Tech operating the AVITI system machines
Quality Control Technician Lily Crespin operates the AVITI sequencer at Element’s headquarters in San Diego.

For a long time, the world of genetic sequencing has been largely dominated by one company, namely, Illumina. Molly He helped design and drive forward some of Illumina’s best selling technology, but is now forging her own path as CEO and co-founder of sequencing start-up Element Biosciences.

Molly He
Molly He

Originally from China, He did a PhD. in protein biophysics and biochemistry at the University of California, Los Angeles. After working in protein engineering and drug design at Chiron and Sunesis Pharmaceuticals for a number of years, she started a job at the then relatively new sequencing company PacBio.

After helping to develop PacBio’s technology, He was offered a job at Illumina in 2009. She spent almost eight years at the company gaining valuable experience building a global team and creating innovative protein reagents for Illumina’s sequencing machines.

Inspired by the need to improve affordability and access to sequencing around the world, He and her co-founders, also ex-Illumina employees, decided to set up Element Biosciences in San Diego in 2017. They have since launched a new and disruptive sequencing platform in record time and achieved an impressive $276M Series C Financing round last summer, with more than $400M raised in total.

He spoke to Inside Precision Medicine senior editor, Helen Albert, about the fast-changing world of genetic sequencing, her pathway to founding Element Biosciences, and why new decentralized approaches to sequencing are needed in order to democratize access to this vital technology around the world.

woman scientist
There is a lack of women in biotech and pharma, particularly at the senior level.

 

What inspired you to go into industry after you finished your postdoc?

When I was doing my postdoc, my advisor gave me a lot of freedom to explore, which I’m very thankful for. I found a project that used structure-based design as a tool to design better antibodies.  I got very, very interested in that and I thought to myself, “Wow, if I’m part of the drug discovery process and made an impact on healthcare, then wouldn’t that be really something I can be proud of. I can tell my kids I was part of that process.” I really wanted to do something practical and useful.

 

How did you become interested in the world of genetic sequencing?

I stumbled into it. I was in drug discovery for quite a few years. My background is in protein engineering. At that time, I felt the pace of drug discovery was a bit too slow for my liking. I enjoy the process of building something from an idea all the way through to a product in a few years. So, I was talking to a Stanford professor I used to know from my earlier career, and he introduced me to PacBio and I started to learn about genetic sequencing.

At that time, PacBio was not sequencing at all, they were just starting to put things together. I thought that’s really cool. If we can understand the genetic predisposition of all diseases, really trying to understand genotype-phenotype linkage, how wonderful that will be. Since then, I stayed in genetic sequencing.

 

Why did you decide to move to Illumina from PacBio?

There were multiple reasons. It was a better career opportunity for me, so that’s one. And the second. I also felt in order for the sequencing to be more accessible, we needed a technology that was higher throughput, because that would drive down the cost of sequencing dramatically.

That was in the very early days of sequencing and Illumina had already shown the promise of a very different type of sequencing platform. Their first paper on massively parallel sequencing grabbed my attention, because I felt if you can do this, you can eventually drive the cost down and you can decentralize sequencing and give the tool to everybody who wants to use it.

 

What inspired you to set up your own sequencing company?

A lot of people have asked me that question, I always default to, “It was not my original plan”. It all came together organically. When I was at Illumina, I was involved in developing the critical piece of SBS chemistry that makes Illumina successful today. I started a group from scratch and recruited a few really, really great scientists. We were the recipients of two Innovation Awards, which is Illumina’s ‘Nobel Prize’ for employees that made a significant revenue contribution to Illumina through technical innovation.

Towards the end of my Illumina days, I felt like the technology had started to plateau, it had already been developed for 8 to 10 years. I left and then two of my teammates who I hired at Illumina also left, within two or three months of me leaving. They approached me and had an idea of starting a company, but they did not know exactly what that company was.

We brainstormed quite a bit. Originally, we wanted to be a reagent company because this is what we’re good at. We’re protein engineers, we made great reagents for Illumina and for PacBio before. So that was our original thinking, but quickly we pivoted to a brand-new system. We saw the opportunity. Illumina was dominating the market. We felt like the field needs competition, because competition will increase innovation.

 

Why do you think Element will succeed in such a competitive field?

