Founders of biotech company MiRXES were working on the PCR technology well before Covid-19 struck
Apart from the terms ART, MCO, PPE and WFH plus many others, the Covid-19 pandemic has acquainted the world with the acronym of another medical term: Polymerase Chain Reaction (PCR) test. PCR tests are typically administered to detect genetic material from specific organisms, such as the Sars-Cov 2 virus.
Interestingly, Singapore’s very first lab equipped with PCR technologies was set up at the National University of Singapore (NUS) in 2000, well before the pandemic. Being the first in the region meant that many people were perplexed over what PCR tests could do. “Everybody was like, ‘this bunch of people are doing something called PCR. Anybody knows what it is?’,” Zhou Lihan, co-founder and CEO of biotech company MiRXES, recalled in a recent interview with The Edge Singapore.
The 39-year-old Zhou was then pursuing a doctorate in biochemistry and molecular biology at NUS. One of his first projects was to create a dengue PCR assay with his mentor Associate Professor Too Heng-Phon and collaborations with, pharmaceutical company Roche Diagnostics and the US National Institutes of Health (NIH).
The team wanted to create a more efficient way to test for dengue — a longstanding disease affecting tropical countries like Singapore and Brazil.
Improving and saving lives
While Zhou is not sure if the PCR assays are still in use, the process of creating them led him to a simple goal: to improve and save lives. This saw him, Too and Zou Ruiyang (now the co-founder and chief technology officer (CTO) of MiRXES) looking into a more efficient meth- od of detecting and possibly even curing other medical ailments.
When deciding on what disease to look into, Zhou says the trio did not feel like they needed to focus on another infectious disease. “A lot of other people could do it,” he explains, adding that they settled on the early detection of cancer, which is a more difficult problem to solve.
Traditionally, most cancers are detected through imaging techniques such as a CT scan or MRI. This is later confirmed by a hispathological examination of biopsied tissue, for symptomatic patients. Doctors use protein tumour markers to monitor a patient’s disease progression after symptoms occur. However, this process is not effective at detecting those with asymptomatic cancer, explains Zhou. The problem with this is that the cancer will only be detected at a later stage, meaning that the intervention would be late and treatment pre- scribed different.
Early detection is critical as it makes available a wider array of treatment options. The survival rate is also much higher at 95% for Stage 1 cancer, says Zhou. Earlier detection also means substantial cost savings, with Stage 1 patients paying about $30,000 while those with cancers detected at a later stage may have to spend half a million dollars for the latest cell therapy treatment. “Yet, often, the patients are alive for only about six to 24 months. So there’s a huge advantage in being able to detect the disease early,” stresses Zhou.
With these considerations, Zhou, Too and Zou started looking at microribonucleic acid or microRNA — the smallest strands of genetic material in the bloodstream. As these molecules play an integral role in cell function, any aberration in their quantities could indicate the presence of diseases such as cancer, even before the symptoms show up. The trio ventured into this in 2000 when most medical re- searchers were working on Deoxyribonucleic acid (DNA) which is a hereditary material in humans and almost all organisms.
Over the next decade or so, Zhou and his team developed what he calls “a good technology” that could detect RNA very well. The process also involved conducting a preliminary proof of concept that was able to see new dis- ease biomarkers in the blood.
During this time, the researchers transferred their operations from NUS to the Agency for Science and Technology Research (A*STAR) to tap on the agency’s downstream research capabilities as well as expertise in scalability and commercialisation.
four years of incubation under A*STAR, in 2014, the team spun off to form MiRXES. In 2016, Isaac Ho, joined MiRXES as an investor and adviser, and subsequently became Chief Investment Officer in 2018. “At that point, we had done enough proof of concept and we had matured the technology to the point where we were able to provide that as a product or service for research use to pharmaceutical companies and clinical groups,” explains Zhou.
Alleviating gastric cancer
MiRXES’ RNA research technology was first applied to GASTROClear — known to be the world’s first molecular diagnostic test kit for gastric cancer. While gastric cancer is the fifth most prevalent cancer in the world and the third most deadly one, very few researchers, especially those from the Western countries, were looking into it. “Gastric cancer is an ancient disease and is very prevalent in China, Japan, Korea, parts of Southeast Asia, parts of Eastern Europe and parts of South America. But it’s pretty low in Western Europe and the US so the big biotech companies will not focus on it since there aren’t enough patients in those regions,” explains Zhou.
