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I'm ready.
All right. Good afternoon, everyone. Tyler Van Buren here, Senior Biotech Analyst at TD Cowen. Thank you very much for joining TD Cowen's 45th Annual Healthcare Conference. For our next session, I'm very excited about a hybrid presentation and Q&A that we have with Spyre Therapeutics. And it's my pleasure to introduce Cameron Turtle, the CEO. Cam, thank you very much for being here. I'll go ahead and pass it over to you to start the presentation.
Thanks, Tyler. Thanks for having us. It's a great conference, as always. I'll start with the quick disclosure slide. I'll make a handful of forward-looking statements, so they're accurate as of today, but subject to the usual risks and uncertainties. We launched Spyre almost two years ago now with a focus of addressing what we saw as the unmet need in inflammatory bowel disease in really two particular angles, which this is a disease that affects more than 2 million people in the U.S. It's a commercial market that's growing from 20 billion today to expected to be around 30 billion by the end of the decade. We still see two clear unmet needs in that, in one case, the efficacy of agents in this space is limited to about a 25% clinical remission rate.
Patients and physicians have to cycle through multiple medications to get lasting remission. The product profile of products today in IBD is substantially inferior to what you see in other INI indications. Drugs today are dosed as frequently as every two weeks subcutaneously, and there are still multiple intravenous infusions that are on the market today. What we saw to address both of these features is really two aspects of our strategy. First is to take what we see as the best targets in IBD. This is alpha-4 beta-7, TL1A, and IL-23, and engineer improved antibodies against these targets. In particular, what we're looking for is extended half-life antibodies that allow us to take the dosing interval from that two-week to month schedule that we see today. We're aiming, and I think we can accomplish, quarterly to twice-annual dosing with our products.
What we've seen in this space is the monotherapies get to about this 25% clinical remission rate. We launched Spyre just a few months after really a paradigm-changing study in this space called J&J's Vega study, where they showed that addressing two aspects of the pathophysiology of the disease simultaneously delivered basically double the effect compared to the individual monotherapy. They showed a 47% clinical remission rate. What we're doing is putting both of these things together. We're taking what we believe are optimized antibodies against the best targets in this space that can be dosed quarterly or twice annually.
We think we're uniquely able to combine these into co-formulated combinations that we think can aim for that same level of efficacy as we've seen from other combinations, but do it on a much more convenient quarterly dosing schedule with targets that we, frankly, think are better than those that were tested in the first combination. Lastly, we added to this portfolio, though we think we're a predominantly IBD company, we have a set of TL1A antibodies that we think are quite a bit superior to the first generation of TL1A antibodies that were developed. We think it's important to test the opportunity for this target outside of IBD as well. We've announced that we'll be launching a rheumatoid arthritis study starting in the middle of the year after we pick our preferred molecule from the phase one studies.
To show this a bit more visually, as a next consultant, I can't help myself but showing a two-by-two here where on the x-axis, we're looking at the dosing interval of agents today, and on the y-axis, the efficacy. As I mentioned, the standard of care today is in this bottom left-hand quadrant where we're seeing agents that can't get above a quarter of patients into clinical remission, and many of those lose it over time. The drugs are dosed between every two weeks to every couple of months. The only proof of concept that has meaningfully improved that is the J&J combination study that I mentioned. What we're aiming to do with Spyre is moving to this upper right quadrant here where we're taking these monotherapies, extending their dosing interval to quarterly or twice-annual dosing.
We're optimizing the dosing of each of our agents as well, learning from what the previous molecules have done, which we think can improve the efficacy of each of these individually. We're testing these combinations that we think have the possibility of dramatically improving the efficacy. To start with the monotherapies, why did we pick these three? We're again focused on three things here: extending the dosing interval, testing higher doses to get more efficacy, and then moving forward with combinations. What we're focused on here is taking agents that are clean from a safety perspective and still deliver high efficacy. We're taking these three classes here: alpha-4 beta-7, TL1A, and IL-23, none of which have black box warnings for infections or malignancies or substantial monitoring requirements that you see from other classes in IBD.
We're thinking about combining these together to develop our products. For each of our antibodies, we're learning from the previous molecules in this space. For both our alpha-4 beta-7 and IL-23 program, we're leaning on what's been demonstrated for two excellent products in this space: vedolizumab or Entyvio from Takeda, and risankizumab or Skyrizi from AbbVie. We've engineered antibodies that target the same epitope as vedolizumab and risankizumab with very similar potency as is shown here. On the TL1A case, however, we made a slightly different decision where each of the TL1As ahead of us we thought had pretty substantial liabilities from an antibody property perspective.
