Are we live yet? Okay. All right. Thanks, thanks everyone for coming. My name is Yanan Zhu. I'm one of the biotech analysts here at Wells Fargo. It is our privilege to have the management team of RAPT Therapeutics here for this fireside chat with me. Here is Brian Wong, CEO of the company and president of the company, and also Rodney Young, CFO of the company. Brian and Rodney, thank you for being here with us. Thanks for having us. Thanks. Great. Appreciate it. I think, with, you know, obviously RPT-904 being the lead asset for the company now, maybe, Brian, if you can start us off with some high-level overview, you know, of the company, of that program, and particularly interested in the licensing deal that happened a year ago. What drew you to this asset, and what opportunity do you see? Sure. Yeah. First of all, Yanan, thanks for your continued support for the invitation to the conference. Thank you to the Wells Fargo banking team. We really appreciate the invitation here. So just by way of context, RAPT Therapeutics is focused on therapeutics that can transform high-value I&I diseases. We define high value as the ability to disrupt the standard of care in multi-billion-dollar opportunities. So to that end, as you pointed out, we late last year in-licensed an asset called RPT-904. This is a next-generation long-acting anti-IgE antibody that we believe can transform the treatment of both food allergy and chronic spontaneous urticaria. So the reason why we became very excited about RPT-904 was for the following reasons. The first is that it very much fit within our therapeutic interests. As you know, we were developing an oral small molecule for a range of TH2-driven disorders like atopic dermatitis and asthma. And this particular asset fell right in that therapeutic sweet spot. The second was really when we were looking at the food allergy space, we saw that Xolair, which was just approved in February of 2024, already had 30,000 patients on food allergy. It actually has become one of Roche's fastest-growing products in the United States. And what this told us is that there's a huge opportunity, an unmet medical need in food allergy that's untapped, and it's ripe for innovation, including biologic therapy. The second is that we're also very excited about chronic spontaneous urticaria. Anti-IgE antibodies are the standard of care, and we think that there is a lot of room to improve upon omalizumab or Xolair in CSU. CSU is a $5 billion market in the United States. Food allergy is a $40 billion market in the United States. Finally, when we were looking for assets, 904 was the most advanced, so it's in phase 2 development, and we think it has the highest probability of technical success because it shares the same epitope and mechanism of action as omalizumab, which is quite proven. So I think with respect to RPT's, with respect to efficacy and safety, we think that there's a high probability of seeing these changes translate positively across these indications. Got it. Got it. Thank you. Maybe, maybe speak more to the various indications of Xolair. Obviously, this is a $4 billion drug, very successful. With the four approved indications, you are, I think, interested in two. Yes. Right? So can you give us a sense of how the revenue breaks down between those four indications? Sure. Yeah. So as you said, Yanan, it's about a $4 billion drug. We think asthma and CSU are probably about even, although CSU is growing faster than asthma. Food allergy, as Roche has said, right, is the fastest growing of the three. You know, roughly 60,000 patients already. So we think they're actually gonna catch up to asthma and CSU fairly soon. Yeah. And just to put that in perspective, 60,000 patients in the first year outpaces drug launches such as Dupixent and Skyrizi. So I think it shows you the huge unmet need and the market size actually for food allergy. There are about 17 million food allergy patients in the United States, which is roughly equivalent to the number of atopic dermatitis patients. Right. Got it. Yeah. Those, those are very helpful context. Yeah. For us to understand the story. Then maybe talk about Xolair's perhaps the strengths. Why is it so good and its limitations, i.e., how do you hope to differentiate? Yeah. So, as you pointed out, omalizumab is the approved anti-IgE. IgE is the key driver for many allergic disorders, including food allergy, CSU, chronic rhinosinusitis, and asthma. And it was actually one of the first drugs and continues to be the standard of care for many of those indications. It's a 22-year-old drug. It was one of the first antibodies ever approved for a non-oncology indication, and so there have been a lot of advances in the field to improve the drug-like properties of antibodies, including affinity, including half-life, including other drug-like properties. So, one of the issues with omalizumab is that