The founders in our leadership team really sacrificed a lot, because there are many other opportunities that could have paid better or be an easier job, but we are all here because we’re excited, we believe in the mission, and we really want to be here.

I mentioned to you that my transition between PacBio to Illumina was really about decentralized sequencing. But towards the end of my Illumina days, I felt like Illumina was going in the opposite direction, because the only way Illumina could push down the price per genome was through scaling up the number of samples being sequenced. When you scale the economy gets better at the per sample level, but it doesn’t really solve the problems of smaller labs, especially in developing countries. They do not have that capital, or they really do not have that many samples to run. It doesn’t stop the problem of access to sequencing.

We are very passionate about truly decentralized sequencing, giving people the best data quality, lowest cost and ease of use so everyone, every lab can have access to sequencing.

 

What makes your technology stand out from your competitors?

We deconstructed the entire sequencing platform down to each technical element, this is where the Element company name came from. There are six or seven major components contributing towards our sequencing platform. We innovated every single one of them from the ground up. Some of them we developed from new in house, some of them we borrowed from different industries. Because the technology has progressed so significantly in the last decade, there are a lot of things we can leverage that are more difficult for mature companies to adopt. As a whole, when we put all these innovative pieces together, we have a much better system.

We have a high signal to noise ratio. High signal to noise ratio is like seeing stars at night. If you interrupt the noise of sunlight, the stars show up much brighter. You can use your naked eyes to identify the stars with no problem, you don’t need an expensive telescope and you can identify stars much more easily on a completely dark night. That’s kind of what we tried to do.

Our accuracy is better than Illumina. We have many papers in the pipeline and our raw data is also freely available to download, so everybody can play with it, because we value transparency tremendously. We share our data with everybody so they can see it and our data quality is better than Illumina’s. That’s been shown in many, many different applications. Our cost is also much lower because of our technology advances. That enables us to provide high quality, reliable, low-cost sequencing to everybody.

 

Could you give me an example of how you’re managing to keep the costs down and also have high quality?

One reason we can keep the costs really low is our innovative proprietary sequencing chemistry. We call it Avidity. Without going into too many technical details, the idea is that we are fundamentally using 100 times less reagent than Illumina. If you look at Illumina’s reagent bottle and our reagent bottles side by side, Illumina’s reagent bottle is actually colored, because it has a lot of high concentration dye in that reagent bottle. Our reagent bottle also has dye in it, because that’s the way you read out the bases, but it’s almost clear. This is because we use so much less reagent, and we pass on that saving to our customers.

 

Why are there lots of sequencing startups right now?

That really is the reality. Many sequencing companies have been founded this decade, or in the last couple of years. There were also many others that came and went and were not successful. I still think some of these newer competitors may not be successful, because this is a highly competitive field right now. Not because there are many players, it’s really because Illumina has such a strong market muscle, an 80-90% market share.

My hypothesis for this is twofold. One is, a lot of people saw the opportunity, even though it’s a very, very difficult challenge to penetrate a monopoly market, and realized competition is needed. The other reason doesn’t apply to us, but probably applies to other sequencing startups. Illumina’s core patents have expired recently.

AVITI System
Avidity Sequencing reimagines the critical components of NGS and maximizes the combined impact on the accuracy and efficiency of the cycled reaction. At its core, the AVITI System is built on the unique properties of its avidite chemistry, which has binding efficiencies that yield high accuracy and reduce reagent consumption. This innovation allows the system to produce state-of-the-art sequencing quality at unmatched sequencing costs in a benchtop format.

 

What impact has the pandemic had on Element and the sequencing industry in general?

It was definitely very challenging for us to keep on innovating, keep on working, because of COVID. We went through a certain period of evolution, working out how we actually could make our employees feel safe coming back to work. But on the bright side, our employees were extremely dedicated to building a great platform. And we pretty much worked through the entire pandemic. We came out with a platform built from scratch in a record time in the in the industry -less than five years which is pretty much unheard of.

When COVID-19 broke out in early 2020 we were only sequencing short numbers of bases. But we were already talking about how we could make our instrument faster, make our chemistry progress faster. COVID actually motivated us to work faster, and work through the timeline. About a year later, we did put together a very robust system and then we had a collaboration with Jumpcode Genomics and with a few other entities to really look at COVID surveillance, and we had a white paper published on that.

