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With Single-DNA Target Assays, Genomictree Sees Room to Improve Early Cancer Detection


NEW YORK – South Korean cancer testing firm Genomictree aims to expand into the US market with its single-target DNA methylation biomarker tests, starting with a screening test for bladder cancer.

Sungwhan An, founder and CEO of Genomictree, said his company plans to start clinical trials in the US in early 2024 for the company's EarlyTect BC test for the detection of bladder cancer in patients with hematuria. The trials and commercialization would be handled by the firm's US subsidiary, Promis Diagnostics, which said in April it had secured US Food and Drug Administration breakthrough device designation for the assay.

"Hopefully, we'll finish bladder cancer quickly and we'll jump into others – lung cancer and other cancers, too," An said.

That lineup includes the firm's single-biomarker colorectal cancer screening test, EarlyTect C, which it has been marketing in South Korea since 2019. While the firm received CE-IVD marking for the colorectal cancer test in 2015, An said the firm ran into commercialization challenges that stalled deployment in Europe.

Genomictree's EarlyTect BC test uses a two-step process of amplification and detection of the DNA methylation marker PENK. All the company's tests use an amplification process involving an oligonucleotide primer designed for hybridization with a methylated DNA site and linear amplification, followed by methylation-specific real-time quantitative PCR, An said. Quantitative methylation-specific PCR alone often failed to identify the target, especially in early-stage cancer, so the company added the earlier amplification step.

In a paper published recently in the Journal of Molecular Diagnostics, authors including An said the results of two studies indicate the EarlyTect BC test showed promise as a screening tool for bladder cancer among patients with hematuria, which is a common symptom among bladder cancer patients. They wrote that cystoscopy is costly and invasive, yet urine cytology has insufficient sensitivity, especially for low-grade bladder cancers. Urine-based biomarker assays also have low sensitivity and high false positive rates.

"To be routinely used in clinical practice, urine-based tests must be highly sensitive and accurate for detecting a small number of tumor-derived specific biomarkers, usually accompanied by highly nonspecific backgrounds," the authors said. "This study reports development and validation of a highly sensitive methylation test to measure PENK methylation status in urine."

The first of the two studies was a retrospective examination of urine samples from hematuria patients at Chungnam National University in South Korea, 175 of whom had bladder cancer and 143 who did not. The firm used its linear amplification step and performed quantitative methylation-specific PCR on Thermo Fisher Scientific's 7500 Fast Real-Time PCR system. The authors found EarlyTect BC performed with 87 percent sensitivity and 92 percent specificity with an area under the curve of .89.

A subsequent prospective clinical validation study involved testing on urine samples from 418 hematuria patients who were scheduled for cystoscopy at Chungnam National University and comparison of the results with cystoscopic findings and pathology outcomes. In that test, 38 patients received diagnoses of bladder cancer and the authors reported EarlyTect BC performed with 84 percent sensitivity, 96 percent specificity, and an area under the curve of .90. The test performed weakest with early-stage cancers that released lower volumes of tumor cells into urine.

The authors wrote that their studies show the test was robust, precise, and capable of detecting single-digit copy numbers of methylated PENK DNA. It also showed no cross-reactivity with other organisms or substances in that testing.

A single target test offers a few advantages over a multi-marker one, according to An. While incorporating multiple biomarkers into Genomictree's tests might increase their sensitivity, he expects they would have lower specificity. He also said the price per test is a key consideration when entering the market, and he hopes the lower price of targeting a single biomarker will make payers more likely to cover the test for broad use among patients with hematuria.

Based on US Centers for Medicare and Medicaid Services and private insurance rates, he expects reimbursement for the test to be about $150.

Assuming the test makes it to market in the US, it will compete against other urine-based tests intended to deliver non-invasive disease detection.

Nucleix secured US FDA 510(k) clearance in May for its Bladder EpiCheck cancer recurrence test that uses 15 DNA methylation markers in urine using qPCR. In 2022 the firm expanded its European Union label indication to include primary bladder cancer and upper tract urothelial carcinoma in patients with hematuria. UK-based Nonacus launched this year its Galeas Bladder liquid biopsy test for genetic alterations connected with bladder cancer. Meantime, New Zealand-based Pacific Edge uses five mRNA biomarkers in its RT-PCR-based Cxbladder tumor test, while Abbott's UroVysion Bladder Cancer Kit identifies chromosomal aneuploidies through fluorescence in situ hybridization.

More broadly, other firms have been developing PCR assays for methylated biomarkers of other cancers. 

Genomictree also has its eyes on the colorectal cancer screening market where Exact Sciences has cornered the space with its stool-based ColoGuard, which includes DNA methylation markers among its targets. But An said preparing the EarlyTect C test for the US market will involve substantial work including rigorous clinical trials, which is why the firm focused on initial commercialization of its bladder cancer test.

Genomictree's colorectal cancer test uses the syndecan-2 methylation biomarker,. Meanwhile, the firm is developing a lung cancer test using the PCDHGA12 methylation biomarker. An said that the company is focusing first on fluid-based detection of cancers that are accessible through scoping, which he said has made it easier to design studies for marketing approvals.

An said that when he cofounded Genomictree in 2000, he saw the potential to use DNA microarrays to identify cancer-specific aberrant DNA methylation biomarkers that could form the foundation for better early cancer detection tests. In the company's early years, his team developed methods of capturing methylated DNA fragments using a truncated methyl-CpG-binding protein gene and identified methylation patterns characteristic of solid tumors. The firm began receiving cancer research grants from the South Korean government in 2004.

An said the company developed the EarlyTect BC test through that system of DNA microarray-based analysis, and company researchers determined that PENK methylation was common across almost all bladder cancer tumor tissue samples they examined and rare in patients without bladder cancer.

Genomictree went public on the Korean Securities Dealers Automated Quotations, or KOSDAQ, board in March 2019, a few months before the launch of EarlyTect C in South Korea. The company formed Promis Dx as its US branch in September 2019 and it has since established CLIA-certified, CAP-accredited laboratory facilities through that branch.

Through Promis Dx, An said the firm is pursuing premarket approval through the FDA as well as preparing to offer EarlyTect BC as a laboratory-developed test. The company also hopes to forge licensing deals or partnerships that could further help it commercialize its bladder cancer test in the US.

"It was difficult, but we fortunately selected, I think, a very good bladder cancer biomarker," An said.