Hey everyone, we're back. Happy to introduce Brian Wong and Rodney Young from RAPT Therapeutics as our next presentation this morning. Maybe I'll kick it over to Brian for a brief overview of the company, and then maybe just sort of, you know, how you got here, right? How you got RPT904 and sort of that progression there would be helpful. Brian, over to you. Yeah, sure. First, I'll explain something in the invitation today. I really appreciate it. Just for a quick introduction, RAPT Therapeutics' mission is to discover, develop, and commercialize high-value therapeutics for a range of inflammatory disorders, particularly where we can disrupt the standard of care in multi-billion dollar markets. Our lead asset is called RPT904. This was in-licensed recently from our partner, Jemincare, in China. This is a next-generation, anti-IgE antibody that's designed to improve greatly upon omalizumab or Xolair. We're particularly excited about two indications, including food allergy and chronic spontaneous urticaria, which we estimate conservatively at $40 billion and $5 billion markets, respectively. Currently in phase II, we have multiple milestones coming up, which we could talk about, including two phase II trials that are being out this year from our partner, Jemincare. Yep. Cool. We also have a portfolio behind it, including our next-generation CCR4 antagonist. Yeah, that's us in a nutshell. Yeah, maybe, can you walk through the deal terms for the RPT904 deal before we jump into the broader space? Yeah, I'll let Rodney take that. Yeah, so Alex, it was a $35 million upfront payment. There's about $670 million in milestones. Two-thirds of that, about $450 million, are what we would call commercial milestones, post-approval. You know, $200+ million developmental milestones. The royalty rates are, the highest tier is low double-digit royalties. What geographies does this include? Yeah, we have rights, worldwide rights, excluding China, for all indications. Okay, cool. Yeah, so obviously the IgE space and the food allergy and urticaria space, super interesting, a lot of interest right now. What is the white space opportunity? What does that actually look like, you know, beyond what omalizumab is doing today? Yeah, so just maybe a quick introduction for food allergy, since it is a relatively new indication. This is a, it's a massive opportunity. There are 17 million diagnosed patients in the United States. Three and a half million of those are children. This is a disease that can land you in the ER due to anaphylactic reactions. Prior to omalizumab's approval in February 2024, there was really only one major therapeutic approach, which was oral immunotherapy. Sulfafurazole was a good example. The market is relatively untapped. Xolair was approved in February of 2024. What got us really excited is that, as of today, one year after approval, there are already 60,000+ patients on Xolair for food allergy. There's over a $1 billion run rate. I think that suggests that there's a very, very high unmet medical need and a huge white space for new biologic-based therapies. Yeah, I guess in particular, when you think about the design of RPT904, what are the key elements of improvement for this molecule versus omalizumab? Yeah, I mean, Xolair is a good drug. It's highly effective, but it's also a 20-year-old drug that is sort of badly in need of improvement. That's where RPT904 comes in. It was designed based off the omalizumab sequence, but it has improved half-life based on a YTE mutation, as well as improved affinity and other mutations to improve drug-like properties. We're estimating that, compared to Xolair, which has Q2 or Q4 week dosing, we're expecting Q8 or Q12 week dosing. Most food allergy patients are actually on Q2 week dosing, which is very, very inconvenient. Yeah, so I mean, other folks, including Novartis, have tried to make next-gen anti-IgE antibodies like ligelizumab. You know, what can you learn from that? Why are you confident in RPT904's design here? Yeah, that's a really important question. So ligelizumab from Novartis and Roche was designed with higher affinity, like, you know, two orders of magnitude higher affinity than Xolair. Ultimately, it failed in the clinic, particularly in asthma and in food allergy as well as CSU, despite having better IgE reduction. We really strongly believe that it depends on the epitope or the mechanism of action. Ligelizumab doesn't share the same epitope. It's partially overlapping and then has very different biological properties than omalizumab, which is why we think RPT904 is the drug with the highest PTS. It does share the same epitope as omalizumab. We have high confidence in its ability to show efficacy and good safety. Okay. Obviously the launch that you pointed out has not been lost on others. There's a lot more programs out there, including extracellular degraders, other IgE antibodies, novel approaches like a T cell engager, like what Regeneron's doing. I guess how should we think about the growing competitive landscape here? How do you see YTE, IgE antibody fitting into some of those approaches? It's really exciting to see others start in this market as well. I think it just speaks to the high level of interest. We don't, we're not afraid of the competition. We actually like it because, first of all, there is a huge space to fill. Often these indications can take multiple entrants. What I would say is that, first of all, our molecule is one of the most advanced. It's in late stage, mid-stage development, potentially going to phase III next year, possibly. What we think is that while those other technologies are very interesting, I think the key question is what medical problem are they trying to solve? Because Xolair actually does show very robust activity and relatively quick onset of action. We'll see how those assets differentiate themselves. We've seen that potency is not the only game in town from ligelizumab. We'll see how those assets differentiate themselves as they enter the clinic. Yeah. Maybe the other big question from the market is just how will this market evolve with omalizumab generic entry fairly soon? Like, how do you think that that's going to play out from a competitive perspective? Yeah, I'll just start and I'll let Rodney answer that because we've done a ton of market research, including payer research with over 45 payers. I think the key factor is whether