NEW YORK – After changing its name this summer, Helio Health (formerly Laboratory for Advanced Medicine) now aims to validate its circulating tumor DNA (ctDNA)-based hepatocellular carcinoma (HCC) screening assay by comparing it to standard ultrasound screening with the US launch of a multi-center collaboration.
The Irvine, California-based firm also hopes to raise more than $100 million in a funding round by the end of the year to launch its liver test in the US and China in 2021, as well as to further develop assays for colon, breast, and lung cancers.
To screen for liver cancer, clinicians typically use methods such as imaging tests, MRIs, and ultrasound exams on patients at risk for the disease. However, several challenges hinder these screening methods, including poor sensitivities and poor diagnostic results for obese patients.
"With the increase of non-alcoholic fatty liver disease and obesity, which is a risk factor, [ultrasound detection] is becoming increasingly challenging," Kenneth Chahine, CEO of Helio Health, explained. "It is [also] inconvenient versus a simple blood draw, [which] doesn't require specially skilled healthcare providers."
Helio Health believes its liquid biopsy assay, which it refers to as the "Helio Liver Test," will be able to non-invasively screen for early-stage liver cancer before ultrasound and other methods identify the disease.
After collecting a 10-ml tube of a patient's blood sample, the firm extracts cfDNA and performs a bisulfate conversion step to differentiate unmethylated versus methylated cytosines. The firm then runs the purified sample on an Illumina next-generation sequencing (NGS) instrument to detect the methylation sites.
Helio Health also performs enzyme-linked immunosorbent assays (ELISA) to identify protein biomarkers linked to tumors of specific cancers, such as liver cancer.
"We haven't disclosed all the proteins we're using, but we're looking at molecules like alpha fetal protein, which is a well-known marker for liver cancer," Chahine said. "Those markers have been known for a while and are good for prediction, but not enough for [cancer] screening."
By combining methylation data, protein biomarkers, and a patient's demographic information into a patented algorithm, Helio Health's assay aims to determine whether the patient has early-stage hepatocellular carcinoma.
"We've been primarily doing methylation, but we've begun [exploring] a multiple analyte approach as well," Chahine said. "Our thinking is that while methylation works quite well, there are things out there known to help with diagnosis that we're more than willing to process."
Chahine said the current version of the Helio Liver Test can produce screening results for liver cancer in one to two days.
While Helio Health's platform initially applied PCR-based cfDNA methylation, Chahine said his team is moving to NGS because PCR has a fixed number of samples per run. In contrast, he noted that NGS reduces the cost per sample and "allows for economies of scale."
Originally offering a noninvasive, multi-analyte, laboratory-developed epigenetic test called IvyGene, Helio Health has discontinued the assay and instead will commercialize the Helio Liver Test for the US and Chinese markets.
Validation trials
In the firm's recently announced FAST-MRI prospective trial, Bachir Taouli, a professor of diagnostic, molecular, and interventional radiology at the Icahn School of Medicine at Mount Sinai and his team aim to identify and further validate sensitive methylation markers of HCC. The group will enroll more than 820 patients with liver cirrhosis and thus at risk for developing liver cancer.
"We would like to demonstrate the added value of the Helio Liver Test, a blood test utilizing circulating tumor DNA and other analytes, for HCC screening," Taouli explained in an email. "We are also hoping to demonstrate that abbreviated MRI performs better than ultrasound for HCC screening, and that it is cost effective."
Chahine noted that the University of California, San Diego, the University of Washington, and Duke University Medical Center are also participating in the cross-sectional trial.
While Taouli and his colleagues will assess different types of MRIs to observe what methods they could use to identify potential markers of early-stage liver cancer, Chahine said that they will also compare the performance of Helio Health's assay to abbreviated MRI and ultrasound for liver cancer detection.
Helio Health is also engaged in two separate projects with US and Chinese academic collaborators to validate the Helio Liver Test.
In the US prospective trial, dubbed the "Clinical Trial to Detect Liver Cancer through Quantification of ctDNA Methylation in Blood Samples" (CLIMB), Helio Health has partnered with researchers to validate its liver test on individuals at high risk for liver cancer. The researchers will then compare the assay's results to ultrasound results to demonstrate the assay's potential superiority.
