OmniAb, Inc.

11 a.m. Eastern time, so we'll kick it off. Good morning, everyone. I'm Matt Foer, CEO of OmniAb, and I want to thank you all for joining our first research and technology event. We're presenting today from NASDAQ's Entrepreneurial Center. Good morning, everyone. in downtown San Francisco, which is just a short drive across the Bay Bridge from our headquarters and our labs over in Emeryville. It's been just over a year since OmniApp became an independent publicly traded company listed on the NASDAQ exchange. And I want to thank the NASDAQ team here in San Francisco and back in New York, but especially the team here in San Francisco for hosting us today and furnishing this great space for our event this morning. But before I begin, I'd like to remind you that we'll be making forward looking statements during our presentations. These forward looking statements, of course, carry risks and uncertainties and actual results may be different from those that are projected. So I'd urge investors. to please consult today's earnings release, as well as our SEC filings for more information on these risks. So again, welcome. I'm gonna provide some opening remarks this morning, some updates on the business, and also give a bit of a roadmap to today's presentations. But before I do, I wanted to introduce you to our presenters. We've got a wider cross-section of management. I'm excited that investors and analysts get the chance to meet more of our management and leadership team here. So you'll see presentations from Todd Pettengill, who's our VP of Business Development and Strategy. Todd's been with the OmniAd business really since the beginning of forming the foundation of what has now become OmniAd. He played a critical role in all six of the acquisitions, the company and technology acquisitions that we did in less than a six-year period to form what is now the foundation of the business of OmniAb. Bill Harriman heads our antibody discovery. Bill was a founder of Crystal Bioscience, which was the innovator and inventor of OmniChicken. Bill's had a really illustrious career in the antibody discovery space, is also the inventor of the GEM assay, which is part of our technology. And Bill has the honors of doing the Omnidab launch today, and you'll hear more about that as I run through the agenda. Bob Chen runs our discovery systems. Bob joined us when we acquired Accela Biosciences. Bob was the co-founder of of Accela. He co-founded it along with Dr. Jennifer Cochran, who also sits on our board of directors. The Accela business was spun out of the Stanford School of Engineering, and Bob is an inventor of our exploration technology, which has become a key part of our business as well. And you'll also get to meet Doug Kraft. Doug is a well-known individual in the scientific circles around ion channels and transporters. He's had a long history of firsts, scientific firsts, around the ion channel and transporter space, and heads our ion channel and transporter team based out in Durham. And then you'll also get to meet Kurt. Obviously, many of the investors on the line and analysts know Kurt very well. Kurt joined us not long before the split, when we split the business off and became an independent publicly traded company. He has a long career in biotech and technology. longest of which was at Amgen for many years, heading their European finance operations. So excited that you'll get a chance to meet all of these colleagues who I'm honored to work with today. Today's agenda, again, I'll provide some opening remarks. Todd's going to give an update on creating value for partners. That's something, obviously, that's very important to us. And Bill will be launching the Omnidab technology today. We'll talk a lot about that, get into the science, get into where it fits in the industry and why it's important. Bob will highlight how we enhance discovery with OmniDeep, which is our suite of in silico tools that are woven throughout our technology stack. And Bob will provide details there and provide some case studies and other details that we think will be interesting to the investment community. And then Doug will talk about the ion channel opportunity, some high value partnerships that we have there and why we see unlocking the antibody potential in ion channels as an important part of the future. And then Kurt will review financials. Obviously, we reported our Q3 financials earlier this morning. He'll review those and also provide some other financial insights into our portfolio of partnerships and our business. But I'm going to start with our mission. We are a mission-driven organization. This is what guides us. This is what keeps us focused. And our mission is to enable the rapid development of innovative therapeutics by pushing the frontiers of drug discovery technologies. highly focused on this, we're highly committed to this, and I think that clarity of mission is one of the things that attracts new partners and also causes a number of our existing partners to expand their use of our platform. Our business in many ways is quite simple. It's a licensing business. So we license our technologies to the industry to allow them to more quickly and efficiently discover antibody-based therapeutics. Our technology offering addresses some of the most critical needs in discovery today. And we're operating one of the largest green fields in the pharma industry. I'll talk more