NEW YORK – After raising $55 million earlier this week, Israeli molecular diagnostic firm Nucleix is eager to push further into the lung cancer diagnostics space by identifying new biomarkers and validating its methylation-based lung cancer assay.
The Rehovot-based company also expects to receive 510(k) clearance from the US Food and Drug Administration for its Bladder EpiCheck assay later this year.
Nucleix's EpiCheck platform searches for tissue-specific methylation patterns on circulating tumor DNA (ctDNA) in a liquid sample, specifically blood and urine.
After extracting ctDNA from a sample, EpiCheck digests it using methylation-sensitive enzymes, followed by processing on a real-time PCR instrument. The platform then evaluates the result using its EpiCheck software, generating a numerical score (EpiScore) between 0 and 100 using relative methylation levels across the test's markers. If the score is equal to or above a certain threshold, the sample is viewed as positive for cancer.
Nucleix CEO Chris Hibberd noted that the firm has spent the past year improving EpiCheck by developing a next-generation sequencing (NGS) version of the platform. He said that NGS allows the firm to identify new lung cancer-linked methylation and other potential biomarkers in a blood sample.
Nucleix is currently using Illumina's sequencing instruments for the NGS assay, but Hibberd said that the assay is flexible enough to run on other instruments. The PCR version of the assay, which identifies up to six methylation biomarkers in a patient's blood sample, can run on Qiagen's RotoGene-Q and Thermo Fisher Scientific's ABI 7500 instrument.
"We're looking [to build] a version 3 [of Lung EpiCheck] that brings these improvements together, along with substantial validation efforts like the additional methylation biomarkers," Hibberd said. "The question is whether we can find one to two more methylation markers … to add to the assay."
Nucleix published a study in October in the European Respiratory Journal that highlighted Lung EpiCheck's ability to diagnose different stages of lung cancer. Using cohorts of European and Chinese lung cancer patients, the team found that Lung EpiCheck had 87 percent sensitivity and 64 percent specificity across all lung cancer stages. The test produced 78 percent sensitivity and 64 percent specificity for stage I NSCLC.
The firm has also begun a multi-year prospective study with undisclosed clinical partners to validate the assay on a cohort of heavy smokers that it will monitor over time for lung cancer. While the initial group for CTC screening included patients 55 years and older who smoke 30 packs a year, Hibberd said that the US Preventative Services Task Force updated its recommended guidelines in March to include smokers above 50 who smoke 20 packs a year.
"That effectively doubled the number of patients that were available for screening in our study," Hibberd added. His team now aims to monitor between 3,500 and 7,500 patients during the first phase of the study.
Nucleix plans to look at several different lung cancer subtypes in smokers enrolled in the study. Specifically, Hibberd said that the firm will target subtypes that are "rapidly growing" and are "often deadly," such as small cell lung cancer and NSCLC. His team will enroll patients over the course of 2021 and continue the trial following conversations with the FDA.
Following the completion of the new validation study for Lung EpiCheck, Nucleix aims to file for 510(k) clearance.
Hibberd highlighted that Nucleix has also built a new lab in San Diego. The firm expects to receive CLIA certification within the next couple of weeks, followed by CAP accreditation later this year. The firm hopes to eventually offer a research-use-only version of the Lung EpiCheck assay in 2022, with an estimated price tag of $250 per test. The firm had previously planned to launch the laboratory-developed test by this summer.
While Hibberd declined to provide details about the RUO service, he said that users can expect to receive results "within a few days."
Nucleix also has filed a 510(k) submission with the FDA for the Bladder EpiCheck assay, which analyzes 15 methylation biomarkers for bladder recurrence, following the completion of an unpublished multicenter validation study last fall.
While Hibberd acknowledged that the FDA response has been slowed due to the COVID-19 pandemic, Nucleix expects to hear back in the next couple of months. The firm is also looking for commercial partners to expand Bladder EpiCheck's presence in the US after it receives clearance and anticipates working with a commercial partner to offer the kitted version of the test.
Liquid biopsy firms besides Nucleix like Grail and Guardant Health are also developing or offer methylation-based assays to detect early-stage cancers such as lung cancer. Hibberd believes that EpiCheck stands out from typical methylation-based methods because its proprietary enzymatic-based approach avoids destruction of starting genetic material and has low background noise.
"Previous discovery work suffered from a harsh treatment step and only evaluated a limited number of methylation sites," Hibberd said. "Using our technology and NGS ... we are surveying a broader array of sites with a clean enzymatic approach."
Outside the US, Nucleix currently offers the Bladder EpiCheck assay as a CE-marked and commercially launched test in Europe, and it is currently evaluating the best time for a CE mark for the Lung EpiCheck assay. He also noted that the firm is looking at potential commercialization partners for both assays in China.