Spyre Therapeutics, Inc. ($SYRE)

Okay. We'll continue with the next session. I'm Paul Choi, and I cover the mid-cap biotech sector here at the firm. It's my pleasure to have Spyre Therapeutics here and Cameron to my left.

Maybe 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.

Yes, good. So as a brief background, Spyre is a company that's aiming to improve the standard of care across the range of autoimmune diseases. Our initial focus was inflammatory bowel disease, where we're working on 3 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. And really, the next 12 months, I would say, is one of the most interesting kind of periods for the company and I think more broadly in I&I or biotech in that. We'll have 5 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, the monotherapy in IBD, NRL 23 as a monotherapy in IBD in the third quarter. And 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 fondoloarthritis in the fourth quarter of this year. And if that's not enough, as we get into '27, where we expect to read out our combination therapies. So again, we expect this to be kind of 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. So very busy next 12 to 18 months for you guys. But 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 to what is -- or what Spyre 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. That's a word of antibodies here.

Yes, 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. But 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. And we spent quite a while picking antibodies that could do that. We had to throw multiple ones that could not be co-formulated at high concentrations. And what we've seen in IBD, there was these really interesting proof-of-concept studies that read out a couple of years ago. And seeing that, we -- in our discovery campaign, we picked antibodies that could be coformulated 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. So our ability to get kind of both of these agents that high concentration in a single injection is quite unique.

Okay. I guess maybe at a high level, what are the advantages to developing co-formulations versus bispecific antibodies, there's some companies working on just dual targeting approaches within a single asset versus your strategy. maybe walk us through what are sort of the pros and cons here.

Yes, sure, it's a topic that we've thought about for years, obviously. And even as we were kind of deciding how to pursue these, we consider the bispecific format. And the fundamental reason that we went after this 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 the goal is bringing 2 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 2 targets independently of each other. And in fact, I think there could be, in some cases, especially where you have a membrane-bound target on 1 side and inflammatory cytokine on the other that you actually get biology, you don't want it all when you bring these things together, and you could actually get immune activation instead of the suppression that you're targeting. And so really, that was the fundamental reason that we pursued kind of the coformulation approach of independent antibodies versus the bispecifics. I think in terms of the product profile of our combination, 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 1:1 or 2:1 or whatever the bispecific construct that's chosen. Two, I think we've seen avidity issues with multiple antibodies as the engagement of each target is different when they're in a bispecific construct and when you have independent antibodies that I think we're pretty well characterized. And then lastly, immunogenicity is always a concern for biologic targets where you form antidrug antibodies against your therapeutic antibodies. And we know on at least one of our targets, TL1A, can be immunogenic on its own, you can get antidrug antibodies. And typically, when you move to a multi-specific construct, it increases the immunogenicity. I think we've actually seen that with the 2 TL1A bispecific so far that have reported data that the immuno gusts 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 when 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. And what we saw is that the addition of an IL-23 actually suppresses the immunogenicity to the TNF. So whereas in the bispecific construct, I think immunogenicity is more likely than not to increase. I think the co-formulation or co-administration is actually more likely to decrease immunogenicity and get greater functional exposure of your antibodies. So yes, something we thought about a lot for years. I think there are many reasons why we believe the coformulation 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 from your lead asset 001. Can you maybe briefly recap the data for us, Cameron in UC? And I think earlier, you said the approach is to work on developing assets for validated targets. So I think investors kind of knew that this would likely work. But you're also surprised by showing efficacy those much better than expected? And can you maybe elaborate as to why you think that might have occurred?

Yes. So for background, our first age, which is called 5001 targeting alpha 4 beta 7, the same target as Takeda TVI. And 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 and TiVo 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. And so 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. And so what we intended to do, and I think what we've shown with this is test a much higher concentration overall, with 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 improvement that granted is a small open-label 40-ton patient cohort, but I think supports the idea that it's at least as good and potentially might have superior efficacy compared to ENTYVIO. And as we think about the totality of our pipeline, it's really a great place to start. I mean, as exciting as those data are, I still think it might be our fourth best product in IBD and that I think the combinations with TL1A 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 getting into that fourth quartile of sort of AC and exposure compared to what has historically been seeing within TYVIO. And so not to necessarily create outline is 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 the respective historical comps?

I would love if that were true. But 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. So in both cases, we have 3 first-generation molecules in the TLA case. It's now Merck, Roche and Sanofi, now IL-23 cases AbbVie, J&J and Lilly, who have IL-23s and across 3 and both indications, we don't see a dramatic difference between these 3 agents in terms of placebo-adjusted efficacy. And I think the most likely read of that is that these are at the plateau or kind of the top of the exposure response relationship for each of these targets. And so really for both 002 and 003. What we're expecting to see is that these kind of 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 kind of YTE modified antibodies. We can do the same thing that also doing with grams and grams of drug with a much smaller amount. And that is incredibly important as we think about these coformulations. And I think uniquely to get to a single shot kind of co-formulation that is able to fully engage both targets, you again really need both antibodies 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 1 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 3 drugs? And then do you think maybe just sticking with 001 and then extrapolating to the other 2 candidates, the maintenance data versus historical comps might be improved upon? How do you think about the 2 different areas?