about that in a couple of slides. But the antibody element of an antibody related therapy elements of the industry continue to grow. We have a leading and proven technology now with a growing number of partners and a growing number of programs. And we are committed to continued innovation and what we call intelligent expansion of our technology. Because of where we sit in the industry we have a bit of a unique position where we can have deep technical dialogue with our partners not only understanding where they are today but where they are headed and that informs how we invest in and how we innovate around our platform. So a little bit on Omniab today. We, as I said at the outset, we just passed the one year mark of being an independent publicly traded company. And we really do feel like all of the pieces in the business are beginning to become aligned as we look forward into 2024 and beyond. we do feel like we really have a business that is positioned to sing if you will going forward that the pieces have come into place and we really do now feel like we have a business that's positioned to sing. Our work is centered on driving the business on accelerating innovation around the platform, and consistently staying ahead of our partners' discovery needs. We're 112 employees across three primary US sites. Our headquarters here in the San Francisco Bay Area, over in Emeryville. We have an ion channel and transporter team in Durham, North Carolina, as I mentioned. And then also an Insilico team that's based in Tucson, Arizona. And then we've also built up our business development team more broadly. and recently established ex-US business development presence as well. We see the need for only minimal future headcount growth to support substantial growth in our portfolio and our partnerships. There's a lot of leverage in this business, a lot of efficiency that's been built in over time, and we feel like we're really well positioned to take advantage of that leverage. Despite a macro landscape in the pharma tools and technology space that has obviously been widely reported and has had a number of headwinds associated with it, our business metrics in our business continue to demonstrate the value that our platform brings to the industry. We've had nice growth and new partners, nice growth and new programs over the last 24 months while the industry has been facing substantial headwinds. We've also seen nice partner program advancement and announced this morning that we now have five new clinical entrants in this calendar year 2023. Our work and our technologies are really having an important impact, not only on our partners' R&D pipelines, but also on patients' lives. This is something that really motivates us. It motivates the rigor that we put into the science, how we challenge ourselves to stay ahead of partners' needs, but we're quite proud of the fact of where we sit in the industry, and it's quite rewarding to see the impacts we're starting to have on patients' lives. There are over 170 active or completed clinical trials that are testing OmniAb-derived therapeutics. That's a testament not only to our partners' commitment and conviction around the antibodies that have been discovered out of our technology, but it also speaks a lot about the impact that we can potentially have on patients' lives. There are over 30,000 subjects either enrolled or to be enrolled in those trials. We have three approved OmniAb-derived drugs. All of those are in cancer currently, and a growing portfolio of clinical programs that I'll touch on a little bit later in this section. Our business is really designed and funded for continued innovation and intelligent technology expansion. We're obviously launching an exciting new technology today, our Omnidab heavy chain only chicken. And importantly, our innovation engine for either producing new transgenic animals or new elements of our technology is becoming more and more efficient. We're able to do it faster. We're able to do it more cost effectively. And that's something that I think will feed the business well into the future. We will launch other novel technologies next year as well. And we also expect to roll out other new partner experience enhancements as we call them in 2024 and beyond. So I'm going to step back for a moment and talk a little bit about the antibody market. This is a growing market for a variety of reasons. The antibodies are projected to have sales of $279 billion by 2025, up from $238 billion last year. There were 51 blockbuster antibodies. So these are antibodies with sales of over a billion dollars in 2022. and the five best-selling antibodies had approximately 75 billion of sales last year. The importance of discovery technology focused on antibodies continues to increase for a variety of reasons. There have been decades of foundational and basic biology research, and scientific advancement that are helping create what I see as a continuing need for cutting edge antibody related discovery technologies. A lot of foundational investment that is driving that present day and future demand. Really starting all the way back with Nixon's war on cancer back in the 1970s and then a number of other scientific advancements that contributed to antibodies becoming a more and more important modality for treating disease. Those include hybridoma, the cloning, obviously the human genome project, and the advent of proteomics, as