Afternoon, everyone. My name is Yatin Suneja. I'm one of the biotech analysts here at Guggenheim. Welcome to our SMid Cap Biotech Conference. Our next presenting company is AnaptysBio. From the company, we have President and Chief Executive Officer Daniel Faga. Dan, why don't you make some opening comments, give us some highlights on the company and some of the near-term milestones, and then we'll go into the Q&A. Thanks, Yatin, and appreciate you having me here today. A lot going on in the company. We have a pretty big month in front of us here. What Anaptys is focused on is the discovery and development of antibodies that modulate overexpressed immune cells. So we're targeting autoimmune diseases that are systemic in nature, heterogeneous in nature. Our lead program is a PD-1 depleter and agonist, which targets PD-1. We're in two clinical trials right now, one in RA, a phase 2b study, 420 patients approximately. We'll talk about this more later, but that top-line Week 12 data is reading out this month in February, and we'll have Week 28 data as well as translational data sets available in Q2 of this year. We do have a second trial going on in the background. We're really excited about it, an ulcerative colitis 130-patient trial. We'll read out top-line results. We're on track to Q1 of 2026, so within a year. We have two other programs in the development stage portfolio, a CD122 antagonist, which is ANB033. We're in the phase I-A dose escalation right now in healthy volunteers, and the second program is ANB101, a BDCA2 modulator, and that's just about to initiate phase I-A. We have $420 million of cash coming into this calendar year. Our cash runway guidance is through year-end 2027. That encompasses taking the programs I just walked through through disease-driven data sets, as well as enabling the phase III programs for rosnilimab. What it excludes is any further inbound capital, which would be $75 million coming in from GSK when they achieve $1 billion of commercial sales of Jemperli, which is a PD-1 antagonist developed by Anaptys, as well as any other future royalty potential from that program, so we're well-capitalized. We have the runway to produce a number of different results, and we have the ability to further capitalize the company off the royalty, as if it's warranted. Got it. Very good. Thank you for that brief intro. So I want to come back to the royalty later because that seems to be a hidden value that you have, which I don't think investors are focused on. But let's focus on the asset first. So rosnilimab, how this asset is different from Lilly, and just walk me through the phase II study that you're running in RA, how you constructed it, what are some of the expectations. Yeah, so I could speak for 20 minutes on this question. I promise I won't. Lilly had a phase II-A study that showed proof of concept in arthritis. This is long ago at this point. Lilly's program was a moderate depleter and a weak agonist of PD-1 expressing T cells. In contrast, we have a very strong depleter, PD-1 high T cells, and a strong agonist. Given the proof of concept that exists already in this disease, we do believe that the differentiation and what we have shown immunologically, and that's in vitro and head-to-head comparisons, through a number of different types of assays, as well as translationally with both of our phase I and phase II data sets and Lilly's phase II data sets, there's a consistency here. Immunologically, we know we're different. We need to see that now translate to clinical differentiation. Okay. And then by being more potent depleter, of PD-1 high T cell, what does that give you, if you could articulate? Yeah, so there's three mechanisms of action with PD-1 depleter and agonist. One is the depletion of PD-1 high TPH cells, and these are precursors in terms of they interact with B cells and induce differentiation into plasma cells and autoantibody production. We will deplete those out, both in the periphery and in the tissue. The second is PD-1 high T effector cells, and in aggregate, when it comes down to depletion, we use this terminology high versus intermediary PD-1 expression. What we mean by high is there's a lot more clustering in terms of the PD-1 expression, and it does facilitate ADCC, and that's why we're seeing depletion with an IgG1 backbone. The third mechanism of action is the agonism of the PD-1 intermediary T effector cells, and what the resultant there is it reduces proliferation of additional T cells, reduces cytokine secretion out of the T cells. There are complementary mechanisms that when you look at the state of disease, that's a multiplier of what you'd see in healthy controls, PD-1 expressing T cells in the periphery. In the synovium of an RA patient, 80% of your T cells are PD-1 expressing. Half of those are PD-1 high. If you're only doing the depletion aspect, you're leaving a lot on the table in case this is what happened with Lilly, where we do believe that you're not clearing out the inflammatory-driven T cells, which should result in additional efficacy. It's three mechanisms of action, and we hit all three pretty hard. Got it. Very