Good morning. My name is Yatin Suneja, one of the biotech analysts here at Guggenheim Securities. And it's my pleasure to welcome you all to our Emerging Outlook Biotech Summit 2026. Our next presenting company is Zura Bio Limited, or Zura, we call it, from the company. We have a few executives here in the room, but I will be chatting here with Kiran Nistala, who is the Chief Medical Officer.
And we also have the Chief Executive Officer, newly minted Chief Executive Officer Sandeep Kulkarni here with us. Sandeep, thank you. Kiran, thank you for your time. Why don't you make some opening comments? Obviously, you know, you took a very long, I would say, sabbatical or, or holiday between Tourmaline and Zura. Tell us why did you join Zura? What sort of triggered that move? I think there was some prior association with Zura.
So just frame that for us, and then we'll go into your programs and the assets.
Sure. That's my pleasure. Thank you to you, Yatin, and Guggenheim for hosting us here at the conference. So I'm two weeks into the job here as Zura CEO. However, as you note, I've been long involved with the company for, you know, for a long time. So, in short, we are focused on autoimmune inflammatory disorders. Our lead program is tibulizumab. It's a bispecific that binds to two important immune targets: IL-17A on one side and BAFF on the other side. And so, like, as I was thinking through, you know, what I wanted to do, you know, post-Tourmaline for, for the next company, next role, in short, this was too compelling opportunity to pass, pass up.
Zura is really an exciting moment where we're transitioning from being an execution company to being a data company with two very important readouts coming for the company from our phase II in the next 12-18 months, all at a time where there have been a number of external developments that I think further strengthen our value proposition and increase the potential of a program like ours. So sure, it wouldn't be great to take a longer sabbatical, more than a few weeks. But this, again, was too compelling to pass up. Now I, again, have been the CEO for two weeks, but I helped found Zura back in 2022. I did some of the early diligence for the assets, helped stand the company up, but have been a board member since day one.
and so with, you know, just the things aligning, there was more, more of a chance for me to play a bigger role. And I'm really excited about what we're working on. There's a lot of interest in bispecifics in autoimmune disease, as we're going to talk through, as a means of kind of breaking through some of the efficacy ceiling and limitations that have been seen with single-pathway modulators.
And even among bispecifics, tibulizumab really stands by itself as a first and only in-class drug that binds to these two important targets, orthogonal in nature. And we think this really opens the door to addressing the unmet needs for any number of complex autoimmune disorders that may not be easily categorized as T-cell mediated or B-cell mediated. But to be at the next to those two things, we think gives us, like, a world of opportunity.
So, two readouts coming. The first one, the first readout will come in Q4 of this year for our phase II in hidradenitis suppurativa. I'm sure we'll talk through it. But complex immune disorder, high unmet need, very few options, you know, that, like, that are out there, like, right now, but a lot of patients in a drug like ours where both sides have, you know, validation.
Then the second study is in systemic sclerosis, which we'll have data for that in the first half of 2027. Kind of a different pattern here, but, you know, but still high unmet need, complex biology, another indication we're excited about. And then beyond it, you know, world of opportunity and additional indications that fit nicely in what we're building within rheum and derm, ones where both BAFF as well as IL-17 have been implicated. So stay tuned there.
But there's a lot of potential that we're really excited about, fully unearthing.
Got it. In terms of your priorities, like, what are some of the key priorities? So you joined. Obviously, Kiran was doing all the work before getting these studies up and running. But just in general, are there certain priorities that we should think about? You also have two more assets. You didn't touch on that. Just maybe articulate for us, how should we think about the two assets that are in the pipeline?
Yeah. So tibulizumab is our, is our lead program. And I dare say this is our primary focus for the, you know, for the company. On a day-to-day basis, really getting the company ready and executing on our clinical development plan for HS and SSC are, are paramount. So all eyes are on, you know, ensuring we're recruiting the right patients for the study. We are following, you know, them appropriately, training our investigators, spending time with them to ensure that the quality of execution here is, is second, second to none. So really, that, that is the main focus, you know, for us. As you noted, there are other indications that we think could make sense for a drug that is unique, like, tibulizumab. We're, we're, we're not funded to do those additional, trials.