well as other advancements in immunology and a deeper understanding of immunology, molecular biology, and higher and higher speed computing, all of which drive that demand for discovery technology. In addition to that, The industry success rates, the success rates that our industry, the pharmaceutical industry, has enjoyed over recent years have been far higher for antibodies than traditional small molecule pills that you may put in your mouth. Overall, the historical success rates for antibodies have been roughly double that for small molecules when you compare it over the fullness of time. There are also other factors that are driving interest in antibodies, the Inflation Reduction Act, which is shifting R&D spending of large pharma partners away from small molecules is also driving interest in antibodies. And then the data on the right-hand side in the blue of this slide is actually very new data. This was just presented a couple of weeks ago by the Antibody Society, who do a very meticulous tracking of antibody success rates for antibodies that are being pursued in a therapeutic way by commercial sponsors. So we find this data, one, extremely relevant and also very interesting given what it's showing. And if you look at it very closely, the way the Antibody Society does this is they're tracking these on an individual basis. And you see in the bar charts moving left to right, and there are overlapping periods here because of the way in which they report the data and the way in which they track the data. But you can see over time that it appears that the industry is also getting better at developing antibody-based therapeutics. So not only have the historical success rates have been better than small molecules, other macro factors driving investment away from small molecules to antibody-based modalities, but the industry is also getting better at developing antibody-based medicines. So I'm going to talk a little bit about some recent metrics in the business. We've signed eight new license agreements so far this year. We announced new platform agreements with Gigimmune and Polaris Therapeutics that were both signed in Q3 and more recently entered into a new platform license agreement with a global pharma company, a well-established global pharma company that was also signed recently. So our active partner count has grown to 76 as of the end of the quarter. And as you can see in the bar chart, we've continued to grow the number of active partners net of attrition over a number of cycles in the biotech space. We also think there's strength in diversity in the types of partners that we are attracting and bringing in. And that creates multiple paths to potential value creation downstream. We've also seen nice growth and advancement of active programs. We started this year with 291 active programs. And we ended Q3 with 314 active programs net of attrition. So you can see that growth reflected On the left hand side in the bar chart and then in the pie chart in the right, you see that we've had nice growth and diversity as well as graduation and advancement, if you will, of programs. So we've had a number of programs move from discovery to preclinical. We've had five programs move from preclinical to phase one clinical trials and one program move from a phase three to its first international filing. I want to note here as well that our definition of preclinical is something of a high hurdle. We don't put something in that preclinical slice of the pie chart unless it is in pre-IND studies And the partner is moving towards filing an IND and entering into clinical trials. So that's quite a high bar that we use in defining preclinical. But as you see, there are 14 programs in that slice. We've also had growth in active clinical programs. We started off 2023 indicating our expectation publicly that we expected three to five new clinical starts this year. And at the end of Q3, we are at five. So we've had five new clinical programs of OmniAb-derived antibodies enter the clinic this year. Cgen had a bispecific. Immunivant entered the clinic with IMVT. 1402, which is a next generation FCRN antagonist. They've also already reported out positive data for that program and indicated this morning they expect more data for that program before the end of this month. Gloria entered into its first clinical trial for an anti-LAG3. And then in the third quarter, Roche entered into the clinic with a bispecific antibody and cessation therapeutics entered into clinical trials with an antibody with a very interesting and important medical use as an anti-fentanyl. Obviously, fentanyl, a lot of reporting of the medical tragedy and growth in medical need around preventing fentanyl overdose and this is a really interesting use of an antibody and that's an issue not only here in the United States as has been widely reported but also now becoming more of an issue in other countries as well. I do want to note here on the Roche program which entered the clinic in Q3 That is a program that is subject of a fully paid license that was essentially a grandfathered license that we inherited from a company that we acquired. So there are no economics to that program. So I want to be clear about that. But it is a further validation of the importance of our technology in a variety of disease spaces. We continue to monitor the progress of the 14 preclinical stage programs as those approach phase one