Richard Van Etten, lead investigator of CLIMB, expects the trial will demonstrate the advantages of the Helio Liver Test over ultrasound for detection of HCC in cirrhosis patients.
"In the US, the racial [and] ethnic background of cirrhosis patients and the etiology of the cirrhosis is more diverse than in China, where much of the epigenetic biomarker discovery [for the project] was done," Van Etten, a professor of medicine and biological chemistry in the School of Medicine at the University of California, Irvine, explained in an email. "We are monitoring the effect of this variance on the endpoints of the trial … [but] may experience some delays in obtaining MRI scans for some centers."
The team has so far enrolled 500 of 800 high-risk patients and anticipates releasing the results of the trial by early next year.
"The CLIMB trial represents the first of its kind as a prospective trial to assess a blood test based on DNA methylation to diagnose cancer," Van Etten added. "This technology has the potential to change the entire paradigm around early cancer diagnosis for cancers where early detection is essential for curative interventions."
In a second multi-center trial, called "Evaluate Methylation Markers for Detection of Liver Cancer Study" (VICTORY), Helio Health partnered with Chinese collaborators to validate the Helio Liver Test in a cohort of about 1,100 patients with varying cancer-related conditions: examining individuals with stage I, II, III, and IV HCC; distinguishing between patients with non-alcoholic fatty tissue disease, cirrhosis, chronic hepatitis, and liver cancer; distinguishing between liver and other cancers (i.e. lung, colon, and breast cancer); and validating the test on a healthy, non-cancerous patient cohort.
Initially launched in February 2019, the VICTORY trial involves collaborators from the Sun Yat-Sen Cancer Center in Guangzhou, First Affiliate Hospital of Guangzhou Medical University in Guangzhou, and General Hospital of PLA Beijing.
While the team aimed to complete the initial project in less than a year, Chahine noted that it faced a four-month delay due to the COVID-19 pandemic. The researchers finished the VICTORY trial in the summer and anticipate publishing the study later this year.
In addition to the multiple ongoing and recently completed projects, Helio Health aims to raise $100 million in funding by the end of the year. Chahine said that the firm will primarily use the proceeds to launch the Helio Liver Test in the US and Chinese markets, as well as to develop additional assays for colon, breast, and lung cancers.
Helio Health has been issued four patents by the US Patent and Trademark Office for its methylation-based approach. Following the publication of the CLIMB study results, the firm expects to initially launch its liver cancer assay as a laboratory-developed test in early 2021.
Rebrand motivation
Chahine said that the firm rebranded as Helio Health earlier this year to appear more customer friendly as it expands into the competitive liquid biopsy space. The firm also fleshed out its management team by hiring members outside the cancer space.
"As we move toward commercialization with a new, energized team, we felt that 'Laboratory for Advanced Medicine' was too clinical, and we wanted to reflect the holistic nature of a multi-analyte test and the actionable information it provides to patients," Chahine explained. "We see [the name] as the centerpiece to health and wellness."
While declining to share the potential price of its envisioned liquid biopsy assays, Chahine said the firm aims to drive the overall costs of cancer testing down and offer an affordable test that "can go out there and penetrate the market aggressively". He highlighted that the cancer market is enormous because it a "repeat business," where people at risk of developing the disease may test negative one day but return and find that they are positive later.
"In the US, there are roughly five to six million people with liver disease and high risk of liver cancer, and in China, there's at least eighty million patients with hepatitis B, a well-known high-risk precursor to liver cancer," Chahine said. "With the liver cancer market … it's one cancer that's really increasing due to NASH and other issues like non-alcoholic fatty disease."
Acknowledging that several US groups are applying methylation and other liquid biopsy methods to identify a variety of cancers in a patient's blood sample, Chahine noted that few players are actively pursuing early-stage liver cancer using methylation. One is Exact Sciences, which has previously explored liver cancer detection via methylation and protein biomarkers, and acquired pan-cancer liquid biopsy test developer Thrive Earlier Detection earlier this week.
Researchers at the University of California, Los Angeles have launched a startup called Early Diagnostics to commercialize a methylation pattern that tracks DNA methylation patters of ctDNA in HCC. Another group at UCLA is separately developing an extracellular vesicle (EV)-based method called "EV Click Chip" — which uses a custom microfluidic chip that integrates nanowires and a network of microchannels — to detect early-stage HCC.