RAPT Therapeutics, Inc. (RAPT) Earnings Call Transcript & Summary

Good morning, and welcome to RAPT's conference call. [Operator Instructions] And as a reminder, today's call is being recorded. I will now turn the call over to Sylvia Wheeler. You may begin.

Thank you, operator, and good morning. Thank you for joining us to discuss our press release issued this morning, which is available along with accompanying slides in the Investors section of the company's website at RAPT.com. On the call with me today are Dr. Brian Wong, Chief Executive Officer; and Dr. Bill Ho, Chief Medical Officer, with prepared remarks; and Rodney Young, Chief Financial Officer, who will join us for the question-and-answer period. In addition, we have a special guest, Dr. Ana Maria Giménez-Arnau, Professor at the Hospital del Mar Medical Research Institute in Barcelona. As outlined on Slide 2, we remind you that during this call, we will be making forward-looking statements that are subject to risks and uncertainties. Our actual results may differ materially from those described. We encourage you to review our risk factors in our most recent quarterly report on Form 10-Q, which can be found on our website. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so even if our views change. I will now turn the call over to Brian.

Thank you, Sylvia. Good morning, and thank you for joining us. Today, we are presenting top line results from a Phase II clinical trial evaluating RPT904, also known as JYB1904 in patients with chronic spontaneous urticaria, or CSU. The Phase II trial was executed by our partner, Jeyou, formerly known as Jemincare in China. RAPT owns all ex-China development and commercialization rights to RPT904. This study marks an important step forward in our mission to develop innovative therapies that address the immunologic drivers of inflammation. Starting on Slide 3. The top line data from this Phase II study are highly encouraging and have exceeded our expectations. This trial was a randomized double-blind trial comparing RPT904 dosed every 8 or 12 weeks to omalizumab dosed every 4 weeks with a 16-week treatment period. It was not a formal non-inferiority study and no statistical hypothesis was tested. Results from this study suggests that the efficacy of RPT904 administered either every 8 weeks or every 12 weeks is comparable to omalizumab, which was administered every 4 weeks. Both RPT904 dosing arms showed numerically superior efficacy to omalizumab on UAS7, the primary endpoint as well as a key secondary endpoint called the UAS7=0 or complete response across all time points, which are week 8, 12 and 16. In addition, in the Q12-week arm where only a single dose of RPT904 was administered, numerically superior efficacy was sustained out to 16 weeks, indicating a highly durable therapeutic effect versus omalizumab. RPT904 was well tolerated across both dosing regimens. There were no drug-related serious adverse events or discontinuations and no adverse events of special interest, including anaphylaxis. We believe these efficacy and safety data support advancing RPT904 into pivotal Phase III studies. We and our partner, Jeyou, plan to engage with regulatory authorities in our respective territories to discuss potential registrational pathways. Additional data, including from the follow-up period and secondary efficacy endpoints will be presented at a future medical conference. Before we review the data, let me first highlight the mechanism of action and competitive advantages of RPT904. Starting on Slide 4, immunoglobulin E or IgE plays a central role in the pathogenesis of CSU, food allergy, asthma, rhinosinusitis and other allergic disorders. Upon initial allergen exposure, antigen-presenting cells activate T helper 2 cells, which stimulate B cells to produce allergen-specific IgE antibodies. IgE binds to the high-affinity Fc Epsilon receptors on mast cells and basophils, which upon allergen rechallenge can trigger immediate hypersensitivity reactions, including anaphylaxis. RPT904 acts to interrupt these allergic pathways in 2 ways: first, by blocking IgE from binding to its receptor and secondly, by removing IgE from the cell surface of mast cells and basophils. These actions have the additional effect of down regulating the Fc epsilon receptor, which further desensitizes these cells to further antigenic stimulation. Moving to Slide 5. Omalizumab is currently the standard of care for CSU patients who are inadequately controlled by high-dose antihistamines. This is due to omalizumab's high degree of efficacy combined with a well-established tolerability and safety profile. Other agents in development have shown variable efficacy and safety, but none have demonstrated clear advantages to omalizumab. Despite omalizumab's position as standard of care, it has limitations in terms of durability and convenience. It requires monthly dosing, which can impact compliance and roughly 20% to 30% of CSU patients require up-dosing to produce adequate benefit. We believe RPT904 has the potential to address these shortfalls and become the preferred choice therapeutic option in patients inadequately controlled by antihistamines. Slide 6 highlights RPT904's unique design and potential best-in-class characteristics. RPT-904 was engineered to have a longer half-life driven by the well-validated YTE mutation, a higher affinity for IgE, which should reduce overall dosing burden and improved drug-like properties, including improved stability and manufacturability as well as reduced immunogenicity. Importantly, RPT904 targets the same IgE epitope as omalizumab, and therefore, we believe RPT904 carries a high probability of technical success. The molecule has strong intellectual property protection with composition of matter patent applications that, if issued, support exclusivity to at least 2041, excluding patent term extensions. This intelligent engineering was designed to enable less frequent dosing and greater durability our modeling suggested that a dose every 8 or 12 weeks instead of every 4 weeks for omalizumab should be sufficient in patients with CSU, which translates to just 4 to 6 injections per year versus 12 injections per year for omalizumab. This increased dosing convenience should increase patient adherence and therefore, better clinical outcomes. In addition, the increased affinity and half-life may also reduce the need for up-dosing. Primary market research surveying 50 allergists show these advantages will quickly drive RPT904 to become the preferred treatment option in CSU patients eligible for advanced therapies. With this background information, I will turn the presentation over to our Chief Medical Officer, Bill Ho, who will walk through the Phase II CSU data in greater detail.

