Can one company simultaneously work on solving the problems of Ebola, influenza, neurodegeneration, cancer, tuberculosis, and enterotoxicogenic E. coli? If you are AbCellera, a Vancouver-based biotech on the hunt for novel antibodies that can be used to fight these diseases, the answer is yes. The company has built the world’s leading platform for the discovery of monoclonal antibodies and the profiling of natural immune responses. This proprietary platform, which uses a combination of microfluidics, genomics, microscopy, and machine learning, allows for screening millions of single immune cells in a single day in order to find rare antibodies that are suitable for development as the next-generation therapeutic antibodies. Working with some of the world’s most innovative biotech and pharma companies, AbCellera is harnessing the power of natural immune responses to help develop new therapies across diseases including cancer, inflammation, neurodegeneration, viral infections, and fibrosis.
Earlier this year, the company was named LifeSciences BC’s Growth Stage Company of the Year. The company’s growth is undeniable: it has quadrupled in size over the last three years, and, having outgrown its original UBC location, has recently moved to a brand new facility on Yukon street. The company employs over fifty people, most of them homegrown, BC talent, and continues to hire and expand.
The BC REGMed team met AbCellera’s CEO, Dr. Carl Hansen, at the company’s new facility. The bottom floor, an airy, open-concept space, holds collaborative working spaces for the engineering, bioinformatics, operations, and business development teams. The laboratories, located on the floor above, are all shiny glass and still have the distinctive, plastic smell of newly unpacked equipment when we visit, a few weeks after the company’s move from UBC. We sat down with Carl to talk about how AbCellera began, the exciting projects they are currently working on, and his philosophy of success and innovation.
AbCellera got its start at UBC
AbCellera’s roots are firmly planted at UBC, and not just because the company was first formed in 2012 on the UBC campus, where Carl is an associate professor. Carl’s own journey, that eventually led him to take on some of the world’s deadliest diseases via antibody discovery, began at UBC, where he completed a degree in engineering physics before moving to Caltech in California for his PhD in Applied Physics and Biotech, in the lab of scientist and inventor Steve Quake.
“After completing my undergraduate studies in Engineering Physics, I was looking for an opportunity to connect with the biological sciences, a field that seemed so ripe with opportunities for science and innovation,” Carl tells us. “The opportunity to work on microfluidics with Steve Quake at Caltech was a perfect opportunity to bridge engineering and biotech. Most importantly, from grad school through to my work as a faculty member at UBC, this field has given me the chance to work alongside world-class researchers in multiple fields where I had no formal training. Over the years this has given me the opportunity to stay on a steep learning curve.”
Microfluidics is a technology that deals with the control and manipulation of fluids at a tiny scale. Shortly before Carl arrived at Caltech, a new type of microfluidic device with active microvalves had been developed that promised to allow for increased complexity and better control of fluidic circuits. For the next four years, he worked with a small team dedicated to taking this technology from proof-of-concept to something capable of making many thousands of valves on a device. That was the technology he took to UBC.
“At UBC I set up a group trying to use microfluidic technology to miniaturize and improve the capabilities of biomedical research broadly,” he says. As it turned out, because it allowed media manipulation and flow through small chambers, the microfluidics technology was particularly well suited for performing single-cell analysis, the growing field of making measurements on individual cells to help understand biological complexity.
“I have benefited from close collaborations with terrific researchers from MSL [Michael Smith Labs at UBC] and the BC Cancer Research Centre, including Connie Eaves and Keith Humphries, Jamie Piret, Chip Haynes, Marco Marra, and Sam Aparicio. Through those projects we put in place fundamental capabilities in culturing cells, in measuring the genomic and RNA content of cells, and in performing single-cell secretion measurements,” Carl explains. “Our work was motivated by a desire to enable basic biomedical research. It wasn’t focused on translation or starting a company.
“In 2012, three things came together: first, I had my tenure which allows you to take some bigger chances in your career. Second, the single-cell analysis technologies we developed were well established. And third, I had trained a really outstanding group of engineers and scientists who were either graduating or finishing post-docs and now looking for a new opportunity to stay in science and in Vancouver. There were not many positions in biotech, so we decided to start AbCellera. This decision was made easier by the fact that I had, 2 years prior, been a co-founder of another company called Precision Nanosystems. Through that experience I had a good idea of how to get a company off the ground and knew that great things could be accomplished here in BC.”
AbCellera’s technological advantage
So, in 2012, AbCellera was founded. “We realized [that] we could take these different technology pieces and wrap them together around an interesting and commercially important problem – single-cell immunology,” Carl says. “We formed the company on the simple idea that we would build a platform that is much faster and better at finding therapeutic antibodies, and that we could build a viable business by working broadly with biotech and pharma. This is exactly what we did. It is one of those rare cases when you set off with you first business plan, and that idea turns out to be exactly what sticks. We have learned a lot about the science and the business along the way, but there haven’t been any major pivots.”
