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

All right. Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, Priyanka Grover, Joyce Zhou and Rati Pinge. Our next presenting company is RAPT Therapeutics and presenting on behalf of the company is CEO, Brian Wong.

First of all, I'd like to thank Anupam for the very kind invitation to speak today. I'd like to thank the entire JPMorgan team for a long-standing relationship. I'd like to thank all of you actually for coming and showing your interest in RAPT Therapeutics. So I was told I should share this. This is a disclaimer for forward-looking statements. I will not read through this. So just by way of introduction, RAPT Therapeutics is focused on developing transformative therapies for high-value inflammatory disorders. Our lead asset called ozureprubart is a novel next-generation omalizumab bio-better anti-IgE designed for less frequent dosing and greater compliance with the potential for broader efficacy than omalizumab. We believe that ozureprubart has the potential to transform the treatment of food allergy as well as other allergic disorders, including Chronic Spontaneous Urticaria, or CSU. Both of which are estimated to be greater than $40 billion and greater than $5 billion market opportunities in the United States. Late last year, we reported data from a Phase II study in patients with chronic spontaneous urticaria, demonstrating 16-week durability, supporting a best-in-class profile across multiple allergic disorders. In addition, we have multiple milestones anticipated over the next couple of years. Our Phase IIb food allergy study was recently initiated with top line data expected in the first half of 2027. In addition, due to the very positive Phase II results in chronic spontaneous urticaria, RAPT plans to initiate its own Phase III study in CSU before the end of this year. The company is well funded with cash runway projected through multiple clinical milestones, including the Phase IIb food allergy readout. 2025 was a transformational year for the company. From the clinical development standpoint, we received FDA clearance for the IND for ozureprubart and initiated the Phase IIb clinical trial in food allergy. We also reported data from our partner in China, Jeyou, showing positive Phase II data supporting 16-week durability and a best-in-class profile. We're also very excited to introduce new Board members, Lori Lyons-Williams, an executive with significant commercialization experience as our Board Chair and also expanded our Board of Directors adding Scott Braunstein MD as well as Ashley Dombkowski, who is actually sitting in the audience here, two industry veterans with extensive experience in drug development. We also added significant talent to our team, including Jessica Savage, an industry vet who trained under Bob Wood, one of the luminaries in food allergy research. We completed a $265 million follow-on offering to extend the cash runway to mid '28. We've also expanded our pipeline with the selection of our next-generation CCR4 antagonist. This is the RAPT Therapeutics pipeline. Wrap is focused on the development of ozureprubart in CSU, which has just completed Phase II as well as food allergy, and that Phase I is ongoing. Our outstanding partner in China, Jeyou is planning to initiate Phase III studies in CSU this year and completed an asthma study in Phase II which should enable initiation of Phase III asthma development this year as well. Let's move to our lead program, ozureprubart -- by way of introduction, this is the mechanism of action of ozureprubart. IgE is a key driver of allergic reactions and is responsible for many different allergic disorders, including food allergy, chronic urticaria, asthma and chronic rhino-sinusitis. Upon allergen challenge, antigen-presenting cells result in the activation of Th2 cells which stimulate B cells to produce allergen-specific IgE. This IgE then binds to receptors on the cell service of mast cells and basophils, which upon rechallenge results in the activation of those cells leading to allergic reactions and potentially life-threatening anaphylaxis. Ozureprubart works in two ways, the first is that it binds to IgE and prevents its binding to the Fc Epsilon receptor 1. But in addition to that, it can actually remove IgE that's already bound to the Fc Epsilon receptor. We believe both of these mechanisms are required for full clinical benefit. This strategy of targeting IgE has shown to be highly effective in reducing allergic reactions to multiple food allergens, which has led to a very broad label. This is the result from the OUtMATCH Phase III study. This is a double-blind, placebo-controlled, randomized study for omalizumab across multiple allergens demonstrating that omalizumab can elicit a very high response rate in protecting patients against exposure to these various allergens. You can see here across the primary endpoint, there was a 67% response rate in the patients who were -- reached the threshold for desensitization against peanut allergy versus only 7% in the control. And you can see these results extend to other allergens, including cashew, egg, milk, walnut, hazelnut and wheat. Based on these data, along with excellent safety, omalizumab was granted a broad label for all food allergens for patients 1 year and above. Omalizumab is also the standard care in chronic spontaneous urticaria due to its optimal balance of efficacy as well as excellent safety. Here, you can see the urticaria assessment score over 7 weeks, the placebo-adjusted change at week 12 across multiple Phase III trials -- and what you can see here is that omalizumab elicits a very high response rate on the UAS7 score change from baseline relative to other mechanisms, including dupilumab, remibrutinib and rilzabrutinib. [ Borzolumab ] also shows a high response rate, but may be limited due to some safety concerns. So where does ozureprubart come in? Ozureprubart is a next-generation anti-IgE bio-better antibody with several potential advantages over omalizumab. ozureprubart was designed using omalizumab as a template. It was engineered with a longer half-life via the YT mutation as well as additional changes in the variable domain to enhance potency and improve drug-like properties. What's essential for the engineering of this molecule is that it shares the same epitope as omalizumab, and we think this is critical in conveying maximal clinical benefit. In addition, the changes made to this molecule convey with its strong IP. There's composition of matter that has a loss of exclusivity out to at least 2041. And without additional patent term extensions or any other formulation patents. So how do these changes translate clinically? Based on our projections, we believe that in contrast to omalizumab, which is dosed every 2 or every 4 weeks, ozureprubart can be dosed every 8 or every 12 weeks. This translates into four to six injections per year for ozureprubart compared to 13 to 26 injections per year of omalizumab. And keep in mind that this is not a single injection. Many patients taking me require up to four injections. So the shop burden essentially is very, very high. But there's another really key advantage here, and