We'll continue with the next session. I'm Paul Choi, and I cover this Mid-Cap Biotech sector here at the firm. It's my pleasure to have Spyre Therapeutics here, and Cameron to my left. What we'll do is kick it off with Cameron talking about maybe what the company's strategic priorities are for the remainder of the year and going into 2027. Sounds good. As a brief background, Spyre is a company that's aiming to improve the standard of care across a range of autoimmune diseases. Our initial focus was inflammatory bowel disease, where we're working on three validated targets, alpha-4 beta-7, TL1A, and IL-23, and developing them not only as monotherapies, but in advanced combination therapies as well, where we think we have some of the most interesting co-formulated long-acting combinations of these agents. Outside of IBD, we're also interested in exploring the potential of TL1A as a pipeline in a product candidate in a range we're testing in a basket of rheumatic diseases. We're looking at rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis. Really the next 12 months, I would say, is one of the most interesting periods for the company and I think more broadly in I&I or biotech, in that we'll have five more phase II readouts this year. We've already had our first a couple of months ago that we thought was quite encouraging. We'll next have our TL1A data as a monotherapy in IBD, then our IL-23 as a monotherapy in IBD in the third quarter. Then on the rheumatic disease side, we expect the RA placebo-controlled data in the third quarter and the placebo-controlled data for psoriatic and axial spondyloarthritis in the fourth quarter of this year. As if that's not enough, as we get into 2027, we expect to read out our combination therapies. Again, we expect this to be one of the most interesting times in the space where we'll hopefully see multiple products that could be indication-leading products across some of the largest markets in the space. Clearly a lot going on here, very busy next 12- 18 months for you guys. Maybe starting with some more background on the company, there are multiple approaches and multiple technologies to creating long-acting antibodies. Can you maybe talk through what is Spyre's sort of special sauce in terms of the approach here, and can you characterize the engineering and the work that goes into developing these co-formulatable, if that's a word, antibodies here? I think you actually hit on, especially in the inflammatory bowel disease side, the key differentiator, which is that, look, it's not trivial to make any antibody, make long-acting ones. I think that's never trivial. Making high concentration co-formulatable ones that fully address each target and have the potential to have additive efficacy in a convenient product format, that's particularly tricky. We spent quite a while picking antibodies that could do that. We had to throw out multiple ones that could not be co-formulated at high concentrations. What we've seen in IBD, there was these really interesting proof of concept studies that read out a couple of years ago. Seeing that, in our discovery campaign, we picked antibodies that could be co-formulated that way. Whereas if you're starting with existing antibodies against the target, it's never guaranteed that you can actually get to that ideal product profile. Our ability to get both of these agents at high concentration in a single injection is quite unique. I guess maybe at a high level, what are the advantages to developing co-formulations versus bispecific antibodies? There are some companies working on just dual targeting approaches within a single asset versus your strategy. Can you maybe walk us through what are sort of the pros and cons here? Yeah, sure. It's a topic that we've thought about for years, obviously, and even as we were deciding how to pursue these, we considered the bispecific formats. The fundamental reason that we went after these co-formulated strategy is that this is a different case than what I would consider some of the really elegant applications of bispecifics, really what you see in oncology, where the goal is bringing two targets together and causing some unique biology, where you're causing the depletion of some cell type or some target that's driving the disease. That's not the target in what we're working in in the autoimmune space. The goal is fully blockading each of the two targets independently of each other. In fact, I think there could be, in some cases, especially where you have a membrane-bound target on one side and an inflammatory cytokine on the other, that you actually get biology you don't want at all when you bring these things together, and you could actually get immune activation instead of the suppression that you're targeting. Really, that was the fundamental reason that we pursued the co-formulation approach of independent antibodies versus the bispecifics. I think in terms of the product profile of our combinations, we do expect them to have at least a high probability of being superior to the bispecific approach as well on a few properties. One, the stoichiometry, we have the ability to flex. They don't have to be one to one or two to one or whatever the bispecific construct that's chosen. Two, I think we've seen avidity issues with multiple antibodies, as in the engagement of each target is different when they're in a bispecific construct than when you have independent antibodies that I think we've pretty well characterized. Lastly, immunogenicity is always a concern for biologic targets where you form anti-drug antibodies against your therapeutic antibodies. We know on at least one of our targets, TL1A can be immunogenic on its own. Yep. You can get anti-drug antibodies. Typically, when you move to a multi-specific construct, it increases the immunogenicity. I think we've actually seen