We actually did a de novo development campaign to identify our TL1As and have identified two lead molecules that are running in parallel phase one studies now that have potency, as shown here, about tenfold the potency of some of the leading TL1As. What is uniquely different about our antibodies and that we are developing them all within a single portfolio is that these antibodies have meaningfully extended half-lives compared to the previous molecules in this space. On the right-hand side, we are showing head-to-head data in non-human primates for our TL1A and our IL-23 antibody, where we see between a doubling and quadrupling of half-life compared to the previous molecules. On the left-hand side, we are showing projections based on our human data from our alpha-4 beta-7 molecule, where we see approximately a fourfold improvement in half-life compared to vedolizumab .
Going into a bit more detail on that alpha-4 beta-7 molecule, what this extended half-life allows us to do is that in the induction setting, we aim to have greater exposure than vedolizumab, which we think may be able to capture greater efficacy than was achieved with Entyvio. In the maintenance setting, as you can see here, we are trending towards the same concentrations of vedolizumab, but we are able to do this with a twice-annual dosing interval or four times annually compared to 26 shots a year of vedolizumab. In that interim phase one study, we also showed that the molecule was well tolerated, and we were able to show that we could demonstrate complete target engagement even with the lowest dose of our molecule three months out at concentrations that are far lower than what we expect to see in phase two.
We're still able to fully saturate the alpha-4 beta-7 receptors, which we think should lead to great efficacy. Moving on to our combination strategy, as I mentioned, this is predicated on the J&J result that is shown here, where, as I mentioned, monotherapies typically have a hard time getting above 25% clinical remission, as was shown in this study. For the first time ever in a randomized controlled study, we saw a combination compared to those monotherapies where they functionally saw additive efficacy between the two. This is a groundbreaking result, and I think if we talk to KOLs and strategics and payers, I think everyone recognizes this is paving the way for the future of IBD care. I think it's unlikely that combinations that include TNF are likely to be the best combinations in the long run.
TNF carries with it a fairly substantial warning for serious infections and malignancies, and it's also not the most efficacious class in IBD either. In fact, our portfolio, we think we have one agent that has already beaten TNF head-to-head, and that's the alpha-4 beta-7 molecule. In the Varsity study, Takeda showed that alpha-4 beats TNF head-to-head on both safety and on efficacy. Though it hasn't been tested yet, the efficacy that's been seen from the TL1A agents also looks superior to what's been seen with TNF as well. We think taking a proven combination that was seen in the Vega study and replacing the TNF component of it with agents that have superior efficacy and likely superior safety as well is likely to lead to better combinations as well. To develop these combinations in an efficient manner, we're running a platform study.
We think this is a unique study to run in this space that we are kind of only a company like us is able to accomplish because we own all of these assets that are all on the same dosing interval. We plan to test all three of our monotherapies and our combinations on a quarterly dosing basis in a study that will start in just the upcoming months. The study will start with the monotherapies tested open label, and we will read out the monotherapies next year. We will continue to randomize across all the monotherapy and combination arms against placebo, which we expect to read out in 2027. To highlight the uniqueness of this portfolio compared to what others are doing in this space, I think it is clear on the left-hand side here how the alignment of dosing intervals in this study allows us to blind the study.
It allows us to be clear that whatever wins of this study in terms of the optimal combination to move forward, we'll be able to do it with a single co-formulated shot of our agents and lead to a single product that we can gain access and price as a single agent. In contrast, kind of a contemporary study run by one of the leaders in this space, combining agents that weren't designed to be combined originally, highlights kind of the difference here between our approach, where agents are dosed on an every two-week, four-week, or eight-week basis with a mix of IVs, subcutaneous injections, and on-body devices. As a result, the study is open label, cannot have a placebo control, and it's unclear how these will be moved forward as a single product going forward.
In addition, we've had many questions about why pursue kind of co-formulated combinations versus putting these together as a single antibody in a bispecific. We think there's really three compelling reasons why we chose to do it this way rather than put them together in a single agent. The first, I think, is something that is particularly challenging in IBD, which is that we know that it is critical to have the right amount of target engagement for each target that you're going after. There are very strong dose and exposure responses for biologics in this case, and the ability to mix them together in not necessarily a fixed ratio in a co-formulation is a substantial advantage to molecules that are together in a multi-specific.
