Discovery of High-Affinity Human PD-1 and LAG-3 Antibodies Using Novel Microfluidic and Molecular Genomic Methods
Kent Simmons:
Welcome everyone to this Cambridge Health Tech Institute podcast presented in conjunction with the 14th annual PEGS event, which will be held April 30th through May 4th, 2018, at the Seaport World Trade Center in Boston. I'm Kent Simmons. I'm a program director with CHI and with me today is Dr. David Johnson the CEO and co-founder of GigaGen. Dr. Johnson is presenting in the engineering antibodies program at PEGS, which will be held on May 2nd and 3rd. Thanks for joining us today Dave.
Dave Johnson:
Thanks. I'm really happy for the opportunity.
Kent Simmons:
So as a starting point maybe tell us a little bit about your company, GigaGen, and how you came to focus on antibody discovery and development.
Dave Johnson:
Yeah. GigaGen was founded about six years ago by myself and a friend of mine from grad school, Everett Meyer. I'm a genomics guy and he's an immunologist. What we realized is at the time, I think things have progressed since then, but at the time there really weren't many groups working in immunology and genomics, kind of combining the different technologies for each. And so what we set out to do was create a technology that would allow us to profile the genomics of millions of single immune cells in a single experiment. We had all sorts of applications that we could go after using such an approach, but we landed on antibody discovery as a really pressing need, and frankly, a really exciting opportunity to build a drug discovery and development company based on a real world leading platform.
Kent Simmons:
So tell us a little bit more about how your platform works.
Dave Johnson:
So, it's a microfluidics based platform. What we do is we isolate millions of single B cells into picoliter droplets. The picoliter droplets contain a lysis mix and a RNA-capture bead, and then what we do is run those into another platform of droplets where we amplify the heavy and light immunoglobulin which then we drop into protein expression libraries for screening for the best antibodies in the library. We do this on human samples, so we've taken blood draws and found one in a million antibodies for the flu in human samples. Then we also do humanized mice, so we immunized mice with gene targets of interest and then captured B cells from the repertoires using our platform.
It's really a replacement for hybridomas. A lot of people in the industry are using hybridomas to isolate human cells and mouse cells, but those methods are very inefficient. Most people say you get about 0.1% of the diversity back from a repertoire when you use those methods. We're getting 75% of the repertoire back based on some studies that we're actually about to publish in the next few weeks. So, really exciting, different kinds of methods for discovering antibodies in diverse repertoires.
Kent Simmons:
So thinking about your technology and others now at play in this space, what do you find most exciting about antibody discovery in the current environment and where do you see this heading in the next couple of years?
Dave Johnson:
I say there is really two things that are really exciting. The first is that we are really starting to understand the disease immunology much better than we have in the past. So most diseases, if you think about it, have some kind of immune component. Cancer is the most obvious one these days, but, you know, 20 years ago people didn't really think of cancer as an immune disease. So what's really exciting now is that, you know, sure the genome was sequenced almost 20 years ago now, but the exciting thing is now we are finally really starting to understand what all the genes do.
Then using that knowledge to discover new drugs. Our platform is set up really well, by the way, to describe basic immunology, translational immunology of diseases, really identifying targets using our single cell genomics platform.
And then I think the second thing that is really exciting is we are a small company, we are only 13 people. Actually 14, we just hired our 14th. And we are really discovering antibodies faster and much, much cheaper than the biggest pharmaceutical companies out there. That's pretty exciting that you can use technology to really go out there and compete and bring new drugs closer to the clinic. So that's going to be really good for patients. And it's really going to capitalize on all those new discoveries that are coming out of basic disease immunology.
Kent Simmons:
In implementing these new technologies in smaller and larger organizations with these new understandings we are gaining in immunology, what do you think are some of the most pressing challenges for the researchers working in antibody discovery today?
Dave Johnson:
I think that's true no matter where you are. Even if you are a big company with all the capital. I think there are a lot of groups that are good at discovering lots of antibodies. I think the challenge is finding the ones you want to spend the money developing further. You know, no matter what you do it's several million dollars to make a cell line, produce GMP protein products, to then bring those to stage one to develop clinical studies, that's hundreds of millions of dollars. So I think the biggest challenge for any group on the early side is really choosing a winner. How do you do that?
