
With the right kind of diagnostics tests, check-ups could be administered more often to at-risk populations and cancers caught and treated earlier.
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Cancer could become a chronic condition rather than a terminal sentence with the right diagnostic tools, says Sidney Yee, CEO of the almost four-year-old Diagnostics Development (DxD) Hub, a national initiative led by A*STAR’s commercialization arm, ETPL. “I strongly believe the key to managing oncology is early detection. And, if we can make minimally invasive or non-invasive tests, it’s convenient, which means people can test more frequently if they have a high-risk profile.” Sometimes, however, research that could make this possible isn’t making it to doctors and patients.
Founded in 2014, the DxD Hub’s role is to accelerate the process of taking diagnostic devices to market. The hub was seeded as part of the Singaporean government’s Innovation Cluster Programme, and its work covers a number of key areas: to make sure that researchers with intellectual property, or ‘IP’, connect with the right business partners; to test their findings to make sure they are clinically reproducible; to design application devices that meet regulatory standards; to look for pain points in the adoption of a diagnostics tool; and, to mine data from Singaporean research spanning the last two decades for insights that could be turned into useful diagnostic tests.
“We don’t do any of the research,” says Yee. “Instead we develop already existing IPs that have sufficient evidence to support diagnostic use, meet clinical needs, and have a market demand. The output of that co-development is actually a regulatory dossier that goes to the government regulatory authorities for approval.”
Making better diagnostic tools for gastric cancer
One of the DxD Hub’s first diagnostic tools to jump the regulatory hurdles is a genome liquid biopsy test (i.e. a test taken from a blood sample) for the early detection of gastric cancer. Gastric cancer, which kills more than 700,000 people worldwide each year, is currently only detectable via an uncomfortable inspection using a long tube called a gastroscope.
“It is expensive and invasive for people with a high-risk profile to be doing these scope tests all the time. Some countries like Japan and Korea, with among some of the highest rates of gastric cancer in the world, hugely subsidize scope tests for at-risk parts of the population, yet we still see gastric cancers that are detected late,” Yee says.

Endoscopy tests done with a scope, or similar tests for gastric cancers done with gastroscopes, are uncomfortable and expensive tests that stop at-risk populations from being tested more often.
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Cutting-edge research is revealing that many microRNA levels change during disease and, as they become accessible via blood tests, they make good diagnostics biomarkers.
The genome liquid biopsy test sprang from a microRNA platform that A*STAR and the National University of Singapore had been developing for some years. DxD Hub led the miRNA development platform and partnered with commercial cancer diagnostic company MiRXES, an early Hub collaborator and a spin-off company from A*STAR’s Bioprocessing Technology Institute, on a liquid biopsy early detection test for gastric cancer, or GastroClear. DxD Hub’s productisation effort led to the approval of GastroClear for the European market (32 countries) and the collaboration hopes to introduce the test to the Singapore market by the end of 2018.
The DxD Hub’s framework means it invests in diagnostics all the way to the market stage. “My job is not finished when something gets regulatory approval. I also have to make sure that it reaches its intended patients,” Yee says. This, as well as an accessible and standardized legal framework for sharing IP, signals to commercial partners that their initial input will quickly result in something useful to the market. From a national perspective, she says, that’s an ideal outcome: “If research doesn’t change clinical practice, it’s probably not going to make any difference to patients.”
From her experience as both the DxD Hub’s CEO and an executive vice president at the ETPL, Yee observes that while scientific creators of IP possess technological know-how, there is little awareness of how to turn that technology into a product.
“DxD is a high-throughput engine to help startups and researchers develop diagnostic tests. Those startups may then later translate IP on their own or they can continue to work with us. So, the DxD Hub will have a multiplier effect too.” Yee notes that it is often not appreciated that IP translation is an industrialized process that produces regulated diagnostics solutions, and requires the careful integration of biology, engineering and technology platforms. The hope is to educate and train people on how to translate research into new commercial products in companies all over Singapore, she says.

Alrik Tan doing tests at the DxD Hub.
© Courtesy ETPL
While the DxD Hub is led by A*STAR’s ETPL, it is a nationally funded program and many of its projects also come from external parties. Oncology diagnostics is currently its biggest portfolio, followed by cardiovascular and infectious diseases, metabolic diseases and neurological disorders. Currently, the hub is actively working on 25 diagnostic projects.
The DxD Hub is careful to select the right projects and to keep their attrition rates in line with industry. The hub is in the preliminary stages of assessing over 400 different projects, with a projected attrition rate of approximately 90 to 95 per cent. That’s roughly the same as commercial industry, Yee says.
Of these 400, a subset with evidence to answer specific diagnostic questions will be identified (at the moment the subset stands at about 150 projects), which will then be examined from a business development standpoint. At any one time, DxD Hub will be in discussions with potential business partners on 40 to 50 of the projects.
Asian research coming of age and ready for translation
With the acceleration of genomics and technology, Asian research as a whole is turning its attention to translation. There is currently a market of 700 million people or more people in the ASEAN region who are starting to spend as much, if not more, per head on medicine as their western counterparts. “We’re also getting more information on how the Asian phenotype is unique and different, and so everything is coming together at a time when it’s not just information we need, but also actionable information,” Yee says. Singapore has been investing in biomedical research and engineering for many years. It will serve them well, she says, as clinical solutions customized for Asian populations become much more important to markets. “We were always developing healthcare solutions for a global population, but not really paying attention to the differences in the different populations. Now we need to look at solutions for Asian populations more specifically.” The idea of personalized medicine like this is not new, she says, but it’s only now possible because technologies like deep learning are converging with genomics.

Many researchers are looking into liquid biopsies, which detect DNA and RNA fragments in the blood. These can be used to more easily diagnose cancers.
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The DxD Hub is very well placed geographically to use existing Asian data to look for these solutions. And, it has already found some of its ideas for diagnostic tools, such as the gastric cancer test or staging and differentiating liver fibrosis for better treatment outcomes, in pre-existing A*STAR research. “We don’t do discovery of any genetic biomarkers or protein biomarkers, instead our job is to mine what has already been done in the ecosystem,” Yee says. The hub also hopes to curate existing data so that artificial intelligence (AI) is better able to deliver personal and multimodal healthcare solutions – a process that Yee calls “digital diagnostics”.
“To do digital diagnostics, we need a lot of correlated and curated data. It would take us years to gather the data if we started from zero. So, we’re looking back at what we’ve already done.” Over the last few decades, Yee says, Singapore has invested heavily in medical research. “Now is the time to harvest tangible results.”
The A*STAR-affiliated researchers contributing to this research are from the Diagnostics Development (DxD) Hub, a national initiative led by A*STAR’s commercialization arm, Exploit Technologies Pte Ltd (ETPL).