All right, good afternoon, everybody, and thank you once again for joining us for our second day of our first I&I Summit. I'm Yaron Werber from the TD Cowen Biotech team, and it's really a great pleasure to have the next chat with RAPT Therapeutics. With us today, Brian Wong, President and CEO, and Rodney Young, Chief Financial Officer. Gentlemen, thanks for joining us. We appreciate it. Thanks for the invite, Yaron. Really appreciate it. Excited to be here. Exactly. There is a lot going on in RAPT, and the stories really come together on the heels of really sort of the next tranche of the company with a new drug and a new name, ozureprubart. It is RPT904, which is a half-life extended anti-IgE, both in food allergy, CSU, and there is obviously a small sort of PK and biomarker study going on in asthma as well. Maybe, Brian, in terms of the structure of RPT904 and the differentiation from Xolair, can you talk about the potency, the half-life extension, and also how ultimately, and more importantly, for food allergies, you can really round out the label and some of the issues with Xolair? Yeah, thanks, Yaron. First of all, Xolair is a 20-year-old drug, but you can't teach an old dog new tricks. What's been very exciting is that despite its relatively frequent dosing and relatively lower potency, it's shown very, very robust results in food allergy and has become the standard of care in food allergy. As many of you know, it is the standard of care in chronic spontaneous urticaria as well. There are several issues with Xolair. The first is it's dosed relatively frequently and sometimes requires two to four injections per dose. In addition, the molecule is limited. In food allergy, roughly 25% of food allergy patients are excluded from the label due to high weight and high IgE. In CSU, for example, roughly 20%-30% of patients require Xolair updosing, which is also off-label as well to get maximum benefit. This is really where ozureprubart comes in, and we call it ozu. It's been designed for it uses omalizumab as the base template. It preserves the epitope, which we think is absolutely essential for success. Around that is the increased half-life via the YTE mutation. In healthy volunteers, we've seen that half-life increase from 24 days for OMA versus 60 days, as well as changes in the variable domain to improve potency as well as other drug-like properties, including stability and manufacturability. This is a novel molecule, so very strong IP. Loss of exclusivity through composition matter at least to 2041 without additional patent term extensions. How that translates into is less frequent dosing. As opposed to Q2, Q4 week dosing, we think we're probably closer to Q12 week dosing. That limits injections to four to six per year as opposed to 13-26 for Xolair. In addition, we can access those patients that are off the OMA label as well as limit the need for updosing, which is required, seen in many patients treated with Xolair. Let's maybe discuss the first study that just read out about two or three weeks ago with your partner, Jemincare, which was a Chinese phase II CSU. Your partner, Jemincare, is running the study in China. It was two different dosing, testing Q8 weeks and Q12 weeks versus OMA, Xolair every four, essentially 46 patients an arm. It showed that both Q8 and Q12 weeks looked the same numerically, actually, were even better than OMA when you're looking at the UAS7 scores. It actually looked like the durability even lasted as much as 16 weeks. By the way, OMA did as well as historical. The data pretty much checks out with respect to U.S. studies in terms of baseline enrolling criteria, how OMA has performed in Western population as well. Even some of the CR rates were fairly encouraging too and very competitive with all the other drugs out there. Maybe putting it all together, how does that translate into what you might do in phase III? Yeah, so obviously you captured the results extremely well. In addition to that, they were very well tolerated and good safety as well, and certainly no different than omalizumab. It really hit the highest, exceeded our highest expectations for the drug because now we're seeing this incredible durability up to week 16 at least. From the phase III study, we think that the Q12 week beta-nomogram dose is very well supported by the data and that we certainly will pursue that in phase III. There's also the chance if that numerical improvement over OMA continues to hold through that we're essentially addressing patients that are suboptimally dosed with Xolair as well, which is a factor that we didn't even consider initially as part of our modeling. We are contemplating roughly two, well, two phase III pivotal studies. We're thinking roughly 300-350 patients each with UAS7 at week 12 being the primary endpoint as the basis for approval. At that point, because you are using the same epitope, you don't need the same kind of size study, let's say as Xolair, is needed to get approval. That's right. Yeah, I think the FDA is very familiar with the IgE mechanism of action. Beyond that, we share the identical epitope with omalizumab. Correlations with PK/PD and other factors, we think, are we're going to get credit for that with the regulators. In addition, as you know, our partner, Jemincare now they're called Jeyou from the spinout, they're going to be running phase III studies in China, roughly a 1,000-patient asthma study and several hundred-patient CSU study as well for approval. We absolutely should be able to use those patients as part of our overall safety database, which should also contribute, I think, to the overall data package