it's relatively less affinity, lower affinity, and a relatively short half-life. So the half-life is on the order of 24 to 26 days, and the affinity is sort of in that nanomolar range, so it could be improved as well. And what that translates to clinically is Q2 week or Q2 Q4 week dosing. Typically in food allergy patients, most patients are treated every two weeks. CSU is every four weeks. In addition, omalizumab excludes about a quarter to a third of food allergy patients that are particularly high IgE or high weight. So that's roughly a third of the market that's not accessible and not reimbursed, because of the potential lack of activity of omalizumab in those indications. So what 904 does is it introduces mutations and engineers an improved half-life, improves the affinity, improves other drug-like properties. That allows us to treat what we think most likely is Q8 week or Q12 week dosing versus omalizumab Q2 Q4 week. And it also allows us to access those patients that are currently ineligible for omalizumab therapy. Got it. Got it. Can we maybe talk about Xolair biosimilars? When will that, you know, be a presence in the market? What is the expected price point? Mm-hmm. because that could be your, you know, competition. Yeah. Yeah. So the patent on omalizumab expires later this year. So I think Roche has said they expect biosimilars on the market, you know, sometime in the latter part of next year. So it's imminent. You know, we would expect price erosion in the branded OMA. And if you look at analogs and all that, you know, we kinda expect it to be in the 30%-40% range over time. We do expect branded OMA to price at a premium to the biosimilars though. And what we're as we think about our pricing strategy and all that, we are looking relative to the branded to branded OMA. Got it. Got it. Thanks. So, you know, let's maybe talk about diving a little into 904's difference from Xolair. Can you talk about structurally? Yeah. Is there any difference? And also maybe affinity-wise, 'cause you mentioned the affinity is not quite high for Xolair. Yeah. Yeah. That's it. So I think what attracts us to this molecule is the fact that, you know, first of all, they used omalizumab as the base template to derive these additional modifications. And what that does is that it preserves the omalizumab epitope, which, we think, is absolutely essential to optimize efficacy and safety. Other potential next-generation IgE use different epitopes, and they haven't fared so well. And we can get into that. So it was really important for us to preserve the omalizumab epitope. There are multiple changes. On top of that, there's a YTE mutation. This helps with FcRn-mediated recycling. And this is seen in other drugs such as barzolvolumab, some RSV drugs as well, and some of the Apogee drugs as well. So it's a very common, well-validated way to extend half-life. In fact, in our phase one, we've seen over doubling of the half-life, in healthy volunteers. In addition, in the variable domain, there are some changes in the CDR domains to improve affinity. So there was some affinity maturation, and there's around a four-fold increase in affinity. And beyond that, there were changes in the framework to reduce immunogenicity and to increase stability in other drug-like properties, including manufacturability as well. Got it. Got it. You touched on some of the, you know, perhaps the follow-on that Novartis had for Xolair with higher affinity, but I think the efficacy is exactly the same. Yeah. If I remember that correctly, right? Yeah. Yeah, so can you elaborate a little bit more? Yeah. No, this is a really important area that we had to get, we had to really understand as we made our selection for what anti-IgE to enhance. So Novartis actually took a next-generation anti-IgE forward, because of their strong interest in extending the omalizumab franchise. And their drug was called ligolizumab. Ligolizumab was about a hundred-fold higher affinity than omalizumab, roughly the same half-life, but importantly used a different epitope than omalizumab. And what they saw is that in phase three, despite better free IgE reduction, better pharmacodynamics, they didn't see superior efficacy, which they were hoping to see in CSU. And in fact, in head-to-head studies in other diseases like in asthma and in food allergy, they saw inferior efficacy to omalizumab. And again, despite higher affinity for the target. And what this taught us is that when you change the epitope, you have to reestablish your PD efficacy relationship. You can't just use free IgE alone as a basis for a surrogate for efficacy. It actually has to be coupled with the right epitope. So based on that, Novartis stopped ligolizumab development, and it taught us a very important lesson about the importance of the epitope. I see. So with your 904 targeting the same efficacy and now have a higher affinity, the