All right, welcome everyone to day two of the Cantor Global Healthcare Conference. For the next session, we are very excited to host the team of RAPT Therapeutics. Myself, Prakhar Agrawal, I'm a biotech analyst at Cantor. Representing RAPT, we have Brian Wong, President and CEO, and Rodney Young, Chief Financial Officer. Gentlemen, thank you for joining us for the conference. Thank you for the invitation. We really appreciate it. Obviously, since the last year, there have been a lot of changes at RAPT, so I think maybe it might be useful for people to get an overview of the company and the key priorities from here on. Yeah, so what certainly hasn't changed is that RAPT's focus remains in inflammatory diseases, particularly in what we call high-value indications. These are indications where we can disrupt the standard of care in multi-billion dollar markets. To that end, we recently licensed our lead asset called RPT904. This is a next-generation, half-life extended anti-IgE antibody that we believe is highly differentiated from the first-generation molecule called Xolair. We think this molecule has the ability to transform the treatment of multiple allergic diseases, including food allergy, which we're very excited about, as well as chronic spontaneous urticaria and potentially others. That is our lead program. We have two important priorities under 904, Food allergy and CSU. We have partnered with a Chinese company called Jemincare that owns China rights. RAPT owns all ex-China rights, including all indications. Jemincare is actually Phase 2 trials, and we'll have some data read-out before the end of the year. We're really excited to see that. Just one other note, we're really excited about food allergy because of the recent launch of omalizumab last year, where they now have 60,000 patients in the first year of launch. Okay, super helpful. I definitely want to get into the specifics of the market, but maybe on 904, if you can just talk about the similarities and differences compared to omalizumab. Yeah, so we were really attracted to 904 specifically because their design principle was maintain what works. We know that the omalizumab epitope is highly active and safe, but engineer around that to improve half-life, affinity, and other drug-like properties. That's exactly the approach that Jemincare took. It was based off the omalizumab sequence. There's a YTE mutation to improve half-life, and that's very similar to other half-life extended antibodies, so it's very well validated. Light engineering in the variable domain to improve affinity, so there's roughly a four-fold affinity. We think that will translate to some very clinically meaningful advantages over. Right, so affinity is better, half-life obviously better. What about maybe other attributes, bioavailability, or other molecular characteristics? There have been some changes to reduce immunogenicity, and also improve stability and other drug-like properties. So far, those look like they have translated well, and we'll see how that translates into the final product. Okay, can you just walk us through the data that has been generated by the partner in China? Yeah, so Jemincare, which is a large $6 billion per year pharmaceutical company in China, ran a healthy volunteer Phase 1 study demonstrating that 904, in a direct head-to-head comparison with omalizumab, has a better half-life, 60 days versus Xolair's 26 days, so over twofold increase in half-life, and showed deeper and more sustained reduction in pharmacodynamics. The PD effect was deeper, and that's usually measured by looking at free IgE. Okay, yeah, on free IgE, because that's something that we've been trying to do some work on as well, just walk us through free IgE versus total IgE, because I think investors can often get confused with that. Yeah, so you know what you're trying to do basically is reduce the amount of IgE that's available to bind to mast cells and basophils. You're looking at a reduction in free IgE. Roche, Novartis has 20 years of experience here, and there's a clear threshold that you need to reach to generate efficacy. Total IgE, though, is expected to go up, because essentially what you're doing is you're binding IgE and then stabilizing that to some extent. The half-life goes from typically for IgE, it's two or three days to closer to a week. That's why total IgE does go up. Right, total IgE goes up, but a lot of it is driven by inactive IgE, which might not be biologically relevant. It's inactive. It can't bind to the receptor. Right, and maybe you said that the partner in China showed a little bit better data on reduction in free IgE. What's, in your view, is that due to better affinity of the molecule or something else? Yeah, so it's probably both, although we think that the YTE mutation, the extended half-life, is what really drives the ability to dose less frequently. The affinity certainly helps with the initial reduction in IgE, but once you get past that stage, it's the FcRn engineering which really takes over. That's why we think that these changes will allow for much less frequent dosing than