you’ve ever been through a colonoscopy, it’s not pleasant and it’s very inconvenient, and 35% of the people simply don’t take the colonoscopy even though they’re eligible. This idea of taking a simple blood draw is really revolutionary.”

Colorectal, stomach, and other digestive cancers are one of three cancer categories for which the company is working to validate its tests in around 50,000 patients each, through grants awarded by China’s National Cancer Center. The other two are liver and lung cancer.

Lung, breast cancer tests on deck

Lung and breast cancer tests are next in the company’s pipeline, probably in the 2021 timeframe. “We’d like to start validation of breast and lung in the second half of this year and then have it potentially ready in 2021,” Chahine said.

LAM is still committed to the goal articulated by executives last year to GEN Edge sister publication Clinical OMICs—namely, increasing its test portfolio to a dozen or so assays, then bundling those tests into a panel using biomarkers that are sensitive to various cancer types. But the speed of rolling out that timeline may have to change depending on clinical and commercial progress.

LAM is not joining other diagnostics developers that are scrambling to develop multi-cancer tests. On Wednesday, for example, GRAIL announced the launch of PATHFINDER, a prospective, multi-center study designed to return the company’s test results to healthcare providers and communicate them to participants, in order to guide clinical care for more than 50 types of cancer across all stages.

“From a regulatory standpoint, it’s really hard,” Chahine observed. “There’s no precedent for anything like that. Even if it’s a great idea, I think it’s going to encounter a lot of resistance. Second, just from a statistical standpoint, having a test that performs that well for multiple different markers is going to be very, very difficult. When you don’t have a high risk population, you have the risk of false positives that’s going to be really high.”

Chahine has brought on board executives with commercialization expertise. On February 18, LAM named a former AncestryDNA colleague of Chahine’s, Benjamin Oyler, as COO. He previously led AncestryDNA’s end-to-end supply chain as VP of Strategy and Business Operations for the division.

Last December, LAM named Aarif Nakhooda as CFO, citing his 25+ years of financial, commercial, and operational experience with Amazon and other companies. LAM recently named new board members that include Christopher DeRosa, MBA, who brings medical insurance and reimbursement experience as COO of Cigna’s US Commercial Markets; and oncologist Alan List, MD, President and CEO of Moffitt Cancer Center. List has since left the board.

At deadline, LAM was expected to announce a new CEO for its operations in China.

Pursuing additional capital

Privately-held LAM is also working to support its commercialization plans by raising additional capital. The company has raised about $120 million in total financing, mainly from its founder Li, who is chairman of the angel investment firm J&J Investments, and several “offices” or managers of investments and trusts for high-net-worth families. Much of that cash was an $86-million Series B round last year, two years after LAM garnered $30 million in Series A financing.

LAM is headquartered in Irvine, CA, with additional U.S. operations in West Lafayette, IN, and the Dallas suburb of Coppell, TX. In China, the company has offices in Beijing, Bei Dai He, and Guangzhou. While LAM completed a headquarters expansion last year and opened a support office for its sales and marketing team in Coppell in 2018, the company has no current office expansion plans, Chahine said.

Also expected to stay constant, for now, is the size of LAM’s workforce, which is about 100.

“The senior team now is in really good shape. We’re looking for a couple of other key hires in certain areas, but I would say we’ll grow modestly,” Chahine projected. “We probably won’t grow too much until we finish this next round of financing. Obviously, if we get some investor money and want to accelerate development, then we can maybe bump that up more significantly.”

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