good. So we have already seen positive data, as you mentioned, from Lilly in RA. So what benchmark would you set for your drug in the upcoming phase II RA readout? And also talk about the size, also about the arms and the dosing that you're using there. Yeah, okay. So I'll start with the phase II trial design. So it's a 420-patient study, three active arms versus placebo. We are looking at every other week and monthly dosing within the active arms. The primary endpoint, the primary statistical analysis will be at Week 12. It's DAS28-CRP, the change from baseline through Week 12. That's a well-controlled historical endpoint. What's going to matter commercially are the higher-order responses at Week 12. Now, I'm going to come back to the specific targets. But in the real world, the way physicians treat this disease is they look for the beginnings of response, treat-to-target through Week 12, so things like ACR20. And that's traditionally the regulatory endpoint in a phase III, in the phase III trials. If there's a sign of response, you continue on treating out through Week 24. Across all classes of drugs that are approved, whether the biologics, the JAKs, you do see increasing efficacy, deeper response rates between Week 12 and Week 24. Now, our trial, and this is driven by the regulators, after Week 12, the primary analysis, at Week 14, you assess for low disease activity based on the CDAI score of less than or equal to 10. It's a pretty common assessment of disease used by the rheumatologists. If you have hit that response rate, you can stay on drug through Month 6. What we'll be looking for out to Week 28 is sustained responses from those patients. What that also means is that if you did not hit response, you could have hit ACR20, but you weren't low disease activity, you're out of the trial. It's not a real-world study in that sense. Placebo patients are also out of the trial. So what I'm also implying is you're not going to have higher response rates out to Week 28 because those patients aren't there to respond deeper than they got to at Week 12. I'm making this point because if you look at the comparisons in the marketplace, Week 12 data sets need to be compared to Week 12 data sets, Week 24 to Week 12, 24 data sets. Our trial enrolled bio-experienced, i.e., post-two-year in most cases, as well as bio-naive patients. 60% were bio-naive. And what we're going to do is break down the results by those two different populations. We stratified, so we should have balance across arms, those populations at Week 12. What we're guiding everyone are not Lilly data, right? That's behind us. Yeah. They're not moving forward, so their data is not even relevant. What matters here is what's the commercial bar when you look at all the other biologics, and we clearly need to be better than the biologics and approaching JAK-like efficacy. What that translates to on some of these higher-order numbers, which are high bars at Week 12, ACR50s of 30%, ACR70s of 10%. When you look at that CDAI low disease activity benchmarking, 30% in the bio-experienced population, and those are clearly differentiated than any other biologic class. Bio-naive, slight bump up from there across each of those three outcomes, so again, the DAS28 is a great control. We feel very confident that we're going to be statistically significant here in this disease, particularly given Lilly did this with a weaker drug in a very small study. But we're setting a very high bar that we do think you can credibly launch into second and third line and get pricing power if you look have that type of profile and you're tolerable. Very good. Very clear articulation of what you expect. What about the doses and the regimen that you're using? Yeah, so I mentioned there's three active doses, and it's a 12-fold delta between the low dose and the high dose. The low dose does hit IC90 on administration. However, it does dip below that at trough, so you know, we're reasonably confident we should see efficacy across these doses. It's rational to think there'll be dose response, but we're just going to have to get the data to see it. We're looking at every other week or monthly dosing depending on the arm that you're in. Got it. Got it. Safety? How? What is your expectation on the safety? I mean, you have studied this drug in many patients now so far. Anything particularly stands out? How is the safety and tolerability looking? We're happy with what's happening here in the class. When you look at all the publicly available data sets and the number of drugs that have been developed so far, including ours, they've been benign safety profiles in the phase I and former phase II study that we ran with rosnilimab, which was six months in duration at 400 milligrams monthly dosing. There's nothing there. On a blinded basis in our study, we're not seeing any signs of a signal. We have an independent DMC. They see unblinded data. They've raised no flags, and we're clearly well through this study at this point, and that also goes for the colitis trial that's happening in parallel. Backing up from here, though, things also have to be put in perspective