Welcome back. Good afternoon, everyone. My name is Yatin Suneja, one of the biotech analysts here at Guggenheim. Welcome to our inaugural Guggenheim Innovation Conference, Healthcare Conference. Our next presenting company is Zura Bio. We have a few members from the company here. We have the CEO here, Rob Lisicki, and we also have CMO and Head of Development, Kiran Nistala, here with me. Rob, why don't you maybe give us an overview of what's going on at Zura? Obviously, you have a few assets that you have sort of accumulated over time. Just talk about some of the upcoming milestones, and then we'll go into sort of the Q&A discussion. Sure. Yeah, first, on behalf of the company, just thank you for the chance for today's update. Zura was founded as a private company in 2022. In April of 2023, they IPO'd with an $80 million raise. And through that process, we've in-licensed three clinical stage assets. All of those assets are bispecific antibodies, meaning that they have two different targets to demonstrate their effect. It's an exciting time now. I think everyone's been waiting for the initiation of the trials. We are pending a cited trial initiation for systemic sclerosis with our lead asset, tibulizumab, which is a BAFF anti-IL-17. And then in the first half of 2025, a trial in HS. We're also excited because there'll be a direct read-through for Q32 Bio's IL-7, and AD and AA. And then in the first half of 2025, read-throughs in COPD with an IL-33 and an ST2 receptor. Very exciting time for the company. Okay. So let's just first discuss the lead asset, right? I think you made some updates on the quarterly call. I think things are moving fine on the SSC and HS. So can you just tell us why, number one, you prioritize these two indications, scleroderma and hidradenitis suppurativa, where exactly we are on these two studies and what the plan is when you run these studies? Yeah, so the company's strategy since inception has been to explore and understand where there may be scientific validation or support for those assets, those molecules, and then to wait for clinical validation before we move forward. So in SSC, there's strong scientific evidence in support of IL-17 and BAFF, but more importantly, there's clinical validation as well on the IL-17 side with brodalumab and on the BAFF side, belimumab. That was really the basis for that decision. That trial is scheduled to initiate in Q4 of this year, so it's pending. Hidradenitis was very similar, IL-17, well characterized in HS. There's somewhere between eight and 10 Phase II, Phase III studies. So as a foundation, we know we'll demonstrate effect with that portion of the asset. But there's an emergence of B-cell data and neutralizing and depleting data in HS. So the opportunity for this asset in HS is '17+, right? So think of the benefit, the clinical therapeutic benefit of IL-17 inhibition, and then add potentially BAFF on top of that. I see. I see. And on a timing piece, I'm sorry, that's scheduled to initiate in the first half of 2025. Okay. So for SSc, obviously, pretty tough disease to treat. How is the study set up? What are the timeframe from an enrollment standpoint? Do we have an understanding on the dose, the frequency that you are trying to evaluate in the Phase II? Yeah. Kiran, do you want to take that? Yeah. Hi, Yatin. Nice to meet you finally, face to face. So SSc, maybe at a high level, I just kind of give you the strategy, which is deliver on the skin, mRSS, and really understand the lungs. So that's kind of the goal of the study. We've done a lot of work thinking about the dose. And there, in terms of what we've done, is really made sure that we've modeled target engagement in the tissue so that we have adequate target engagement cover. In terms of size, it's 80 subjects across three regions. And our goal is to complete all the enrollment by sort of February, March 2026. So we're in time to deliver the study by end of 2026. How many arms in the study? And it's just one dose? Yeah, so just one dose, Q4W, and placebo. Okay. And then just the expectations from the study, obviously, it's a decent-sized 80-patient study. What would constitute a success there? How should we think about what are the comparables that we should think about? Yeah, I mean, I think, as you know, there is no currently approved therapy for scleroderma, right? So part of it is really we want to understand our effect on both the skin and lung. We've powered the study looking for MRSS change that's around MCID, which is kind of three to four. And so our goal is to deliver success there. Clearly, one of the challenges in scleroderma is that we've seen a lot of negative studies. So we spent a lot of time trying to think how to de-risk that. On the lung side, what I would say is you need a really big study to show FVC as the kind of more registrational endpoint. So we've taken what I think is quite an innovative approach, which is to look at using a more sensitive endpoint like HRCT, which, if you've seen the tocilizumab data, shows really high concordance with FVC, but shows more rapid change. So we can do zero in 24 weeks, right, which is the randomized