The research by Zhou and his team led them to see that there is a strong microRNA signal circulating in the blood when a patient has gastric cancer. What this means is that the RNA molecules are secreted into the bloodstream — making it possible for detection. As such, MiREXS’ non-invasive GASTROClear test kit uses only a vial of blood sample and is said to complement other traditional diagnostic tools for gastric cancer. It can assess the quantities of 12 microRNA biomarkers, thus allowing for the detection of around 87% of gastric cancers. These include patients with high-grade dysplasia, more commonly known as stage 0 gastric cancer.
In developing the test kit, MiRXES worked closely with the Singapore Gastric Cancer Consortium and A*STAR’s Bioprocessing Technology Institute and Diagnostics Development Hub to conduct the world’s largest clinical trial for a microRNA blood test involving 5,248 patients. The successful outcome of the trial led GASTROClear to receive regulatory approval as a Class C medical device from Singapore’s Health Sciences Authority in 2019. The company is now conducting a clinical trial among 12,000 patients in hopes of having GASTROClear registered as a screening test administered by China’s Medical Product Association.
MiRXES now aims to improve the accuracy of its gastric cancer test kit to 92% and to also develop similar kits for lung, colorectal, liver, breast, pancreatic and ovarian cancers. The company is already able to detect cancer mutations such gastric cancer since the microRNA fragments are often already present in the blood. Against the advice of many, the company also made “a conscious decision” to build its own manufacturing plant in Singapore, instead of in China or Malaysia, where manufacturing costs are seemingly lower.
“They thought we were nuts. They asked us ‘why do you want to do that? And why do you want to do that in Singapore?’,” Zhou recalls. While the decision exhausted some 70% of the cash the company was holding at that time — it proved to be a wise one when Covid hit.
Zhou recalls that in February 2020 — some 10 days after Singapore reported its first Covid-19 case — MiRXES was approached by Tan Tock Seng Hospital (TTSH) and A*STAR to create 100,000 pairs of Covid-19 test kits. “At that point, we literally thought 100,000 tests should be okay,” says Zhou, basing his estimates on the 2003 Sars pandemic which subsided in six months.
However, with the Covid-19 pandemic worsening, Zhou and his team soon realised that the volume needed is way past 100,000. Furthermore, very few countries had Covid-19 test kits in the initial days.
MiRXES rose to the challenge. In February 2020, the company had lifted its production to 100,000 kits a week. At its peak in 2020, the company was operating at 16 hours a day, seven days a week so it could produce 1 million test kits in a week. More recently, MiRXES has set up a new manufacturing facility where it can manufacture test kits for an array of cancers and infectious diseases. With this, its output has now quadrupled. The company also has a stockpile 1 to 2 million test kits, that can shipped out whenever needed. From a dire shortage at the start of the pandemic, Singapore now has enough test kits not only for its own use but to also export to friends overseas, says Zhou.
The company’s efforts saw it logging $61.6 million in revenue for the year ended Dec 31, 2020, 17 times the $3.6 million it recorded a year earlier. Singapore is MiRXES’ largest market, making 66.1% or over $40.7 million of revenue. Indonesia is its next largest contributor at 11 %. Zhou reckons the company is in a “good position” to acquire smaller companies in the preventive healthcare space. He is hoping to beef up MiRXES’ digital and physical infrastructure so that home-testing could one day be a possibility.
When asked if he has any plans to list, Zhou chuckles and says he is “open to various options”. He quips that he is studying the options presented by the US, Hong Kong and Singapore Exchanges. For now, he is looking to raise funds again sometime next year so that MiRXES is in good stead for its R&D, commercialisation and M&A.
Aside from having a strong brand name and stable financials, MiRXES has another thing to be proud of: winning the EY Entrepreneur of the Year award for the Biotechnology sector, and being the overall winner for Singapore. For Zhou, his team’s win is also recognition for Singapore’s biotechnology sector as a whole. “It's a recognition of the maturation of the ecosystem, which started 20 years ago. We hope to use this opportunity to articulate preventive healthcare,” stresses Zhou.
Cover image of Zhou Lihan: Albert Chua/The Edge Singapore