The use of a microfluidics platform to rapidly screen individual immune cells is one of the innovations that enables AbCellera’s antibody discovery. Currently, immortalized B cell lines – hybridomas – are widely used to generate monoclonal antibodies. However, this process is labour-intensive and inefficient, because B cells from immunized animals have to be selected, fused with a cell line, and expanded before they can be tested for their ability to produce the specific monoclonal antibody of interest. In contrast, AbCellera uses microfluidic single-cell screening to systematically and directly select the single B cells that express the desired antibody. Because the process is miniaturized, 1 million B cells per day can be screened in 1nL secretion assays in AbCellera’s pipeline. The whole process is 3 to 5 months faster and can uncover orders of magnitude more antibody hits than a hybridoma assay.
Microfluidics underlies the antibody discovery capabilities of AbCellera, but the company leverages many more areas of science for its work. “In building a technology, you can’t just solve one part, you must solve the entire thing. This means breaking out of your comfort zone and chasing the problems wherever they take you. At AbCellera, we started from microfluidics and this has been a key element of our success. But the technology has pushed us upstream into antigen generation, immunology, media conditions, assay development, and on the back end into genomics, bioinformatics, and biochemistry. In the whole pipeline, there have been innovations on every front,” says Carl.
Tackling the world’s deadly pandemics
A particularly exciting project that AbCellera has recently taken on is to lead a team on pandemic response, a contract they have been awarded by the United States Defense Advanced Research Projects Agency (DARPA). Established in response to the USSR’s launch of Sputnik and tasked to maintain American technological superiority, DARPA also endeavours to address some of the biggest risks to US national security, one of which is infectious disease and the emergence of pandemic viral outbreak.
Five years ago, DARPA initiated the ‘ADEPT-PROTECT’ pandemic response program to mitigate this threat. “The concept,” explains Carl, “is that if a pandemic outbreak happens, you obtain blood from a convalescent or infected patient, and search their immune system to isolate, monoclonal antibodies that are potent neutralizers of the virus. Then you can select the best antibodies and use gene therapy technology to deliver them back to the population as a prophylactic “firebreak” to infection.
“One of the big challenges with that is that it currently takes us somewhere around 8-12 years to take a new monoclonal antibody, bring it through clinical trials, manufacture it, and make it therapeutic. And DARPA envisions doing this in sixty days. Obviously, ten years is too long, and sixty days is at the very limit of what is possible. Achieving this will require a combination of technologies and the tight coordination of groups working together,” Carl says.
AbCellera was part of that original pandemic response program, working on several pathogens, including Ebola, Klebsiella, Pseudomonas, and enterotoxicogenic E. coli. “Through that work, DARPA was comparing various groups across the United States and the world for rapid antibody discovery. Even though our technology was still being refined and we were a very small company at the time – I think we were 7 people when we started working with them – we outperformed the other performers. It was a wonderful opportunity for us connect with many leading groups in industry and to build our capabilities in human antibody discovery and immune profiling. This work has lead to several new projects in infectious disease, autoimmunity, and vaccine development,” says Carl.
The follow-up program was called P3 – Pandemic Preparedness Program. “This is a $150 million program with 4 groups involved: Medimmune, Duke University, Vanderbilt, and AbCellera. We are leading a team of leading virologists, biochemists, and gene therapy companies to create an end-to-end platform for pandemic response. If a pandemic happens, we expect to be DARPA’s first call for response (…) That is a big responsibility. It is amazing to be at the front lines of such an ambitious, cutting-edge, and exciting program.”
The DARPA program is one example of a cutting-edge scientific collaboration with government and academia, but AbCellera’s main business is based on partnerships with biotech and pharmaceutical companies in a variety of different research areas. Collaborations with Pfizer, GSK, and Teva Pharmaceuticals on antibody discovery for membrane protein targets, with Denali Therapeutics on antibodies against neurodegenerative diseases, and with Sanofi Pasteur on an influenza vaccine are some examples. “Our business model requires that we are at the leading edge of the industry,” Carl stresses. “That means that you get to work with some of the most innovative and ambitious groups around the world.”
A success mindset
So, what is Carl Hansen’s philosophy of success? “Recognize when the rules change,” he says.
“In technology, there are some people who recognize early when the rules change, when technology advances and lets you do something that for a long time was impossible. If, for decades, you haven’t been able to do something, it becomes ingrained in your assumptions and your approach to solving the problem. Originally those ideas are founded on facts, but the facts change. It’s human nature that when the facts change, we don’t immediately revisit all our assumptions about what is possible, and what is not. The people that I have seen who are consistently the most innovative and productive are the ones who seem to make a conscious effort, when technology moves and rules change, to look up and say: what does that mean and what can I do?”
Certainly, this philosophy is paying off for AbCellera. As we conclude our interview, Carl stresses his commitment to growing the local BC biotech environment: “If look forward to where growth and opportunity will be, where economic prosperity will come from, here in BC, biotech is a big part of the puzzle. We have great science here and great people, and we should be aggressive in chasing the big opportunities, (…) and trying to grow something special here in BC.”
By Elizabeth Bulaeva (@LisaBulaeva).