portion, and try and show the differences in HRCT. But we also have a further six months of open-label extension. So we'll be able to look again at the HRCT and FVC at that time point. I see. So the patients will continue even after the randomization into an open label. Correct. Yeah. That are longer-term follow-up. Okay. So similarly on the HS side, I think we have seen data that IL-17 definitely works, maybe BAFF. I mean, I think BAFF is better. If you look at the bimekizumab data, we still have to see what MoonLake has to produce. Where are you on that '17 sort of from a mechanistic standpoint? And then also, so first talk about the IL-17 piece, how you are attacking it. And then are there data that you can put in perspective for where B-cells are showing benefit in HS? Yeah, I'll take the first part of that. I think that the rate of attrition in the bimekizumab data from Phase II to Phase III in HS was atypically high, I think. So when I look at the Phase III combined delta, it's 17%. If you look at secukinumab, it was 6% in one study, 17% in another. So kind of worlds apart, in my view. So I think the question on HS is still an open one. The IL-17 component of this asset is ixekizumab. Ixekizumab, in terms of potency, is far more potent for AD and BAFF than either secukinumab or bimekizumab. So we certainly think that we can show an inline effect, perhaps more. Kiran, do you want to talk a bit about the validation and scientific support for BAFF? Yeah, I think maybe start with a general point, which is if you talk to some of the kind of key opinion leaders in the field, Dr. Kimball and others, there's a real desire for broader therapeutic. And that's because even the ambition with FF was to try and solve this disease, and it hasn't done that. So I think there's a lot of excitement about the potential for us to bring now two complementary mechanisms. So why BAFF? So actually, there's two really nice pieces of work. One is Sabat et al. and then another one out of the Johnston group showing that there's very high expression of BAFF, both in the nodules, the abscesses, and in the tunnels. And actually, they looked at the transcriptome signature when they modeled that in vitro. When you block BAFF using actually a BTK inhibitor, you find that all of that pathogenic signal is taken away, so there's data in silico, there's data in vitro, but now there's also clinical data, and we were excited to see the Novartis readout with their BTK inhibitor, remibrutinib, and that obviously is very close to the mechanism that we're targeting, and that showed very exciting results, so I think it really kind of goes back to what Rob was saying, which is we wait to see if there's clinical validation. We feel now, given the strong pedigree of IL-17, now with BAFF, this really is a winning combination. Got it. So how is the study set up in HS? Generally, many antibodies are dosed higher. So just walk us through your study design, and the end goal is, given that this is sort of a combination approach, do you think we can break the efficacy ceiling with your approach? Yeah, well, maybe I'll start with the last question first. I think absolutely. And that speaks to some of the science we've been talking about. In terms of the study design, we're still kind of in the process of finalizing some of the details, but maybe at a high level, the goal is to have a 16-week study with two dose arms and a placebo, so three in total. And we are having likely a continuous variable as the primary, something like AN count. But what we really need to show is kind of competitive result on HiSCR75, which is really, I think, the new standard of care. So in terms of the dose, the thinking for us is exactly to your point, which is there's a very big inflammatory burden. Some of our competitors have struggled with this kind of inverse dose response. So really understanding and being confident when we take two doses and a dose that's even higher than scleroderma because, as I say, of this inflammatory burden. So by the end of this study, we'll really have confidence around what the right dose is, Phase III. So for the SSc study, have you filed the IND, or that sort of is just the gating factor to get an approval? Also for then the HS, what is the gating factor there? Just filing of any IND or any sort of coordination you need to do with the FDA? Yeah, it's both. So the IND for SSc, we've guided to Q4. Post the IND, it allows us to initiate the SSc study. The IND for HS will go to a separate division. And the current guidance is a submission on early Q1. That would enable us to potentially start that study in the first half of 2025. Got it. And my understanding is that even though HS is starting later, you will probably get data before SSC. Can you confirm that? What are the timelines for the readout for HS? Yeah, we expect that to be the case. SSc is an orphan disease. Obviously, there's a fair amount of competition for those patients, multiple regions. HS is a shorter study in terms of duration, much larger population of patients. Need is still high. And it's largely a U.S.