I think this is particularly true when one of those targets is a membrane-bound target like alpha-4 beta-7 that exists in the peripheral circulation, whereas inflammatory cytokines like TL1A and IL-23 are located in the tissue itself. There's no kind of single agent that can bind both of those at the same time. In addition, we think that the design and engineering of our monoclonals is likely to have longer dosing intervals than we've seen as doable with bispecifics. In addition, we know that multi-specific antibodies tend to have a much higher immunogenicity rate than monoclonal antibodies do. We think that the co-formulation of our antibodies is likely to outperform from that perspective as well. Lastly, as I mentioned, we're interested in testing the opportunity for TL1A outside IBD as well.
It's not lost on anyone that this is a target that has been implicated in more than a dozen different diseases. We spent the last year and a half prioritizing these based on the commercial opportunity in each of these indications, as well as our ability to execute a study in this space rapidly, as well as the scientific evidence for this. RA really checked all of our boxes here. This is, again, a tens of billions of dollars market where agents are struggling to get to complete remission, and patients have to cycle through multiple medications as well. We think our TL1As, which we expect to be dosed on at least a quarterly basis subcutaneously, if they can match the efficacy of other products in this class, would be a choice for physicians that would be a leading choice and multi-billion dollar opportunity.
From a scientific perspective, we think TL1A and RA have functionally as much data as you could expect for a program that hasn't yet been shown to have clinical proof of concept. Beyond genetic association between TL1A and RA, there are also human tissue data that demonstrate that TL1A levels are elevated in RA patients and they correlate with disease severity. From a causal perspective, we have animal studies in both directions that animals with arthritis, if you administer TL1A, their disease is exacerbated. If you administer anti-TL1A antibodies, the disease is ameliorated. We saw these data published by third-party groups and decided to replicate this study, these studies on our own.
We tested our TL1As against TNF in a rat model of arthritis and see that in one form or the other of this assay, we see that our agents are at least as good as TNF, if not better. We are excited to move this into the clinic and see if we can see the same thing in RA patients. Overall, we think the portfolio here sets up for an exciting couple of years. We will have our additional phase one data from our TL1A assets in the upcoming months here in the second quarter. We will have phase one data from our IL-23 in the second half of the year. I view that as proving the promise of each of these molecules, that they are extended half-life improved versions of the previous antibodies in the space.
We will move into testing these agents in the phase two studies that I described previously, the large ulcerative colitis phase two platform study, where all three of these agents will be added as they finish phase one, and then the RA study that we plan to test for the TL1A. Altogether, I think it's a portfolio of kind of relatively low-risk proven biology in inflammatory bowel disease and making what we believe are potentially better assets against each of the best targets in this space, exploring novel biology of TL1A and new indications where it could be a meaningful product. Lastly, testing these combinations could really be a dominant product in the inflammatory bowel space that addresses that unmet need that I mentioned at the outset of simultaneously improving efficacy meaningfully and moving to a much more convenient profile than is available today.
With that, I will turn it over to Tyler for questions.
Wonderful. Thanks for the presentation, Cam. We'll go ahead and get some Q&A started. I wanted to start with SPY001, naturally. Impressive 90-day plus half-life in humans. I guess beyond the obvious convenience of less frequent dosing, which you covered, how do you see it stacking up against Entyvio on the efficacy front? Does greater exposure and/or trough concentration matter with this target?
Yeah, for each of these targets, we have the ability to learn from what prior sponsors have done in this space. For Entyvio, we saw both in the phase three study, the Gemini study, and in the FDA review.
In the real world as well, what's described as in the induction setting, for the first three months in the acute inflammatory phase of this disease, the more drug you have on board, the better. Patients with Entyvio, both in the phase three studies and in the real world, those that have fourth quartile level of exposures of Entyvio have a 37% clinical remission rate in the Gemini study, whereas the average overall was in the high teens. A substantially better clinical remission rate is seen in that high exposure group. We think the opportunity, as I mentioned for O1, is actually to test that. This is a very well-tolerated molecule. Physicians double-dose it regularly, and it's very well tolerated. Our intent is to move our exposure to that fourth quartile level and see if we can optimize the efficacy of this agent as well.