that with the two TL1A bispecifics so far that have reported data that the immunogenicity has actually gone up when they add another target to it because you can form these large immune complexes. Interestingly, in contrast, we have an example of a co-administered or co-formulated product from J&J, where they looked at a TNF and IL-23. TNF has a lot of similar properties in terms of TL1A, including why it can be immunogenic. What we saw is that the addition of an IL-23 actually suppresses the immunogenicity to the TNF. Whereas in the bispecific construct, I think immunogenicity is more likely than not to increase, I think the co-formulation or co-administration approach is actually more likely to decrease immunogenicity and get greater functional exposure of your antibody. Yeah, something we've thought about a lot for years. Yep. I think there are many reasons why we believe the co-formulation approach is likely to be superior in the long run. For those listening online and in the audience who may be unaware, you recently top-lined some results for your lead asset, 001. Can you maybe briefly recap the data for us, Cameron, in UC? I think earlier you said the approach is to work on developing assets for validated targets, I think investors knew that this would likely work, but you're also surprised by showing efficacy that was much better than expected, can you maybe elaborate as to why you think that might have occurred? Yeah. For background, our first agent, which is called SPY001, is targeting alpha-4 beta-7, the same target as Takeda's ENTYVIO. We knew that the epitope and the potency was quite similar, but what we found interesting from the phase III and real-world data from Takeda's ENTYVIO is that what they saw is that individuals that had higher exposures of the drug, both in the phase III context and in the real world, tended to have much higher rates of clinical remission. What we were aiming for with 001 was to test whether that was correlation and just something that occurred, but not due to the drug itself, or causal, as in the more drug actually does lead to higher remission. What we intended to do, and I think what we've shown with this, is test a much higher concentration overall, put the majority of patients in our study into the fourth quartile of where vedolizumab exposed patients, and we saw, as you mentioned, what we thought were really encouraging results on clinical remission, on endoscopic improvement, on the histologic improvements that, granted, is a small open label, 40-some patient cohort, but I think supports the idea that it's at least as good and potentially might have superior efficacy compared to ENTYVIO. As we think about the totality of our pipeline, it's really a great place to start. As exciting as those data are, I still think it might be our fourth-best product in IBD in that I think the combinations with TL1A or IL-23 are reasonably, if not very, likely to add efficacy on top of that, and I think those products could be some of the best in the space. You talked about 001 getting into that fourth quartile of AUC and exposure compared to what has historically been seen with ENTYVIO. Not to necessarily create outlandish expectations, but does this, in your view, potentially indicate that your next in-line assets for 002 and 003 could similarly see better results than their respective historical comps? I would love if that were true, unfortunately, I don't think the data really suggest that that's likely. In alpha-4 beta-7, I mentioned we had this historic data that higher exposures lead to better efficacy. I'm not sure that's the case for TL1A or IL-23. In both cases, we have three first-generation molecules. In the TL1A case it's now Merck, Roche, and Sanofi. In the IL-23 case, it's AbbVie, J&J, and Lilly who have IL-23s. Across three in both indications, we don't see a dramatic difference between these three agents in terms of placebo-adjusted efficacy, and I think the most likely read of that is that these are at the plateau or the top of the exposure-response relationship for each of these targets. For both 002 and 003, what we're expecting to see is that these replicate the first-generation molecules in terms of efficacy, but we're able to do it with much less drug because we have these long-acting, YTE-modified antibodies. We can do the same thing that others are doing with grams and grams of drug with a much smaller amount, and that is incredibly important as we think about these co-formulations. I think uniquely, to get to a single-shot co-formulation that is able to fully engage both targets, you again really need both antibodies to be designed for that, to be long-acting as well, so you can just deliver much less drug and get it into a single injection. That's very hard to do if you have even one agent that isn't modified in this way. Great. Maybe just to double-click on that, is that something that will only be true for the induction data that you're currently pursuing right now with the three drugs? Then do you think, maybe just sticking with 001 and then extrapolating to the other two candidates, the maintenance data versus historical comps might be improved upon? How do you think about the two- Good point two different areas? Yeah, I should have mentioned, I think TL1A and maintenance, I think that answer is not yet, no. I think in all three of the first-generation TL1A cases, I do believe there's some evidence that we may not have fully saturated TL1A in the maintenance setting, whereas in contrast, I think in induction we have. I think we may see more TL1A maintenance data both from others and then us, we'll get our maintenance data next year. There, I do think it's possible that TL1A has not been fully saturated, and I think for the first-generation molecules, it's for different reasons, actually. It could be a relatively short