for RA patients. Yeah. The comorbidities are multipliers of what you would normally expect in a healthy population, whether that's malignancy risk, DVT, MACE, infection risk. And one of the reasons for that is not just the disease. All these patients are on background methotrexate. Many of them have some level of steroid use in parallel that's constant in our trials. And this is consistent across all trials. So you're going to see low-grade infection. You're just going to with these patients. And then a second, you know, really a reminder for Wall Street is the biologics, pretty much all of them that are being used to treat RA have black boxes that came from their RA trials that are exacerbating those comorbidities. So the bar is, you know, unfortunately really low here in what we're talking about for a tolerable drug. And you have to put that in context. And so then when we look at what's going on with Lilly, right, they did run a 60-week trial. So six zero weeks, that's over a year in 500 patients. All of those patients were eligible through six months, and responders stayed on from Month 6 through Week 60. It's almost guaranteed you're going to see events. There's no control. You're going to see events. It doesn't mean it's a class signal, and it doesn't mean that's why their drug's not moving forward. But as it relates to our program, things look good so far in our trial on a blinded basis, and we'll see soon enough. Okay. Got it. I want to go back to CRP. What impact does PD-1 mechanism have on CRP? And could you be at a sort of disadvantage, just if we look at the DAS28 CRP? You have to hit DAS28-CRP regardless, and other biologics like Orencia, which is an immune cell modulator. It antagonizes dendritic cells, but it's still upstream. So there's other mechanisms of action that do not target a macrophage directly or the specific cytokines that are related to CRP, slightly upstream that have had effect, and IL-6 antagonist. You see an immediate reduction in CRP. That's unique. Over three months, we should see that reduction downstream from targeting T cells, depleting or agonizing, reducing their proliferation, and we should see ultimately signaling on reduction of CRP, on how they're activating the different monocytes or macrophages, which are releasing IL-6, releasing TNF, and are upstream from CRP. It might take long, more time to get there, but it's happened with other classes of drugs in this timeframe, so it's not something we're concerned about. Lilly actually put out some translational data from their phase II-A study that was good to see where they showed IL-6 reductions that were separating from placebo somewhere around Week 8. And so even with a weaker drug that's upstream from where you'd be targeting CRP, they were seeing the reductions in IL-6. So we should anticipate seeing that as well. Our baseline characteristics, the baseline scoring are all within a normal range. Lilly's phase II-A trial is a quirky thing with their trial. They were pretty low on CRP, but that was probably because it was just a smaller trial. So we're starting off with a baseline characteristic where we need to be with moderate severe disease. And there's nothing weird on an aggregate basis with CRP numbers. Anything particular you've done to minimize the placebo response? I mean, the journey tends to be within a particular range, but just curious, any particular steps you've taken and how should we think about it? This disease has been studied for over decades, and these are composite endpoints, right? DAS28-CRP is just the nature of looking at a biomarker on top of the decrease in tender and swelling joints. It helps control for placebo. It's a pretty tight spread historically over these decades of what placebo looks like, whether that is the primary or these higher-order responses with things like ACR70, which have very low placebo rates. And particularly at Week 12, you're not getting placebo ACR70 responders at Week 12 in any meaningful way, right? And there's decades of experience on this. So that's just the background here. We have a big study. It's distributed across the U.S. and Europe. We know it's all seropositive patients that are enrolled here. We know they have inflammation, so you know, it's the right patients that were enrolled. It's broad, robust study. So we feel pretty good about where we should be coming into this. It's not, it's not like atopic dermatitis, which is a visual assessment with a lot of variability and flaring. Got it. Very good. Then moving to the UC study, I think last year is when you narrowed the guidance, right, for the readout. Like, how is the enrollment so far? Because I have experience with other companies there. There have been some delays, but it seems like you are tracking. So number one, how is the enrollment? And how strong is the mechanism of PD-1 mechanism in as it relates to UC? Right. So we're not aggressive with our guidance here, in general. And we narrowed, you're referring to historical guidance of first half of 2026 to Q1 of 2026. We wouldn't have done that if we weren't confident we were going to hit the timelines. It's a 132-patient