Afternoon. It's past noon. My name's Akash Tewari. I head our pharma and biotech efforts on the research side here at Jefferies. We are in beautiful Times Square, and this is our day one of our public portion of our healthcare conference. We have the Spyre management team. Cam, why don't I hand it off to you for some intro remarks, and we'll get started. Sure. Thanks for having us. It's always a great conference. The background for Spyre is that we're working on a portfolio of therapies that we hope will elevate the standard of care in autoimmune disease. Our first and initial focus is on inflammatory bowel disease, where we're working on what we believe are optimized antibodies against the best biologic targets in IBD, alpha-4 beta-7, TL1A, and IL-23. We're developing them not only as monotherapies, which we think would provide substantially improved convenience and potentially better efficacy on some of these targets than the first-generation molecules, but perhaps more excitingly, testing them as combination therapies, which we think have the prospects of dramatically improving the standard of care in terms of efficacy in this space. Outside of IBD, we're evaluating a different TL1A asset, a second TL1A antibody in a basket of rheumatic diseases. That's rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis. We think TL1A has great evidence in those indications and will have a first and potentially best-in-class molecule in those indications as well. Cumulatively, we think it's one of the more exciting portfolios in I&I, certainly. We'll have five more phase II readouts this year, and then the combo data to come next year. We think it's a really exciting time for the company. Understood. I really appreciate it. Yeah, look, I think it's funny. The discussions you and I had last year, DUET was this overhang, and we're waiting for it to come out. I want to talk about your read on the DUET data, and then also you get this happy, randomly on a call, validation of your combination approach. I think it certainly accelerated the potential of your combo strategies in GI. I actually do want to hit on DUET because I think there is room to chop in terms of how you look at that data versus maybe that initial read, "Well, hey, it only worked in this kind of refractory subset of patients," and Spyre's talking to us about frontline combination regimens and going for a broader population. Why is that possibility still open from you looking at the DUET trial? Yes, fundamentally, we started focusing on combinations after the J&J read out their VEGA results. Right? If we look at the totality of the J&J development program, they read out the VEGA results a little over three years ago now, and then just recently, the DUET results. If we look across lines of therapy and how that combination performed, the results in the frontline setting in the VEGA study was very impressive. More than a 20-point delta on clinical remission compared to both monotherapy components in that study. When they moved to the DUET populations, now it's 100% refractory population. We saw in the data set that we reported a few weeks ago on the ulcerative colitis side, it was about 70% had failed a prior TNF. On the Crohn's disease side, it was more like 90% of the population had failed a prior TNF. J&J's combination, it's TREMFYA, is one of the components. An excellent IL-23 inhibitor. Their other component is golimumab or SIMPONI, which I think it's fair to say within the TNF class is not the most effective of the TNFs. After these populations had 70%-90% TNF refractory, the golimumab or SIMPONI arm added very little. We saw the monotherapy arms in the DUET studies had mid to low single-digit remission rates alone. Yes. The delta over TREMFYA looked promising, particularly in the late-line patients. It was clear that one golimumab component added very little. Right. When we look at the totality of it, I think it's fair to say that what your components are matter, and having better components, which I think is our premise here, is having the best possible components of our combinations. That matters a lot. Two, the population you study it in matters as well. That's why in the design of our SKYLINE study, we have half of the trial is a naive set of population. I think that should look like the VEGA results did. Right Then our other half that is a refractory population, I don't think it's fair to say that it's likely to look like the DUET result because we're not going to have 70%-90% having failed one of our mechanisms. We're capping the number that have failed our mechanisms at a relatively low rate. It'll be a minority that have actually seen our mechanisms, and I think that bodes well overall for how our combos. W e expect to perform across the totality of the population. In contrast, I think DUET was like 90% TNF failures. When you say minority, is there a ballpark range? Yeah. We expect it could be single-digit patients. Okay In our study on each of the arms having failed the prior agent. I think it's very likely to show a different type of result, both because the agents themselves, I think, are likely to be superior. Yeah Golimumab, the trial population, I think, is also set up for a different type of result. To your initial point about them now advancing that agent in the third-line plus population in the phase III studies, I'm hopeful that won't have to be our development plan for our agents. I think what we know about IBD from the PROFILE study and others is that top-down therapy is the best for patients in this space, what that means is put patients on the best drugs first, that leads to