Building better antibodies in pursuit of a broad-spectrum vaccine with Jacob Glanville
How he got started
After he joined Pfizer in 2008, he asked to use the deep sequencing instrument to look not at the genome, but to look at the hundreds of millions of antibodies to try to figure out how to make them better. When looking at the antibody libraries, he figured out they were about one thousandth of the size people thought they were because of the redundancy of genetic information in the library. Also, many of the antibodies were not well-suited to fold up properly.
He published a series of papers describing how to improve those libraries using DNA synthesis methods. He would take libraries of 36 billion antibodies, heat it, sequence it before the antibodies fell apart under the heat, and learn the rules of how to make more thermostable antibodies. This was one of the examples of cool things you could learn, according to Jacob, by looking at large pools of data points. In other words, he came up with algorithms to analyze the immune system.
His goal was to study how to human body produces antibodies, so that he could find ways to copy that process and avoid weird, synthetic things that don’t show up in a person.
This led him to found Distributed Bio, which later was bought by Charles River Laboratories, because he felt there was still a lot of room to improve. He started licensing out his algorithms, which provided him with the funding to build a better antibody library. He had the tools to see more antibodies than anybody else had. With a better library, he was able to go after the “tough stuff.”
That was how he made a name for himself.
Public health lessons learned from his Guatemala childhood
He grew up in Guatemala, on Lake Atitlan. His parents owned a hotel and restaurant between three volcanos on the south side of the lake in a Mayan village. The country was in a civil war when he was growing up. It was unstable and unsafe, yet his parents somehow managed to build a business anyways.
It had a profound impact on his career.
He learned how to judge a person effectively in the absence of resumes and work documentation. He learned that if you look them in the eye, you can learn a lot more about them. His father was good a placing people in the right position so they could be effective without trying to grind them down. When he was building Distributed Bio, he kept remembering Guatemala.
Medical care was limited. He had asthma, but he had it better than many of the children he saw who were needlessly suffering from preventable diseases. For example, children’s growth was stunted by lack of deworming medicine and other chronic infections. It heavily influenced his belief that medicine can make things better and allow us to focus more on achieving their potential instead of being sick.
Why he sold
When he started Distributed Bio, he drew out a four-step plan on a napkin.
He planned out the first vertical as the software platform, because it had the lowest amount of capital investment required.
The second was going to be the antibody library.
The third tier was going to be services which would require them to build out a team.
The fourth was going to be a series of tools used to discover new medicines. The support infrastructure was around the broad-spectrum vaccine idea he had had since 2012.
He was publishing quite a bit, and other companies were starting to copy his designs. He knew they were going to catch up. After he had the initial win with the libraries, he felt that selling to a bigger partner would enable him to maintain that advantage. Glanville was ready to go all-in on the universal vaccine technology which was the fourth step.
What is a broad-spectrum vaccine?
Glanville feels that vaccines are one of the greatest medical advances since sanitation and fire. But, in their current form, they do not do a good job against mutating viruses. The issue is that they take time to generate, so the vaccine that you get injected with doesn’t deal with the same type of virus that you were infected with – because of mutations. That is why we have to make a new flu shot every year.
A broad-spectrum vaccine would mean a single flu shot that would actually work 80% effectively against all forms of the flu, and you wouldn’t have to change it every year. To create it you would need to have antibodies that hit certain “conserve” sites within the virus. They are also called, “universal vaccines.”
Composing great teams
Glanville says that the ability to size people up, developed in his childhood in Guatemala, has enabled him to select great teammates for his company. He says that in order to build something great you have to get over yourself and become comfortable working with someone who is better at what they do than you, and not be intimidated by it.
He’s also inspirational. When trying to pitch his company to a prospective employee, he looks for “the person who is thinking about the problem in the shower.” He finds these people by asking them if what they are doing will have an impact on society in 1,000 years.
Those are the highlights – we hope you’ll listen to the full show to catch all the details of Glanville’s pursuit of the broad-spectrum vaccine!
About Jacob Glanville
Dr. Jacob Glanville is a serial entrepreneur, and computational immuno-engineer. He built and sold his first company Distributed Bio from founding in March of 2012 to a $104M sale to Charles River Laboratories in December of 2020. During that period, he developed the core business model, the research teams, and the technologies that enabled Distributed Bio to become profitable without investment. As part of the acquisition agreement, he founded Centivax Inc and spun-out his assets in COVID-19 therapeutics, broad-spectrum vaccines, antivenom antibodies, anti-wound pathogen antibodies, anti-CXCR5 autoimmunity therapeutics, and blood-brain barrier translation technologies into Centivax, where he is now CEO. He has developed multiple seminal methods in the fields of high-throughput antibody repertoire sequencing (PNAS 2009), repertoire decoding algorithms (Nature 2017), single-cell TCR receptor and phenotype sequencing (Nature Biotech, 2014), deconstructing genetic variation in the adaptive immune system (Nature Communications 2015, Nature Reports 2016, PNAS 2011, TI 2017), and computationally guided antibody library engineering (JMB 2011, JMB 2013, COSB 2015). He is the inventor of the Centivax Universal Vaccine technology, the SuperHuman discovery library technology, and the Tumbler technology.
The information contained in this website and podcast are purely informational and not considered investment recommendations. Tim Dougherty’s participation in Biotech Insights is separate and apart from his role as an investment advisor representative. Nothing contained herein may be construed as a recommendation or endorsement of any of the companies discussed. Tim Dougherty has no financial affiliation with any of the companies mentioned in this communication. Tim Dougherty makes no representation that the information conveyed in this material is accurate and is under no obligation to update this information as changes occur.