Thank you, Brian. I'll start on Slide 7 to review the trial design. The Phase II study was a randomized, double-blind, active controlled trial conducted at sites in China. The study had a 16-week treatment period and then an additional 16-week follow-up period without additional treatment. The data reported today are from the 16-week treatment period. Planned enrollment was 135 adult patients with CSU who were inadequately controlled by H1 antihistamines. Patients were randomized in equal proportions to receive 300 milligrams of RPT904 every 8 weeks, corresponding to doses at weeks 0 and 8, 300 milligrams of RPT904 every 12 weeks, which was represented by a single dose at week 0 in this trial or the approved dose of omalizumab, which is 300 milligrams every 4 weeks, specifically in this trial of weeks 0, 4, 8 and 12. Patients were able to remain on stable dose of background antihistamines throughout the study. The primary endpoint was change from baseline in UAS7 at weeks 8, 12 and 16. Secondary endpoints included complete response defined as UAS7=0 as well as itch severity or ISS7, high severity or HSS7, angioedema severity or ASS 7, and the quality of life by DLQI. Results from the complete study, including additional safety and efficacy data from the 16-week follow-up period will be presented at a later date. Turning to Slide 8, which covers patient disposition. Of the 187 patients screened, 137 were randomized. Completion rates were high across all arms with 94% of patients in the Q8-week group 98% in the Q12-week group and 96% in the omalizumab group completing the 16-week treatment period. Discontinuations were minimal across groups and due to standard reasons, including withdrawal of consent, noncompliance and insufficient efficacy but none due to adverse events. Moving to Slide 9. Baseline demographics and disease characteristics were well balanced between groups. Mean UAS7 scores were approximately 29 across all arms, representing a severe population. Baseline disease severity generally was similar to other reported omalizumab studies in CSU. Only about 10% of patients had prior exposure to omalizumab. Note that patients were required to have at least 4 months washout from prior biologics and could not have had an allergic reaction or poor efficacy to prior omalizumab to be eligible for the study. Moving on to efficacy on Slide 10. This shows the results on the primary endpoint, which was the least squares mean change from baseline on the UAS7 score, 7-day urticaria activity score. On this endpoint, both RPT904 arms showed rapid and at least comparable and even numerically superior efficacy compared to omalizumab at all time points. At week 12, which is the time point commonly used as the basis of approval. The RPT904 Q8-week arm in gold showed a 22.1 points improvement. The Q12-week arm in orange, which was a single 300-milligram dose of RPT904 showed a 21.7 point improvement while the omalizumab Q4 week arm in gray showed an 18.5 point improvement. At week 16, the Q8-week arm showed a 23.2 point improvement. The Q12-week arm showed a 22.2 point improvement, while the omalizumab arm showed a 19.1 point improvement. The Q12-week arm was particularly notable since only -- after only a single 300-milligram dose at the beginning of the study, RPT904 delivered numerically superior efficacy to 4 monthly doses of 300 milligrams of omalizumab out to and including week 16. These data indicate a superior durability of RPT904 compared to omalizumab. However, no statistical hypothesis was tested to this Phase II study. Slide 11 provides results from secondary endpoints for itch and high severity. Itch as measured by the 7-day itch severity score or ISS7, and high as measured by the 7-day high severity score, or HSS7 are components of the UAS7 score. Similar to the UAS7 score, and as expected, both RPT904 arms demonstrated numerical superiority or an ISS7 and HSS7 compared to omalizumab at all time points. Slide 12, a depicts the patients with complete responses as assessed by patients who receive a UAS7 score of 0. At week 12, RPT904 showed a numerically greater percentage of patients achieving complete response. At this time point, 37% and 39% achieved a UAS7 score of 0 in the RPT-904 Q8 -- week and Q12-week arms in gold and orange, respectively. Versus 24.4% in the omalizumab group in gray. The percentage of complete responders continued to increase at week 16 are 46% and 44% achieved a complete response in the RPT904 Q8-week and Q12-week groups, respectively, versus 32% in the omalizumab. Therefore, RPT904 can elicit a high degree of complete responses at least similar, if not better, to omalizumab, but a much lower dosing frequency. Let's now move to Slide 13, which summarizes top client safety fund. Safety data from the 16-week treatment period were favorable. No treatment-related serious adverse events or adverse events of special interest were reported specifically, there were no reports of anaphylaxis. The incidence of treatment emergent adverse events were similar across groups and no patients discontinued due to treatment-related events. Overall, there were no new or unexpected safety signals associated with RPT904. Moving to Slide 14. I'd like to now turn the call over to Dr. Giménez-Arnau. a professor at the hospital at deleverage Mar Medical Research Institute and Pompeu Fabra University in Barcelona and a world-renowned expert in CSU. Given Dr. Giménez-Arnau's extensive experience in the space, we've asked her to provide her perspective on these results and how they could influence the treatment landscape. Ana, please go ahead.