omalizumab. both, although we think that the YTE mutation, the extended half-life, is what really drives the ability to dose less frequently. The affinity certainly helps with the initial reduction in IgE, but once you get past that stage, it's the FcRn engineering which really takes over. That's why we think that these changes will allow for much less frequent dosing than omalizumab. both, although we think that the YTE mutation, the extended half-life, is what really drives the ability to dose less frequently. The affinity certainly helps with the initial reduction in IgE, but once you get past that stage, it's the FcRn engineering which really takes over. That's why we think that these changes will allow for much less frequent dosing than omalizumab. Can you remind us about the assay that was used by Jemincare to measure these free IgE levels? Because as I understand, it's not standardized. Yeah, so there's really no standard assay available commercially. That being said, Novartis and Roche essentially over the last couple of decades have standardized an assay format. Jemincare decided to use their own format, and you can still compare within a study 904 versus OMA in a relative fashion, but you just can't compare across trials, particularly the Roche trials that use a different assay. We have developed our own assay that looks very much like the Roche Novartis assay, and we have plans to deploy that, including, and Jemincare has agreed to this, samples provided by Jemincare. From the ongoing CSU studies, asthma studies are providing samples so that we can test it through the more standard assay. Right, and you'll be testing it against Xolair? Yeah, their studies are against omalizumab because of Xolair. That'll be very interesting to see the extended pharmacodynamics that we're expecting to see. Can you talk about the patients who are excluded from the Xolair label, and how do you plan to address that? Yeah, so just by way of context, as you know, Xolair has a very complex dosing table. There are eight different dose level strengths and two different dose frequencies, equating to 13 regimens. What they do is they look at patients' body weight and IgE to assign a specific dose and frequency. When they did their modeling, they realized that there's a large fraction of patients that probably wouldn't be treatable with omalizumab because of its limited half-life and potency. There's what we call the OMA ineligible population. It's the high IgE, the high weight patients. In all of our KOL checks, we estimate that to be around 25%- 30% of all food allergy patients are going to be excluded from the label, meaning that they will not be reimbursed. Okay, do you, I guess, based on your research, are these patients not being treated at all on Xolair because it might be more severe with the high IgE levels? Yeah, so typically they're not being reimbursed and they're not being treated. Some of the academic labs or investigators are trying to apply for exemptions, but it's pretty rare. I think importantly, 904 in all of our modeling, we can address those patients with either Q12 week or Q8 week dosing. Okay, yeah, maybe just walk us through the plans for the Phase 2b study in food allergy and when is it expected to start? Yeah, that's right. We are planning to initiate a Phase 2b Food Allergy study before the end of the year. The initial interactions with the FDA have been favorable, and they support the trial design that we're proposing. Hopefully, if everything continues to move along that track, we can start the study before the end of the year. We're expecting it to take about 18 months from study start to top line data. Okay, got it. You don't have to wait for some of the assay work that you are doing independently? No, we think that's not a critical path and that we're going to be able to establish that in time. Got it. Any other gating factors before you initiate the trial? No, not at this point. Got it. I guess, will the China data, which is obviously Phase 1, 2, be part of the sort of interactions with the FDA and whether they accept some of those data to start the Phase 2b? We have already had interactions with the FDA and the interactions actually are very favorable. We think that we have a line to start the Phase 2b study just based off of the Jemincare Phase 1 healthy volunteer study. Okay, got it. What are your expectations on the dosing frequency? Yeah, so as you know, omalizumab is dosed every two weeks or every four weeks. In food allergy, about 60% of patients are treated with every two week dosing. In our projections with 904, using the same model that Novartis and Roche have used to establish their dosing frequency, we expect mainly Q12 week dosing or Q8 week dosing and maybe the highest IgE high weight patients. Okay, so the high IgE maybe every eight weeks. Yeah, yeah, and the table actually goes up only to 1850 IgE. We know that there's actually a large fraction that go beyond 1850. Again, we can access those patients with either Q12 or Q8 week. Okay, given, you know, this market seems big, why would it take 18 months for the