study. It's been ongoing for over a year approximately. And we are tracking towards that readout. We have a lot of sites in the study across the U.S. and Europe. And so we're not, we're also not conservatively running the trial. And I think that's also important. We have a lot of sites. We're going to have dispersion across sites and not over-consolidation in one site or one country, particularly in Eastern Europe. When you look at what you're actually doing in these trials, you need an endoscopy to get in with a certain severity. That'll be done again at the end of the study. That helps control out of the gates. I mean, these are e-diaries. And there's a certain level of severity. So between the way the inclusion criteria, which you have to go through a procedure that assesses the inflammation at the time of randomization, it's an important way to help manage. But I also want to highlight one other thing as it relates to placebo here. You look at the TL1A classes. The lowest placebo was Prometheus on clinical remission in induction phases. Low single digits. Most of these trials are 5%-10% on clinical remission. Sanofi Teva was the highest placebo. It was something like 20%. But you know which one had the best placebo-adjusted response? Sanofi Teva. It was two points higher than Prometheus. So it had the highest placebo, but also had the highest placebo because the drugs work, right? And you see separation. So I think we have to keep this in mind that there's a range here, on placebo. If your drug works, you're going to see it separate. Yeah. In UC, what do you think, you would need to show? We haven't guided yet here, and we will post the RA data. The markets have been more in flux. What's unique about RA, when we initiated this trial over two years ago, and now multiple times through, what you need to hit is no different because there's been no success in the last two years, and you see it's evolving, so from a conservative basis, we'll give some guidance, later this year, more specifically, but just like observationally, clinical remissions is going to be the commercial bar that you need to hit at 12 months. You need to see a substantial number of patients there. The TL1As are all the same. They're all plus or minus 25%. The IL-23 P19s are high teens, low 20s. So you get this range that is not too differentiated and not too different from where RA would have been a long time ago. The difference with the UC market is in the future you're going to have more biologic choices, and you should see more class switching. In RA, that's exactly what happens now. So for the reasons that we need to be bio-better, JAK-like in RA, it's the opposite in UC where if you're more bio-like, you're going to have a substantial market share still because patients are going to cycle through these drugs. One half to one, one third to one half of patients on biologics in UC lose response at one year. There's going to be class switching. So it's a different growth market there. And so we're optimistic that it's a lower bar, which is important because when if we hit the TPP in RA, there should be read-through to UC. If we miss the TPP in RA, but we still work, there should still be a positive read-through to UC. I think it's an important point to keep in mind here. It's a different bar. Very good. What is the strength of mechanism in UC, PD-1? So similar to RA, PD-1 positive high T cells are amplified in the periphery. There's literature that exists in UC that by just eliminating those cells from the periphery in the blood, it correlates highly with clinical remissions. Entyvio works just by blocking T cell trafficking from the blood to the tissue that's inflamed in the lamina propria. Those T cells are PD-1 positive. They're activated. That's all they do. The S1P is block the efflux from the lymph nodes through the periphery into the tissue. That's all they do is block that. So if we're depleting out these TPH cells, which are PD-1 high by definition, they're all PD-1 high expressing, we should see effect. Translationally in the RA study, we'll be able to show you that in Q2, that in an amplified state of inflammation versus healthy controls, we've showed 90% depletion. In these amplified states, we'll see that in the blood in the translational data sets in RA. That's pretty similar. In the lamina propria, which is the inflamed tissue in the colon of UC, there's 40% approximately positive PD-1 cells. We'll see what we're doing in the synovium of the RA patients. We'll see the cytokine reductions. We'll see if we're impacting downstream things like IL-23. Cytokines we know that are highly upregulated in UC. That should be an important read-through as well, in Q2 translationally. So we're excited about the opportunity in UC. And we think that, positive results, just stat sig results in February here in RA, as well as the translational data sets in Q2, will continuously de-risk what's already a very strong preclinical data set. We have animal model data and, in mice, there's literature, all the in vitro work that supports why we should work in UC. So we do see a consistent de-risking into our