Thank you so much. You can hear me, correctly? Thank you very much for the excellent presentation that you've done regarding this new anti-IgE treatment, which really shows extremely some benefits compared to the therapy that we have now. My first comment is that, first, nowadays, chronic spontaneous urticaria is a prevalent disease worldwide still is an unmet need to do its early diagnosis. And still, we have many of people worldwide who do not obtain as fast as we want an anti-IgE therapy. And they are loose in the [ Magma ] of different consultations with GPs and pharmacies [indiscernible] and they make an early and good treatment with it's CSU and probably also for the [indiscernible]. This made [indiscernible], which is important, still the anti-IgE therapy, still omalizumab is not completely used by all the potential population that need to use. This is my first thing that they should translate. That means any anti-IgE therapy has a potential number of people who will -- who can really benefit or receive the benefit of its use. The second one is currently, after the anti-H1 we just have omalizumab as the potential or the indicated drug. Recently, dupilumab has been approved for CSU, and also remibrutinib was approved for CSU, but both drugs have different mechanism of action, both are really interesting, but omalizumab has at least 12 years of experience. That means we are using it by routine when the anti-H1 fails. And the question is that omalizumab has been demonstrated that is so safe, so effective, it can be used with other comorbidities combined with other drugs, even using pregnancy and even in childhood. That means that not omalizumab, but also the anti-IgE therapy, in general, still will be extremely useful during the next years. Sure. Ligelizumab you know very well, such people who follow this type of indication for CSU that it was also a very important anti-IgE therapy, but it stops the development for different reasons. But the anti-IgE therapy is addressed to the main key the principle, the most important key that is capable to activate for autoimmune mechanism, the mast cell and the basophils to degranulate and induce the disease. Then we have still many people to be used and we are using an anti-IgE have experienced, and we are really confident -- very confident with this because the risk of anaphylaxis in CSU does not exist. And then we have another this improvement that has been presented now with RPT904 that really -- the data that came from this Phase IIb are very clear. And after we can discuss and we can't talk if there is any questions, but the most important question is that it seems, it's even more effective than omalizumab. We will never want to demonstrate to be more effective than omalizumab. But we want to be demonstrated that we are extremely safe for CSU also for inducible. And we need to increase the compliance of our patients to the treatment and this new development really offers a posology which is extremely, extremely interesting because commonly, we treat our patients during the first 6 months with omalizumab [indiscernible] and each 4 weeks, they should be administrative subcutaneous, the subcutaneous drug. In this case, we have even more benefit in the urticaria activity score 7 showing double benefit of the minimal important difference. That means a reduction of 20, 20 is twice the minimal important difference in the urticaria activty score 7 demonstrated efficacy reducing itch and high. Then it really benefit do not use the drug each month is a benefit, if we can use just 4 injections per year. If you ask me how long a patient with CSU will be treated with an anti-IgE therapy for our omalizumab, it was demonstrated that the mean is 3.5 years for CSU and for the inducible 4.5 years. Then the compliance will be good because if it's subcutaneous, we can control or when it's administrated and obviously, for the patients who will be easy to control the disease with less number of injections. Then I suppose that probably will be some questions, different things that maybe you should ask yourself comparing, for example, with dupilumab with injection in each 15 days and the efficacy is very slow or with the oral treatment that commonly will be 2 pills per day, et cetera. There are different things which are interesting in all of these drugs that we can go easily accurate or could be fine because all of them are very interesting. But I must admit that based on the confidence that we have on the anti-IgE therapy in general in all the patients that we treated, the things that we've shown today are really very interesting to be follow and to continue on its research. I don't know -- I don't want to say nothing more if there is any questions from drug company, do you want to comment something, please let me know.