In the platform trial, will you be testing multiple doses with the monotherapy? How are preparations for that trial going?
Yeah, the preparations for this trial are going well. I think we're reaching out to hundreds of sites at this point. This is going to be a large global study. We think we'll have between 200 and 300 sites in this study. It will be a large effort, but I think we have the right team to go do it, having just executed studies well in this space. In terms of the design, we'll initially be taking forward the single doses of the monos in the open label portion. There may be an opportunity to dose range in the study as well to solve that.
For the combinations, we expect to take forward a single dose that we believe maximizes the efficacy of each of the individual components.
Okay. I guess just focusing on the dosing interval, what do you need to see from the platform study to get confidence in potentially moving forward with the every six-month dosing?
Yeah, I think for the alpha-4 beta-7 molecule, I think we have high confidence based on what we've seen already that we could move forward with a twice-annual dosing. We, of course, do not yet have our phase one data from our TL1As or our IL-23s, and this platform study is starting imminently. We think the quarterly dosing basis is the right place to start for each of these. It's typically dose ranging and maintenance is often done in phase three in inflammatory bowel disease.
We think it's a rational thing to test kind of the longer dosing interval, potentially with a lower dose as we get into pivotal studies.
Got it. Okay. And as we think about the initial 002 and 003 phase one readouts later this year, what's the, I mean, obviously you need to see clean safety, but what's the bar for half-life in order to get a three or six-month dosing?
Yeah, so for, they're interestingly a comparable half-life that we need for each of them, about 45 days to dose quarterly for these. And then on the order of 60-65 days is what we think would be required to dose these on a twice-annual basis for each of these assets.
In terms of how do we translate from the non-human primate data to human data, we had thought previously that our alpha-4 beta-7 was going to be the shortest human half-life. It had a low 20s half-life in non-human primates, which we did not expect to translate to the 90-plus day half-life that we saw initially. I think that removes it as the likely dose-limiting agent in our combinations because it certainly can be dosed twice annually on its own. The next most challenging is likely to be our TL1As. In non-human primates, we saw a mid-20s half-life. We think kind of that 45, we think it should be achievable in humans. As we get in kind of the 60-day range, that kind of would likely cross the error bars there.
I think we're likely to have at least a quarterly TL1A, but the fact that we have two of them going in phase one, we think there's a reasonable probability we'll have a twice-annual version. IL-23, we have a 30-day half-life in non-human primates. We would expect that to translate to the longest human half-life. I think that one's probably the lowest risk in terms of our ability to move forward with certainly a quarterly, but probably a twice-annual basis.
Before going in full combo mode, I just want to ask at least one or two more on 001, alpha-4 beta-7. As we think about that phase two monotherapy readout, what's the bar for success in terms of clinical remission and/or other endpoints?
Yeah.
I think in general, what we're hoping for for our monotherapies is to really replicate the data that's been seen with the parental molecules. I think there's an opportunity, as I mentioned, that we can improve the efficacy either in induction or maintenance based on kind of greater target coverage, depending on what we've seen from the prior molecules. I think a quarterly or twice-annual version of each of these is a win. I think particularly as we use those as tools to move into our combinations, I think that that's all we really need to see. I think in general, yes, these are going to be small open label readouts. There's necessarily going to be reasonable error bars there.
I think as long as they're in the range of what we've seen for previous molecules in the class, I think we'd be excited by that.
As we think about enrollment timeframe for monotherapy and the timeline to top-line data, can you just give us an overview of that and when we might expect data next year that's going to come before the combos, right?
That's right. Yeah. We expect the entire study is approximately the size of the duet studies that were recently enrolled in this space. Those took a little over a year and a half to enroll the full studies. We think that's a reasonable benchmark and precedent that we think we should be able to go out and achieve as well. That's for the entire study. We've guided to having these monotherapy readouts next year.
I think we expect the alpha-4 in the middle of the year with the other two to follow. Enrollment in any clinical study typically follows a hockey stick shape. I would expect kind of the amount of time that it takes to get the first one is not the same amount of time that it takes the second and third and so on. It should shorten for each incremental agent.
Do you prioritize enrollment in 001 or the alpha-4 beta-7 cohort before getting to the others? How does that work?
Our expectation is to start with the alpha-4, and then when the TL1A is ready, we'll randomize between the two. When the IL-23 enters, we'll randomize between the three.
Got it. Okay. You talked about optimizing the components of the combinations. How do you expect to do that and figure out the proper dose?