But it's an area of interest and planning for what might come beyond. We do have two additional programs, two additional assets: an IL-7 receptor antibody, crebankitug that we got from Pfizer, as well as an IL-33 torudokimab that we got from Lilly down the pipeline. Those are an active area of focus for us right now. Really interesting biology supporting both those. But as a, you know, midsize company, with a lot we can do with tibulizumab, we are ruthless in our capital allocation. So, I would say stay tuned for more updates. But again, focus is on tibulizumab.
Got it. Got it. So then, I don't know if Kiran wanted to talk about it or you. Just, can we just talk a little bit about the antibody, what it is, where it came from, how important it is, what's the backbone?
Yeah. I'll take that on behalf of Kiran for any additional commentary. So we licensed this from Eli Lilly in 2023. Tibulizumab is a bispecific that they engineered using these sequences for tabalumab as well as ixekizumab. Tabalumab was a phase three program that Lilly had advanced using that targets BAFF. And then onto that backbone, they grafted on the CDRs for ixekizumab. What I think makes this molecule special is that there's a lot of evidence for both sides of the antibody here, especially on the ixekizumab side, the IL-17 binder, where ixekizumab has been approved as Taltz. It's a very good IL-17 antibody, been approved for a number of indications, is a blockbuster in its own right.
and so we kind of can bring, like, the best of both worlds for these two, you know, highly characterized, high-quality, antibodies into a single, single molecule. Lilly did the engineering work, for this. We know a focus for them was getting good drug-like properties, including low immunogenicity, you know, naturally long half-life, for it. So we kind of benefit from all the work that they had put into the program. They tested the drug, in 78 subjects across, three different, phase I programs, in healthies, as well as a cohort in RA, as well as a cohort in Sjögren's as well. So we have a fair amount of data that we got from Lilly before we started, our, for our phase II trials.
Got it. So you touched on the immunogenicity. One of the concerns that we hear in general on bispecifics is immunogenicity. But it doesn't seem like your antibody has that. Can you just tell us what exactly is there? If you see anything, why you don't have that?
Yeah. Kiran, do you want to take that?
Yeah. So in the, I mean, I think the best way to test immunogenicity is a kind of multidose study. So in their MAD study, only one person had a treatment-emergent autoantibody, right? And so out of, I think, 24, so it's roughly around 5% or under 5% of the total had an ADA, which is low, right, for bispecifics. And I think it speaks probably to the kind of excellent bioengineering and also maybe the targets, right? So some targets tend to be more associated. I think these are well chosen. So I think the other thing maybe that Sandeep didn't touch on, but I think it's really important to say, is they also designed it so that both arms have relatively, well, high potency, but relatively similar affinity, right?
And that's important because what you want to have is equivalent target engagement for both BAFF and IL-17. And that's exactly what they found in their phase I-B.
OK. And what about the dosing? Like, how are you thinking about conceptually, eventually, the dosing? Is it, like, a monthly, weekly, every other week? How, what is the view?
Yeah. So in the phase II study, the steady state dosing is Q4W. The first four weeks, you have three doses. So essentially, every two weeks is in effect to load. And then you're onto the Q4W. In terms of the dose and how it's chosen, it was really done off the Pop-PK model, as I mentioned. And from that model, we predict that there's at least 98% target engagement for both arms at our top dose, 300 mg Q4W.
Got it. So first, I mean, maybe not the first indication. But I think at least we're going to get HS data first. And that study is up and running. Why was that indication chosen? What, at least on the IL-17 side, we know they are drugs approved. So I can understand from that perspective. But on the B-cell or the BAFF side, there is nothing approved. So if you can articulate for us and help our audience understand how strong is the evidence of, B-cell involvement in HS, and how you're addressing it and what we have seen.