outcome should could be different than that. And we could only see the improvement due to the efficacy affinity increase, right? Yeah. I think that because 904 shares the same epitope as omalizumab, we are much more confident in the ability to translate PD to efficacy. Mm-hmm. Based off of that analysis, we believe that we can capture the same efficacy as OMA, but with much less frequent dosing. So, Q8 and Q12 week dosing. Got it. Okay. As opposed to Q2 week. I see. So yeah, let's do talk about the less frequent dosing. Mm-hmm. You know, I was wondering, you know, you there, you know. I first of all, you know, we should highlight that there is a third to a quarter of patients that aren't even. Mm-hmm. on their label or being treated. So that. Yeah. Obviously, that is a big, Right. Advantage. Yeah. For 904. Mm-hmm, but for those who are treated, being treated with Q2W, Q4W, and now you're turning it into Q8, Q12. Mm-hmm. Exactly how much of a differentiation that might be? You know, what do you hear from patients and physicians? Yeah. Yeah. Yeah. Obviously, we had to get really comfortable that this would be a meaningful step change for patients, both for patients, prescribers, but also that payers would recognize that this was truly differentiated and it would demand premium pricing. And so, our head of commercial and Rodney and others at the company have been doing a lot of primary market research. We've been talking to hundreds of prescribers, hundreds of patients, and about 45 payers as well. And what we learned from that is that even Q8 week frequency would be a major benefit to patients who are seeing their physician maybe, you know, 13 to 26 times per year. Now you can get away with maybe once a quarter or once every, you know, once every few months. And that, that's a big difference. What's very important, particularly in food allergy, is that what you're trying to do is protect patients from landing in the ER, which is a huge burden to the healthcare system. There are 3.4 million patients that have visited the ER in the last year, which puts an enormous financial burden on the healthcare system and on the patients and their families. So if you can increase compliance and improve protection and keep patients out of the ER, that's already an economic benefit that can demand, you know, payers to pay and is very attractive to prescribers as well. From the patient level, in all of the surveys that we've performed, and Rodney can talk about this in more detail, a vast majority of patients prefer the Q8 or Q12 week dosing, preferably at home as well. That's something that we're really targeting. I mean, we wanna be flexible. Some patients like to get injections in the doctor's office, but that flexibility to allow at-home injections infrequently is a huge deal. Imagine, you know, sending your kid to college, right? Are they gonna take an injection every two weeks? Maybe, maybe not. So I think this allows patients to take their drug at home, do what they need to do, live their lives, go to school, come back, and take another injection. So that's a real benefit to patients as well. So from a payer, prescriber, and patient perspective, all three groups really were very attracted to the profile of 904. Yeah. And, you know, just to put a finer touch on it, you know, for most of the food allergy patients, they tend to be on Q2 week dosing. They also tend to be younger. And a lot of kids don't like to take shots. Yeah. So if you can reduce that dosing frequency, that burden, you should increase compliance. And again, the goal is to keep them on the drug because you're trying to reduce the effect of an accidental exposure to the allergen. You know, the other differentiating factor, which you touched on, Yanan, is the omalizumab-ineligible population. And for those patients, if we can show safety and efficacy in that population, you know, they really have no alternative. So 904 would literally be filling an unmet need there. Got it. That's super helpful. Then maybe to summarize all of this, you know, wanted to hear your strategy for positioning RPT-904 against Xolair biosimilars. Mm-hmm. What is the minimum product profile that you're hoping to hit and such that you can win payer coverage? Yeah. It's super simple. So in food allergy, what we're hoping to see is omalizumab-like efficacy and safety, but with every dosing at every eight weeks as the base case. The upside case is every 12 weeks. And that's the same is true for CSU as well. Xolair is approved at every four-week dosing. We hope to have every eight-week dosing, similar efficacy. That's the base case. Upside would be every 12-week dosing. Very simple. Got it. And that's all been pressure tested with KOLs and payers and patients as well. Got it. Great. Let's maybe talk, you know, maybe give us an overview because you have several initiatives going on around 904. You know, give