half-life to the dosing interval, could be a potency weakness, could be immunogenicity, bioavailability issues with those molecules that could lead to incomplete target coverage in the maintenance setting. I think with our molecules that have the high potency, low immunogenicity, great formulation, and bioavailability, I think we'll be able to test whether TL1A has not been fully saturated in maintenance, but we'll see those data next year, not in the induction readout that we have in the upcoming weeks and months. We have a little more data given that there are multiple commercially available IL-23s. Does this also hold in your view for that target as well? No. I think IL-23 and alpha-4 beta-7 look like they're saturated in maintenance. Even for ENTYVIO, we don't see the same striking exposure response that we did in the induction setting. It really weakens and goes away in maintenance. I think the increased target coverage in maintenance may lead to greater efficacy for TL1A, whereas in induction, I think the best bet is for alpha-4. On the IL-23 cases, I think that target's been pretty well covered. Your combination products, which as you mentioned, will start to read out in 2027. We have some historical precedent data from J&J, as you referenced. First, the VEGA data from many years ago, and more recently, we got an update from the DUET program. Can you maybe talk a little bit about what are the learnings from those two studies? Then we'll turn to maybe some of the other competitors working on combinations as well too. Sure. I think first of all, the field owes a debt to J&J in terms of taking on the first randomized combination study in the space with VEGA, which really set this field on fire. For background, two decades of development, half dozen approved classes. We've hit a therapeutic ceiling, as the physicians refer to it, of about 25% placebo-adjusted remission in the space. Then the J&J VEGA study comes out, first-line naive patients, roughly double the remission rate in that population compared to either of the two components, and I think really directs everyone who's serious about IBD that combinations are likely the future. I think the challenge with that combo has become evident in the more recent DUET studies, in that in the DUET trials, we moved from an all naive population in VEGA to a fully refractory population, so they failed at least one drug, and in many cases, two or three plus drugs. What was observed in that study is that one, the overall deltas declined as a combination relative to the components. What we saw in particular is that one of the components, golimumab or Simponi, the response and remission rates to that drug in the context of having previously failed another TNF, low single digit in some cases, response and remission rate for that arm. I think it helps explain why the delta for the combination doesn't look as good, and I think really highlights the fact that what components are in your combo matter and what your trial population or your target population is matters a lot. For us, we think it's a very encouraging setup that replacing a TNF, in particular, not one of the leading TNFs in the space with a definitely superior class in alpha-4 beta-7, or a likely superior class in TL1A, is likely to lead to a better outcome than using a TNF in your combination. Then beyond that, running the trial in a population like ours, where we have about half of the study is naive, so it'll, we think, look more like the VEGA results. In the half of our trial that is refractory, we're actually limiting the number of patients that have failed our mechanisms in that portion of the study, and so we think it's much less likely to see the decline of the individual contribution of our mechanisms in a population where they haven't failed our specific classes. In total, I would say the J&J data, incredibly encouraging in that combinations can be additive even with these weaknesses. I think really sets an opportunity for us to come with combinations that are both better components individually, and then a trial population that doesn't limit the efficacy of our drugs. There is a competitor who's, instead of using a TNF, using two of the targets that you guys are prosecuting, which is AbbVie's 382 plus SKYRIZI, the alpha-4 beta-7 plus IL-23. Can you maybe comment at a high level what you think of that and just what that may inform for your potential learnings here? We were surprised and encouraged to see the data. Granted, we haven't seen the totality of the data, one endpoint, one time point, interim readout of an ongoing open label study, so we wait to be seen the totality of the data. Certainly encouraging to see that an alpha-4 beta-7 based combo showed roughly additive efficacy in the Crohn's population. Prior to that readout, I would say, the leaders in the field, some of our scientific advisory Board Members would have said alpha-4 beta-7 may not be a great target in Crohn's disease because we see that the ENTYVIO efficacy is not quite as good there. Now, I think that might have been slightly biased- versus UC versus UC, where ENTYVIO is an excellent product. I think partially that might have been biased by the fact that when ENTYVIO was initially approved in Crohn's, it looked at a week six endpoint, which we know is just too early for maximum efficacy of alpha-4 beta-7. So we've always wanted to test our combos in both indications, even including alpha-4. This AbbVie disclosure, I think, really increases the probability that alpha-4 beta-7 is a great component in both ulcerative colitis and Crohn's. In fact, I've always thought it's one of the better choices as we think about combinations in general for a GI-predominant disease to use one component that is gut selective and has the cleanest safety profile of any mechanism in the space, combined with a systemic