your drug is differentiated from branded and ultimately the omalizumab biosimilars. All of the research we've done with key opinion leaders and with payers as well as with patients, RPT904's more convenient dosing, which would translate into better compliance and ultimately, you know, keep children and other folks out of the is highly differentiated. In terms of premiums as well as the ability to limit or eliminate step-throughs, we had a very positive response to that. Yeah, just to add a little color to that, right? As Brian said, the less frequent dosing regimen is far less burdensome, right? Far more likely to keep the patients on the drug. Obviously, patients prefer that, prescribers like that for their patients. Very critically, as Brian mentioned, the payers recognize that because if you keep the patients on drug, keep them out of the ERs and all that, that has healthcare system benefits, health economic benefits. They recognize that and they're willing to pay a premium, relative to branded OMA, or reimburse, relative to branded OMA at a premium. We do expect biosimilar entry to pressure the branded price. The history would show that to be the case. As we had done all our modeling and all that, we expected branded OMA to erode probably 30%, 40%. We would still expect to be able to price above that. The other really important differentiating factor, which I'm sure Brian will get into when you get to the clinical side, is there's a fairly high percentage of the food allergy population that are excluded from the omalizumab label. These are the high IgE, high weight patients. We think we will be able to address those patients. Those patients, if we can, will literally have no alternative except for RPT904. Yeah. Maybe, you know, can we, I'd love to talk about dose selection in that context. As we tail into talking about your phase III design, I think maybe Brian, do you want to start off with that thread and how you think about dosing, your confidence in dose selection to get that breadth of the population? Yeah, so based on the phase I data with RPT904, it showed over doubling of the half-life of omalizumab. As I mentioned earlier, this will translate into at least Q8 week dosing, but more likely Q12 week dosing. Based on models that have been used for about a decade from Novartis and Roche, we have high confidence in the modeling as well. In the food allergy study, we are aiming for a reduction in free IgE that mimics omalizumab with Q12 week dosing, but we also have a Q8 week arm, which should actually provide even greater target coverage there. We have high confidence in the dose. In addition to that, we are highly confident that we can target those high weight, high IgE patients that Rodney mentioned and still bring benefit. You can imagine that if we have a broad label that is independent of your weight and IgE, that's going to be very highly attractive to the market as well as payers. How much confidence do you have in getting those high weight, high IgE patients? What kind of trough coverage do you need to see? How can you extrapolate that from the phase I work that you've done so far? Yeah, so you know, it's not like there's some magic to those patients. It's just that omalizumab models, and then we've confirmed that they can't get to this target trough level of free IgE of less than 25 ng per mL. We do know anecdotally that some investigators have used Xolair at higher doses and have seen better efficacy, but now you're up to 1,200 mg or once weekly dosing. It's very unlikely Novartis will pursue a label as well to expand the dosing table. Here's a real opportunity for RPT904. We do actually think that with Q12 week dosing or Q8 week dosing, we can address those patients and get really patients as high as 5,000 units per mL of IgE, which is really an awful scale. Can you touch on the design of your phase II-B study? Yeah, so our phase II-B study, which we're on track to start before the end of the year, is very much based on the phase III OUtMATCH study, which was the study that was the basis for approval for Xolair in food allergy. This is a double-blind, placebo-controlled food challenge study. Essentially, you include patients that are sensitive to a specific set of foods at a certain threshold or lower. After the dosing period, they have an exit food challenge to look at that increase in threshold. If it hits a certain mark, which is well defined in the OUtMATCH study, then those patients are considered responders. We are planning to study initially adolescents and adults and look at all the major foods that were studied in the OUtMATCH study, including peanut, milk, and egg. We estimate roughly 18 months from study start to top-line data. We have 100 patients. 75 of those patients are OMA eligible. There's a separate subgroup of 25 patients plus, so we have the ability to go higher than 25, that are OMA ineligible. The reason why we broke those two out is because we're looking for OMA-like activity at Q8 week or Q12 week in the OMA eligible population. In those patients that have no option, the bar is lower. Any activity in those OMA ineligible patients will be of high interest. I guess in sort of the OMA eligible population, pushing the exposures with Q8 week, is there an opportunity to demonstrate better efficacy as well in your view? Yeah, we're certainly not ruling out that better PD and better target coverage will result in more robust activity, although just to mention, Xolair has a 60%- 70% response rate. It's already quite robust. Our target product profile that we've tested with payers and prescribers is really equivalent efficacy to omalizumab, but at less frequent dosing and the ability to address those high IgE and high weight patients. Okay. You said yes to 18 months from start, so we're talking about like a 2027-ish readout. Mm-hmm. Okay. Right. In the meantime, as you mentioned, you know, Jemincare is running some studies in China. Can you go over what those studies are and when we'll learn more and maybe sort of how that might relate to your decision making on indication expansion? Yeah, so Jemincare is running two phase II studies, and we think the data will be important for both validating RPT904's extended half-life with respect to efficacy, but also could set us up for accelerated development here in the United States and in Europe. They are running a 135-patient CSU study comparing Q8 week