trial to read out? It seems a lot of conservatism is baked into your guidance. Yeah, I think there's a double-edged sword with the extremely rapid launch of Xolair in the U.S. We do know that those patients, there's a high demand for Xolair, which is great. It says there's a huge market demand. We're also being cautious here in that it's going to maybe limit the pool in the U.S. to those who would be available for a trial, because obviously we're trying to include only Xolair naive patients in our first study. Okay. That being said, we definitely think we can enroll in the U.S., but we're adding sites in Canada and Australia. A really important point, OMA will not be approved outside of the U.S. for food allergy. Okay, got it. What percentage of the site may be ex-U.S.? We haven't reported that, but it's going to be a pretty large fraction. What about Europe? Is that something? Europe, you know, just from a timing perspective, we probably will include those in our Phase 3 trial. Right now it's focused on fast enrolling, fast setup sites. Okay, got it. Maybe just talk about the market dynamics here. Why has Xolair been seeing such a strong uptake in the food allergy market? I can start and then maybe Rodney can say. There really has been no biologic therapy for food allergy established until Xolair. Prior to Xolair, patients were treated mainly with either food avoidance, which is obviously imperfect, or oral immunotherapy, which only treats one allergen at a time. Xolair's label is very broad. It's all food allergens, patients age one and above. That broad label, plus the multi-allergen feature, and the convenience of every two week or four week dosing is attractive. Yeah, I mean, I think the, first of all, the response rate was really high, right? That's obviously really important. Then as Brian pointed out, the multi-allergen part is very significant too, because more than half of food allergy patients are allergic to more than one allergen. You know, OIT, you're limited allergen by allergen. If you can take a shot from like omalizumab, you can protect across allergens. I think the efficacy and that across allergens are the really big factors. Got it. Just a little point too, in the OUtMATCH study, which was the phase 3 basis for approval, there was a head-to-head comparison of OIT versus omalizumab. Omalizumab was numerically more effective and had fewer AEs, including anaphylaxis. It is a safer option, which also addresses multi-allergy. Got it. Obviously, I think 60,000 or more patients have been treated with Xolair. For food allergy. For food allergy, who are these patients? Like, you know, based on your research, if you can just provide some context there. Yeah, they're all in America. They tend to be younger, sort of adolescent to early young adults, up to say 30, 35. That's the bulk of them, probably about two-thirds of them. The rest of them are a little bit younger than the, you know, the younger children. Okay, Xolair has been approved for a while. The safety profile in the food allergy market, any concerns or issues that have come up? is 20 years of safety experience. The allergists are very, very comfortable with Xolair. Even the dermatologists, when we do those surveys, at least half of those would actually lean towards Xolair over other drugs like Dupi. Got it. One sort of key long-term question is how will the market evolve when the biosimilars for Xolair will come to the market, which may happen next year, still TBD. What's your feedback been? Yeah, so first of all, the market itself is huge, right? There's 17 million Americans diagnosed with a food allergy. That's on par with AD. It's very big. Similar to AD, roughly about a quarter of them are severe, so you're talking about a pool of probably about 4 million patients. I think from our perspective, RPT904 has two really important differentiating factors vis-à-vis OMA and OMA biosimilars. The first is the less burdensome dosing requirement. That's really important because that will increase compliance and that should enhance patient outcomes. This is a disease where compliance is really important because you have to be on the drug to protect yourself, for the patient to protect themselves against the accidental exposures. The other thing is you can't see the effect of the drug. Your skin doesn't get better, so it's really important to make sure you stay on drug. That compliance aspect, which patients, providers, and payers all recognize, is super important. The other aspect where we think we can differentiate is obviously the OMA ineligible population. If we can show efficacy in that population, those patients literally have no alternative, so we would be able to treat those. All of that we believe will allow us to differentiate versus the biosimilars and then give us some pricing leverage to be able to price at a premium to both the biosimilars as well as branded OMA. Okay, those high IgE patients, that will be part of the Phase 2b trial, right? What percentage would you expect? That's a very important segment. The way we're planning to do it, we'll get into the trial design, but we have a bulk of the trial. It's a 100-patient study. 