drug like a TL1A or an IL-23, which both individually clean, but the combination then is dually suppressing the immune system in the target tissue, the gut, but only single suppression everywhere else. I think that's how it's most likely to develop an ideal risk-benefit ratio for an IBD patient. Do these J&J and AbbVie data between DUET and what they've recently disclosed with 382 give you any insight beyond what you've said might be the best combination here in IBD? You haven't really spoken to TL1A necessarily here, so I'm just sort of curious if that is substituted for golimumab or TNF alpha, might that be a potential avenue for improvement here? Yeah, I think prior to the AbbVie disclosure, you might have said our TL1A IL-23 combination is most similar to the J&J combo, that TNF and TL1A have some similarities, so we might expect the type of additivity or synergistic activity seen there. Now, we see that alpha-4 and IL-23 work pretty well together, at least in the Crohn's disease side. I think when we look at the totality of our portfolio, I think they're all quite validated in terms of the likelihood that these will work in both ulcerative colitis and Crohn's disease. I think the way that we've optimized each of the individual mechanisms and can dose them together sets them up to be really a differentiated product compared to what both of those companies are planning to advance in monthly formats, including as on-body devices. Yeah relative to auto-injectors. I think we have the best possible versions of these combinations. This is more theoretical, your choice of words earlier was primarily around the word additive versus synergistic. Just curious, how you think about room for incremental improvement. Are there synergies potentially from the combinations you're pursuing? I would agree, I think most investors would agree that the DUET data and the VEGA data look more additive than anything else. It's just maybe your high-level thoughts there for the potential for incremental improvements. Yeah. In general, we start with the biology that we think across these mechanisms, in particular with alpha-4 beta-7 combined with the cytokine. They're very orthogonal, as in they're blocking different pathways of this disease. Alpha-4 is a trafficking mechanism in terms of immune cells getting into the affected tissue versus TL1A and IL-23 cytokines blocking the inflammation itself once you're in the target tissue. I think those do seem like additive effects with alpha-4 combined with each of these other two. In terms of synergy, I think it may be more likely that you would see what I would call synergy between TL1A and IL-23. Maybe in terms of the signaling pathways, there's some described escape pathways between TNF signaling and IL-23 signaling that could be evidence for synergy. I would also describe, as I mentioned previously, the reduction of immunogenicity to other targets. I would describe that as a synergistic activity. Yeah. That IL-23 actually reducing immunogenicity to your other targets, I would call that a synergistic effect. I think depending on which combination we look at, could be somewhere between additive and synergistic. How that will translate to the endpoints in IBD is why we're running this trial. I don't think we know exactly the endpoints in IBD. They tend to be threshold measures. At this level of response, it's a response, at this level it's a remission, at this level, et cetera. How those additive and synergistic effects translate to those endpoints, we'll have to see as we run the study. Great. Can you maybe provide a quick update on the enrollment status for your combination programs and just how, at least at this point, you might think about the potential timelines for those studies reading out in 2027? Yeah. As a reminder, it's a two-part study. Part A, which is the monotherapy open label portion, and then in Part B, it's the six different active agents against placebo. We announced back in April that we finished enrolling in Part A, which sets up the Part A readouts over the next few months, and the initiation of Part B enrollment. Now we're enrolling across more than a dozen countries, all of these different arms. We expect ultimately to have almost 300 sites active in this study, north of 150 already going. The enthusiasm I've always suspected would be high. I think it has been in terms of both the low placebo rate, proven mechanisms, and three very interesting combinations. We're only two months in, so far our guidance is reading out this next year. I would expect as we get towards the end of this year, we should be able to narrow the window in terms of when we'll expect the full readout next year. Okay. Maybe turning towards how you think about clinical development strategy of whichever combo sort of emerges as the potential winner here or best product. Can you maybe talk to us about the rationale of pursuing a development plan in naive patients versus treatment-experienced patients, just as you think about maybe both regulatory and payer considerations, in particular, down the road? Yeah. First, we think it's important to generate broad data, and that's why we're running a study that will include naive as well as refractory. We'll see the response from first-line to likely third-line plus in terms of the response of our combinations in all those different populations. Of course, that will help us guide where we advance it. I think we can learn from J&J, as we've talked about, that the naive setting is really where they saw the most impressive results in terms of the delta, maybe again in the very refractory population, but I think that might be due to the particular mechanisms that they have and their populations, as we talked about. I think in general, what we would love to see in this space and what I think the physicians would be hoping for, this