A Unique Approach To Antibody Discovery with Dr. Aaron Sato, CSO of Twist Biopharma

This is the third article in a three-part series of Q&A conversations with Dr. Aaron Sato, CSO of Twist Biopharma. Part one focused on how Twist is adapting to the ongoing COVID-19 crisis and appeared in the spring edition of Benchtalk Journal, while part two covered his approach to running a life science R&D business and appeared in the summer edition of Benchtalk Journal.

A Unique Approach To Antibody Discovery with Dr. Aaron Sato, CSO of Twist Biopharma

Dr. Aaron Sato is the Chief Scientific Officer (CSO) of Twist Biopharma, a division of Twist Bioscience, where he is leading the biologics drug discovery program. Prior to Twist Bioscience, he led the California Antibody Center as CSO of LakePharma, which discovers novel antibody therapeutics for its clients. This was preceded by senior leadership positions at Surrozen, Sutro Biopharma, OncoMed Pharmaceuticals, and Dyax Corporation. He earned his Ph.D. from the Massachusetts Institute of Technology in biological chemistry where he studied the structure – function relationship of proteins. He has dedicated his career to protein engineering and antibody discovery and is an author of over 30 peer reviewed papers and 40 issued patents in the antibody space.

Twist Bioscience is a leading and rapidly growing synthetic biology and genomics company that has developed a disruptive DNA synthesis platform to industrialize the engineering of biology. The core of the platform is a proprietary technology that pioneers a new method of manufacturing synthetic DNA by “writing” DNA on a silicon chip. Twist is leveraging its unique technology to manufacture a broad range of synthetic DNA-based products, including synthetic genes, tools for next-generation sequencing (NGS) preparation, and antibody libraries for drug discovery and development. Twist is also pursuing longer-term opportunities in digital data storage in DNA and biologics drug discovery.

We had the chance to sit down with Dr. Sato to learn more about his career, the unique approach Twist Biopharma is taking to antibody discovery, and his thoughts on the role of a biotech CSO.

An Early Interest in Science

Q: Talk to us about your early interest in science.  How did you become interested in protein engineering and antibody discovery?

As a kid, I always loved math and science - that was even before people started calling it STEM. Initially I wanted to be a medical doctor, so I took a lot of science classes in my undergraduate, and I really fell in love with chemistry because of some fantastic teachers. But at the same time, I was also taking a lot of biology classes and also really loved the idea of applying more of a chemistry outlook to a biological system.

Dr. Sato at the bench during his graduate program

After I finished my Ph.D. on crystallography and the structure-function relationship of immune system proteins at MIT (lab of Dr. Lawrence Stern), one of my contacts from MIT offered me a job at an up-and-coming biologics discovery company called Dyax. It was a  fantastic opportunity for me because it allowed me to apply my interests in tinkering with proteins and understanding protein structure and function but in a way that was focused on drug discovery. I learned all about antibody discovery and protein and peptide engineering using synthetic libraries. It laid the groundwork for the rest of my career.

A Unique Approach at Twist Biopharma

Q: Walk us through the strategic thinking and planning that went into spinning up Twist Biopharma from the larger Twist Bioscience organization?

Twist Bioscience really started to think deeply about all the different products they have and how potentially they could use those as a platform to revolutionize specific application areas. The two that they identified were data storage and biopharma, which I'll focus on today. Biopharma was a natural fit, given we had customers purchasing DNA libraries from us and concurrently asking us to do more and more of the discovery workflow.

There was this idea that I could come into the organization, build a team, and we could create our own proprietary libraries as well as a platform for antibody optimization. Then, we could offer an increasing level of service for our customers to not only give them DNA but also help them discover and optimize antibodies as part of their own workflow.