So, let me start off then, Kiran. Please add any commentary. So HS, taking a step back, hidradenitis suppurativa is a chronic inflammatory dermatologic condition, mainly affecting the skin around, you know, skin folds. All right. Now, the pathobiology here is complex, OK? And, there's, you know, it's not as simple as just IL-17 being involved or any, any single pathway. Here, I think that is supported by the data, where we see, you know, evidence of activity for different mechanisms, but nothing kind of achieving the, you know, sort of clearance of skin that you see in psoriasis and certain other disorders. And so I think this kind of speaks to the fact that there's a heterogeneous biology that underlies the, you know, disorder. You are right.
There is, like, strong evidence for IL-17 inhibition with a couple of approved programs within the IL-17 family that have had good activity but not perfect. And I think most docs and most patients would agree that the response rates that we see, again, it's OK. But there's room to improve, improve upon that. And so one of the areas of biology that we were pretty interested in for a couple of years, a couple of years now, is just other components of disease, including the B-cell story, where B-cells are detected in lesions of patients who have, who have HS. BAFF, BAFF specifically, is also elevated in those areas. And so this is part of the story, I think, wasn't fully elucidated a couple of years ago.
But there were some early signals of activity with B-cell-directed mechanisms that, you know, it supported or were concordant with the, the translational evidence. And we were eager to kind of pursue that all on a backbone of having a very good IL-17 inhibitor on the other, other side. Fast forward a couple of years from that time, there have been additional data sets that continue to come out implicating B-cell pathways in HS, including for a BAFF pathway modulator, ianalumab from Novartis that had evidence of activity and kind of signals that are getting concordant with what we are saying here.
So I think this is part of the story that, you know, continues to gain traction and interest from investigators, is really kind of parsing out and talking through the B-cell component here that we might not have been underappreciated in some of the early studies with, you know, more focused on the T-cell kind of directed pathways.
Got it. Got it. So the main read-through comes from ianalumab. But what about any other approaches in the B-cell landscape that gives you a little bit more or there is more data in HS?
Yeah. Kiran, you want to take that?
Yeah. Yeah. So I think there were what was nice about the Novartis' platform study is, you know, to Sandeep's point, we, we had a lot of preclinical data to say BAFF is very highly expressed in all three different types of lesions in HS, so abscesses, nodules, and draining tunnels. Draining tunnels have very high levels of B-cell infiltration. So there was a lot of translational data. But what is really nice, I would say, for us now this year is to see those, those clinical results from the Novartis platform, three drugs, right? Remibrutinib, which is the BTK inhibitor. There's iscalimab, which is a CD40, which is a key molecule between B and T cells. And then finally, ianalumab.
And what's, I think, important for our molecules are all three of those molecules that are really around the B-cell axis had clinical efficacy. So I think there's a lot of comfort to be taken from that. And hopefully, we'll reflect, you know, in our ongoing results.
Got it. Got it. Then, in terms of the study, I think this is, you've increased the size to 225, or I think it's now a 225-patient study. How? What are you doing on the execution fronts to make sure that the study is well run? I think there is a consideration of a placebo response there. Because in this disease, you do have very high placebo response. So what are you exactly doing to manage that?
Yeah.
Yeah. So I, I think, there are two components to that. One is the, the design element, right? So when you're setting up the study, you, you want to choose a CRO, which we've done, which is a derm-specific CRO that has insights into the disease, knows the right sites. We only choose PIs who have HS experience. So one is the kind of setup phase. And then the monitoring in study, we've been incredibly close to the CRO.
I think it's tracking, not just discontinuations, tracking, the fact that we have an independent medical monitor who looks at the individual lesion counts and makes an independent assessment of where there is a discrepancy between what you'd expect. Is there a sudden change in any of the counts? Are some of the sites behaving differently, or outliers compared to the total data set? So that, I think, is incredibly important.
Because that's about ensuring data quality in stream. And I think maximizes the chances, you know, the signal to noise, right, given HiSCR can be a bit bumpy at times. So, so I think those are all the points that sometimes, I guess, get overlooked. And, and that is not something we're doing.
OK. In terms of, are you allowing an IL-17 exposed patient in the study?
So, I think it's a super interesting question, in terms of whether tibulizumab is likely to work. And we can kind of come back to that in IL-17. For this study, given this is our first study, it felt important to really identify the signal first. And therefore, if you have IL-17 failures, it, you know, there's a potential here that it kind of can makes it more complex. So we allow TNF failures, up to 30% of TNF failures. But otherwise, they're biologic-naive.