is a top-down market, meaning that physicians want to use the best drug first because there are irreversible and substantial consequences of this disease. Hospitalizations, surgeries, resections, you don't get that back. What physicians have learned, and we have great studies, the PROFILE study in particular, showed that top-down therapy is not only better for long-term outcomes for patients, but it also is cost-effective. I think that is really what we are hoping to see, which is that use line as a naive population. I think that's where we're going to see the largest benefit, and that patients can hopefully get a higher proportion of them into remission early and keep them on there longer, avoiding some of these extraordinary costs of caring for IBD patients. I think what's interesting about this space, if we look back over the last few years, we've seen head-to-head efficacy improvements of about 10% on remissions. This is about ENTYVIO beating HUMIRA. Yep. This is SKYRIZI and TREMFYA beating STELARA, have led to massive practice shifts towards those drugs, including in very early-line for second-line patients, even though there's a pretty substantial price differentiation between the biosimilars now and these branded drugs. I think if we're able to deliver a combination product that beats those drugs by that type of level and we can get it early, I think this is really what will be best for physicians, patients, and payers alike. Yep. No, you're right. The availability of biosimilars has not stopped ENTYVIO from becoming a multi-billion dollar product in recent years. Maybe putting it all together, Cameron, as you think about your pivotal studies down the road after you present all the data coming up here in 2026 and 2027. In a situation where your combination candidates or monotherapy candidates are more differentiated by inches versus yards, how do you think about selecting either one candidate for advancement into pivotal versus multiple candidates and just sort of what is the, I guess, the calculus behind that? Linking to my prior question, I think we're going to find in the 5-plus year timeframe here that combinations provide some level of additive efficacy. Even the TNF combo from J&J did not see meaningful safety downsides for that combination. It's just a superior product if it's priced rationally. I think what that will lead to is a substantial shift of this market towards combination therapies over time. I think we may have three of the best combinations product profile relative to others in development. I think it may be more one going forward. Really our question is which one comes first, second, and so on. I think really it will come down to, of course, what we see in the data, and it will also come down to what our long-run view is. If I had to pick today, I think alpha-4, beta-7, and IL-23 are the two safest approved classes in the space. I think they're very likely to work across both UC and Crohn's, since we have so much data, and I feel pretty comfortable about that combination. That said, it's very hard to ignore TL1A, which is perhaps the most interesting monotherapy efficacy in both spaces. That's why we're running them head-to-head. We'll see the data next year and be able to compare and decide what order of programs we advance forward. Okay, great. Speaking of TL1A, I want to turn to your rheumatic diseases program and the SPY072. Can you maybe compare and contrast 072 versus some of the other agents we've seen in the field? We do have some more data on those from Merck, Prometheus, Teva, and others, just sort of what are the key properties, I think, that you've seen so far that make you like the asset? Yeah. For us, in contrast to our 001 and 003, where we thought that building on the proven efficacy and profile of ENTYVIO and SKYRIZI made a lot of sense. For our TL1A molecule, we thought each of the first-generation programs had enough issues that we wanted to start de novo. In particular, we think our product is unique in that it has very high potency, great bioavailability, great formulation, much extended half-life compared to any of those first-generation molecules. I know, I think, we'll see data here, but I think it could be a best-in-class TL1A agent. In IBD, we know we won't be first as a monotherapy. I'm not even sure we think the monotherapy is really the most valuable thing in IBD, as we've talked about the combinations of TL1A likely being the highest value there. Whereas in the rheumatic diseases, we actually have the opportunity to be first. I think we have a potentially best-in-class molecule and a potentially first-in-class molecule, that's usually a good place to land if it's successful. Great. Maybe just the strategy behind choosing 002 for the IBD space and 072 for the rheumatic space pursuing two individual molecules versus a single one. Yeah. We advanced both TL1As into phase I due to the immunogenicity uncertainty around TL1A. For at least one of the first-generation molecules, we've seen pretty high rates of ADAs, something that you would want to avoid. That's something that's quite hard to de-risk pre-clinically, and you need to look in humans. When we saw our phase I data for both of our TL1As, we saw that they both looked excellent. No safety concerns, highly potent, and no immunogenicity problem in terms of ADA formation against either. In terms of what we decided to do there is advance one in the IBD portfolio, 002, which was really the tiebreaker there was that it was a better co-formulation with the other two assets. Kind of lower viscosity, able to get into a single auto-injector with single-digit second injection, really an excellent combination product. Whereas 072 to explore as a monotherapy, again, a great 200 mg/mL format of it as a monotherapy. That's why we chose to use that one in rheumatic disease. We think