clinical trials. As I mentioned on the prior slide, we have a very high hurdle for what we call preclinical. These are programs that are in pre-IND studies that are approaching the clinic. This next slide is becoming a bit of an eye chart. As more and more things enter the clinic, we are now at 31 programs that are either in clinical trials, in registration, or approved. This is becoming harder and harder to read on a slide. We are considering other ways to reflect our pipeline to investors in the outside world, bullseye charts and the like, which may be more amenable to showing not only the diversity of partners, the growing diversity of therapy areas as we get deeper into the pipeline, but also the progression as well. And importantly now, as I kind of wrap up my section here, we're announcing today that we are launching Omnidab. In fact, we've already launched it. We have partners now that are already leveraging this newest technology of ours in active programs. Omnidab, put simply, is the first and only transgenic chicken that is producing single domain antibodies. And this is a growing important class And one that creates a lot of interesting opportunities, not only medically and scientifically, but for the business as well. And Bill is going to talk more about that. And Todd will also talk about partner perspectives around Omnidab as well. And as I wrap up here, I just want to talk a little bit about our key areas of focus going forward. We believe we are well positioned for future growth, and we believe we are making an enduring and significant impact on human health and on the industry as a whole. We feel like as we enter 2024, as I said, the business, the pieces are aligning for the business and we feel like it's positioned to sing and we're leveraging a highly scalable business where investments in technology and innovation really are informed by deep discovery relationships with our partners. We have quite, I'll use a non-scientific word and say, quite intimate relationships with our partners around not only the challenges that they're facing today and the types of antibodies and antibody-based modalities that they want to pursue, but also the challenges that they're facing tomorrow. We're focused on partner pipeline development and expansion. continued what we call workflow versatility initiatives, expanding the reach of our platform, as well as new technology development and launches. At our foundation is a focus on stakeholders. That's a really important part of our foundation. I'm quite proud of the team that we have. Fantastic colleagues to work with. We have a strong culture. We really do focus on developing, hiring, and motivating the best employees. We focus all the time on our partners, making sure We're focused on customer service. We're focused on future needs and that deep collaborative scientific dialogue that they're looking for. And of course, you investors as well. That's obviously superior. Business execution is extremely important to us and will continue to be committed to that going forward. And then we're also committed to leading with integrity and responsibility in the communities in which we operate. So with that, I'm going to introduce Todd, who just a little bit ago got back from BioEurope. He's looking fresh and ready to go. So Todd, welcome. Thanks.

Good morning, everybody. Great to be here with you. Today I get to speak about a good topic, the value that we're creating for our partners and what's driving that. As Matt mentioned, we've had a really good run over the past several years of increasing our partner base, especially in the last 24 months, which is especially encouraging in light of the recent market headwinds. So as we think, what is driving that? You know, there are several factors that jump out at us, but really we have had a good run to improve and increase the platform visibility, both through our business development efforts, but also through our partners as they've pushed antibodies into the clinic and also gotten them approved. We've also put, as Matt mentioned, we've put a lot of investment into our business development and marketing presence, both increasing the size of the team, but also spending a lot more time at conferences. And that's really been helpful as we've been able to have cutting edge science that's backed us up and made the message clear. Finally, we're able to be creative in how we license. We don't take a one-size-fits-all approach with our partners. We have a range of different contract types and different things that we can work with to find a deal that works for all of our partners. So with that, we're able to attract a diverse set of partners. We're now starting to define our partner base as different areas, as each one has a unique characteristics. First, we have our discovery technology access partners. These are partners who have full access to the platform for both current and potential programs, but also they can develop and commercialize antibody or OmniAb-derived antibodies. And that's the majority of our partner base. Next, we have the commercial partners. And these are the partners who have geographic or therapy area rights to commercial and development stage OmniAb-derived antibodies. They're developing and they're commercializing. Finally, we have our academic partner licenses. These are working with academics and institutes. And these licenses are designed for revenue