us an overview of the development plan. Yeah. I wanna make this clear. This is not an early-stage project. We're very much in phase 2 with our partner, Jemincare. By the way, Jemincare is a multi-billion-dollar Chinese pharmaceutical company, with a large R&D center and multiple manufacturing sites. So they've been very enabling for our development. And it's been a great collaboration. From the food allergy perspective, we are planning to initiate a phase 2b study, a double-blind randomized placebo-controlled food challenge study, before the end of the year. And we expect top-line data roughly 18 months after study start. After that, we expect to move to phase 3 pivotal studies in food allergy. For CSU, which is our second indication that we're very interested in, and that's again a large market, we are waiting to see Jemincare's data coming out this year. They're running a 135-patient phase 2 study in patients with antihistamine-refractory CSU. And assuming that data are positive and we can define a go-forward dose, we would look to go directly to phase 3. So we would have an end-of-phase 2 meeting with the FDA and look to initiate a pivotal study in CSU. That actually could accelerate our time to market by a couple of years potentially, so that's potentially very exciting for CSU. Got it. Let's definitely touch on those programs. But you also have a PKPD study, right, in the U.S., even though Jemincare had healthy volunteer data that you have shared with investors. Can you talk about the rationale for your own PKPD study? Yeah. And actually, that's evolved a bit. So, as a reminder for everyone, Jemincare's phase one healthy volunteer data were highly encouraging. Again, they saw overdoubling of the half-life versus omalizumab, and that was a direct head-to-head comparison. And they also saw deeper reductions in free IgE and more sustained reduction versus omalizumab in that study. But one of the limitations was that that was performed in healthy volunteers. And so we asked the question, will this PKPD, you know, extrapolate to higher IgE patients? We assume it will, but it's always good to show that. And so we were thinking of running our own PKPD study, with high IgE patients. Fortunately, Jemincare has made available patients from their asthma and their CSU studies, to us. We actually can then go back and run our PD analysis on those samples, with those elevated IgE and get the same information. We think that available will be available this year. I think that'll be very supplemental to some of the data readouts that we're gonna see this year, the CSU study from Jemincare, the asthma study that's reading out as well this year, and additional PKPD information from those studies as well. That is going very smoothly. We have developed our own assay, which actually matches the Roche Novartis assay very well. We're transferring that to a CRO in China, and we're planning to run those samples this year. Right, and the Jemincare data set should also have Xolair-controlled samples. Yes. So we can see clearly the IgE reduction. Yeah. Between the two, right? Exactly. Got it. Okay. Yeah. So. Yeah. Yeah. Maybe a little bit more word on that because the Jemincare readouts are going to be very valuable to us this year for a couple of reasons. The first, as I mentioned to you, is that it could enable our development in CSU, but the second thing is that they're studying RPT-904 at Q8 week and Q12 week. So there's two active cohorts versus the omalizumab control, which is at Q4 weeks. So these are. This is the same dosing frequency that we're planning in food allergy as well. And because omalizumab has been shown to work across populations, across ethnicities, across continents, in fact, the labeling is very similar across Asia and Western countries, we think there's going to be very strong read-through between, you know, Asian and Caucasian populations as well. We think it should be a very strong proof of concept as well for the molecule. Got it. Got it. Obviously, in addition to the PKPD information from Jemincare's phase 2 studies, obviously, they will report efficacy data as well. Right. Right? So let's talk about that. You know, these are due second half of the year. Right. Any color on when and how these data will be disclosed? Second half of the year is still our guidance, and we're in the second half of the year, so you know, it's coming soon. In terms of the way we're planning to disclose, actually, I'll let Rodney talk about that because I think that's important. Yeah. So we've had a number of conversations with Jemincare, at least for the CSU data. Our plan is to do a joint release of the top-line data in a joint press release, probably followed by a call for investors. And then our understanding is Jemincare will want to submit for a medical meeting to make a more fulsome disclosure, sometime probably early next year. The