Since Twist is one of the premier clonal gene providers in the industry, we can make hundreds of thousands of different clonal genes quickly, accurately, and cost effectively. For an antibody person, that basically allows us to make lots of antibody clones as part of our workflow, which is a huge advantage. And on the library side, Twist can make unprecedented synthetic libraries. And as someone that's come from that side of the shop, I saw that as a fantastic tool that we could use to create some of our own libraries at Twist.

The Antibody Development Process at Twist Biopharma

Q: Compared to a traditional contract research organization (CRO), what makes Twist Biopharma’s approach to working with clients unique?

When you're a CRO, people often see you as a pair of hands or an extension of their workforce. That’s totally fine and it's a great business, but what we've been trying to instill in our collaborations is that we're a value added partner. We work closely with you to help you innovate. And we will go above and beyond what's written on the paper, whereas if you're working with a CRO, they typically adhere strictly to the statement of work. I call it a premier level service that we can offer.  In my opinion, the ends justify the means because we make sure that the customer is really happy with the final outcome that we deliver.

"There was this idea that... we could offer an increasing level of service for our customers to not only give them DNA but also help them discover and optimize antibodies as part of their own workflow."

All the projects that we're doing are just really tough projects. And our partners know that, otherwise they would have done it themselves.

The Role of the CSO

Q: Zooming out a bit – can you distill down the hundreds of things that you're doing into a soundbite about the role of a CSO in the biotech and pharma industry?

In my mind the CSO wears two major hats. I service the scientific side to look at projects and understand the science behind what we're doing, provide insight and work with the internal team to make sure that we're heading in the right scientific direction.

But then there is a second hat, which is more of a business hat. Basically, I help the business development leaders by serving as an expert in the room to help them get people excited about what we're doing and sell our vision for antibody discovery R&D. Excelling under both the business hat and scientific hat is key to the ultimate success of what we're trying to do.

"All the projects that we're doing are just really tough projects. And our partners know that, otherwise they would have done it themselves."

Q: As you've grown into this role, what skillsets have you developed? Have there been any big surprises in that journey?

One of the most important skills I've had to develop is being able to provide a clear, succinct, consistent message to people like the Board of Directors and other investors. That's something I've really focused on myself - that higher level interaction which comes with being a C-level person.

I think one of the biggest challenges I've had is I thought that as I transitioned to higher level roles that some of the people manager responsibilities like dealing with conflict within the team might go away. But that hasn't happened. What I’ve learned is that as you go up the food chain a bit, your responsibilities just expand. The things you were doing before just don't go away. You just have to get used to this idea of having more and more responsibility and at the same time learn how to delegate when appropriate to help manage these increasing responsibilities.

Q: From a CSO’s perspective, what role does mentorship play in building great teams?

I've always seen an important part of my role being creating a team that can basically run on its own. We have leaders in the team that feel that they have the responsibility and capability to lead and manage the team independent from me. I actually see it as something I must do, to really help teach and mentor young scientists to become the next leaders within the organization so that we continue to grow and expand our impact. And, if some day down the road I move into a different role, the business has continuity with the leaders already in place.

If I look back at all the different companies I've been at, every single group that I left remains strong, because I trained the people that had director level roles or manager roles to take up the lead, manage and be inspiring leaders. I actually really enjoy mentoring and leading scientists.

"As an antibody engineer myself, I think the special opportunities arise when you get the chance to apply your technology to create a drug or therapy that can actually be given to people and have a real impact on their lives."

Closing Thoughts

Q: Looking back at your career so far, what are you most proud of?

My dream someday is to have a therapy that I worked on get to the market and make a real-world impact. I track the antibody candidates that I have helped discover very closely to make sure that they continue to move ahead in the pipeline and have the chance to realize their potential to positively impact people’s lives. But the destination is nothing without the journey, so I'm also proud of all the teams and technologies that I've helped to create, which have been a part of the process to create those promising candidates.

As an antibody engineer myself, I think the special opportunities arise when you get the chance to apply your technology to create a drug or therapy that can actually be given to people and have a real impact on their lives.