sharing. We provide the discovery technology platform, and the understanding is that they're going to use this to do proprietary research and spin out assets for development and commercial entities. So what's driving the interest from our partners in using the platform? Well, this is our platform. So this is our tech stack. We like to define it into three separate buckets, if you will. First, create. We help people create a large diverse set of repertoire of high quality antibodies to select from. We have a wide range of transgenic and and other animals that we consider biological intelligence. And that drives how we create antibodies for our partners. Next, we screen. We help our partners screen through millions of potential antibodies to find the right therapeutic. We have a high throughput automated version, and then we also have a manual version that also digs deep into the repertoire. Finally, we deliver. We help people characterize and select and optimize the right antibody. We do that through traditional wet lab work and we also have recently incorporated in silico tools to expand and build upon the assets that we provide to our partners. So go back to the create section. It's driven by biological intelligence. So what is biological intelligence? We define biological intelligence as using mother nature to do what it does best, to generate antibodies in vivo. So we believe that in vivo generated antibodies are superior because they're generated through an iterative process that selects for antibodies and then increases the specificity and helps select for those with superior developability profiles. On top of that, our suite of transgenic animals allows us to provide antibodies with fully human variable regions. So not only are these strong antibody candidates, but they don't need to be humanized. They've already passed that key step. So that's what we call biological intelligence. And with that, we view that this increases the efficiency and the probability of success for our partners to bring them a lot of different options to potentially go to the clinic. Now let's talk about our platform. What makes us different? So we have multiple technologies that make us unique. I'll go through them high level. So on the first column, we have our chickens. So our chickens consist of three different technologies. Our omni chicken, which is a chicken that makes fully human antibodies that are standard sized antibodies. Then we have a chicken called Omniclick that makes human antibodies that have a fixed light chain. So that's useful in making bispecifics. Then we have Omnidab, which I won't speak too much right now because that's what Bill's going to be speaking about in just a few minutes. But why is a chicken important? Really, it's an evolutionary distance play. Our last common ancestor with a rodent was, call it 90 million years ago. But with a chicken, it was closer to 300 million years ago. So a chicken is that much more different from a human, and therefore that much more likely to identify an antigen or a target as non-self. So what that allows is our partners can use these chickens to identify antibodies that have a broad range of epitope coverage and a wide range of targets. Next we have our rats. So we have two technologies with our rats. We have our OmniRat, which is full standard antibodies. And then we have OmniFlick, which is fixed slide chain antibodies. Again, useful for bispecifics. So why would you use a rat? Well, a rat looks similar to a mouse, but it actually is different. And so it can react to an antigen in a different way than a mouse can. So you can get a different response. But it has a similar ease of use as a mouse. Also, a rat's bigger, so you can get higher B-cell quantity, which can potentially lead to broader diversity. Our OmniRat was our first technology that was put into operation, and we have multiple approved antibodies from the OmniRat, both in the US, in the European Union, and in Asia. Next we have our cow technology. Omnitor makes antibodies that have these unique characteristics. They have these ultra-long CDRs that stick out from the variable region of an antibody and look almost like a finger that can reach out and access recessed epitopes such as interior of ion channels or different parts of GPCRs that are normally not accessible to a standard full-length IgG antibody. So really, the Omnitor antibody opens up a broad new class of potential targets on the discovery side. Also, these ultra-long CDRs can be cleavable into a very small, fully functioning protein that's about a third the size of a nanobody. We call it a picobody, and they're useful in a lot of different functions. Finally, we have our exploration technology. This is a high throughput B-cell screening platform, which has a large amount of throughput, over one and a half million B-cells at a time it can screen. It also uses integrated artificial intelligence and sequencing to maximize repertoire mining. So these technologies, not only are they driving new partners to us, but they're keeping partners within our ecosystem as they continue to use the innovation that we have to find new antibodies. This is a quick breakdown of how our partners are using the different technologies. As you can see, OmniRad is leading the pack at the moment, but that's largely based on the fact that it was put into operation prior to all the other technologies. But as you can also