the best long-term outcomes for patients. Not only the outcomes for the patients, I think there's actually good health economic data from those studies as well, showing that. Sure. It's not just better for patients, it's actually better for health systems as well, given that the cost of care for IBD is so large. What we're hopeful that if we can deliver these combination therapies that substantially improve efficacy, don't have safety downsides, as we didn't see for a TNF combo in the J&J trials, and then we can deliver them at a reasonable price point as a co-formulated product, and I think that product overall has very few qualities that don't make it best in indication. Understood. I find it interesting too, you're not stratifying necessarily by two prior lines of therapy. Right? I think you look at the DUET data like, okay, well, it's enriched there. If I look historically in some of these trials, that's usually about 25%, 30% of patients. I would say, "Oh, well, you guys can enrich for that and make it 40%, 50% for this subgroup of patients who are refractory." You're not saying that, though, necessarily. It's more about prior treatment rather than prior lines of therapy. How are you thinking about what percentage of those refractory patients are you targeting for your SKYLINE trials? Yes. overall naive refractory, about 50/50. In terms of the demographics. For stratification in a phase II study, you can't stratify for too many things. We can only stratify for two features here, which is severity of disease at baseline and then naive versus refractory. Yeah. Those are our stratification factors. We think those have the best evidence for mattering in terms of impacting response rates in IBD, and I think that sets us up well to have a reasonably balanced set of cohorts across the trial. Understood. Now when we think about contribution of components, what's also kind of interesting to me is look, when I look at your indications, there's some where I feel like there's a dose response, right? I think you can see that with your ENTYVIO. There could be other targets where maybe not so much. TL1A, I think signs of a dose response, but it's more TBD. You get into this kind of interesting question of, "Hey, I need to show contribution of components in the phase III." When I think about that contribution of components, do I take two monotherapy arms, maybe one that's underdose, and then when I go do my combo, I might be able to take the high doses in combination compared to, let's say, a mid dose on my mono arm. Is that regulatory flexibility exist? You look at the FDA guidance, it's almost purposely vague, but to me there seems like there's some shades of gray here. How are you guys thinking about that? I think in IBD we're learning, right? These are the first combinations that are advancing. The J&J combo is the first one going to phase III, and so I think that is the most helpful precedent to understand what's required from a regulatory perspective. Outside in, reading through the lines of their phase III design, so on the back of the VEGA study, both DUET trials, and they ran an AFFINITY study in psoriatic arthritis as well. Technically, none of those four phase II studies hit their primary endpoint of the monotherapies, both beating placebo and then the combo beating both of the monotherapy components. Yeah Yet what we see in their phase III design is a relatively straightforward phase III. It's a two-arm study comparing just the combination to TREMFYA alone. I think what's helpful there is it implies some amount of you can solve contribution of components in parts. Meaning in the phase II studies, they showed that the monotherapies have beaten placebo, and then they showed that the combination beat golimumab alone, and now in phase III, the only comparison that they need to show is the combination against TREMFYA, which they have not shown on a primary endpoint to be successful. In our study, the intent of this phase II is to solve contribution of components. I think it's a robust, well-designed study where we have placebo, monotherapies, and combinations in one study. Our high doses of our monotherapies are the doses that we're studying in our combination dose. I think if successful, I think we could have said we've achieved contribution of components with this phase II study, and I think that would enable quite a bit of flexibility in terms of what we choose to advance in phase III. Understood. Given the dose response and that, because you also have to think about what you can co-formulate in your phase III in these IBD indications. If you were to pick an ideal kind of monotherapy comparator arm within your own subpopulation, which one would that be right now? Yeah. I think it is critical in terms of combination therapies about how you think about the ultimate product profile of what you're able to do. I think we're uniquely able, given that we have long-acting versions of each of these where we pick the antibodies ensuring that they were able to co-formulate with the others at high concentration. That was a unique background. If we just think everyone in this space saw the VEGA results and said, "Let's start making combos" and combined basically what they had or tried to cobble together different combinations. You see that with some of the other combinations in development, where you're seeing mixtures of different dosing intervals. Even orals and injectables together, and that is very challenging from both a convenience and adherence perspective. Even a pricing and access perspective, it's challenging if you can't administer these as a single