that gives us maximum strategic flexibility here in the upcoming months as we get these large phase II readouts across both IBD and the ex-IBD portfolio and the ability to, we could partner, sell, license, develop royalties against one without impacting the other business. I think that gives us the maximum ability to ensure the maximum sum of the parts for the total portfolio. Great. The same sort of principles, in terms of YTE engineering, underlie 072 that underlie 002. Can you maybe talk about how you think about potential efficacy in RA here might look like versus some of the historical benchmarks? There are obviously multiple therapies, multiple classes approved in RA. As you think about sort of the key clinical endpoints that you're going to be looking at, like DAS and so forth, what are sort of your potential expectations here? Yeah. This is first- in- class, right? I think there's great evidence for why TL1A should work in these indications, human genetics, human tissue, animal studies, mechanistic rationale for it's first in class, it is kind of a normal biotech uncertainty around the readout. In terms of what we expect is necessary to have an attractive product here, I think it's first to look back and notice this is a $15 billion+ post-TNF biosimilar market. It is a very large commercial market. If you look across the existing commercial drugs, you still don't get the majority of patients into long-term remission. They lose responses over time, and patients still cycle through many products and run out of options. When we look across the existing commercial drugs, most of them have black box warnings. Most of them are dosed monthly or more frequently. The efficacy range is reasonably tight. It's around one on the DAS28-CRP, a placebo-adjusted change from baseline. Across ACR20, 50, and 70, the placebo-adjusted ranges are about 30, about 20, and about 10. I think if we have a TL1A asset that is dosed two or four times a year in an auto-injector, so far, we don't have safety signals from TL1A that would justify a black box warning. If we have efficacy that's in those ranges that I just described, I think this could be a leading branded product in the space. Given the scale of the market, this could be a very large opportunity. Assuming positive proof-of-concept data for 072 later this year, starting with RA and with the other indications after that. Can you advance directly to a pivotal study? How does that work? Do you feel like you need to do potentially more investigation before going to a registrational study? The intent, if successful, would be to go to a pivotal study starting next year. This is two doses against placebo with placebo-controlled readouts and additional indications as well, totaling approximately 300 patients across this. It's a relatively large phase II effort here, and we've seen precedents actually in these exact indications with the TNF class, where studies very similar to this led to immediate pivotal studies afterwards. Again, we'll see these data in the next six months here, but I think if they were encouraging, we'd be interested in going to phase III immediately. You're obviously already prosecuting three indications with 072, there are implications for TL1A across a number of diseases outside of the rheumatic spectrum, including lung fibrosis-related diseases. How do you think about the opportunity there and the applicability of your candidate for those areas? Yeah. I think between Merck and Roche, we expect phase II data to be available in SSc-ILD, MASH, atopic dermatitis, and HS, all within the next 6 to 12 months as well. Now, I think I have different probability of success assumptions for some of those indications relative to what we're doing, but obviously would be convinced if they have encouraging data, and I think we'd be excited to go pursue some of these also large commercial markets where a new entrant with the product profile that we have could be super attractive, even if we were a year or two behind players that we think we have a differentiated product relative to. Okay. As CEO, you're obviously going to have to monitor the competitive landscape. Is there anything, any program out there, whether it's at a large pharma or a rival biotech, that keeps you awake at night as you look at the competitive landscape and say, this is the key company we need to look out for down the road? Look, I think in all these cases, we either have first-in-class TL1As in the indications that we're pursuing, and on the IBD side, I think we're right in the game in terms of when these combinations are being first in class with our combinations. I think the product profiles that we have are unique relative to ours that are within even a couple years of us in either direction in terms of their profile. I think we're pretty well-positioned here. Of course, things can always come out of the woodwork, but if anything were in the clinic that I thought had likelihood of being superior to us, I really haven't seen it yet. Great. Just since we're coming on time here, can you remind us how you're thinking about potential timelines to commercialization? You said you might go directly into pivotal for the rheumatic programs following your phase II data here, but just generally how you think about reaching the commercial stage. I think in terms of phase III initiations, we're expecting them that it could be as early as next year for the rheumatic disease portfolio, and then the following year for IBD. Enrollment in each of these spaces is slightly different, but approximately a year and a half to enroll and data thereafter. I think early next decade, I think, is the likely launch timeframe for these, depending on which indication we're talking about. Okay, great. We're at time here, my thanks to Cameron and Spyre for joining us today, and we'll end it on that note.