see, the other technologies are becoming a bigger presence, and we're moving to be more and more diverse from our technology usage standpoint. As far as potential uses for our OmniAb antibodies, they're useful for anything that is, that could be used, that an antibody could be used for. So this is the breakdown of what our partners are doing. So a lot of mono-specific antibodies on their own, but also multi-specific, think bispecifics or more, tri-specifics. But we also have antibody drug conjugates in our pipeline. So there's a wide range. But also, they're still useful for other technologies, CAR-T, TCR memetics, things like that. Our antibodies can be useful in a wide range of applications. Bill's going to talk today about Omnidab. And that really opens up a, in a way, it blows the roof off of other potential formats that can be used with our technology. So the last slide, just before Bill talks about Omnidab, I'll just talk about why is it important to it? Why is it important to our partners? Well, our partners are interested because these are quotes from our partners. They can generate a panel of multiple multi-specific antibodies using tethered single domain antibodies. They can also rapidly generate high-affinity human sequence from the Omnidab. These molecules can be used to penetrate deeply into solid tumors. 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, you know, we'll present today, but there are several upcoming presentations that if you happen to be at, I would recommend you join. 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 will deal specifically with Omnidab. That's it for me. I will now turn it over to Bill.

Thanks, Todd. So I'm going to take you a bit deeper into the technology behind Omnidab and single-domain antibodies. Let me start first with a conventional antibody, so an IgG molecule. This is the predominant antibody form in most vertebrate species. And it consists of two heavy chains and two light chains held together by a disulfide bridge. 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 llama 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 size binding unit. And this compact size just 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 onto a variety of different types of molecules. So on the left-hand side of this slide, I'm showing where it's been FC scaffolding. So in the 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 against 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 raised with 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, this ultra small size 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, including radionuclides. These are very small therapeutic agents, or imaging agents that can penetrate deep into tissues and have a variety of uses. So you can use these well as mono-specific, so 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 other types of antibodies, like single chain antibodies and FABs. So the point here is there's a lot of flexibility just on the therapeutic protein side. And in addition, 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. I should mention these single domain antibodies are very stable and relatively protease resistant. They can be delivered orally or intranasally. They can actually, depending on where the target is, you can deliver these molecules directly to the target. So that's an advantage in particular of this type of compact antibody. And also related to that is tumor penetration, tissue penetration, and potential for getting across blood-brain barrier to deliver therapeutic molecules across that. For imaging, quite useful, the fast clearance rate. If you don't have an FC or you haven't done anything to extend the half-life, these molecules are cleared very quickly out of the serum. For imaging applications, that's really important because molecules which are bound to the target can bind there quickly, but then everything else is not bound, it's cleared quickly, creates a very high contrast, so it makes them very ideal molecules for that situation. So overall, there's a lot of broad therapeutic applications of single-domain antibodies in medicine, and it's growing. So let's talk about how, as of today, single-domain antibodies have been made. What's the process? Or at least maybe the ones that are in the clinic now or approved drugs, how were they made? And again, the single-domain antibodies come from llamas, so you need to immunize a llama. And when you immunize a llama, you get llama antibodies. That's fine, but more ideally for a therapeutic use in humans, you'd like to have a human-based framework. And so a lot of the molecules that are in the clinic now have been originally from LAMA immunization, but they've been humanized. And what humanized really means is you take the frameworks. Within the V region, there's framework regions and there's CDR regions. CDR regions are the variable sequences which determine the specificity of the antibody for the target. You can't generally change those too much without altering the binding. So those usually stay. But the framework itself is an important thing that you can change to human. However, if you just simply change the LAMA frameworks to human, that particular molecule is not that stable and not that developable in a way because it's not really evolved. Human V genes, the frameworks, have not evolved to be expressed on their own. They're always paired with VLs. And so that