product. I think we're uniquely able to do that with long-acting versions of the best biologics, and I think that sets us up very nicely here. In terms of which one the winner is, and that's why we're testing them all head-to-head against each other. I would say a few months ago, most of our advisors would've told us that the alpha-4 beta-7 combos may not work so well in Crohn's disease, and so your TL1A IL-23 combo might be the overall winner. I've always been a little bit skeptical because I think ENTYVIO is still a big drug in Crohn's disease. Yeah. Their data, if you don't look at the week six endpoint, but if you look later at week 12 and 14, where some of the others use their primary endpoints, I think it looks quite good, and it's always seemed elegant to me that in a combination, one of your agents is gut selective and very well tolerated if the other is a systemic immune suppressant. Given that the AbbVie data suggests that an alpha-4 beta-7 IL-23 combo shows additivity in Crohn's, I feel pretty good about all of our agents across both UC and Crohn's, and we'll see the data head-to-head across the three different combinations. Right Then decide maybe not what the winner is, but at least what our favorite is to go first, and then maybe second and third, depending on how good they each look. Understood. My question is a bit weirder, which is in some sense you want that comparator arm to not have as much of a dose response, right? The question is really, cause again, to your point, no pharma company yet has shown contribution of components. There's a lot of positive trends, not yet a positive phase III trial. When you think about, hey, the regimen that I want to compare to, that I feel most confident. Yeah I'm going to be showing a contribution of components. That might be that there's additive synergy, right? You're testing three different combos here. What's the comparator arm that you think will set you up the most to show that contribution of components? Yeah. I know it's a tricky question. I don't think we're going to be able to take a lower dose of our monotherapy. Okay as a mono and compare that to a higher dose in a combination. Maybe that'd be a little disingenuous, and I think in general one of our core hypotheses here is that the better components will translate to better combinations. I actually think the J&J data supports that. When you had a relatively ineffective SIMPONI arm as a monotherapy, the combination didn't add that much on top of TREMFYA. I think the fact that we're seeing what we think are excellent efficacy. Yeah Readout on alpha-4, I think it's reasonable to believe that that will translate to greater efficacy for the combos as well that include that component. May make the mono harder to beat, in the end, I think ultimately physicians aren't going to look at the delta of your combo versus your components. They're going to look at the label of your combination product against the label of other combination. Right Products in the space. Ultimately, you just want that to show the greatest efficacy possible with the fewest safety warnings and the best convenience. I think having the best monotherapies is likely to lead to that. Understood. That totally makes sense. Now, I think maybe stepping back, I'd love to get also your take on that AbbVie data set, which again, very provocative because these are exactly the combinations you're looking at, and you see a doubling in terms of response rates. It's hard because you look at even the monotherapy efficacy that you're seeing, and it's not comparable to some other historical trials with either of those targets. This kind of signal noise question is tricky, I think, for us and I think for investors to really interpret. How does Spyre think about that? Yeah. I mean, the challenge is we really don't have a total data release from. Yeah We got one data point from a 2/3 enrolled study. At a different time point than we've seen for others as well. I'm encouraged to see this proof of concept. That alpha-4 provides additivity on top of IL-23. I might have assumed that anyways. I think these are very orthogonal mechanisms, and it makes sense to me that they could work well together. It's very encouraging. That said, I think it's really hard to know without seeing more than just one endpoint at kind of a not a complete disclosure of the results. Okay. Understood. Maybe kind of just stepping back, there's this kind of question. You have two additional monotherapy data sets that are coming out. The question I'll often get from investors is, "Oh, is that going to be a big catalyst?" I personally am a little more, I think, tempered where I feel like when I look at TL1A, when I look at IL-23, you've already seen some of those dose exploration trials done by your peers where you're dosing IV, you're really hammering these targets. I'm not necessarily sure we're going to see a clear dose response in the same way that we saw with your ENTYVIO with these other targets. Is that the right framework? How should we think about those two data sets? No, I think that's right. In contrast, alpha-4 beta-7, as we've talked about, we see both in the GEMINI studies and in the real world that they have this very striking exposure response and a limited exploration of higher doses. Even in the BLA, FDA suggested they should test a higher dose. That never happened. In contrast, in the TL1A case, we've seen three first-generation molecules. Some of them dose, frankly, an extraordinary amount of drug in the induction setting. If eight grams of antibody isn't enough to saturate the target, I think that'd be a surprise