data, in Q1 2026. Could there be some patient that have RA and UC might have gotten enrolled in the RA study? Is that a possibility? Or no? I mean, it's not something I'm aware of or tracking. Okay. Very good. So I want to spend a little bit of time on the pipeline and the royalty stream. So, you know, ANB033, CD122, how is this asset differentiated? What are you doing right now? When will you disclose new indication? CD122 receptor is what ANB033 targets and blocks. It is a dimeric receptor that's found on NK cells, CD8 positive cytotoxic T cells, CD8 positive TEMRA cells, resident memory T cells. These T cell subsets that are linked to very specific disease sets. It is a dimeric receptor. It blocks IL-15 and IL-2 on those, on those cells. These cells are very sensitive. In particular, NK cells are very, very sensitive to IL-15 reduction. Any CD122 blocking program is going to knock down any NK cell that expresses CD122. That is not all of them. About three quarters of the NK cells express the CD122 receptor. You should see a pretty potent reduction of that specific type of NK cells across all of us. There are differences in potency that can be driven by affinity and epitope that are going to matter here. We will put out data later this year that shows differentiation relative to the two other CD122 programs that are currently in clinical development, and we will do a teach-in on why we think blocking CD122 is much more powerful in terms of treating these specific inflammatory diseases than just blocking IL-15 on its own, so that's coming. We've committed to an R&D event later this year. We're building up data now. We're in the phase I-A, like I mentioned earlier, moving through the SAD, MAD, dose escalation. We're looking at IV and subcutaneous dosing in parallel, and we are on track to initiate the phase I-B this year, and we will disclose that indication at the time of that R&D event. So more to come. I think there's some competitive data coming also in this space. Yeah. And I'll just highlight a couple of things. Incyte talked about vitiligo data coming this summer. They have a CD122 they acquired from a company called Villaris. And there's a company called Forte that's talked about celiac data coming up here in Q2. Yeah. Got it. Both 1B trials, so small, small, small, small trials. So going back to the GSK royalty agreement, could you just talk about, you know, how the dynamic, because you've monetized a sub-billion dollar, but now the sales is going to reach above billion. So how is that set up? What sort of is the potential? GSK is starting now to sell a lot of Jemperli, and it's off the back of a frontline endometrial approval for about 80% or so of the patients that have endometrial cancer just based on subpopulations. They just announced their quarter this morning. If you take Q4 run rate, so just times four, it's between $750 million and $800 million of revenue. So they're tracking with any modest growth to hit $1 billion this year. That's my guidance, not theirs. Right. So that's just very simple math. When they hit $1 billion, we get a $75 million payment direct to us. That's not been monetized. I think it's reasonable. It happens this year. If not, it'll happen in 2026. Is that a billion in one calendar year? One calendar year, so it has to happen this year. Yep, but if it doesn't happen this year, based on the growth rates, it's, and they just received frontline approval in endometrial a couple of weeks ago in Europe, so that's not in any of the numbers so far. It will be in 2025, and they have a number of additional catalysts upcoming, but they've guided at $2.5 billion, which they reiterated today, of peak Jemperli sales, which is based on monotherapy indications. Wall Street consensus as of November, which is what they published on their website, was $1.2 billion. There's a lot of upside there, and this is by 2031, so in the next seven years, a lot of upside there. If you take a DCF of the Wall Street consensus from November, which is dated, it is worth more than my market cap right now after we pay down what we've already monetized. So the simple way to think about the monetization is it's, we have to pay back $600 million. We've paid back $90 million coming into the year. Sounds like it's a lot, but these royalties are very big. We've disclosed all the royalty tiers. It's 8% up to $1 billion. It escalates to 25% at $2.5 billion. So it's a substantial royalty. Wall Street consensus, again, dated and very conservative, suggests we'll pay that down into 2028 sometime. And I think it's, again, I think it's upside risk from there. The reason this is important is we will ultimately need more money in this company. And this will help subsidize us moving forward, something like UC into phase III on our own. It's not the total money we'll ever need in life, but it's a lot of capital coming in with risk of the upside. So we're excited about it. A year ago today, it wasn't this substantive as it is coming into this year. Very good, Dan. Thank you so much. That's all I have for you. We'll wait for data in the next few weeks. Excellent. Thank you for your time. Thank you.