for the FDA and limit the need for large studies as well from our territory. You mentioned that the primary would be at 12 weeks, and I imagine you probably need some kind of a longer follow-up as well. Yeah, of course. Yeah, 12 week is the basis for approval for other drugs. Of course, we'll want to see additional time under drug as well. As you probably saw at week 12 and 16, there was deepening of response at week 12 and 16. That's something we want to carry through for a longer period of time and then allow for the placebo patients to also crossover. There will be additional follow-up as part of that main study, but the primary top-line data will be at week 12. Would you consider maybe doing a Q16 week arm, or would that be something you might want to do as a separate study? Yeah, that's a good question. Maybe I'll let Rodney take that because we've done some sensitivity research around different dosing intervals. Yeah, so one of the key attractions of ozu is the less frequent dosing. But when we query prescribers, patients, and payers, Q8 week was good. Q12 week was better, but you do not really get that much more at Q16. It remains to be seen whether commercially that would be that additive. Another key aspect is Q12 seems to be kind of in that sweet spot as to kind of fitting the frequency at which patients are seeing their doctors, the allergists. That part kind of fits really well with practice. We think Q12 is probably the sweet spot. Okay. I imagine that the head-to-head against OMA at that point is a non-inferiority, or is there a chance to even do a superiority look? Yeah, for the basis of approval, FDA will want placebo-controlled randomized studies. We are thinking about a comparator study, perhaps a separate study really as a way for payers outside of the U.S., but certainly for approval, not necessary. Okay. Okay, let's move to food allergy because Novartis has been very upfront emphasizing how well Xolair is doing in food allergy. The good news is they're not going to see biosimilars until next year, and it might be even later on next year. I believe the latest numbers, over 80,000 patients now, right, have been on Xolair, and this is the second year on the market. One of the extremely fast launches, the KOL checks have been coming back that oral immunotherapy is effective. It's obviously very effective for peanut. It's not that well tolerated. If you're very active, you can actually have paradoxical hypersensitivity, and patients really don't like it. For them, Xolair has been really a game changer. It's certainly for patients who can't tolerate OIT or kids and anybody with several allergies as well. Can you maybe talk about what's really been in your market checks driving that launch overall? Because it is still an injection. Is it mostly getting used in adults? Is it also getting used in kids? To your point, what's the unmet need still? Yeah, I'll let Rodney talk about our script-level work that we've done, but some very interesting findings that are going on. Yeah, I mean, to start with, Jeroen, I think you correctly point out Xolair has been a really good addition to the arsenal for food allergy patients. But it does have limitations, right? The Q2 week dosing, and our research suggests that most patients are on Q2 weeks because they tend to be higher IgE patients. So that's a challenge. When you kind of query patients and prescribers, would you take this every two weeks, or would you prefer it every 12? Vast majority are going to prefer it for every 12 weeks. In our research, what we see is about 60% of what we think are the current scripts are probably adolescent to young adult, and about 40% are peds, younger than 18. It's mostly the younger population, but proportionately, since there are relatively more adults who have food allergy, proportionately, the children are actually using it more. Again, that's a pretty high dose burden having to take your child in every two weeks to get the shot. We think should ozu get approved and be able to treat it every 12 weeks, that's going to be really important for that patient population. You mentioned about 25% have very high IgE, and they just can't get the dose, and they can't get adequately treated. Can you maybe address that as well? Yeah, that's right. There are high-weight, high-IgE patients that are not on the dosing table for omalizumab and are not being reimbursed. We estimate that, and really very consistently, roughly 25%-30% of patients fall in that category. They really have no option aside from the oral immunotherapy with all its issues as well. Also, it's a single allergen really that you're treating there, whereas Xolair can treat multiple allergens. All of our modeling suggests, and now with the CSU data in hand, that we can address pretty much the entire dosing table, both the OMA eligible and many or most of the OMA ineligible patients with Q12 week dosing, with the highest IgE and highest weight patients reserved would require maybe Q8 week dosing. What we hope to have eventually is a label that's independent of IgE and weight. Wouldn't that be great, right? As opposed to any restrictions, completely remove those. That is a big, big differentiating feature that the prescribers and the payers recognize. I believe in last month, in October, you started the prestIgE, the 100-patient study testing ozu, Q8, Q12 in adolescents and adults. Can you talk a little bit about maybe how the study is powered and what are the endpoints? Yeah, so great question. Yeah, we're really excited about the prestIgE study. It's roughly 100 patients. We have the ability to expand more. The way we're