to me. I think we're likely at the plateau in terms of induction efficacy for TL1A with what we've seen in the first-generation molecules that I think look comparable on a placebo-adjusted basis. I would expect our molecule to be able to do that with a lot less drug given the improvements in the molecule from a bioavailability, immunogenicity, potency, and half-life perspective. Similar for IL-23. Again, three first-generation P19 inhibitors. The deltas in efficacy are pretty small between them. Yeah. The most likely place that lands on a dose or exposure response curve is at the plateau. It'd be weird if they were all at the same place on that curve if it's not at the plateau. Understood. maybe to that point, I know there's limited you can say about the dose and exposures you're taking often for competitive reasons here. when we think about, let's say, the high dose of Teva with their TL1A trials, are you testing doses that get meaningfully higher exposure than the highest dose that Teva looked at? I mean, the Teva one is particularly hard to comp against because. The data is. the peak to trough ratio is huge given the short half-life of the molecule. On average, yes, I think we'll have at least the same if not better target exposure, but we're nowhere near th e Cmax levels. Yeah The antibody. I think that's one of the advantages. Again, coming back to what do we think would these combo products look like? There's a big advantage of having highly potent, long-acting, co-formulatable antibodies and that we can actually get to reasonable doses of subcu co-formulations. If even one of your components requires grams and grams of drug, very difficult to imagine how that becomes- a very convenient format. It's not just kind of that one TL1A that we're discussing. Some of the IL-23s are dosed in terms of grams and grams of antibody. Yeah. Hard to imagine how you could ever get to a subcu induction, whereas I think with our profile, I think subcu induction is doable even with two agents together, and only a handful of monotherapies are able to do that. Understood. I thought of this question right now. I apologize if it's a bit unpolished. I remember reading some clinical papers that there is this kind of thesis that in TL1A, we've talked a lot about ADAs, we've talked a lot about potency and half-life, but there's also competitive binding. I think there's a hypothesis that when we look at the Teva Sanofi data, part of the reason it was so good was actually that it was a non-competitive binder, and it wasn't about the ADAs, it wasn't about the potency. How much do you ascribe to that theory? Can you kind of give investors a bit of background on, you know, what that competitive binding dynamic is and then apply it to your programs as well. Yeah. I think when the TL1As were all running their proof of concept studies, there was a lot of debate around a few things about the epitopes they're binding to. Is it the trimers versus the monomers that you're blocking? Is it DR3 versus DCR3, the decoy receptor as well? I think there's been a number of publications from some of these sponsors either claiming it matters or claiming it doesn't matter in both directions. I tend to look at the phase II data on a placebo-adjusted basis that, in my interpretation, are within low single digits of each other. Yeah In terms of their efficacy, I'm not sure it made much difference in terms of the efficacy of this, and that you block the target one way or the other, and you lead to a very similar efficacy safety profile of the molecules. It's hard for me to ascribe much to any of those mechanistic differences. Right Until we actually see some separation in terms of their impact clinically. Understood. Maybe just on TL1A and ADAs, again, debatable if they've had any impact at all. I know your team and the Paragon team when they think about designing molecules, why not optimize when you can? Can you talk about A, do you feel like there is any evidence ADAs are having an impact on clinical efficacy, maybe in certain indications or maybe in maintenance? Then number two, how did you design your molecules to avoid that, some of the dynamics we've seen with the Roche molecule? Yeah. The evidence that it matters, I think, is scant right now. In terms of knowing that you're seeing a decline in efficacy due to immunogenicity, I don't think we have that yet. I expect we'll continue seeing data from Roche and others suggesting that they may not be seeing an impact from it. The ones where I think it's clear that you do see an impact, actually, we have two TL1A bispecifics where the immunogenicity is yet higher again than the monoclonals are, and there you are seeing clear impacts on PK and other effects that tell you that those ADAs are having an impact. I'm not sure we've seen that yet for any of the monoclonal- Right TL1As yet, it's hard to say that we're going to see a major impact due to a lower immunogenicity rate. In terms of picking our molecules, one of our funnel criteria, there's a handful of in vitro assays that you can use to look at the formation of immune complexes between your antibody and your target. They've been called an SEC-MALS assessment that you can do. We looked at that for all of our antibodies, and really what you're trying to avoid is the formation of these large complexes where your antibodies are cross-linking the target and multiple of the target to form these large complexes. That's exactly the problem that was described for the Amgen TL1A bispecific was the formation o f these very large immune complexes. We certainly selected molecules that didn't have that