75 patients will be OMA eligible. We're powering the study to look for OMA-like activity. 25 of those 100 patients will be OMA ineligible. The reason why we're breaking that out is because the bar for success is lower because there's no option for those patients. Right, just walk us through the trial design as well. Yeah, so this is very much designed off of the OUtMATCH study, which was the Phase 3 that Novartis and Roche use as the basis for approval for omalizumab. It's a double-blind, placebo-controlled food challenge study. Just briefly, the way this works is that patients are enrolled if they're sensitive to a certain level of food or below. There's a treatment period. After that treatment period, there's an exit food challenge. If their threshold to the food increases to a certain threshold, then they're considered responders. In the OUtMATCH study, the typical response rate was 60%- 70% versus the placebo less than 10%. We're planning 100 patients and 24 weeks of therapy from the first baseline food challenge to the exit food challenge. These are patients, adolescents and above. It really matches where Xolair is getting prescribed at the moment. We do plan to, though, to have a pediatric plan to go younger in subsequent trials. Got it, got it. I guess you mentioned, Rodney, about possibly pricing at a premium to Xolair because of the data that you may have. That's an ineligible population for Xolair as well. Do you think, like, will payers need any data around reduction in hospitalization, ER visits to really support that adherence argument? We don't think we're going to need that for approval. When we talk to and survey the payers, they recognize, first of all, a lot of the patients are children. The ability to keep them out of the ER and protect them is, you know, it's a really high priority. They're willing to spend for that. I think they recognize that the compliance aspect here is very important and that the less frequent dosing is going to really help with the compliance. That's really what I think is driving that. We talked to over 45 payers, and none of them really pushed back on the need for data that proves the compliance argument. I think compliance and adherence and better patient outcomes is a pretty well-known established benefit. Okay, when you tested all these pricing scenarios, what sort of percentage premium are these payers willing to cover? What about just pricing it at parity and then getting the volume that you need? That more than compensates for the 20% premium that you're getting on pricing. Yeah, so when we talk to the payers about pricing, you know, you get a range, obviously, but it kind of all centers around, say, 15%- 20% versus branded OMA. We're kind of comfortable with that. You're absolutely right. You don't necessarily have to charge a premium given how many patients there are. I think one of the challenges you face, though, is you generally don't want to compete on price, so to speak, because especially with biosimilars, you trigger a race to the bottom there. I think you do want to keep some differential there. Got it. You could in theory price it at parity if the pricing for Xolair biosimilars is enough. I mean, just doing simple math, right? If the net OMA biosimilar price is $12,000 or $13,000, multiply that by 800,000 patients. Exactly. Or 1.7 million patients. Yep. You can get to big numbers quickly, no matter where you place. Got it. Is the ex-U.S. market going to be important here as well because Xolair is not approved? It's the really interesting aspect here where we don't think there's going to be as much pricing pressure because there's no option for patients outside the U.S. It's something that we think we could, you know, help in our sort of parity pricing across different countries. Okay, got it. On the CSU and asthma as well, Jemincare also has data for that. Maybe just talk about the expectations there. Yeah, they're completing two Phase 2 trials in CSU and in asthma, which should read out this year. We're excited to see that data and report that with them. Their CSU study is large, it's reasonably large. It's 135 patients. They have an arm with Q8 week dosing of 904, Q12 week dosing, and it's directly compared to omalizumab at its approved dose at Q4 week, all 300 mg. I think that data will provide, you know, proof of concept that the long-acting drug converts to, translates to clinical efficacy. There's good translatability between Chinese and Caucasian patients, by the way. That's been established by omalizumab pretty clearly. In addition to that, it could allow us to move directly to a Phase 3 trial if we can clearly define that go-forward dose. Okay, and so between CSU and asthma, because asthma is obviously, you know, supremely crowded and takes a large amount of capital as well, which one do you think is more attractive? I mean, CSU, I think, has a higher amount of need, I think, for long-acting IgE. Just to be clear, Xolair is the standard of care in CSU, where it's not the standard of care in asthma. We