Okay. Thank you, and thank you, Dr. Arnau. Let's move to Slide 15. Before I summarize results and next steps, we'd first like to thank and recognize our partners at Jeyou for well-run and informative study and for their partnership and highly collaborative spirit. The Phase II data for RPT904 in chronic spontaneous urticaria demonstrate that the molecules extended half-life, enhanced and enhanced pharmacodynamic effects translate into deep and durable clinical benefit. Specifically, dosing every 8 or 12 weeks showed comparable efficacy to omalizumab dosed every 4 weeks. Durability of RPT904 exceeded expectations, particularly in the Q12-week arm, we're a single 300-milligram dose of RPT904 showed numerically superior efficacy to 4 300-milligram doses of omalizumab up to and including week 16. The safety findings of the study also suggested that RPT904 is well tolerated with no significant differences from omalizumab observed. In totality, these results support the promise of a best-in-class profile across multiple indications, including CSU, food allergy and other IgE-driven disorders. With respect to CSU, we believe that data justify advancing to Phase III trials in CSU and both RAPT and Jeyou plan to approach regulatory agencies in our respective territories to seek alignment on registrational paths. With respect to food allergy, we are on track to initiate our Phase IIb trial before the end of the year, with top line data expected in the first half of 2027. Segueing into food allergy. The design of our Phase IIb trial called prestIgE as shown on Slide 16. Food allergy represents a massive market opportunity, and we believe that RPT904 is projecting for long-sequence dosing and broader efficacy in omalizumab ineligible patients has the potential to position 904 as the preferred therapeutic option in this indication. This Phase IIb study is a randomized double-blind, placebo-controlled trial of 904 monotherapy in 100 patients with food allergies. That is modeled off the recently successful OUtMATCH trial, which formed the basis of approval for omalizumab in food allergy. The trial will assess Q8-week and Q12-week dosing of RPT904, identical frequencies to the CSU trial for a 24-week dosing period. The primary endpoint will be a double-blind placebo-controlled food challenge, and we plan to enroll patients over to 1 or more of the 5 common food allergens, including the key foods in OUtMATCH. The study will include approximately 30 clinical sites in the U.S., Canada and Australia, and we estimate it will take approximately 18 months from study start to top line data. Moving to Slide 17, we anticipate several key milestones in the RPT904 development program. Today, you heard the top line results from the Phase II CSU trial Jeyou is planning to approach the Chinese health authorities and could begin a Phase III trial as early as the first half of next year. Full data sets from this week 16 treatment period and the completed study, including the 16-week follow-up period will be presented at future medical conferences. We also plan to present additional PK/PD data, including free IgE measurements from the Phase II CSU study. Jeyou is completing a smaller Phase II study in moderate to severe asthma, and we expect data readout by the end of the year. That trial is primarily oriented in assessing PK/PD to refine doses for an asthma Phase III trial, which assuming positive data is anticipated to begin next year by Jeyou. With respect to RAPT's development program, as just discussed, we are on track to initiate the Phase IIb study for RPT904 in patients with food allergies before the end of the year and expect top line data from that trial in the first half of 2027. These milestones reflect our commitment to advancing RPT-904 across multiple allergic and inflammatory conditions. With that, we'd like to open up the call for questions.

[Operator Instructions] Your first question comes from the line of Sam Slutsky with LifeSci Capital.

Congrats on the data. Just 2 for me. I guess, first one is just based on the data so far. Can you just talk about your confidence level of the Q12-week dosing being basically effective and the right one for food allergy. And then I guess, as we think about Phase III CSU, could you just kind of review historical time lines, how big of a study you might need given that you can use probably Jemincare safety database? And just any additional details there?

Maybe I'll start first with the potential translatability across indications. We do think that, of course, the translatability and the level of confidence is higher now that we've seen that the increased half-life and improved pharmacodynamics will translate clinically. And as just mentioned, we are planning to study the same dosing frequencies in the food allergy study as you've seen in the CSU trial. So I think with the data in hand, we're walking into this Phase IIb data with a high degree of confidence. With respect to the CSU safety database and timing, I'll let Bill Ho speak to that.

Yes, thanks. The number of patients needed for Phase III trial in CSU are probably going to be driven, like you said, more on for the safety database than powering to show efficacy given sort of the degree of efficacy that's expected. The safety database is one of the things we'll definitely want to discuss with the FDA and other regulatory agencies. And as you mentioned, Jeyou will be running trials also in parallel, including Phase III at CSU and possibly in asthma. Those should count towards the safety database. So we're pretty confident we're not going to need large 1,000 patient studies like some others may be doing. We think it's maybe a couple of trials that could be just a few hundred patients each. But again, we'll have to do the calculations and discussions.

Your next question comes from the lot of Thomas Smith with Leerink Partners.

Congrats on the [ Scalar ] data. First on the dosing frequency, given the strong durability you're seeing with the single dose now up to 16 weeks, how are you guys thinking about the optimal dosing interval going forward? Is there a potential for you to explore 16 weeks or maybe less frequent dosing in either food allergy or CSU? And then secondly, on safety, I know there weren't any treatment-related discontinuations or SAEs but could you just elaborate on some of the most frequently observed treatment-related AEs. Was there any pattern there? And did you see any injection site reactions?

