And that’s different than what the mouse version of this protein is. Let’s say, the mouse protein a red apple. So you inject the human protein into the mouse, the mouse will say, yes, that’s different, and I’ll make some antibodies. And we expect this. This happens. Lots and lots of literature and progress based on this, okay? So I’m not saying that doesn’t happen. However, you take that same human protein and you put it in the chicken, man, right? The chicken sees this is a very different protein. I mean there’s places all over this target that the chicken recognizes as different. And those places on the protein, those are called epitopes. So you can talk about the epitopes diversion, and I’ll talk about that some more, too. But that’s one of the key things that chicken bring is a recognition of all these different epitopes and they’re diverse.
They’re all over the target of interest. And this is sort of fundamentally an advantage that the chicken brings. And in fact, all of our chicken-based platforms bring this. They’re all in a chicken host. So it doesn’t matter if it’s OmniChicken with a VH, VL antibody. It’s a matter if it’s OmniFlic, with a common light chain antibody and here in OmnidAb. So these are really kind of summarized the two benefits here. The chicken host recognition plus this pre-engineered nature of the transgene, particularly for single-domain antibodies. And just to give you a little data on this, this is highlighting both of those steps. So on the left side, we’re looking at a process called epitope binning. This is looking at a panel of antibodies from one campaign versus panel of antibodies from another.
In this case, the first campaign was performed in OmnidAb. In other case, the campaign was performed in OmniFlic, which is a rat, a common light chain rat. And this process of epitope binning allow you to see where are these antibodies binding, and why are they different from each other? And you can see here, there’s a clear delineation for this target model antigen called NKp46 that there are some common epitopes that both species hit, but there’s a lot of different ones. And the OmnidAb chicken actually brings a lot of new stuff in terms of epitope recognition. Now this can be driven both by, in this case, by the chicken evolutionary distance, but then also just the nature of the binding element itself, which is a single domain. It’s a smaller paratope.
That’s the part that binds the epitope. It’s smaller than a conventional VH by VL antibody. So anyway, a lot of — and all the results we’ve seen so far with OmnidAb, where you can get the sort of unique epitopes. Finally, on the developability side, these pre-engineered single-domain antibodies appear to be very, very stable and robust in systems that we use to measure this. This is an important feature for actually making drugs out of the molecules. And the types of things you look at are thermal stability and there’s a whole host of things. But one very important metric that’s looked at is self-interactions. An assay called AC-SINS. It’s looking at when you take the protein, you put it a very high concentration. What’s a tendency for it to aggregate?
Because that’s a problem for manufacturing down the road. And the panel on the right here shows you, these are just randomly selected positive binders from OmnidAb, showing you the range. In this case, a low score is better. So you’re seeing the AC-SINS score being quite low for those. And if you can compare it to some other molecules on the right, the very high scores, those are actually clinical failures, which had a problem in this area. But then further to the right, you’ll see a couple of other approved — currently approved antibody drugs, including one, which is an engineered llama-based antibody. And in this metric, those don’t score as well as just a collection of antibodies from OmnidAb. So to summarize, OmnidAb transgenic chickens express an optimized single-domain human framework.
So again, pre-engineered, OmnidAb being a chicken that targets distinct epitopes. These are robust animals, you get bit tighter upon the immunization and high-quality antigen-specific antibodies with good developability profiles and a good expression levels. So we think this is a very strong platform for therapeutic antibody discovery going forward. A lot of options for partners, especially when you think of this in the context of all the other platforms that we have. And this is a good segue speaking on the kind of the more in silico and screening side of things. I’ll turn it over to Bob Chen. He will tell you about how we’ve really developed and push the technology on that and to get the very most we can out of the repertoires we generate from our transgenic chickens.