think that actually creates fertile ground for our next generation molecule to take the market. We've heard numbers as high as $8 million- $10 million for CSU as well. Yeah, and the differentiation that is there for the food allergy market in terms of the label, any sort of differentiation you would expect in the CSU market? There are other drugs that are being developed in the CSU space, obviously Dupixent and BPKs. You have the CKID as well that will be reading out the Phase 3 as well in the coming years. You know, in all of our market checks and KOL checks, even the Q8 week convenience sets us apart from Xolair. Obviously, Q12 week would be even better. We're not, we don't think we need additional differentiation from that. I think because of Xolair's long safety record and the fact that, except for the CKIDs, it's the most active agent, even more active than dupilumab and maybe even the BTKs, I think it will remain the standard of care. We hope to displace OMA as a standard of care. That's the likely scenario. Beyond food allergy and CSU, any other broader allergic diseases where either Xolair hasn't been tested previously, you think might be possibilities for 904? Yeah, no, I think right now we're really focused on these two indications. There's a lot already to digest. Ultimately, we think that the broader label will sort of lift the overall market share of the product. Another area of high interest is seasonal allergic rhinitis, where there's 40, 50 million patients in the U.S., of which a large fraction are refractory to corticosteroids, topical corticosteroids. A non-steroid, more convenient dosing regimen actually in early checks could be quite attractive to prescribers and patients. Okay, as we think about the competitive landscape, are there other YTEs in development for Xolair? Other YTEs potentially include, there's a competitor called LongBio, which is a Chinese company developing a long-acting IgE. We believe that though it doesn't use the same epitope as omalizumab, it uses one that might be used by Novartis called ligelizumab. That's the most advanced. They're focused on right now CSU and allergic rhinitis. That is the most advanced. There's one other asset from a South Korean company in Phase 1. That's it. Amongst other novel options for markets like food allergy, there are IgE degraders that are being developed. How would they play a role in the food allergy market related to, let's say, Xolair? To us, seeing all these companies pop up over the last eight months, I think speaks and validates the landscape. We're seeing, you know, IgE degraders, we're seeing IgE proteases, we're seeing, you know, other mechanisms of action. I think the key question we ask is what clinical problem are they trying to solve, right? We don't think that IgE reduction in and of itself is sufficient for clinical efficacy. It has to be combined with the right epitope and mechanism of action. I think it will remain to be seen how those new mechanisms translate to efficacy and safety. Okay. They're still preclinical, right? Got it. On the CCR4, you are working on next-gen oral molecules. Just remind us, how will it differ versus 193? CCR4, we believe, remains a compelling target for an oral across a range of TH2-driven disorders, including atopic dermatitis and asthma. We have a second-generation molecule that's more potent and selective. Even though zelnecirnon was quite good, there's always room for improvement. We're bringing forward another molecule, different chemical structure, with higher potency and selectivity. We just selected the molecule in Q2. We're in the process of running and completing GLP studies, usually 12 months, typically, from preclinical compound selection to IND. Okay, we haven't seen the data from 193. Is that something you plan to disclose? Yeah, ultimately, I mean, I think what we know other companies are playing in the area. We wanted just to not enable them with our data, but we do plan to share the data when we're closer or in the future. Got it. I guess because you are focusing on a next-gen molecule as well, you've not given up on the target. Is it fair to say that you did see signals of efficacy? Yeah, we wouldn't be spending resources unless we remained excited about the target. Got it. Rodney, the cash runway that you have right now, what does it really cover? Yeah, we reported our Q2 cash at just under $170 million. Our projections are that we have enough cash to get through the first- half of 2027, which should get us to when we expect the food allergy top line readout. I know you had an oncology program as well that you were exploring partnership opportunities. Is that something that we could expect in the near term just to strengthen the balance sheet and look for non-dilutive options? Yeah, I think we're still exploring partnership opportunities there. Prefer not to speak to timing on that because it's just really hard to predict. Got it. All right, that's all the questions we had. Thank you to the RAPT team for joining us today. Thank you to the audience for listening in. Thank you. Thanks for talking to us.