requires you need to sort of introduce some of these LAMA sequences back into the human frameworks. You've got to re-engineer those back in in order to have a good developable molecule. So all of this is just a lot of engineering, a lot of processing after that initial discovery of the antibody. And this is where Omnidab can really streamline the entire process. So Omnidab is a transgenic chicken that has, starts with a human framework, but not a 100% human framework because we've introduced stabilizing mutations into certain regions that are important, that are known to support solubility and stability as a single domain antibody. And in this slide here, it's rather busy, but what we have on the top line is actual fully human sequence. And then just below that where you see the purple arrow, you can see the positions where we've put these stabilizing mutations in. And then below that are all the clinical molecules, including some that are FDA approved. And what you can see collectively is those positions where we've introduced our stabilized mutations are consistent with how these clinical molecules have actually turned out, how they've been engineered after all this effort to come at those sequences. Now, of course, the CDRs are highly variable because they're all different targets. They're different antibodies. But the point is that the basic scaffold that you want to have in the end that's engineered already into the chicken. So that means that when you immunize Omnidab chickens, you'll come out with a panel of antibodies that will already have these engineered attributes to them. So this allows you to get much closer to your final molecule directly from the animal, which basically saves time and decrease risk of things going wrong during the engineering process. So that's one key benefit, this pre-engineered aspect of the transgene. It's a key benefit of Omnidab. But also, as Todd mentioned, this is in a chicken. So that's a different animal too. And one way to understand the advantage here is basically all mammals genetically are more related or closer to each other than they are to birds, let's say. So if you're talking about raising antibodies, any animal who is responding to a foreign antigen, the degree of foreignness, the degree of difference is important. And so within the realm of mammals, there are differences. You can make antibodies in a mouse to a human to various species. You can get antibodies out. they don't tend to be recognized as foreign within that group of mammals as if you were to immunize any of those proteins into a bird. Another way to think about this, if you indulge me in a metaphor here, let's say your target of interest is a green apple. And that's different than what the mouse version of this protein is. Let's say that the mouse protein is a red apple. So you inject the human protein in the mouse. The mouse will say, yep, that's different. And it'll make some antibodies. And we expect this. This happens. Lots and lots of literature and progress based on this. So I'm not saying that doesn't happen. However, you take that same human protein and you put it in a chicken. man, right, the chicken sees this as 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 epitope diversity, and I'll talk about that some more too, but that's one of the key things that the chicken brings 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 VHVL antibody. It doesn't matter if it's OmniClick with a common light chain antibody. And here, an Omnidab. So these really kind of summarize 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 things. 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 a panel of antibodies from another. In this case, the first campaign was performed in Omnidab. In another case, the campaign was performed in OmniFlick, which is a rat, a common light chain rat. And this process of epitope binning allows you to see where are these antibodies binding and 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 peritope. That's the part that binds the epitope. It's smaller than a conventional VH by VL antibody. So anyway, in all the results we've seen so far with Omnidab, you can get this sort of unique epitope. 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 some of these molecules. And the types of things you look at are thermal stability and a whole host of things. But one very important metric that's looked at is self-interaction. So they call it AC Sins. It's looking at when you take the protein and you put it at a very high concentration, what's the 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 and showing you the range. In this case, a low score is better. So you're seeing the ACSYN 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 farther 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 transiting chickens express an optimized single-domain human framework. So again, pre-engineered. Omnidab, since being a chicken, it targets distinct epitopes. These are robust animals. You get good titers upon immunization, and you get high-quality antigen-specific antibodies with good developability profiles and 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 more in silico and screening side of things. I'll turn it over to Bob Chen. He'll tell you about how we've really developed and pushed the technology on that to get the very most we can out of the repertoires we generate from our transgenic chickens.