effect. I think in our phase I studies, we've not seen the impact of ADAs on PK, PD, anything like that. I think we were successful in that we haven't seen an impact. Understood. Maybe a secondary question. I do feel like in maintenance, we've seen this with Sumi and IL-13, where you do see there's not necessarily a trade-off that a company like yours would have to make in terms of dose and then also target engagement. Maybe we could see continued improvements. Because again, you're healing the body, and it just takes a longer time. Help us frame. We have multiple maintenance data sets with TL1A coming out. Do you feel like we're going to start to see differentiation with some of these products in the maintenance setting where they are giving up too much on their dosing profile and you're going to see efficacy start to wane? Is there a pitch internally that you might actually see the curves continue to go up given the engagement that you have with longer duration? Yeah. As much as what I said for induction is true, that I think we're at the plateau o f efficacy for the target. I think I'm not convinced yet we're there for maintenance for TL1A. In some ways, the overall maintenance data haven't lived up quite to the hype of the induction of some of the best induction in the space. I think for each of the first-generation molecules, there's different reasons why you might not be getting full target engagement, whether it's the immunogenicity that we talked about or bioavailability, half-life relative to dosing interval. Right In some cases are challenging, and potency in other cases. You just may not be having enough target engagement during the entire dosing interval for any of those three. I think our molecules have excellent potency, long half-lives, low immunogenicity. I think we'll be able to test whether that is the maximum maintenance efficacy. When we look at the curves of responses, I know we've only shown the first one so far for alpha-4 beta-7. Week 12 is a bit of an arbitrary time point to pick. In terms of efficacy, we see in our data that those curves haven't plateaued in terms of efficacy there. You're still seeing patients improve when you get there. If you wait till week 14, I bet we would've gotten even nicer data with the alpha-4 beta-7. Wouldn't surprise me if we see something similar for TL1A and IL-23 as well, that the week 12 endpoint is pretty standard, but some people look at 14. Six, I think, was too early, but I think week 12 is a reasonable time and aligns well with our Q12-week dosing. Okay. Understood. Okay. Again, kind of a random question that I just thought of right now. In terms of contribution of components, it seems like, okay, you have to show contribution of components within arms. What if you went to the FDA and said, "Look, we have a combo that we're very confident is going to have best-in-class efficacy, and we think this is just kind of silly that we need to show contribution of components." Why not let us run a trial against the best biologic out there? Right? Run a trial head-to-head against HUMIRA, run a trial head-to-head against SKYRIZI, and if we're able to show an improvement on an active comparator, what are we doing here? Right? Yeah. I know that hasn't been talked about in the past, but again, this could be a different FDA. Is that even a thought process with your team, or do you- Look, I think we're better off the more of contribution of components we show in this study, gives us the most flexibility possible. Best case scenario, and look, we have three shots at this, right? We have three combos. Yeah I think all could provide the additivity that we're talking about. I think if at least one of them shows the contribution of components, that would maybe help us prioritize which agents are best to go first. If you have that clean contribution of components in this study, I think we will have a lot of choices about what we want to use as a comparator for phase III. I think historically, you've seen placebos required for phase III development in IBD. Until very recently on the first combo, phase III, where. Yeah It's not. It's an active comparator. I think we may have some flexibility here in terms of what we choose. I think our monotherapies, these classes have beaten the two biosimilars before. Alpha-4 beat TNF head to head. The P19s beat the p40s head to head. We would feel confident in our monotherapies beating the biosimilars by a clinically meaningful difference, which is about 10 percentage points. If our combos beat our monos, we could choose just about anything. Right As the active comparator for our combos, and there is a trade-off between very few other things can be dosed on our dosing interval, and so it's some amount of operational trade-off versus what do we want to beat from a pricing and access perspective. Understood. You mentioned you have three phase III combo studies reading out next year. I know the street, we're personally quite excited about those readouts. I also have to say, you see the pharma companies miss on the phase IIIs showing contribution of components. The expectation that you'll show a stat sig difference in phase II, to me feels, is that misaligned? Have you designed these trials so that your phase IIs should be able to show contribution of components? Is the right perspective, we're going to be looking for trends and an eight-point difference in a phase II trial is easily designed. We can easily design a phase III to hit that bar. Should we expect stat sig contribution of components with these phase II readouts? Yeah, I think the more of that we show, the easier it will be