-based study. So the expectation is that study likely comes in about a quarter prior to the SSc. But we think in 2026, we'll have two pivotal top-line data readouts for 106. What is the size of the HS study, three arms? Yeah, we haven't kind of made that public, but I think what you'd want to understand is we're looking to power for a competitive HiSCR75. So that's usually around the region of kind of 60 or so per arm. So per arm. Okay. In terms of, so the asset came from Lilly, right, so I think we do get this question still, and I think more questions will come next year as people start focusing on the story. Why Lilly gave it up, and also, if you can talk about some of the safety data that has been generated with this asset and then the dosing that you're using. Do you have to do any dose formulation work or anything like that? Yeah, I think my short answer, not to be a smart aleck, is I'm glad they did, and I'm glad we got it. Look, in biotech, it's kind of the lifeline of early biotech is to find assets that for whatever reason, large pharma has deprioritized, maybe because of rationalization of their pipeline, and take those assets and then move them into the right studies. In the deal and the agreement that we have with Lilly, they're engaged, they're involved, and they have royalty and milestone payments as well. So I think they certainly see value in this asset and the work that we're doing. Former member of Eli Lilly is a part of our scientific advisory board as well. So yeah, I think it's always hard when you start to speculate on why someone made the decision that they did. But our evaluation of the asset is that there's a really special chance in HS and SSc. Okay. And then the dosing and everything is done, like the formulation, but what is the concentration? We haven't made the concentration public, but maybe I just will touch on a point that you raised before. We haven't spoken to safety. We've got three studies that have already been done on this, and there's nothing from that dataset that is of concern. What I would say is not only, obviously, it's a relatively small sample of studies, the bulk of data from Rob Lisicki and also, excuse me, I think really inform us as to what the expected side effect profile is. I think both drugs are incredibly safe. Actually putting them together, there's no reason why we expect to see anything different. In terms of the dose, as I say, tested previously was up to maximum of 300 Q2W. We'll be looking towards the top end. The bottom of that range is around 30 milligrams. We're looking towards the top end of that range. Okay. With regard to de-risking read-through, I think Novartis is running this platform study. Do we have any sense of whether we're going to see any data from there that could have read-through to you, or how are you thinking about the landscape? No, I think you're talking about their BAFF. There's a couple of distinctions. It's BAFF only, and it's a depleter as well. So I think those are two important distinctions. They have not provided guidance, but what we've seen historically is that the readouts coincide with large congresses. We anticipated perhaps at EADV, but that didn't happen. So maybe in spring at AAD is when we'll see the data. Okay. All right, very good. Then moving on to the IL-7RA that you have, maybe talk about the pathway. How do you see it, the appeal of this pathway, obviously broader mechanism? Where do you think it's applicable, and how are you preparing yourself for some of the derivative read-through, whether it's Q32 or OSE? Yeah, so internally, we do work to, first of all, validate the scientific rationale that other companies may have and to look at their trial designs to see if it aligns with how we would approach it and how we would do that work. The second thing we do is to establish what we think a compelling result would be. And then in background, we do do some early work on potential protocol development, study design, sizing, and cost. So we've been able to do that work for a number of indications or potential indications for 168. So what we're waiting to see now is what does the Phase II data look like from Q32 for atopic dermatitis and alopecia. We'll look at three or four pieces of that data to help inform our decision before we make a decision whether or not we would follow with a similar development plan. Okay, but are those the only indication? If there is a signal there, would you broaden your development scope, or you just sort of go into those indications? Yeah, it's a good question. We're still evaluating that. If you look at, there is a genetic polymorphism for IL-7 where there's a number of indications that could be of interest. Asthma, rheumatoid arthritis, dermatomyositis are all examples of that. So when we think about this, we explore a number of potential indications. Would we potentially make a decision to be a leader versus a follower, and that evaluation is still ongoing. Got it. With regard to the properties of your molecule, can you just help us? My understanding is that you would have even a more potent molecule than Q32. So just help me understand how is your molecule differentiated relative to Q32, also maybe OSE as well? Yeah, so