 

Have you had interest from researchers based in developing countries since you launched your platform?

I came from China many years ago when China was poor and I have a strong passion to increase access to great technology for everybody, including developing countries. This is why we put so much emphasis on lower cost, without sacrificing the data quality. We started shipping in early June and we have shipped quite a few machines. After we launched our product, we got a lot of interest from outside the U.S.

Many people were interested because they felt like this is a really great system. The throughput is perfect for them, because they don’t have many samples to run. Also, at the same time, the price per sample is even better than the NovaSeq today. NovaSeq is the highest throughput platform that Illumina has, but not everybody can afford that. We’re a lot more affordable and easily accessible. This is something I’m very passionate about and we will be looking at getting our product globalized.

 

What key management lessons and challenges have you overcome since becoming CEO of Element?

I love building things from scratch. Even though I’m a first time CEO, this company was not the first team I have built. It always seems like I’m the first or the second one in any group. In my past career I always found myself building something from scratch. At PacBio, at Illumina, I built the entire team. At Illumina, I built the entire team across three different countries. But, at Element there’s additional challenges. In the Illumina or PacBio environment I was well funded, more or less, and I didn’t have to worry about the infrastructure. Here, that is definitely a lot more challenging. It has made me appreciate how important culture is and how important the people are for the success of the company.

One of our culture values is grit. We overcome challenges with grit and this is something I hold very close to my heart. At the beginning, we were in a basement of around 1200 square feet. It was very small, no air conditioning, no Wi-Fi, because we wanted to save money. We had five or six people, and we started to prove a concept. That was actually a fun time, because everybody was so excited. Everybody worked well together.

But, when a company starts to grow so quickly, the challenge is how do you keep the culture to be continuously gritty? Now we’re moving into a fantastic brand-new building that is custom made for us. We have more than 300 people. How do we keep that startup grit and innovation, when we feel like we are well funded in everything? So, I think this is a pretty big challenge, but I think the best way to overcome this challenge is through leading by example.

Element field application scientists
Element field application scientists Saeed Ahmed, Brandon Pool, Terrence Gelineau, and Kesterlyn Wilson during a demo of the sequencer at a recent event in San Diego.

 

There is a lack of women in biotech and pharma, particularly at the senior level. What’s been your experience? Do you think things need to improve and if so, how?

It’s not easy. My own personal experience is as an immigrant, Asian woman, I’ve always been the minority. For example, at Illumina I was the only female director in R&D at Illumina for more than three years. You’ve got to work extra hard and show an additional amount of competency to get the recognition. I find myself still fighting the same thing as a CEO. There’s a certain perception on women, especially Asian woman, to be humble. Just bury our heads, work hard and let data speak for itself. But it doesn’t always work that way. This is the lesson I learned. Society needs to do way more to encourage, to educate about unconscious bias and really to coach women in technology way more, give them more opportunities to shine, because the perception is hard to overcome. I still fight it today.

I’m personally mentoring a group of young women in leadership within this company. I may not have all the experiences that they want, but at least I’m one voice for them and I am extremely passionate about that. At the same time, I try to share my experience as broadly as I can. Don’t be afraid of ‘David versus Goliath’ type of competition or perception. You’re not alone. There are many David’s fighting the same fight. So yes, I think society needs to do more.

 

What advice would you give yourself if you could go back in time to when you first started in your career?

I would look for great mentors that could evaluate my value based on my intellectual curiosity and hard work, not based on where I was from, or my experiences. I personally value intellectual curiosity and learning agility, more than just pure experience, so I would look for mentors who actually value these things and who could be tremendous at helping me grow.

 

Helen Albert is senior editor at Inside Precision Medicine and a freelance science journalist. Prior to going freelance, she was editor-in-chief at Labiotech, an English-language, digital publication based in Berlin focusing on the European biotech industry. Before moving to Germany, she worked at a range of different science and health-focused publications in London. She was editor of The Biochemist magazine and blog, but also worked as a senior reporter at Springer Nature’s medwireNews for a number of years, as well as freelancing for various international publications. She has written for New Scientist, Chemistry World, Biodesigned, The BMJ, Forbes, Science Business, Cosmos magazine, and GEN. Helen has academic degrees in genetics and anthropology, and also spent some time early in her career working at the Sanger Institute in Cambridge before deciding to move into journalism.

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