Yeah.
I think the nice thing here is that both our alpha-4 and the IL-23 dose selection, we have quite a bit of information to select from, given that we're targeting the same epitopes with very similar potency as vedolizumab and risankizumab. Really for our dose selection for this proof of concept study, we're leaning heavily on those and picking agents that we think maximize the dose and/or exposure responses for each of these targets. Now, TL1A is the hardest one because, as I mentioned, our molecules are quite a bit different. If we have tenfold the potency of another molecule, we don't necessarily have to have the same coverage in terms of trough concentrations of the molecule. However, what's nice about TL1A as opposed to alpha-4 and IL-23 is we actually have pretty good pharmacodynamic measures for TL1A as well.
We can measure target engagement with TL1A using either total serum TL1A levels or free TL1A levels. We've seen from the prior molecules in this space that both have worked for picking molecules and picking doses to move forward for successful outcomes.
Since we're on the topic of TL1A, I think it's worth going over monomers versus trimers. I'm not sure that the audience is super tight on the biology of monomers versus trimers. Why target both?
TL1A is a trimeric protein. It's believed to only signal when it's a trimer as well, but it's in an equilibrium between the two. It's secreted as a trimer, and we see it separates into monomers as well.
The arguments for hitting one or the other in terms of if you hit both the monomer and the trimer, you're fully engaging the target, preventing it from associating into trimers. I think we see some evidence in vitro that binding to the monomeric form of TL1A can actually promote the monomerization of the trimer and actually take it away from the signaling form as a trimer. You actually move it away from the active form of the agent as well. In contrast, if you're hitting the trimer only, you're really blocking the trimer, which is the active form. If you kind of disengage from the trimer, it's an active signaling trimer. I think this is all theory because the reality is we have three TL1A targeting agents.
One of them hits predominantly monomers and trimers in the Prometheus-Merck asset, whereas the other two are predominantly trimer binders. I think it's fair to say that all three of them have pretty good efficacy on a placebo-adjusted basis. The efficacy looks quite similar between the three. Theoretically, we think it may be superior to hit both the monomeric and trimeric forms yet, but I'm not sure we've seen that separate in clinical data yet.
Understood. You showed the exciting Vega data on your slides, which is great proof of concept for combinations in the space. The milestone slide has J&J's ongoing Duet study there. I believe that's going to read out second half, right? Late May, primary completion per clinicaltrials.gov. What should we expect from the Duet study readout relative to Vega in both UC and Crohn's?
How will that read through to your programs?
Yeah. I think Vega was a groundbreaking study, but it's quite a bit different than the Duet study. In Vega, the populations were completely naive. This was an ulcerative colitis population where no patients in the study had had prior advanced therapy exposures. The two Duet studies, one in UC and one in Crohn's, are exactly the opposite. They're testing only patients that have experienced advanced therapies. We know what's going to happen to the monotherapies because this has been studied over and over again with monotherapies, is that when you move from a naive population to a refractory population, all of the efficacy numbers are going to come down. We're not going to see 25% clinical remissions from the monotherapies when we move from a naive to a refractory population.
What's interesting and is unknown is what happens to the combination arm as well. I think it's highly likely that number is going to come down as well. The question is, are we still able to see a separation between the monotherapies and the combos in that more advanced, sicker population as well? I think the reality is in the real world today, that refractory population is where combos have been used. It's typically the case that physicians are using individual agents first because that's what's on label and approved. As I mentioned, very few agents lead to lasting remission in this space and it's in a relatively small probability or portion of patients. That is where physicians in the real world today are turning to combination therapy and seeing success.
I think we're optimistic that we're going to see success in the refractory population as well. That really is the key uncertainty with duet from an efficacy perspective. From a safety perspective, it's also quite new what we'll see. In Vega, the combination was only done for the first 12 weeks, and then the TNF part of the combo was dropped for the maintenance setting. In duet, that's not the case. It's a co-formulated agent. We'll see a true combination of TNF and IL-23 throughout the dosing interval. I think the main question is, do we see kind of TNF-like safety? Or when you add an additional immune suppressant in IL-23 on top, do you see something incremental? I think we're really going to learn a lot from these duet readouts in a few months.
I think we may even learn the same combination reading out in psoriatic arthritis in just a few months as well. I think the likelihood is we're going to learn quite a bit about combinations, not just in IBD, but in the broader INI field over the course of the year.