Yes. Thanks for that good question. I think with respect to dosing intervals, I think it's pretty safe to say that the Q12-week is a pretty solid go-forward dose into Phase III studies in CSU and certainly backstops confidence in other indications, including food allergy. Of course, the data that shows durability out to week 16 is quite encouraging as well. So we plan to look at the follow-up data as well as additional secondary endpoints, and we'll make that determination of whether additional doses are warranted in the subsequent studies but right now, moving forward, I think the Q12-week seems to be very, very well supported by the data. And to some extent, it's a little bit of a sweet spot for patients who see their allergists roughly every 3 months. With respect to safety and other -- whether there's any patterns here, I'll let Bill answer that.

Yes. I mean at a high level, there's definitely no patterns of any safety findings of note, again, across 904 versus omalizumab treatment arms pretty much the same thing as you see in other CSU studies. There isn't a signal of anything novel and not that we did note any specific injection site reactions were commented. There are no AESIs that were of significance.

Your next question comes from the line of Yanan Zhu with Wells Fargo Securities.

Great. Congrats on the great set of data. I have a question for the KOL call. I was wondering, could you talk about the efficacy seems to be better numerically. Do you think this could turned out to be a statistically significant effect in a larger trial? And in your practice, how do you think this 904 could be used? If -- even with the presence of biosimilar lower dose more frequently. Can you comment on how would you use this new drug?

This question for me? Yes. Yes. Okay. As I understood currently, how are we using now in the situation that we are now is that we -- during the last week, omalizumab was immediately substitute by the biosimilar. And based on the mandatory behavior of the hospital according with [ politics ] which is a national health politics, changing immediately, we the original product by biosimilar event do not asking us our opinion. We can say that we are similar from Korea, from [indiscernible] has been a lot of a good trial, which is a comparison very good with the trial. And it seems it's exactly -- the behavior is exactly the same even when people were treated with OMA continuously and they change to the biosimilar. This is what the trial said, and we will check what happens in the clinical practice, but also is not just about how we manage with a biosimilar because we will be very aware about what happened with our patients that have more than 300 patients with OMA and 30% of them, they haven't increased those of omalizumab to 450 or even 600. That means 415 each 4 weeks because they are not completely controlled in 3 injections each month. Then the potential need to increase the dose at see what's happened in the real-world practice with the biosimilar and how safe will be, et cetera. Let's see, because by mandate, we should change, which is not really a thing that I like very much. But we deal with this. Then everything that could improve the actual pathology of omalizumab and make a difference in the sense that we'll be more comfortable, even more effective, brings a good opportunity for the anti-IgE therapy to be maintained in a high level of standard level because it is a great service at least for CSU inducible, it is, and it will be -- it will continue to be. But really as clinician, these politics on the national health system and how to manage with the biosimilar, et cetera, is not my objective I will see what happened with the biosimilar in the clinic during the next year. And I will support the use of our new anti-IgE therapy in spite that we have other drugs that will act through a different mechanism and will be very careful for CSU because we need also such drugs because not all CSU is the same, and not all the phenotypes are the same, and not all the triggers are the same. But we think we need to maintain the high standard with the anti-IgE therapy in general. Then if I answer your question regarding safety, so safe. And let's see what really happens in the Phase III. I hope I answered your question.

Yes, that's very helpful. I was wondering, efficacy wise, do you think this could be a better efficacy drug than Xolair? And if that's the case, whether that could impact in Europe, the use versus biosimilar Xolair?

Yes...

I just wanted to add for the company -- last question for the company. Can you talk about for the pivotal trial, do you plan or foresee to do a head-to-head comparison with Xolair study or placebo-controlled study? But doctor, it would be great to hear yourselves on efficacy whether than low...

I think that any drug that will develop for CSU need to make -- okay, it's not necessary to position any new drug for CSU in a position that it will be better than omalizumab. This is a wrong thing. It's not -- it was not useful for ligelizumab. It really was a very extremely, extremely good anti-IgE therapy. I think the best thing is to compare to placebo. And going with a head to head to OMA is not necessary. You can put a branch with OMA and you can compare how it works. So never position -- I will not recommend to position any of the new drugs for CSU as better of omalizumab. You understand me what I said.

The next question comes from the line of Anupam Rama with JPMorgan...

Hang on we need to answer the second half of Yanan's question. Just -- I think, Yanan, to your question about the design of the Phase III trial, obviously, there's details that we'll need to discuss with the regulatory agencies. Traditionally, the FDA is preferred strongly placebo-controlled studies. Obviously, we're focused on U.S. development, although we do think that the European markets are also quite important. It's possible the regulators in Europe may have a view. So we'll have to discuss with them whether a comparator arm would be necessary or not. So we'll be determined.