asthma study, that timing, you know, we don't expect them to be the same. And that, you know, it'd probably be a press release again. Got it. Okay. It's important to note that the CSU study is a relatively large study, and it's efficacy-oriented. So it's 45 patients per arm, two active RPT-904 plus an active comparator omalizumab control. And they will be looking at all the endpoints that, you know, I think are going to be relevant to us, including the UAS-7 score, which is the primary endpoint used for approval. The asthma study, just to set expectations, is a smaller study at 60 patients, three RPT-904 arms versus omalizumab, so only 15 patients per arm and relatively short. So it's more PKPD-oriented to allow them to establish doses for their phase three trial in asthma. It's less efficacy-oriented, not powered, really, for efficacy. Got it. And then let's focus on the CSU readout. What does success look like for that readout? Yeah. So again, in all of our market research, even Q8 week would be a considerable differentiation versus omalizumab. So our base case scenario is omalizumab-like efficacy at Q8 week, with the upside being similar efficacy to OMA at Q12 week, so that's pretty straightforward. Right. I was wondering, based on the PK, you know, and the available free IgE data from other players, do you have a best guess whether, you know, Q8 or, you know, you can hit Q12? Yeah. I mean, I think, and we've said this publicly, and it's in our deck as well, the projections suggest that we can cover many patients or most at Q12 week, but all of our commercial and payer research suggest that Q8 week would be sufficient for clinical differentiation and to command a premium price, so, you know, there's hope that Q12 week could be just as active as OMA, but, you know, Q8 week would be sufficient. I see. Got it. And your intention is to initiate a phase three directly. What to look for in their data to determine whether you're gonna do a phase two or phase three is okay? I think the key aspect is whether we can clearly define a dose or a set of doses to move forward in phase three. So if it's clear, you know, that which dose to pick, I think that would be a key, you know, driver for our decision to move forward. If not, then, of course, it would make sense to do a little bit more dose range finding. But assuming that we can identify a dose, then I think we would try to move forward quickly into phase three. Got it. I see. Well, after they read out the data, how long does it take you to make that decision? If we to make the decision would require, you know, discussions with KOLs to see how encouraged they are with the data, to talk with our clinical pharmacologists around dose, and then talk through the regulatory steps to see that feasibility. It shouldn't take that long to make that decision. I think the real question will be, you know, when to have an end-of-phase two meeting. Some of that will be driven off CMC because we'd want the commercially facing formulation for the phase three trial as well. Right now, we're in the process of, you know, tech transferring all the manufacturing from Jemincare to CDMO in the States or in Europe. Okay. Got it. And as you mentioned, asthma is more of a PK/PD from Jemincare. Are you interested in pursuing asthma further, and what is the gating item for you? So it's not the high-priority indication. I think generally, the way we view this, though, is that down the road, we'd want the broadest label as possible, because, again, we want to be able to, you know, differentiate versus omalizumab. So that could be later down the road in development. Another indication that we're actually pretty interested in, in where omalizumab has shown good activity is seasonal allergic rhinitis, particularly patients who are refractory to topical steroids. I think there are about 40 million patients in the United States, and a large fraction do not respond well to topical steroids, so they're quite severe. You know, I think that could be another potential direction to go in post CSU and food allergy. But again, we wanna remain focused. You know, we wanna kinda be capital efficient right now. Later down the road, once we've demonstrated proof of concept, we'd wanna try to get a broader label. But right now, we think food allergy and CSU provide the best opportunity for differentiation. Got it. Got it. Let's talk about food allergy, where you plan to initiate a phase 2b study in second half. Yes. Again, you know, right, right now, in the period we're in, can you review the study design for us? Yeah. I think our guiding light is the OUtMATCH study, which was the phase three study used as the basis of approval for omalizumab, which was published in New England Journal last year, so the OUtMATCH study was a what's called a double-blind placebo-controlled food challenge study. And the way these work is that patients