RPT904 and Q12 week RPT904, 300 mg versus omalizumab at its approved dose, which is 300 mg Q4 week. They are looking to see on all the sort of key primary endpoints that you'd expect, UAS7 and others, efficacy that's on par with omalizumab, but at Q8 week or Q12 week dosing. That's planning to read out before the end of the year and very much on track to do that. They're also running a smaller phase II asthma study. This is more PKPD oriented. It's 60 patients comparing three different dose levels of RPT904 versus omalizumab. What we're looking to see there is extended pharmacodynamics and reduction in free IgE relative to omalizumab. They're planning to use that information to refine their phase III dose for asthma. We're particularly interested in chronic spontaneous urticaria. If those data are positive, we plan to try to go to phase III if we can define that phase III dose. Okay. You know, will these data be disclosed? Are Are you involved at all in that disclosure? How quickly will we learn the results of that? Yeah, Rodney? Yeah, we've been discussing that with Jemincare. They're private, but they understand we're a public company. The plan is, at least for the CSU data in particular, the plan is for a joint press release. We will probably have a call for analysts and investors after the press release. Our understanding is they would intend to try to present a more fulsome disclosure. The press release is probably more top-line. They would try to present a fuller disclosure at a medical meeting sometime early next year. Yeah, I fully acknowledge there's no right answer to this question, but is it a foregone conclusion that all IgE antibodies will have a black box warning in your view? I don't think so. You know, that's our assumption. That's our base TPP. Given that there's over 20 years of experience with Xolair and over time, the FDA has publicly come out in their, for example, summary basis of approval and talked about omalizumab's good safety profile, I think it's worth a discussion given the years of safety information that are available. The label for omalizumab is really broad, right? It's children one year and above. That was based on data where most of those patients were older, you know, six years or older. I think the FDA could be open to that if it has a good differentiated profile. Is there a part of this in avoiding asthma? Is that a consideration with a label? I think part of the rationale maybe was, you know, exacerbations in asthma looking like an anaphylactic reaction might be challenging. If you don't have asthma on the label, is that helpful? That's a really interesting point. I didn't think of it that way. We prioritize CSU and food allergy just based on the high unmet need there. Certainly, a longer acting IgE could be of interest in asthma down the road. I think a broader label in general will be helpful because a lot of these patients have comorbid conditions. It's something that we might think about in the future. We're also excited about seasonal allergic rhinitis, particularly those patients that don't respond well to topical steroids or don't like to take steroids. Okay. Maybe anything else you want to touch on with IgE before we touch on CCR4 antagonism? Just, you know, one other point is that there's been a lot of experience with omalizumab across different ethnicities and countries. The labeling and the PKPD is very similar. I think the ability to read through and even select doses across different ethnicities, I think, are well founded. That's why we think that the data that are going to be available will be very important for us. I guess as a follow-up to that, do you think that, you know, safety data from the Jemincare experience could support a BLA for you? Or would you need to generate your own? Okay, you would. Yeah, particularly the safety database certainly would carry through, we believe. You wouldn't necessarily need the full U.S. or, you know, Western population for safety. We believe so, yes. That's something you'd be able to talk about post, again, end of phase II meeting potentially? Yeah, absolutely. Okay, CCR4 antagonism, maybe you set things off with sort of what did you see with the first gen that gave you confidence in pushing forward with the next gen? Yeah, so, clearly, we had to stop those studies last year due to that single event. We've seen information that makes us continue to believe in the target. We still think there's a high unmet need for an all-drug for a range of TH2-driven disorders like atopic burn and asthma. That's why we brought our second-generation molecule forward. We selected a candidate last quarter, and we're now bringing it through its paces. Obviously, we're not finalizing this given it's relatively early, but we remain very interested in this approach. As we head towards the clinic next year, we'll be disclosing information. Is this the wholly new scaffold versus RPT193? It's a distinct chemical entity, yes, with a much larger safety and specificity margin. Were you able to track down any key metabolites from RPT193 to give you confidence in sort of preclinical work, or do you still? You know, there's really nothing implicating RPT193, to be very honest with you. A lot of what we've done, though, is, you know, and RPT193 was very safe from a preclinical and even, except for that one event, clinically very, very safe with no evidence of elevation in liver enzymes or anything like that. It's a little bit hypothetical, but we can find ways to greatly increase specificity as well, and we've done that. If there was anything related to RPT193, we've completely generated that out with respect to liver safety. Maybe the final question here, you talk about cash runway and what the embedded assumptions are there? Yeah, our cash at the end of Q2 was just under $170 million. Our projection is that our cash runway will last through the first half of 2027, which is when we expect to get the top-line readout for the phase II food allergy trial. Does that include any initiation of other indications at all or no? We have certain assumptions that we had made regarding CSU, moving forward in CSU. Those assumptions, as Brian said, may change, and it'll be the data disclosure coming. We want to see that data and kind of make a decision there. Great. Brian, Rodney, always a pleasure. Thanks for joining us. Thanks, Alex. Thanks. Really Thanks. Really appreciate it.