Got it. I mean, I noticed that the primary endpoint is reduction in AN counts. But I think at least Wall Street and us, we are just more focused on HiSCR. So if you can articulate, number one, why AN? And then how would you define success here?
So let me start off, then, hand off to Kiran. So, you're right. The primary endpoint is AN count, AN count being abscesses and nodules. That is a continuous, you know, variable. And there's precedent for this from others as well, to kind of use a continuous variable as your formal primary endpoint, recognizing that, you know, HiSCR 75 is important, you know, for us as well as investigators and for the investment community. And so we have powered the trial for HiSCR 75, a delta over placebo between 20%-25% here. And so we will absolutely look at that. I'll just note that between AN count and HiSCR, it's not like these are different data sets. Essentially, you count nodules. You count the abscesses.
And then how you transform it, you know, how you actually determine, are you responder based on these kind of category, like, categories to the HiSCR , is, yeah, just a standard way to do it relative to just measuring the AN count directly here. So these are all both consistent measures here. But again, because the greater power on the AN count, it made sense to kind of choose that, recognizing that HiSCR is what we and others are interested in tracking as well.
Got it. So at least on the 75, HiSCR 75, you are very well powered. Is that the bar? Like, 20% plus is the bar? Like, what are you hearing from your checks from?
Yeah. I think that's generally right. Again, we've powered it, assuming a 20%-25% delta on HiSCR 75, with upsizing the study from 180 to 225, that you know ensures robust powering to kind of achieve that. Good practice is to power your study for what you believe is a clinically meaningful benefit. So I think that holds true here as well. I'd also note that in an indication like HS, where there's so much unmet need and none of the existing options is really curing the disease, I think there's a clear ask from physicians for new ways to treat the disorder.
And so even in a world where, you know, the HiSCR is below that, we think there's different things that a B-cell modulating therapy, like, tibulizumab alongside the IL-17 inhibition could bring to bear, you know, different modes of activity that you know, could be meaningful here. So a lot of room to play here. I wouldn't pin ourselves to a single number. But I think that's a broad, right, like, a roughly right range where we want to be.
Got it. Maybe just one high-level question. So I think on the IL-17, there is enough data there for us to see where it works, how does it improve, let's say, pain, other same things. At least on the B-cell component, how are you conceptually thinking about its impact on disease pathophysiology? Are there parts of the disease that could be better addressed with B, with BAFF or B-cell component?
Yeah. Kiran, to you.
Yeah. Yeah. I think, I think it's a kind of yes-and answer, right? So I think BAFF is expressed in abscesses and nodules. I, I would very much expect that, given the scientific data, we would see that translate to HiSCR, right, in terms of abscess count, nodules. But I think there's also an intriguing possibility that we could have a particularly strong effect on draining tunnels, given that B-cells are actually very key infiltrates, right, into the draining tunnel itself. So I, I think there's different ways to win here. Obviously, we want to see that benefit on AN count. But we might also find that it has that impact in draining tunnels. And downstream of draining tunnels, there are issues around odor, smell, pain, et cetera. So I think there's, we want to look across the PROs too.
Got it. Let's move to sclerosis. Why, why is that indication? Like, why was that indication chosen? Obviously, there is nothing approved there. So maybe the unmet need is significant. But just on the mechanism standpoint, if you guys want to elucidate.
So I'll start off. I mean, SSc, in some ways, it's a different pattern but a similar pattern to what we're doing with HS. Given the complex nature of the disorder, you're right. There's nothing that's been approved for the totality of the indication, you know. And it's an indication associated with high morbidity and mortality, frankly. So, when we were picking indications, you know, we would focus on looking for clear unmet need. And then beyond that, looking for places where both sides of the equation, both sides of the antibody, have at least some degree of validation, you know. SSc historically has been a very challenging disease for the aforementioned reasons. And part of that may just be the limit of using single pathway modulators in a complex disorder here.
