In brief

In this Q&A feature, BTI Senior Scientist Sean Keng Rui Chia reflects on his journey into biotherapeutics development and how his current work can lead to innovative drug discoveries.

© A*STAR Research

To bring biologics to life

11 Mar 2024

Taking lessons from an eye-opening stint in industry, Sean Chia is tackling the challenges of biotherapeutics manufacturing to help bring game-changing antibody treatments to more patients.

They quench the fires of inflamed joints; they latch onto stealthy tumours, marking them out for our body’s defenders to destroy. Whether they’re boosting immune systems against cancer or suppressing them in rheumatoid arthritis, biotherapeutic products have transformed the way we treat many diseases, improving lives across the world.

Also known as biologics, biotherapeutics are a class of medicines based on organic molecules made by living cells. Ranging from hormones to antibodies, biotherapeutics can be more effective than traditional small-molecule drugs as they’re designed to bind to specific disease-related targets without hitting unintended pathways along the way.

However, efficacy isn’t the only factor behind a drug’s clinical success, or developability. Two others are key: its safety for use in humans, and its manufacturability at an industrial scale. However, the same molecular complexity that makes biotherapeutics effective treatments can often also make them more fragile and expensive to produce compared to the simple chemical compounds of small-molecule drugs.

Among those tackling this issue are researchers like Sean Chia, a Senior Scientist at A*STAR’s Bioprocessing Technology Institute (BTI). During his PhD studies, Chia studied the aggregation of amyloid-beta (Aβ) peptides: proteins linked to the progression of Alzheimer’s disease. Moving from academia to industry, Chia worked on drug development for protein misfolding-related diseases in a biotech company before joining BTI, where he is developing new analytic tools to study biotherapeutic developability. In 2022, Chia was awarded the Singapore Biodesign (SB) Innovation Fellowship and dove into the field of health technology innovation.

In this interview with A*STAR Research, Chia shares his reflections on the diverse experiences in his scientific journey, their influence on his current research, and the promise of biotherapeutics for future innovation in Singapore.

What sparked your interest in biotherapeutics?

My PhD degree was focused on understanding the biophysical principles behind protein misfolding and aggregation in the context of human diseases, such as neurodegenerative conditions. From there, I was keen to explore the other problems that these concepts could be applied to.

As it turned out, I found that biotherapeutics development was one such relevant area. It’s fascinating to learn about how protein structures that cause disease, and those that treat disease, share some of the same fundamental principles, yet differ greatly in other aspects.

For me, what adds to the fascination of biotherapeutics development is how it’s an ever-evolving area that operates right at the intersection between basic and applied research. You get to learn a lot of things beyond scientific discoveries!

Tell us more about your current work at A*STAR.

A big challenge in manufacturing biotherapeutics, such as antibodies, is that their structures haven’t naturally evolved to endure the stressful conditions that occur in industrial production. As a result, they often destabilise during the production process, causing unwanted protein aggregation—an effect where proteins unfold and tangle together into clusters, causing efficacy and safety issues.

At BTI, we’re studying the developability properties—such as the specificity and aggregation propensity—of next-generation antibody therapeutics like multispecific antibodies. As part of this work, we design new assays and computational models to assess these therapeutic molecules and optimise their properties.

I find this project particularly exciting as it requires an interdisciplinary approach to effectively tackle what is currently one of the biggest challenges faced in the field. I am fortunate to be collaborating with a talented group of experts; we hope to contribute to the development of faster and more efficient drug discovery processes.

What motivated the different endeavours in your scientific journey?

I am a firm believer that science and research are multifaceted. Hence, I was curious to understand it in different contexts, such as in academia and industry. I am thankful for these experiences, as they really helped me develop a diverse skillset and a broader appreciation for research.

How has your time in industry shaped your approach to research?

I think that my exposure to the fast-paced environment of a biotech startup has instilled a sense of practicality in my approach to research. I tend to have a more pragmatic perspective nowadays, as I’ve learnt to focus not only on identifying theoretical solutions, but also on figuring out how they can be practically translated to real-world applications. My exposure to the business side of science has also made me more aware of the complexities involved when trying to materialise relevant solutions for commercial purposes.

Tell us about your experiences as an SB Innovation Fellow.

I was interested in the fellowship as I wanted to acquaint myself with health and medtech innovation, as well as gain a more general understanding of startups within the ecosystem.

One of the biggest takeaways for me was learning about the business aspects of health and medtech, such as market sizing, intellectual property and regulatory affairs. It was also a fantastic experience to work with and learn from my fellow team of clinicians and the SB mentors, who helped nurture a collaborative and entrepreneurial mindset, and defined my experience in the SB fellowship.

How might your work advance Singapore's biotherapeutics capabilities?

With the recent emergence of novel therapeutic modalities, there’s a need to evolve our current approaches accordingly so as to characterise these agents and determine how to develop them further.

I hope our research in analytical development that is targeted specifically towards these new molecules will allow us to contribute to Singapore’s growing biomedical manufacturing industry. In particular, we hope to attract biopharmaceutical companies to further their R&D and manufacturing activities here in partnership with us.

What’s your advice for scientists aiming for real-world impacts?

Identifying problem statements and market needs are a crucial aspect of developing real-world solutions. To tackle a specific problem in a field, it’s important to identify what exactly the relevant ‘needs’ are, as opposed to the ‘wants’.

For this, I think it’s always useful to read widely and talk to other people working on the same problem. Doing so will help you better understand and frame the problem, which then allows you to develop a solution that is both innovative and applicable to it.

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