actually looking at the study is in two populations. The primary set of patients are the OMA eligible patient population where we power the study to detect omalizumab-like activity. If you recall, the effect size is pretty large, so roughly 60% response rate across all the allergens and a roughly, call it 10% or high single-digit placebo rate. That's 75 patients that's powered to detect omalizumab-like activity in that OMA eligible patient population. Now, there's a subpopulation of OMA ineligible patients, minimum of 25, but we have the ability to enroll up to 40, which would make the overall trial roughly 115 patients. There we're really looking for trends in activity because that population, obviously, the bar is much lower. If the activity in both of those populations looks similar and there's no reason to think it won't because the biology is similar and our drug is more potent, then we would combine both populations together in the phase III trials. If not, if there's lower activity but still clinically relevant, that's fine too. We would move ahead and continue to separate those populations out in the phase III trial. Okay. At that point, just remind us, is there a placebo in that study? Yeah, so it's a placebo-controlled study. It's allocated two to two to one. Q8 week, Q12 week, and 1/5 of the patients will be on placebo. There is the opportunity after a 24-week dosing period for part two where the placebo patients can crossover. Of course, we'll have a continued extension for the patients who are already on ozu as well. Okay. They can cross over one-to-one into Q12 and Q8? That's right. It's powered, it looks like, for the OMA eligible against placebo, and it's powered to show 60% versus 10%. I'm sorry, did you say it's powered at 75%, or did I miss what the power is? Oh, no, I didn't mention that, but yeah, no, it's higher than that. It's 90% confidence. Okay. Powered at 90%. Yeah. The endpoint, is it at 24 weeks? That's right. The primary endpoint is that 24-week endpoint. Basically, yeah, for both arms. Patients are confirmed to have a reaction to their food, and it could be one of five foods, so peanut, milk, egg, cashew, and walnut. They are enrolled. They are given or assigned a dose level based on their weight and IgE. They are randomized either Q8 week, Q12 week, or placebo. After a 24-week period, they are given their food challenge for that exit food challenge to determine response. Based on the OUtMATCH study, was the effect in terms of reducing food allergies the same in all five subtypes, or is some of them better than others? They studied, I believe it was seven foods, and they all looked similar except for cashew, which if you look at their follow-up studies, was slower. They eventually reached that 60% response rate, but it just took a little bit longer. We are planning to include cashew, but actually treat it like peanut. That's what all the KOLs suggested that we do. Instead of having a 300 mg threshold for entry, we've actually increased the stringency to 100 mg. That should actually allow us to see roughly equivalent efficacy across all allergens tested. Okay. Which one of the OUtMATCH, which seven foods did they use, or what's the other two that you're not testing? The other foods are wheat and hazelnut. Hazelnut. Yeah. They're a little bit less, they're not as common allergens. Again, I think the FDA recognized all of these as IgE-driven because the label is for all IgE-mediated food allergy, including allergy to shellfish as well, which was not studied in the OUtMATCH trial. Yeah. Okay. And shellfish is allowed, though, off-label on Xolair? Actually, it's approved for all food allergies. It's okay, all food allergies. Got it. It would be on-label. Okay. So it is on-label. Can we maybe, I know we're probably at time, but maybe final question is Jeyou is also running a study currently in asthma that's going to read out in China. It's 60 patients, I believe, three doses, 150, 300, 450 every eight weeks against Xolair. But that's looking at a PK/PD. Yeah. Again, data by year-end. What should we expect from that data? Yeah. This is the primary endpoint is free IgE reduction. What we hope to see is a deeper and more sustained reduction in free IgE, similar to what we saw on the healthy volunteers as well, relative to the omalizumab control. That's essentially what we're looking for. The study is really too small and too short to be looking at other sort of more classic asthma endpoints. It's really designed to be a PK/PD study. They're going to be looking at it, is it at 12 weeks? Remind us. I believe it's 16 weeks. Sixteen weeks. Okay. They're going to look at phenol. They're going to look at EOS levels, free IgE. Those are secondary endpoints. They probably will come later after the primary endpoint is disclosed, which is free IgE reduction. Just to give the audience a little bit of color here, we have developed our own assay, which is more in line with the Roche-Novartis free IgE assay. Samples from Jeyou are being transferred to our CROs to run those assays, and that's what we hope to report out. On track before the end of the year. Okay. To the Xolair assay. Okay. Got it. And you'll release the data at the same time that they do, or would they release the data first? It probably will be a joint release. I don't know, Rodney, do you have a? Yeah. I think so. think so. Yeah. We haven't formally, but yeah, we would coordinate with them. Okay. Terrific. Brian and Rodney, good to see you. Appreciate it. We will continue to follow closely. My pleasure. pleasure. Yeah. Appreciate the time. Thanks for joining. Thanks for joining. Yeah. Bye-bye.