We have a perspective on this, which is that we want to see what people in the field call developability really early, and Adimab is a leader in this as well, really looking at the specific properties of the proteins very early on in the process to think about developability. What are the proteins that are probably going to manufacture well? What are the proteins that are probably going to have good pharmacokinetics in human studies?
There is a lot you can do in the early stages to wean out the losers. So what I am hoping we can do is really get better at picking winners and then you increase your conversion to commercialization rate much higher than even where it is, and that actually is pretty good still for antibodies. So I think that's the hard part, is really with all these new targets, with all these new antibodies, to get to the target is really a matter of picking the winners. That's the real challenge.
Kent Simmons:
So GigaGen has programs going I think in both flu and in cancer, and I'm curious what made you focus on the PD-1 and LAG-3 targets for your talk at PEGS this year?
Dave Johnson:
Sure. Just to clarify, we published in the flu, but we don't have any commercial projects in the flu. Really the goal there was to publish our methods and to describe them so that the community could understand what we do. But we don't have any commercial projects in the flu. As for why we are talking about PD-1 and LAG-3, these are really well understood targets. The biology of the targets is well understood. So there's a lot I could talk about in terms of validation.
We disclosed 17 of the targets that we are working on in December. We have thousands of antibodies against those 17 targets. Some of those don't have the best biology worked out and maybe we aren't quite ready to talk about our assays that show efficacy. Really we chose PD-1 and LAG-3 because they are well understood. I would say, in terms of commercial opportunities, those are...I don't know, 5 PD-1's in the clinic or on the market. So in a lot of ways they're the least interesting commercially, but certainly something that is very interesting to talk about in terms of the biology and the discovery process.
Kent Simmons:
So a lot of the people watching your talk at PEGS will be industry research groups and I'm wondering what your thoughts are on the implications of the work coming out of your lab on the discovery and development of next generation cancer treatments coming out of the industry?
Dave Johnson:
Yeah. So, as you know biotechnology is a very collaborative industry. We recently closed a large, 50 million dollar financing and co-development deal with a Spanish company called Grifols. That's in an immune deficiency disease state, so not in cancer. Really what we are looking for at this stage in terms of talking to other folks in the industry, we are looking for another such collaboration. We recognize that it's really difficult for a company our size to bring new oncology antibodies to the clinic and to the commercialization stage without the help of a large partner. So one thing we are doing there is hopefully networking with groups and seeing if we have something that they are interested in, let's work together and let's bring it out to market. And that's really, if you look at the model for the kinds of deals that we are looking for…for example Sutro has this big deal with Cellgene for immuno-oncology and discovery…that's the kind of thing that we are looking for. We are publishing, we are networking, trying to find some great corporate partners for the work that we are doing. We think we have a lot to offer.
Kent Simmons:
So what are you looking forward to the most In attending PEGS later this year?
Dave Johnson:
I definitely like always presenting my work. I have an academic side to me. I enjoy publishing, I enjoy speaking. So I think it's exciting to get up in front of an audience and talk about my work and get questions, and there's always people who come up to you afterwards, after the talk and say, “Oh yeah, I'm working on this thing and maybe we should think about collaborating”. It’s not necessarily always big commercial projects like I just described, sometimes it's just, “let's write a paper together”, “let's work on this application and then do something interesting together”. So, I'm hoping that things like that will come out of the conversations. Maybe somebody in the audience, their ears perk up when they have something that they want to hear about.
Kent Simmons:
Well Dave, thank you very much for your time today. We appreciate you joining us for this podcast recording. And I'll look forward to seeing you in May and hearing your talk at the meeting.
Dave Johnson:
Thanks for the time, we really appreciate the opportunity.
Kent Simmons:
So thank you everyone for listening today. This has been an interview with Dr. David Johnson, the CEO and co-founder of GigaGen. He's presenting in the Engineering Antibodies Program at PEGS, which will be held on May 2nd through the 3rd, 2018, at the Seaport World Trade Center in Boston. If you'd like to register for PEGS, or learn more about the 400 scientific presentations at the event, please visit www.pegsummit.com. This has been another Cambridge Health Tech Institute podcast. I'm Kent Simmons and thank you for listening.