Great. And congrats again on the great data.

You can introduce a branch to compare, but never decide to -- decide in the [indiscernible] that means position the drug as better than one after the other even with remi...

Our base case assumption is that we're trying to show similarity or relative similar efficacy to omalizumab, but much more durable prolonged efficacy and much frequent dosing on top of that, and that's a different improvement than head-to-head efficacy.

Next question comes from the line of Anupam Rama with JPMorgan.

Congrats on the data. What do you think is driving sort of this increased complete response signal that you're seeing on UAS7 with longer-term follow-up? And is there a reason to think that the portion of patients continuing achieving a CR may continue to increase with longer-term dosing. And then a second question, with the totality of these data, how do you think about unlocking the 904 potential in sort of the omalizumab ineligible population, particularly in food allergy from like a clinical trial perspective?

Yes, Anupam, thanks for that question. I think with respect to the efficacy, it does look like it's deepening at week 16 I'll just say that we're very pleased with the level of efficacy versus the comparator arm in the study. And obviously, we're already seeing the miracle superiority, which was beyond our expectations. We'll have to see how the -- these both arms perform in the 16-week follow-up period. So that data will be presented at a future medical meeting. Right now, our scenario moving ahead is that clearly Q12-week looks interesting and is very solid moving forward. We'll see how other days play out to see whether it supports less frequent dosing. I think the effect is likely related to the properties of 904, which is the improved half-life and higher affinity which is probably more effective at reducing local IgE and removing IgE down to the Fc [ Stone ] receptor. Maybe I'll let Bill talk about the -- assessing the ineligible population in the food allergy study as a way to really differentiate versus omalizumab.

Yes. I mean it's interesting to trying to translate the CSU data to food allergy, maybe slightly different biology, all driven by IgE, I think we're really excited that this data really is the first set of data in patients with a disease that's driven by IgE has shown such promising efficacy. How that translates into food allergy will be interesting. Again, as what was brought up before. There are different limitations as opposed to CSU where it's flat dosing, you're not restricted by high IgE levels or high weight, things like that in food allergy based on dosing table, there are restrictions that patients with extremely high IgEs or high weights aren't currently eligible for omalizumab. And we've done some modeling with earlier data that suggests 904 should be able to reach more of those patients who are currently excluded from OMA dosing. And we'll be testing that in Phase II, again, of including patients not only who are currently eligible for OMA, but for one significant portion of patients are currently excluded and seeing how that translates and we -- this data sort of supports the idea that, that hopefully will translate either with 8 or 12-week dosing in food allergy.

Your next question comes from the line of Umer Raffat with Evercore.

Just wanted to focus on 3 quick ones, if I may. First, the every 12-week arm did it actually dose at the 12th week or not? And if it didn't, isn't that an every 16-week arm? I'm just trying to understand that. Number two, could you speak to what the baseline antihistamines levels were? And how did that change over time? And number three, as it relates to UAS7 measurement during the course of this trial, was it done in the standard way twice a day done over the course of the full week? And I asked because about 13% of the patients in omalizumab arm were previously omalizumab. So I'm just trying to understand how they qualify?

Yes. With respect to the first question, the Q12-week arm was a single dose which was meant to represent a dosing frequency of 12 weeks or less frequent. As you'll recall, the primary endpoint that's typically used as a basis of approval is at 12 weeks. That single dose is meant to do that. There was no additional dose at week 12. And then with respect to baseline antihistamine use and how the UAS7 scores were run, let me see if we have some information on that. I don't know, Bill, if you have that details?

I don't want the details here in the top line data. Again, the current -- on the protocol where they were allowed to be on -- and need to stay on a stable dose of antihistamine at approved dose. This didn't actually -- the study didn't include the up to fourfold. And similarly, they could have a rescue medication with another antihistamine at an approved dose. But actual dosages and whether how they changed over time, that will be analyzed as part of the full data set.

He asked you about the way how you assess the urticaria activity score 7, if it was the classical one twice a day or just once a day? The classical one, what does mean because -- which is recommended by the guideline is just one time per day. And the used twice per day is the way how it's used in the Novartis trial. It was your question about this?

Yes.

Yes, I can I don't know what you did in this trial, but there are 2 ways to measure. And the -- and it's true that in the Novartis is used twice a day, but it has been published at paper where it's the same. It can be compared to use the assessment once a day than twice a day, which is half of this cost.

So yes, so the UAS7 score, which is the sum of the ISS7 and HSS7, it was a sum of the daily ISS and HSS7 scores, which were the average of the morning and the evening scores for each day.

Okay. Does that answer your question, Umer?

Yes, that's it.

The next question comes from the line of Prakhar Agrawal with Cantor Fitzgerald.