OSE, it's an IgG4. No Fc region. And doesn't have much effect on T cells at all and no TSLP inhibition. Q32 is an IgG1, but it's effectorless. And its TSLP inhibition is modest, I think it's fair to say. For quibanketug, our IL-7, it has an active Fc region. The TSLP inhibition is best in class. And we've also been able to look at Treg, T effector ratios from the type 1 diabetes study. And what you can see is that all study doses, that ratio actually improves. And that is an important indicator for AD effect. And seeing improvement can lead to better clinical responses. So I think we have a more potent asset for IL-7 and for TSLP and potentially a chance to show more profound and faster activity. Got it. Yeah, so yeah, maybe I can just double-click on one of those differences, which is the Fc activity. So part of our hypothesis is that actually by having Fc receptor activity, we can actually have ADCC, so we can reduce some of those effector pathogenic T-cell levels. And also, that's a much quicker onset than waiting for some of those cells to kind of downregulate by just blocking the ligand, right? So if you get rid of the cells, it's faster than just waiting for the IL-7 effect, as OSE might be working. And I think the last thing that I think I'm also excited about is durability. Because if you have got rid of some of those effector cells that were driving the disease, even if you came off dosing or maybe the dosing interval, we could space out, there's an opportunity here for us to differentiate. Got it. Anything to read through from the OSE UC readout? I mean, they have presented some data. I think the drug is active, some interesting dose response, but just anything to you. Yeah, I think, look, it's in a proof of concept study. Those kinds of things never surprise me. I think it's good to validate the IL-7 pathway. I think it's a great thing, actually. And any company that can positively conduct a study in IBD, it's tough. The other piece that we're encouraged by is more safety data. So safety for IL-7 as a class looks encouraging. I think it's tough to read more on the results because it's limited. And you'd want to see things like rectal bleeding, stool frequency, and prior exposure. We'll wait and see if they share that data. Okay. All right, so stay tuned for, let's say, Q32, which is probably going to come next month. That's what they've said. The guidance that we've heard is first week of December, simultaneous for AD and AA. The other piece, as to Kiran's point, we'll be looking for is EASI-75 as one component, but in AD rapidity, onset of activity and itch relief are two important considerations, and ideally, you want to show effect in a post-Dupixent population, so those will be other pieces of data we look for. Any particular bar you have set internally or you would want them to show? I don't know. There's not a specific bar. I think if you look at the AX40, you should see that range of 20 to 30. I think it's one component, but you have to look at that through the lens of the study, the design, did they dose correctly? Would we show a better result? Okay. All right, very good, then on IL-33, obviously, that's an interesting mechanism being explored by pharma. What are we waiting for there? How is your molecule different, and then what would you like to see before you make a decision on your molecule? Yeah, the two we're watching are Roche's astegolimab, which is an ST2 receptor. That's in Q2 of 2025, Phase III, COPD. And itepekimab, the Sanofi Regeneron product, which is an IL-33 inhibitor. We have preclinical data that demonstrates greater potency or inhibition for GM-CSF relative to itepekimab. That's encouraging. And also, we know that we downregulate the RAGE pathway as well. So some of the other cytokines that can induce inflammation, we can have a benefit there. Kiran, do you maybe want to touch on the AZ? Yeah, so it was a little bit surprising that AZ recently kind of updated their clinical trials data. And their Phase II in asthma actually didn't hit its primary endpoint on FEV1. I think if you look at some of the competitors, both astegolimab and also itepekimab, both had maybe positive results, not kind of game-changing. So obviously, there must be some differences. We're not aware of what those are. But I guess to me, the more consistent readouts have been on COPD. So that's kind of why we're excited about it. Yeah. Yeah, I think Anaptys had a molecule also that didn't work in asthma. But yeah, in COPD, definitely more consistent signal. All right, very good. I think we covered most of the asset. Now, how are the financials looking? How's the financial health? How are you funded? Yeah, so currently, cash on hand is $190 million. That fully funds both of the Phase II studies we talked about for 106. And from a cash run rate, it takes us through 2027. So the pipe that we completed in April of 2024 allowed us to fund those two studies. And most importantly, to make sure that the development team was in a position to oversee and execute on the two Phase II trials. Got it. Very good. Thank you so much. We're planning on a pipeline. Yeah, thank you. Thank you.