So, we recognize, like, the challenges of going to SSc. But we think there is potential here by doing something that's so different than what others have done before, where if you kind of look at some of the IL-17 data as well as the BAFF data, there are signals of activity that we think are interesting. But we are trying to formally test that in our TibuSURE trial that we'll read out first half next year.
Got it. What type of patients are you enrolling? Are you going for all cutaneous? You have lung ILD patients?
Yeah. Kiran.
Yeah. So there's different, so the subdivisions of scleroderma are complex. In general, what the unmet need is greatest in those with the diffuse subtype. Yeah. And that's usually defined by the extent of skin involvement. They have more skin involvement. And they tend to have more severe internal organ disease. So typically, ILD, so interstitial lung disease. Yeah. So our selection of patients is essentially to choose those with severe enough skin disease to be able to spot the signal. And in roughly around 2/3 of patients, we are expecting them to have ILD as well. Because the goal here is to demonstrate what our primary endpoint is, which is a modified Rodnan skin score, which is that skin thickness measure, as well as look at sensitive measures of lung inflammation, like high-resolution CT.
OK. So both the study, both patient population. I assume there is no bar here. If we hit statistic, that should be sufficient. Like, what is a good, or what does a success look like in SSc?
I think that's where there are differences between the two diseases, given there is no approved drug, honestly, and the unmet need. I would entirely agree with you. I mean, that said, the MCID is, you know, around four units change in mRSS. So we've made sure that our study is powered around that region, three-four units delta.
Two-four units. And then this is a 24-week study. And is that duration enough for you to capture the benefit, given how severe these diseases?
Yeah. Absolutely. There's it's well precedented that you can see skin changes over that time. One of the challenges has been historically FVC, which is forced vital capacities, a slower endpoint to move, which is actually one of the reasons why we've been using more sensitive techniques, like AI-based quantification. I had to use the word AI, AI-based quantification of HRCT, which is more sensitive.
Got it. Any baseline, like, what is the standard of care that is allowed for these patients on both drug and placebo arm?
Yeah. This is a really serious and severe disease. So there's no question you need to allow standard of care. The most typical drug is MMF. But it also varies by region. Methotrexate is an alternative. But to control for what I assume will be your next question is we make sure people have been on a stable dose for at least four months of MMF. So most of the sort of challenges people have had historically is allowing recent starters of MMF, which can abrogate your signal.
Got it. Sandeep, you mentioned in the beginning that one of the priorities is thinking about other indications, right? Like, where are you on that? Obviously, it's been just two weeks. But what is the plan? What type of indications you are thinking? Are they going to be more sort of orphan-like, less than 200,000, or something like, let's say, HS, which is much bigger?
Yeah. So I think, I think the answer is yes to all of those, all those. Again, like, we've been the seat for two weeks. But we've spent a lot of time as a board and team kind of thinking about additional indications. There's a lot of potential indications to go after. The degree of validation for BAFF or IL-17, you know, varies across them. And so we've tried to be very judicious in how we spend our capital and what we choose to prioritize, for the, you know, for the program. Between HS and SSc, I think these are kind of nice rubrics that we could, you know, potentially follow in terms of number of patients where these aren't ultra, ultra-orphan indications, nor are they mass, mass indications.
So I think the range that you kind of described, number between HS and SSc, are ones that, you know, make sense from a population point of view. Though the clinical validation, evidence, you know, reason to believe, is important. So we're looking for indications that we can build, you know, real conviction around, that this mechanism could be uniquely suited for these indications that we pursue.
Yeah. And then, provided, like, let's say if you have the funding, are those studies going to start, let's say, this year or, or after HS? How are you thinking?
So I think these are, again, like, we haven't committed to another indication, just yet. I think we pursue indications because they make sense in their own right, irrespective of other indications. These should provide different types of shots on goal. The biology is complex in any of these disorders. So, again, we pursue something that is worth it in its own right. So I'll just say, I would say, stay tuned till later in this year as we'll give more color on how we're thinking about what happens beyond HS and SSc.
Well, very good. Thank you, Sandeep. Thank you, Kiran, for your time. This was very helpful.
You.
Thank you.
Thank you. As always.
Thank you. Thank you. Good luck.