So maybe just double-clicking on the efficacy results on why you're seeing better numerical trends compared to Xolair. Have you done any exposure response analysis here as there seems to be some real-world data that Xolair up dosing to even 450, 600-milligram can lead to slightly better efficacy. So I'm just trying to understand how much of this is due to better exposure for RPT1904 (sic) [ RPT904 ] . Secondly, on the safety side, slightly higher treatment-related adverse events on 904 and given it's long-acting, I wanted to better understand the duration of these adverse events relative to Xolair and then third question, the relationship between baseline IgE and efficacy is maybe not that relevant in CSU as it is for food allergy. But in your view, are there any read-throughs to food allergy, especially for high IgE patients and were very high IgE patients included in this trial?

Yes. With respect to PK/PD assessments, those data will be forthcoming. So we can look to see -- I mean we do -- I think it's logical to assume that based on the modeling as well as the healthy volunteer data that there should be better reduction in free IgE and that likely will translate into potentially more robust efficacy. As you pointed out, and Dr. Arnau pointed out, approximately 20% to 30% of CSU patients do up dose omalizumab in the real-world setting and suggests that there is perhaps some under dosing in that population because roughly 70% to 80% of those patients do respond to up-dosing. So that's what we might be seeing here play out. But again, I just want to reiterate that our baseline TPP is comparable efficacy to omalizumab that of less frequent dosing. So I think we're very pleased with the results from the study so far. With respect to the safety findings, maybe I'll turn it over to Bill about those and whether there was any patterns or duration there.

Yes. No. Of course, the full data set will be part of a later disclosure. But as far as we could tell, there was nothing notable as far as difference of duration of adverse events or a difference of signal. And really, there was no -- didn't feel there was anything significantly between the OMA arms and the 904 arms as far as either tube-related or unrelated AEs they all seem pretty consistent with what you see in CSU studies. And then as IgE level.

Yes, the baseline IgE levels have not yet been reported. But and obviously, we don't have yet the patient level data. But once we get that, we can see if there's any correlations there.

Just in general, with CSU, we wouldn't expect patients with very high IgE levels that would translate necessarily to food allergy.

Your next question comes from the line of Kaveri Pohlman with Clear Street.

Congrats on the results. Can you provide any additional details on your plans to discuss the data with the FDA? When do you expect to have that discussion? Can the process be started immediately or you have to wait for additional data to take the package to the FDA? And the current time line of the second half 2026 for trial initiation, does that assume like Phase II or you could initiate big Phase III trials also in that time frame if the FDA agrees? And I also want to understand how much read through this data provides to the food allergy program, because you still have plans to test both Q8 and Q12 dosing in the Phase IIb trial. Does that change any of your current plans for that study and just focus on Q12 dosing.

Yes. I think with respect to the timing of our interactions with the FDA and the start of the trial, I think that's to be determined. And as we get look at this data -- continue to look at this data, we'll make that determination of the timing for that. With respect to the food allergy dosing, just recall that most food allergy patients are treated with Q2-week dosing. So Q8-week dosing would be still a very significant step change for those patients and all of our market research suggests that would be essentially a home run. Obviously, with the CSU data in hand, I think that builds confidence that Q12-week would also be sufficient. But I think we believe that Q8-week and Q12-week would still be -- both be wins in the food allergies setting. So no plans to change dosing at this time.

The next question comes from the line of Yatin Suneja with Guggenheim.

Maybe just a quick one for me on the food allergy side. What do you need to do in order for you to go into younger patient population? I think right now, you are going up to 16 or 12. Could you remind us more work is needed. And anything on the -- on your market access research suggests because at some point, Xolair would biosimilar. So I'm just curious, to understand how the pricing and the access is going to work out.

Yes. Maybe I can get started on the patient age. What's interesting about the script level data for omalizumab is that it does appear that adolescents -- and to young adults appear to be the sweet spot. Roughly 50% of the scripts are there, up 40% are children younger than 12. So this study that we're planning is starting now less than 12 years and above. But we think that was a longer-acting, less-frequent dosing regimen that there would be more -- we would broaden the market and expand the market, particularly in children as well. So we're really excited to get to younger patients. And of course, I'll let Bill opine about this or talk about this, but assuming that the safety looked good, in this Phase IIb study, we will be going and looking to expand the age group to younger groups in the Phase III trials.

Yes. I think the key thing from the Phase II is first to obtain the 12 and up safety and efficacy data through allergy patients. And then based on those results. hopefully be able to support the idea of going into lower patient populations, eventually targeting the ages 1 and up similar to what OMA for has for their approval. But exactly the staging of that will depend on the data and discussions with the agency.

And the second question was regarding the -- I missed pricing -- or I mean, we -- assuming we get the label of 1 and above as with OMA, I don't think we would have any difference in pricing based on age. It's pretty much just based on dosage. So we would assume we would be doing similarly.

The next question comes from the line of Emily Bodnar with HC Wainright.

