MiRXES, an A*STAR spin-off, has developed the world's first miRNA-based diagnostic tool for gastric cancer.

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Leading the way in microRNA technology

21 May 2020

After a decade of research and innovation, homegrown biotech company MiRXES can now call themselves a global leader in developing microRNA-based technology to solve real-world issues.

While detecting any disease early can save lives, this is especially true when it comes to cancer. When cancer is caught early enough, patient survival rates and quality of life can be vastly improved. Early diagnosis also opens up more treatment options for patients, which can be key for beating the disease.

A good example of this is gastric cancer, which has a notoriously poor prognosis and is a leading cause of cancer deaths worldwide due to its tendency to produce significant symptoms only at an advanced stage. However, an early gastric cancer detection test is now on the horizon and the key lies in an unexpected source: microRNA, or miRNA for short.

Once thought to be nothing more than ‘junk’ genetic material, miRNAs are now recognized as central gene regulators and show promise as biomarkers when used as part of early disease diagnostic tools. In response to diseases like cancer, miRNA combinations and their individual amounts can change, leaving a detectable signature. This particular characteristic has led to companies developing ways to harness miRNA signatures as biomarkers for tracking and diagnosing diseases.

One such company is MiRXES, a homegrown A*STAR spin-off led by academics turned self-described ‘accidental entrepreneurs.’ Although starting in the then relatively understudied field of miRNA was challenging, MiRXES has since gone on to champion the development of miRNA-based research and technology, including launching the world’s first miRNA-based diagnostic tool for gastric cancer.

“It was the culmination of almost eight years of work in collaboration with the Singapore Gastric Cancer Consortium and the Diagnostics Development (DxD) Hub of A*STAR,” says Dr Lihan Zhou, Co-founder and CEO of MiRXES. With their expertise in miRNA, MiRXES was perfectly poised to respond to the COVID-19 pandemic, which is caused by an RNA virus, SARS-CoV-2. Building on a test developed at A*STAR and validated by Tan Tock Seng Hospital, MiRXES has scaled up production of the Fortitude Kit 2.0 to 300,000 kits a week, meeting Singapore’s testing needs and beyond.

Here, Zhou shares how the company got its start, the difficulties of pioneering miRNA research, and his hopes of establishing Singapore at the forefront of the global miRNA industry.

1. What motivated you to co-found MiRXES?

As miRNA began gaining steam in mainstream research, my co-founders and I started to explore the clinical relevance of miRNA in many disease areas. While I was a Research Scientist at the A*STAR Bioprocessing Technology Institute (BTI) in 2012, we showed conclusively that our technology could detect blood-based miRNA biomarkers with unprecedented sensitivity, enabling us to detect subtle signals released by early-stage cancer cells even before clinical symptoms became apparent. The desire to translate this discovery to clinical applications inspired us to found MiRXES in 2014 as a spin-off from A*STAR.

This motivation still drives our biotech start-up today. Though we are very much motivated by scientific curiosity and innovation, we don’t just carry out research and develop products for the sake of generating knowledge or proving our capabilities. Instead, we work with the clear goal of developing practical miRNA-based applications that will solve real-world problems, improve healthcare and save lives.

2. What is the core technology of MiRXES? Could you describe how it works?

The development of diseases can be tracked through miRNA signatures, which are specific changes in the quantities of certain combinations of miRNAs. MiRXES’ core technology is a quantitative reverse transcription polymerase chain reaction (qRT-PCR) platform that can accurately and robustly detect miRNA signatures from biological fluids like blood, urine and even tears, paving the way for non-invasive liquid biopsy tests for diagnosis and monitoring of diseases.

Because our technology is built on a patented method of designing unique qRT-PCR primers that can detect and amplify miRNAs sensitively, specifically and reproducibly, our method is also more reliable than other commercially available technologies. In addition, our expertise also extends to the formulation of reagents and design of workflows that are optimized for miRNA biomarker and therapeutic candidate discovery.

3. What would you say has been MiRXES' biggest achievement since its founding in 2014?

There are many. But if I had to choose one, it would be receiving approval from the Health Sciences Authority of Singapore in 2019 for GASTROClear, the world’s first in vitro diagnostic solution for early detection for gastric cancer. With this regulatory approval, MiRXES successfully brought a miRNA-based application from research, product development and manufacturing through to clinical translation and commercialization.

With this first successful application of our core technology, we look forward to working with other partners to develop more game-changing applications that will improve and save lives. In the pipeline are clinical assays for other cancers including lung and breast cancer, as well as other diseases such as pulmonary hypertension.

Beyond that, we started a series of initiatives in 2020 that aims to pave the way for wider clinical validation and adoption of miRNA-based diagnostics at a global level. We hope our work will also continue to help put Singapore at the forefront of the global miRNA industry.

4. What were some of the key challenges in creating your technology and how did you overcome them?

The challenges we faced in creating the qPCR technology behind our miRNA detection platform were no different from those that all researchers face on a daily basis. We took an idea that nobody knew would work, carried out lots of experiments that failed, and learned from each failure. When we finally succeeded in proving the concept, we repeated the experiment multiple times to convince ourselves that we were not crazy. Even to this day, we continue to work hard in the lab, carrying out thousands of qPCR reactions each day to continually optimize our technology.

5. How did A*STAR support your journey from scientist to entrepreneur?

When we first started working on miRNAs in 2010, few scientists knew what they were, and many of those who did thought they were ‘junk’ RNAs since they do not code for proteins. At the time, very little was understood about miRNA’s role as a master regulator of gene expression. So one of the key hurdles we had to overcome was to convince scientists, clinicians, regulators and investors that miRNAs were, in fact, important biomarkers for detecting diseases and could have other uses.

In addition, few researchers and companies were exploring miRNAs as potential biomarkers for in vitro diagnostic applications so there were no ready tools and processes that we could adopt to develop a commercial miRNA-based test kit. We had to develop a lot of these tools and processes ourselves and even build our own manufacturing capability because there was no way we could have outsourced this and still remain confident in the quality of the product. In short, we had to do a lot of experimentation and build capabilities from scratch over the years. We made lots of mistakes but also learned a lot from our experience. We were fortunate to have the DxD Hub as a partner since 2014 in developing these tools and capabilities.

Finally, because GASTROClear was the first miRNA-based diagnostic test to seek regulatory approval in Singapore, there were no established standards and procedures to follow. We had to work closely with A*STAR’s commercialization arm, Exploit Technologies (now A*ccelerate), DxD Hub and the Health Sciences Authority to understand the requirements for regulatory approval.

6. What are some of your future goals for MiRXES?

We are positioning MiRXES as an RNA-focused platform technology company that develops transformative products for health, disease and industrial applications. We will continue to build and optimize our end-to-end capabilities to enable the discovery of novel biology and the development of quality yet affordable products.

While we still have a lot of work to do to prove the clinical utility and the health economics of GASTROClear, we are working with partners globally to undertake a 20,000-strong lung cancer miRNA study to demonstrate the performance of miRNA biomarkers for the early detection of lung cancer. This is part of our long-term effort in eradicating late diagnoses in cancer and other disease cases.

Beyond technology and products, MiRXES is also actively shaping the human aspect of our business. I have thoroughly enjoyed the journey of starting and growing with MiRXES. I hope we can continue to forge an open and innovative environment where we can develop ourselves and have fun while growing the business globally.

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This article was made for A*STAR Research by Wildtype Media Group