Yes. And I should have mentioned, I think TL1A maintenance, I think that answer is not yet, no. So I think in all 3 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. So 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. It 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-23. 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 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. So I think kind of the increased target coverage in maintenance, mainly to greater [indiscernible] TL1A whereas an induction, I think the best bet is for alpha 4 on now 23 cases, I think that target has been pretty well covered.

Okay. I want to [indiscernible] 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 for 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 2 studies? And then we'll turn to maybe some of the other competitors working on combinations as well, too.

Sure. So I think, first of all, the field has a debt to J&J in terms of taking on the first randomized combination study in the space with Vega, which really set the field on fire. I mean for background, 2 decades of development, half dozen approved classes. We've hit a therapeutic feeling as the physicians refer to it of about 25% placebo-adjusted remission in the space. And 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 2 components. And I think really direct 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 study. that is in the DUET trials, we moved from an all naive population in Vega to a fully refractory population. So they failed at least 1 drug and in many cases, 2 or 3 plus drugs. And what was observed in that study is, one, the overall deltas declined in the combination relative to the components. And what we saw in particular is that 1 of the components, golimumab or Symphony, the response and remission rates to that drug in the context of having previously failed another TMS low single digit, in some cases, response and remission rates in that arm. And 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. And so for us, we think it's a very encouraging setup that replacing a TNF, in particular, kind of not one of the leading TNFs in the space with a likely -- or definitely superior class an 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. And then beyond that, running the trial in a population like ours where we have about half of the study is naive. So it will, we think, look more like the Vega results. And then 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. So in total, I would say the J&J did incredibly encouraging and that combinations can be additive, even with these weaknesses, and I think really sets an opportunity for us to come with combinations that are both on better components individually and then a trial population that doesn't limit the efficacy of our drug.

There is a competitor who's instead of using a TNF using 2 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 how -- what that may inform for your potential earnings here?

Yes. We were surprised and encouraged to see the data. I mean, granted, we haven't seen the totality of the data, kind of 1 endpoint, 1 time point, interim readout of an ongoing open-label study. So we wait to be seen the totality of the data. but 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 versus us where ENTYVIO is an excellent product. And 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 6 endpoint, which we know is just too early for maximum efficacy of alpha-4-beta-7. And so we've always wanted to test our combos in both indications, even including Alpha 4. And this AbbVie disclosure, I think, really increases the probability that alpha-4-beta-7 is a great component in both ulcerative colitis and Crohn. 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 has got 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 kind of 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, what might be the best combination here in you haven't really spoken to TL1A necessarily here. And 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.

Yes. I think prior to the AbbVie disclosure, you might have said our TL1A IL-23 combination is most similar to the J&J combo and that TNF and TLI have some similarities, and so we might expect 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. So 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. And then I think kind of 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 monthly formats, including as on-body devices relative to auto injectors. I think we have kind of the best possible versions of these combinations. This is more theoretical, but 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 from potentially from the combinations you're pursuing, I would agree, and I think most investors would agree that the DUET data and the Vega data look more additive than anything else. So it's just maybe your high-level thoughts there for the potential for incremental improvements.

Yes. So in general, we start the biology that we think across these mechanisms, but in particular, with alpha 4 beta 7 combined with the cytokine they're very orthogonal and they're blocking different pathways of this disease, kind of alpha 4 is a trafficking mechanism in terms of immune cell getting into the affected tissue versus TL1A and IL-23 cytokines, blocking the inflammation itself once you're in the target tissue. So I think those do seem like additive effects with alpha 4 combined with each of these other 2. In terms of synergy, I think you 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 kind of TNF signaling and IL-23 signaling that could be evidence for synergy. And then I would also describe as I mentioned previously, the reduction of immunogenicity to -- I would describe that as a synergistic activity. So the IL-23, actually reducing immunogenicity to your other targets. I would call that a synergistic effect. So 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 why we're running the trial. I don't think we know exactly the endpoints in IBD, they tend to be threshold measures, kind of this level of response. It's a response at this level, it's a remission at this level et cetera, kind of how those additive and synergistic effects translate to those endpoints that we'll have to see as we run the stuff.

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 time lines for those studies reading out in 2027.