What do you expect monotherapies to do in the duet populations, I guess, at least in UC? What do you think is enough of a buffer based upon what you're hearing from K-Wells for the combo to be significantly differentiated?
I think we know the monos are likely to come down double-digit percentages and exactly what population they enrolled in that study. How refractory will determine if that's going to be up 15% or a lower clinical remission rate. We just don't know exactly who's enrolled in that study.
It's hard to know how much worse the monotherapies are going to be. I think what's critical about kind of the future of this field here, that we should kind of how we should all be thinking about this is what's the ultimate label that the combinations are going to get and how are they going to compete with what's existing on the market? I think until proven otherwise, I think the base case will be that the pivotal studies for combinations are going to include a mixed population. They're going to include a mix of naive patients and a mix of refractory patients as that's typically been the way that all agents in this space have been approved.
I think what we should all be doing is taking the Vega result in the naive population and the Duet result in the refractory population, kind of envisioning what that cumulative label looks like for the overall population to compare it against other agents that have been tested in a similarly mixed population. I think we also have precedents for what superiority looks like in that type of trial with there's been a handful of head-to-head superiorities demonstrated in IBD. Maybe one to cite here would be the Varsity study where Entyvio beats Humira, alpha-4 beats TNF head-to-head. That delta was about five percentage points. I think we did not see alpha-4 beta-7 then suddenly dominate the market and take all share there, but certainly led to kind of substantial growth in the usage.
I think that would be the bare minimum in terms of the overall population. When we test with physicians, and I think we show a slide in our deck where we look at a 10 percentage point delta in efficacy, that really leads to a substantial difference in preference if you have a 10 percentage point delta in clinical remission overall, looking at kind of a mixed population of naive and refractory patients.
Can you say which combo you're more excited about at the moment?
I love all my children equally. No, I think the reality is that if I were to guess which agents are going to be best in ulcerative colitis, I think it's alpha-4 beta-7 and TL1A. And then on the Crohn's side of disease, I would say it's TL1A and IL-23.
Kind of going into kind of our without seeing human data, that would be my guess is that it's alpha-4 and TL1A in UC and IL-23 and TL1A in Crohn's. You have to run the study. Is that because of expression in the tissues and where the disease is located? I wish it was that complicated. It's literally adding the efficacy results for each of the individual agents and seeing that kind of the monotherapy results for those agents are better than they are in vice versa. However, I think when we talk to kind of our advisory board and physicians in the field, the combination that they're most certain of is the alpha-4 and IL-23 because those are the two agents that they have the most experience with.
We have tens of thousands of patients exposed to those classes in the real world, and they're very well tolerated. Again, safety really is paramount in this space. These are relatively young patients who are diagnosed. We care a lot about the safety here. I think alpha-4 and IL-23 is the most certain from that perspective. It's really hard to ignore that TL1A probably has the single greatest monotherapy efficacy in this space. I think that that could be the one that delivers the best efficacy overall.
Great. I wanted to ask you about the competitive landscape. You have companies emerging in the space going after similar targets on a daily basis. Chinese companies creating copycat antibodies, even Wall Street investors talking about how they could just slap a YTE and then add body and do it themselves.
How do you think about the competitive landscape? How easy is it to do what you all and Paragon have done? What are your latest thoughts?
Yeah. Look, I think the barrier to entry to running this study is harder than folks expect. I think we've seen some strategics go out and buy individual assets here and try and put them together with things they already have to make a combination strategy. I think it results in something that doesn't look nearly as elegant as what we're doing. I think all of the earlier agents, either they're kind of monoclonal new assets coming out of China or even the bispecifics, I frankly don't think they're going to match in terms of efficacy in the long run. I also think we're quite a bit ahead as well.
I think it's really up to us to drop the ball for there to be an opening here.
That's great. We're out of time, but in closing, what aspect of the Spyre story do you believe is most underappreciated by investors?
I think what we just talked about. I think how hard it is to replicate this and that these programs have been going for three, four years at this point with a few hundred million of investment to get to this stage. I think the delta between what we have and what others have is going to look more obvious over time.
Maybe it's a topic for another time, but I think people would be surprised by the amount of primate work that you guys did to get your antibodies.
Yeah, I think we put about a dozen TL1As into non-human primates to pick these two that look really good.
Yeah. Great. With that, Cam, thank you very much. Appreciate it.