for pivotal design in terms of our end of phase II discussion about what we have left to show in phase III. I think this study's reasonably designed to show our monotherapies beat placebo. We know roughly what to expect for each of those. I think no one knows exactly how much the delta is between what our combos and our monotherapies are, and by the sizing of the study, you can tell that they're about the same size of the combination cohorts as the monos. Yeah. Therefore, we need to see roughly a similar delta between the combos and the monos. I think that's reasonable. That's roughly what was seen in the VEGA study in terms of rough additivity. I don't think we need to see that large a result to have a stat sig difference. The more we see, the better. Things we don't see, we could solve in phase III. Understood. Now, again, you have a unique problem. Let's say that you do have a clear signal with all three. Part of me thinks why not develop all three? I mean, really. They all could be best-in-class profiles, but patients want different choice. I know in the past, the last time we had this discussion in Miami, you were kind of saying, Look, I'd rather go with, let's say, an ENTYVIO IL-23 backbone because I don't have to worry about long-term safety with TL1A, which is still going to play out. Do you still have that same view? I mean, what do you think about if you have similar data sets with all three combos in terms of which ones would you move forward with? I mean, the rate limiting step for development in IBD is recruitment. I mean, it takes a while to enroll IBD studies. If you tried to enroll three big phase IIIs at the same time, they would all take a long time. In contrast, what we expect to do here is not necessarily pick the winner from the SKYLINE study, but think about which one comes first to the phase III study. There's 500, 600 good sites in the world. I think we would start enrolling what we believe is the most valuable product first, and then if we believe the next one was justified. Peak sales potential justifies the cost of the phase III, then we would do that one and so on until we got to a product that we didn't think could return the cost of the phase III studies. I think what's helpful is this is a huge $30 billion-plus market. The largest drugs in IBD do high single-digit billions each. I think it's reasonable that the best combinations in development could be in that range, and that would be well more than enough to justify advancing those programs to phase III. In terms of how we would pick between them, yeah, I have some slight bias towards the alpha-4, beta-7, IL-23 combo. Knowing that we have tens of thousands of patients that have been on those drugs for years, and we have very few safety signals from those individually. If we had identical data with that one as the TL1A combos, I would probably pick the ALFA4 IL-23 combo. It's hard to ignore TL1A as a monotherapy agent, as one of the best in the space. Yeah. I think it's plausible that we'll see greater efficacy with that, and we'll have to make that trade-off. Understood. Now, RA study coming up. I think most people appropriately look at this as a shot on goal, but not something that I've never felt for your team you had a ton of conviction on. You're like, "We're going to test this scientific hypothesis. Let's see what plays out." We are seeing, you saw with the FcRn data that there is investor excitement potentially in a refractory RA market, and there could be different pricing strategies there as well. A, what data would you have to see with your TL1A and RA to justify moving that forward? Would it be as good a standard of care, or does it have to be differentiated? Yeah. How do you think about, let's say, a broader RA opportunity versus maybe we should be thinking about this more in the refractory setting? Yeah, it was encouraging to see market appreciating. The RA is still a market. I think there was a perception for a while that after TNFs went biosimilar, that that didn't exist, and I don't think that's true. I mean, we see north of $15 billion of annual revenue of branded drugs post-TNFs going biosimilar. We think that if you have a product that is two to four shots a year, that doesn't have a black box warning and has efficacy in the range of the existing commercial drugs, I think that could be a very large product in that space. Kind of sets our bar, which is that on safety and convenience, we think TL1A is perhaps advantage in the space, at least so far. If efficacy is in line with the existing commercial drugs, we think that could be a really attractive product to advance. Yeah, we'll see those data next quarter, and then we'll see the PsA and axSpA data the following quarter, and that will define the totality of what we want to advance, at least in rheumatic disease. We'll also see as many as four other TL1A readouts across HS, AD, SSc, ILD, and MASH between Merck and Roche, and we could decide, we think we may have a superior product, and that may make sense to advance that one as well. Understood. it sounds like you're not sticking your neck out and making any calls. Look, this is first in class. Yeah. This is the kind of normal biotech risk. We think the evidence is great across human genetics, human tissue evidence, animal studies, mechanistic rationale. Yeah, it's first in class, and so it's a different probability of success assumption than we certainly have in IBD. Understood. By the way, when are we getting that top-line data? Any more specific timing? Q3. Okay, Q3. Next quarter, yeah. Perfect. Hey, thank you. Thanks. Really appreciate it as always.