Yes. So as a reminder, it's a 2-part study. Part A, which is the monotherapy open-label portion. And then in Part B, 6 different active agents against placebo. And we announced back in April that we finished enrolling in Part A, which sets up the Part A readout over the next few months. and the initiation of Part B enrollment. So 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, kind of 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 the very interesting combinations but we're only 2 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?

Yes. So 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. So 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 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 they are irreversible and substantial consequences of this disease. Hospitalization, surgeries, resections, you don't get that back. And so 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. And I think that is really what we are hoping to see, which is [indiscernible] 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 their longer avoiding some of these extraordinary costs of caring for IBD patients. And 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, about ENTYVIO beating HUMIRA, is SKYRIZI and TREMFYA, beating STELARA have led to massive practice shift 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.

So you're right. This -- the availability of biosimilars has not stopped Entyvio from becoming a multibillion 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 '26 and '27 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, I guess, the calculus behind that?

Yes. I mean kind of linking to my prior question, I think we're going to find in the 5-plus year time frame here that combinations provide some level of additive efficacy. And even the TNF combo from J&J did not see meaningful safety downside for that combination. And so it's just a superior product if it's priced rationally. And I think what that will lead to is a substantial shift in this market towards combination therapies over time. And I think we may have 3 of the best product profile relative to others in development. So I think it's maybe more one going forward. And 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. So if I had to pick today, I think alpha 4 beta 7 and IL-23 are the 2 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. I said it's very hard to ignore TL1A, which is perhaps the most interesting monotherapy efficacy in both spaces. So 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. And just sort of what are the key properties, I think that you've seen so far that make you like the asset?

Yes. So for us, I mean, we -- in contrast to '01 and '03 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. And 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. So I know I think we'll see data here, but I think it could be a best-in-class TL1A agent. And 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. And I think we have a potentially best-in-class molecule and the potentially first-in-class molecule, and that's usually a good place to land, if it's successful.

Great. And maybe just the strategy behind choosing 002 for the IBD space and 072 or the rheumatic space and pursuing to individual molecules versus a single one.

Yes. So we advanced both TL1A into Phase I due to the immunogenicity uncertainty around TL1A for at least 1 of the first-generation molecules, we've seen pretty high rates of ADAs and something that you would want to avoid. And so that's something that's quite hard to derisk preclinically, and you need to look in humans. And so when we saw our Phase I data for both of our Las so that they both looked excellent, no safety concerns, highly potent and no immunogenicity problem in terms of ADA formation against either. And so in terms of what we decided to do there is advanced on in the IBD portfolio 002, which was really the tiebreaker there was that it was a better co-formulation with the other 2 assets, kind of lower viscosity, able to get into a single auto injector with single-digit second injection, kind of really an excellent combination product. whereas 072 to explore as a monotherapy, again, a great 200 mg per mill format of it as a monotherapy. And so that's why we chose to use that one in rheumatic disease. And 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 X IBD portfolio and the ability to partner sell license, develop royalties against 1 without impacting the other business. And I think that gives us the maximum ability to ensure the maximum of some of the parts of the total portfolio.

Great. The same sort of principles in terms of YT engineering underlie 072 that underlie 002. And so 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. But 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?

Yes. So I mean 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. but it's first-in-class. So 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 now this is a $15 billion plus post-TNF biosimilar market 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. So -- and when we look across the existing commercial drugs, most of them have black box warnings. Most of them are dosed monthly or more frequently. And the efficacy range is reasonably tight. It's around one on the DAS28 CRP, a placebo-adjusted change from baseline. And then 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 2 or 4 times a year in an auto-injector. So far, we don't have safety signals from TL1A that would justify a black box warning. And so 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. And 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? Or do you feel like you need to do potentially more investigation before going to a registrational study.

Yes, the intent if successful, would be to go to a pivotal study starting year. I mean, this is 2 doses against placebo with placebo-controlled readouts in additional indications as well, totaling approximately 300 patients across this. So 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. So again, we'll see these data in the next 6 months here. But I think if they were encouraging, we'd be interested in going to immediately.

You're obviously already prosecuting 3 indications with 072. But 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?

Yes. So 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, we'd 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 kind of a new entrant with the product profile that we have could be super attractive even if we were a year or 2 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 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 TL1A 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 combination. And I think the product profiles that we have are unique relative to ours that are kind of within even a couple of years of us in either direction in terms of their profile. So I think we're pretty well positioned here. Of course, things can always come out of the woodwork. But if anything, we're in the clinic that I thought had a likelihood of being superior to us, I really haven't seen it yet.

Great. And just since we're coming on time here, can you remind us how you're thinking about potential time lines 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?

Yes. So 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 1.5 years to enroll and then data thereafter. So I think early next decade, I think it's the likely launch time frame for these depending on which indication we're talking about.

Okay. Great. We're out of time here. So my thanks to Cameron and Spyre for joining us today, and we'll end it on that note.

Thanks all.