They can potentially cross the blood brain barrier, and they can also be used as linkers to guide other molecules to various parts of the human body. So after — we’ll present today, but there are several upcoming presentations that if you happen to be at, I would recommend you join. In next week, we’ll be in Lisbon at PEGS Europe. In December, we’ll be in San Diego at the AET Conference. And then in January 2024, we’ll be presenting a webinar series that deals specifically with OmnidAb. That’s it for me. I will now turn it over to Bill.
Bill Harriman: Thanks, Todd. So I want to take you a bit deeper into the technology behind OmnidAb and single-domain antibodies. Let me start first with a conventional antibody. It’s an IgG molecule. This is the predominant antibody formed in most vertebrate species. And it consists of two heavy chains and two light chains held together by disulfide bridge. And at the top of the molecule, there’s two binding domains that are comprised of a VH and a VL. And then at the bottom, the base of the Y, if you will, is the Fc domain. This is important for serum stability and effector function. So that’s a conventional antibody. Now different species will have alternate forms and in particular, relevant here is in camelids. So this includes camels, llamas, alpacas, have an alternate form of antibody called the heavy-chain-only antibody.
So just as it sounds, this form of antibody is devoid of light chains. It just has a VH domain as its binding entity. And this is interesting actually because a typical antibody does need a VH and a VL. And so the llamas or the camelids have had to evolve certain changes in the VH to support stability as a standalone binding element. And that’s actually really important because that allows a very stable but small binding entity to exist. And in fact, researchers have taken this entity by itself as just this 15 kilodalton sized binding unit. And this compact size, this opens up a lot of potential in terms of what kinds of binding molecules you can create with it. And so just to give you a flavor for what can be done here, you can take these individual antigen binding scaffolds and put them on to a variety of different types of molecules.
So on the left-hand side of this slide, I’m showing where it’s been Fc scaffold. So in a llama, there’s obviously a llama, Fc domain, but you can actually put a human Fc domain or put these single-domain antibodies on a human Fc. And there you get the benefits of having a human Fc, again, a longer serum half-life and effector function. So what’s the main benefit of having the single domain antibody there? Well, you can actually control the valency. So how many interactions are you potentially able to have with your target antigen. And so you can stack these single domains together to create a variety of multivalent molecules. You can actually also put the single domains at different ends of the Fc. So there’s a lot of optionality that you have there to create molecules that have certain performance attributes in biological systems.
You can also take two different single-domain antibodies. So raise different specificities and put them together. So you have a path towards bispecifics and multispecifics. These can be scaffolded also on the Fc, but they can also exist sort of on their own as well. So if you look at the middle portion of the slide, here, we’re talking about taking advantage of the smallness, if you will. These are ultra small-sized binding unit. And this allows you to create something with activity that you can deliver drugs. You can conjugate these single-domain antibodies to a variety of different types of molecules included in radionuclides. These are very small therapeutic agents or imaging agents that can penetrate tissues and have a variety of uses. So you can use these well as monospecifics, or single domain units, but you can also tether these together to create a chain of multi-specific molecules.
And you can also tether these to types of antibodies of single-chain antibodies in fact. So the point here is there’s a lot of flexibility just on the therapeutic protein side. And in addition, these have been found — single-domain antibodies have been found to be useful for CAR-T, where you can actually use the single-domain unit as the specifier towards the target, and that’s linked to T-cell signaling. So there’s a lot of potential there, in medicine this can open up a lot of new doors, so to speak. Alternate routes of administration is an important one. So I should mention these single-domain antibodies are very stable and relatively protease resistant. So it can be delivered orally or intra-nasally, so they can actually depending on where the target is, you can deliver these molecules directly to the target.
