SAN FRANCISCO (GenomeWeb) – Hong Kong startup Take2 Health, which said on Monday that it had licensed intellectual property from Grail to develop a noninvasive early detection test for nasopharyngeal carcinoma, aims to launch its first test in Hong Kong and parts of southern China within the next several months, according to cofounder Dennis Lo.
The test will be based on methods for analyzing cell-free DNA that were originally developed by Lo, a professor of medicine and chemical pathology at the Chinese University of Hong Kong, and cofounders Rossa Chiu and Allen Chan, who are also professors at CUHK.
Grail acquired the rights to the IP surrounding the NPC test when it merged with startup Cirina, which Lo founded in 2014 to focus on developing noninvasive screening tests for early cancer detection. Grail had planned to commercialize and launch an NPC test in Hong Kong last year but ultimately put those plans on hold.
Now, the CUHK team, through Take2, has re-acquired the IP for the NPC test. Lo said that he will remain on Grail's scientific advisory board and that Grail will also retain rights to other IP around cancer detection that it had acquired from Cirina when the companies merged. Take2 will focus initially on early detection of NPC, Lo said, but will eventually broaden its scope to "healthcare informatics" more generally.
Lo declined to disclose further details about the license agreement with Grail.
Currently, Take2 is self-funded by its three founders, he said, but will ultimately seek financing from outside investors, although he did not specify a timeline.
Originally, the CUHK team had developed a PCR-based technology to screen blood samples for Epstein Barr virus, which is strongly associated with NPC, describing the test's performance in a 20,000-person study published in the New England Journal of Medicine in 2017. However, Lo said, for that test to be accurate, it had to be run at two different time points, where if a first test was positive, a second test would be run on a different date and only if that test was also positive, the patient would be referred for diagnostic testing. Because the strategy of testing patients at two different time points was not ideal, Lo said, the team continued to work on the technology to try and improve it. In a second study, the researchers demonstrated that for cases positive for Epstein Barr virus via PCR, using a sequencing-based strategy performed at the same time as a reflex test could improve the positive predictive value to around 20 percent from 11 percent, while reducing the need for testing to be done on two different days.
This second-generation version of the test uses a cell-free DNA sequencing strategy that targets the Epstein Barr virus. While some individuals can harbor the virus even when they don't have cancer, the CUHK team previously found that those with cancer tend to have a higher viral load and also that there were differences in the size of the viral DNA in people with and without cancer.
Take2 is also working to develop a third-generation version of the test, Lo said, that will incorporate other features of cell-free DNA to further improve its accuracy and to eventually enable it to be a population screening test.
Lo said the team had not yet settled on a specific strategy for the third generation, but noted that the CUHK team previously published studies usingmethods that take advantage of fragmentation patterns of cell-free DNA and methylation differences. Most recently, it published a study in Genome Research showing that differentially phased cell-free DNA molecules can also provide insight into the molecules' tissue of origin.
Lo declined to disclose what features the third generation of the test would incorporate.
Lo said that recent government and regulatory changes in China also made the timing right for launching Take2. The Chinese government recently launched an initiative to form what it is calling the Guangdong-Hong Kong-Macau Greater Bay Area. That will essentially accord special status to 11 cities, including 9 in southern mainland China, as well as Hong Kong and Macau, so that the regions are more economically and scientifically integrated, Lo said.
"Previously, it would have been very difficult to have samples and data cross the border between Hong Kong and mainland China," Lo said, but the new framework will allow for that. This will facilitate large clinical studies and will also expand Take2's potential market to 70 million people, he added.
Lo said that the test will initially be offered to those considered at highest risk, men between the ages of 40 and 60, and will be primarily a self-pay test. But as the team continues to work on improving the test and increasing its PPV, it could be extended to those at average risk.
Early diagnosis of NPC is important because when diagnosed at stage 1, long-term survival is close to 90 percent, Lo said, while the survival rate drops to below 60 percent when it is diagnosed at later stages.
Eventually, Take2 plans to expand its NPC test beyond Hong Kong and southern China to other areas of southeast Asia, he said, including Indonesia and Malaysia, which also have higher incident rates of the cancer compared to other countries.
In addition, while the company's current focus is on commercializing its NPC early detection test, he is ultimately looking to position Take2 as a health informatics company. "We want to provide empowering information in an actionable and timely manner," Lo said, "first with NPC and then [relating] to other aspects of healthcare."