come in, they're tested against a specific food allergen, let's say peanut. And if they're sensitive, if they have a reaction to, say, 100 milligrams or less, they're enrolled in the trial. Then there's a treatment period, and then there's an exit food challenge to see if that threshold has increased, and there are pre-specified criteria for both inclusion and exclusion. And we're planning to copy that design for the most part, so our trial is also a double-blind placebo-controlled food challenge study. We're looking at all the major allergens that OUtMATCH looked at, including peanut, egg, and milk. We're using essentially the same thresholds for both inclusion and exclusion. It's a 100-patient study, and we're planning to enroll in the U.S., Canada, and Australia, 24 weeks of dosing, so that's to enable us to get two full cycles of 904 at Q12 week, then we have the exit challenge, and then there's a placebo crossover and extension after that 24-week period, but the top-line data will be at 24 weeks, and essentially, the primary endpoint is the percentage of patients who achieve that pre-specified exit threshold, after the period. Got it. What is the age group to be enrolled? Can you start with younger pediatric patients directly? Yeah. So in this study, we're happy that we can move forward with patients age 12 and above, so adolescents and above. Assuming good safety on the study, then we'll move to younger patients in phase 3. The hope is to have the same label off the bat as omalizumab, which is patients one year and above. I see. The OUtMATCH included patients one year and above as well. Their phase three trial. I see. Did you file an IND? And when do you plan to initiate the study? We are on track to start the phase 2b study, before the end of the year. We've had some initial interactions with the FDA that have gone well, in support of our phase 2b design. Got it. Got it. What is the consideration to, you know, do this design, rather than have a Xolair head-to-head non-inferiority trial, for example? That's a good point. So the trial we're planning is a placebo-controlled study. The FDA strongly encourages and actually very much expects placebo-controlled studies as opposed to non-inferiority studies. So we wanna make sure we fulfill the FDA and the U.S. health authority requirements for approval in the United States. Now, in other regions of the world, like in Europe or maybe Japan, an active comparator may be important. So that's something that we're considering as well is to for additional studies whether an active comparator could be helpful for health authority approval in other territories. Got it. Got it. And what about for phase three, you know, in U.S.? Do you still think it's a placebo-controlled? Yes. Yeah. Placebo will be required. Got it. From the FDA. Got it. Again, OUtMATCH was a placebo-controlled study, which was the basis of approval for Xolair. Right. Right. Perhaps, you know, I guess by now, we have a good sense of the bar for success. Yes. right? But can you also, you know, specifically articulate for your phase 2b food allergy study, what is the bar for success? So again, for food allergy, what we wanna see is, again, OMA-like activity at Q8 week as the base case and Q12 week. The response rate in OUtMATCH was roughly 60%-70% across nearly all allergens except for cashew, which took a little bit longer at 16 weeks. We would expect to see similar levels of activity. We're powering the study to detect similar levels of activity in that study. Just one other important point, we also are including in a separate subpopulation the OMA-excluded patients, ineligible patients. Since the bar for success is lower in those patients, we're actually putting that those patients into a separate exploratory group. Nice. Okay. Yeah. That's super helpful for us to know. Lastly, maybe two quick questions. For your next-gen CCR4 antagonist for atopic dermatitis, can you give us some update on where you are? And lastly, can you talk about your cash runway? Yeah. So we've remained very excited about CCR4 as an oral target across a range of TH2 disorders like atopic dermatitis and then asthma. We are moving forward with a next second-generation CCR4 antagonist. We selected a compound in Q2. We're completing GLP studies, and you know, typically, it's around 12-plus months to file the IND. We hope to keep folks updated as we get closer to the clinic. Yeah. So, regarding cash, we reported $170 million in cash at the end of Q2. And our guidance right now is that should last us through second half, through first half of 2027, which is when we expect to have the phase 2b food allergy readout, top-line data readout. Got it. Great. I think that's all the time we had. Thank you, Brian. Thank you, Rodney, for this very enlightening session for your time. Thank you, Yanan. I really appreciate it. Great. Thanks, everyone. Thank you.