This is Joey on for Emily. Congratulations to data. So regarding a Phase III programmation, do you not believe that there is a need for U.S.-based Phase II data from a regulatory perspective? And if these data are increasing development priority in the U.S., what next steps are getting weakened or that [indiscernible] in 2026. And also...

Yes, I think that's a good question. I think we're confident we could initiate a Phase III study based on these data. Obviously, we'll need to have a discussion with the regulatory authorities to align on that plan. There's very good translatability between Asian patients and countries and Western countries. The labeling is nearly identical, dosing is very similar. PK/PD is similar and the safety profile is very similar as well. And just recall that the FDA recently provided us a safe to proceed letter to start a Phase IIb study in the U.S. based off of Chinese healthy volunteer data. So I think the FDA does recognize and is comfortable with the mechanism of action, particularly the omalizumab and epitope. So nothing is guaranteed here, but I think there are a lot of reasons to expect that there will be a path forward to registrational studies there.

Got it. That makes sense. And in the trial itself, do you have any reasons why you think that in the week 12 group for the omalizumab arm, why did the urticaria free rate decline?

In the UAS7? Yes, these are small cohort arms, and there's variability week-to-week. There are small numbers of missing data. There's some imputation done there, but very little data is missing. So it's all within the range of just the 1 or 2 patients that might be different between arms and as far as we can tell, nothing of significance. But of course, we need to continue to follow this and have larger patient cohorts.

And the last question for today comes from the line of [ Etzer Darout ] of Barclays.

I have one question for you and one for Dr. Ana, if you could. The first question, just wondered, based on these results and understanding these are CSU and food allergy are different indications. But is there an opportunity to maybe tweak the food allergy study sort of ahead of starting it? Or is it the data really in CSU today just more confirming of the plans that you already have in place for that study? And then for Dr. Ana, I just wanted to get your sense of how you could see sort of this once every 12-week profile fitting into the treatment paradigm here for CSU and we kind of look at maybe some of the other competitors entering the space like from remibrutinib, which was recently approved. Just your thoughts around that and...

Yes, I think I'll start with the first question here. I think that the data very much are consistent with our modeling. Projections that Q12-week would cover sufficiently the level of free IgE reduction that would be acquired for efficacy. So it really is confirmatory, I think, for that hypothesis and supports the modeling that we've done. And I'll let, of course, Ana respond to the competitive landscape.

And for me. Yes, yes. We have anti-H1, we have OMA and we already have now approved by the FDA, dupilumab and remibrutinib. You know very well, remibrutinib the very selective anti-BTK treatment who goes inside the muscle and modulate the expression of the high IgE receptor independently of the of its accumulation independently of the stimulation is an IgG or IgE or IgG again IgE, et cetera, because there are different endotypes. With oral is 2 pills per day during how long the episode will continue and how long it will be necessary and it will depend on the patient, but the question is that it's very fast and is an oral drug and is effective and is demonstrated to be safe. Dupi is also sale, it was slow and is administrate each 15 days in a subcutaneous way. And we have OMA monthly, very safe. But with 30% of the patients that we need to increase the doses up to 15% for which doesn't work because it's a very low proportion of CSU where the anti-IgE therapy does not work. And there is probably the place for the [indiscernible] et cetera. The question is, we do not -- can substitute the anti-IgE therapy, quite these other new treatments. We cannot do it. Those treatment, all of them are necessary and all of them will have its position. And maybe some of them could even put in the future before the use of the anti-H1 because we are now using everything when the anti-H1 phase. Licensed dose or when we increase the dose. But the anti-IgE therapy will be always be there. And then it will be always there now the new guidelines will put after with the anti-H1 phase. It will put in the same level anti-IgE and the anti-BTK in order to give a sense of freedom to the doctors to choose the best treatment, talking with the patient according with their preference. Because there will be someone that will be used [indiscernible] topic comorbidities and remi when do you want to go fast, but also we don't have 100% of benefits and probably in many patients, could even combine them. But my message here is that the anti-IgE therapy will be maintained because it's so effective and safe. And then the other one will not substitute this one. I think -- so this is my feeling. The question is that after OMA, we just have cyclosporine or corticosteroid or nothing. And we need these other potential treatments. And all of them, we are requiring all of them, and we need to improve the use of the anti-IgE therapy. This is my message.

And that is all the time we have for the question-and-answer session. I would now like to turn the call back over to Brian Wong for closing remarks.

Thank you, operator. In closing, armed with these data, we look forward to an expeditious development plan for 904 in food allergy and CSU. We look forward to keeping you apprised of our progress, and we appreciate your support. I'd also like to thank the amazing team here at RAPT, our partners and collaborators and the patients participating in our clinical trials. With that, operator, we can close the call. Thank you.

Ladies and gentlemen, that concludes today's conference call. You may now disconnect your lines. Thank you, and have a good day.