Making a life-saving drug is no simple feat. It takes teams with a diverse set of skills to crack the code for the next blockbuster medicine. These include chemists, who tweak molecules to hit intended targets; biologists, who analyse and test these molecules to ensure they help rather than harm; and countless others who bring their skills to bear in creating safer, more effective treatments for patients in need.
The complex process of drug discovery and development is all too familiar to Soo Yei Ho, Chief of Staff at A*STAR’s Experimental Drug Development Centre (EDDC), who was also the Group Leader of Medicinal Chemistry during the development of ETC-159, a made-in-Singapore cancer drug. Targeting a range of common cancer types, ETC-159 hit a significant milestone in the EDDC’s efforts in novel cancer therapeutics when it entered clinical trials in June 2015.
In this interview with A*STAR Research, Ho shares her scientific journey to date, including her leadership work at EDDC and her personal role in ETC-159’s development.
1. What sparked your interest in science?
As a child I was always curious, constantly questioning how things worked and why. I would often take apart small home appliances and other objects to satisfy my need to understand their inner workings. As I grew older, this curiosity evolved into a passion for chemistry. I was particularly drawn to the complexities of molecular interactions and how they could lead to profound biological effects.
My interests naturally led me to explore inorganic metal-based drugs during my graduate studies, where I learned about tissue cell cultures, cell assay development and in vivo efficacy studies on top of synthetic chemistry work. I was drawn to the idea that we could design and create molecules that have the potential to save lives.
2. What shaped your scientific journey?
It has been a combination of hard work, perseverance and the invaluable support of mentors and colleagues. During my early years as a researcher, I was fortunate to work with Michael Foley, the Founder of Infinity Pharmaceuticals, who encouraged my scientific curiosity and taught me the value of resilience. He provided an environment where I felt comfortable taking risks and exploring new ideas.
Another key mentor has been EDDC Chief Executive Officer Damian O’Connell, who broadened my perspectives beyond the lab. He offered me the chance to explore areas such as portfolio and resource management, which gave me a strategic understanding of how to run an organisation effectively. Under his guidance, I gained insights into the complexities of decision-making; aligning scientific objectives with organisational goals; and optimising resources for maximum impact. These experiences were instrumental in developing my leadership skills and ultimately paved the way for my current role.
Other mentors and team members have aided me through every step of my career with their guidance, feedback and support. They helped me build confidence in my abilities, celebrated my successes and offered advice when things didn’t go as planned. Working with diverse and talented teams also taught me the value of collaboration.
Now, I hope to pay it forward by mentoring and supporting other aspiring scientists, especially young women, to pursue their passions and realise their full potential.
3. What’s the story of ETC-159’s creation?
When David Virshup from Duke-NUS approached us at A*STAR with the idea of developing a Wnt-Porcupine inhibitor, it sparked a new, exciting direction in our research. When I joined A*STAR, the Wnt-Porcupine project became one of the initial projects I worked on; I was appointed as the team’s chemistry lead.
For context, Wnt ligands are a family of cellular proteins that can trigger a cancer-causing signal cascade when they bind to matching receptors known as Frizzled. However, for Wnt’s successful secretion and binding to Frizzled, Wnt molecules must first be modified by Porcupine enzymes, which are usually situated in the cell’s endoplasmic reticulum—a network of internal membranes. Porcupine palmitoylates Wnt, essentially attaching a strand of fatty acid to each Wnt molecule to activate it. Interrupting this mechanism therefore seemed like it would have promising therapeutic effects.
In our highly collaborative group, each member brought their unique expertise to the table. Together, we designed and synthesised a range of chemical moieties to fine-tune the biological properties of potential Wnt-Porcupine inhibitors. Our goal was to identify a molecule that had the ideal balance of potency, selectivity and pharmacokinetic properties needed to advance closer to the clinic.
With rigorous scientific effort and a bit of serendipity, we arrived at ETC-159, a molecule designed to inhibit the Porcupine gene. In some cancers, it shuts off the Wnt pathway and causes cancer cells to die. In other cancers, ETC-159 also increases the number of immune cells in tumours, allowing PD-1 inhibitors—a form of cancer immunotherapy—to work better.
The development of ETC-159 was both a scientific achievement and a testament to the power of collaboration, innovation and persistence. It was incredibly rewarding to see our work move from the lab to the clinic, where it has the potential to impact the lives of patients fighting a range of aggressive cancer types, including colorectal, endometrial, ovarian and pancreatic cancers. These cancers collectively account for a substantial part of the cancer burden not just in Singapore, but worldwide.
Our work on the Wnt-Porcupine pathway remains a significant part of my scientific journey, reinforcing the importance of interdisciplinary teamwork, bold ideas and the willingness to explore uncharted territories in the quest for groundbreaking medical therapies.
4. What do you hope to achieve at EDDC?
As its current Chief of Staff, my primary aim is to create an environment where scientific innovation and operational excellence thrive side by side. Drug discovery is complex, requiring a delicate balance of strategic planning, rigorous scientific research and efficient execution. My role therefore is to ensure that every aspect of our operations—from bench to bedside—aligns with our overall mission: to bring transformative therapies to those who need them most.
I strive to foster a culture of collaboration, empowerment and continuous learning, as I believe that people are our greatest asset. My goal is to build a workplace where every team member feels valued, motivated and supported in their professional growth. This means providing clear goals, encouraging open communication and building cross-functional teams that leverage diverse skills and perspectives to solve complex problems creatively and efficiently.
In addition, I’d like to maintain a strong focus on operational efficiency, which can help EDDC remain agile, respond quickly to new challenges or opportunities, and ultimately accelerate the discovery-to-delivery timeline of new therapies. This includes working cross-functionally with our resources to optimise workflows, implement cutting-edge technologies, and ensure that all teams are well-supported to be productive.
At the heart of my efforts is the commitment to uphold the highest standards of scientific integrity, quality and compliance. My ultimate aim is to lead an organisation that not only achieves its scientific and business goals, but also makes a meaningful difference in the lives of patients worldwide.
5. What encouragement would you give to other women in STEM?
Science needs diverse voices, and ideas have the potential to shape the future in ways that we can’t yet imagine. It might feel daunting at times, especially in environments where you might not see many people who are like you or share your experiences.
There will be challenges along the way—moments where you doubt yourself or feel like you don’t belong. But those moments don’t define you; your resilience and determination do. Surround yourself with people who support and uplift you, seek out mentors, and don’t be afraid to ask for help or guidance. Trust in your abilities, embrace your failures as learning experiences and keep pushing forward.
Remember, every great scientist started with a question: a spark of curiosity just like yours. Science is about discovery, and that includes discovering your own strengths and capabilities.