this is based on ozureprubart higher potency and better PK. And that is the ability to address patients with high IgE and/or high weight. These are roughly 25% of food allergy patients that fall in this category and are ineligible by label for omalizumab therapy. Based on our projections, we believe we can address these patients and completely address this very high unmet medical need. In CSU, 20% to 30% of patients require up-dosing for full clinical benefit. And due to Ozus higher potency and PK, we believe we can limit the need for dose adjustment in this population. Finally, we have the opportunity to address the very complex dosing table for omalizumab, and you'll see that bear out in the next couple of slides. One important point here is that based on our market research, in food allergy, over 60% of patients are actually treated every 2 weeks. So that's a very high burn for most food allergy patients. How does this translate commercially we have performed an extensive amount of market research with prescribers, patients and particularly payers, with this target product profile of efficacy -- similar efficacy and safety to omalizumab, but with much less frequent dosing. The payers immediately understand the value proposition of the less burdensome dosing to patients translate into improved compliance, which should lead to better patient outcomes. And that should either be better efficacy in the case of CSU, or reduced anaphylactic reactions in ER visits in the case of food allergy. In addition, they recognize the broader efficacy of ozureprubart to treat high weight IgE patients and also limit up dosing. What this actually translates to is a price premium above the branded omalizumab due to these differentiated features. So let's talk about our ozureprubart in food allergy. This is a relatively new therapeutic area. So I'm going to take some time to explain this new indication. There is a massive opportunity in the U.S. and across the globe in developing new therapies for patients with food allergy. There are approximately 17 million diagnosed patients in the United States and 3.5 million of those are children. This puts the prevalence number on the same scale as atopic dermatitis, another very commercially successful indication. Different than atopic dermatitis, though is that this is potentially life-threatening and results in high economic burden. 3.4 million patients have visited the ER at least once in the past year. due to a food allergy-related event. If you put this in the context of other diseases that have been commercially successful, I think you can all see that food allergy is a new and important indication for therapeutic development. Finally, this is an indication that places high socioeconomic and quality of life burn, both on patients and their families with approximately $33 billion expended each year on direct health care costs. So this is clearly a problem. And unfortunately, until the approval of omalizumab was relegated to fairly old therapies. The standard of care prior to omalizumab was oral immunotherapy. This is an approach where you actually give escalating doses of the food that the patient is alerted to [ soft tolerize ] the immune response. There are several issues with this approach. The first is that it addresses only a single allergen in this case, shown here, peanut, requires burdensome titration and often leads to adverse events itself, including anaphylactic reactions. It is also not a cure for most patients and requires daily maintenance to be effective. Omalizumab, which was just approved in February of 2024, has revolutionized the treatment of food allergy. It has several advantages over OIT, including the ability to address multiple allergens outside of peanut, along with a good tolerability and safety record. In fact, in a head-to-head study in the OUtMATCH trial, omalizumab was shown to have at least as good efficacy, numerically superior, but with fewer AEs and better compliance. Based on these attributes, there's been extremely rapid uptake in a very short period of time of omalizumab with over 85,000 food allergy patients taken omalizumab in the first 1.5 years after launch. To put this in perspective, omalizumab is outpacing other very successful launches in the I&I space, including dupilumab in atopic dermatitis. As well as SKYRIZI in plaque psoriasis. This speaks to the incredibly high unmet medical need in this indication. So this is a very complex slide here, but I think it speaks to two major points. The first key point is that based on the data that's been generated to date, along with our modeling using well-established models that have been published by Roche and Novartis, we believe we can address most food allergy patients with Q12-week dosing, compared to omalizumab every 2-week or every 4-week dosing. On the left shows you the omalizumab dosing table. This is a very complex table based on weight, which is shown on the x-axis and escalating IgE, which is shown on the y-axis. Based on the patient's weight and IgE, they're assigned a dose level and a dose frequency. There are eight different dose strength of omalizumab and based on that, they're either given the Q2 or Q4 week dose. Another really important point about this table is that you can see that the high IgE and high weight patients are excluded from the omalizumab label mainly because omalizumab is not able to achieve the appropriate level of target engagement in that population. In addition, patients that are -- have a very high IgE off the table, which is at the bottom of the table here, are also ineligible. 25% of food allergy patients are excluded from the label due to high weight and high IgE, representing a population of completely unmet medical need. When we've modeled ozureprubart across the same patient categories, up to 600 milligrams, we can cover not only all of the OMA-eligible patient population with Q12-week dosing. But also a large fraction of the ineligible patient population with the highest IgE and highest weight patients may require in every 8-week dosing. In either case, this is a massive step change for patients with food allergy. We're very excited that we initiated prestlgE, this is the food allergy Phase IIb trial late October. This is a randomized, double-blind, placebo-controlled study of ozureprubart monotherapy in adolescents and adults with greater than -- or at least one documented food allergy confirmed by skin prick laboratory testing as well as oral food challenge. Roughly 100 patients will be enrolled in the study allocated 2 to 2:1 in an ozureprubart Q8-week arm, ozureprubart Q12-week arm versus placebo. There's a 24-week duration of treatment upon which then there's a second food challenge to look at the threshold change, and that will be the primary endpoint for the first part of this study. We then plan to initiate Part 2, which includes a 24-week extension period as well as a placebo crossover followed by a third food challenge to look at efficacy over a 48-week period. as well as to look at the effect of patients who switch from placebo to active drug. The primary endpoint is very much similar to the OUtMATCH study which is the Phase III study used as the basis for approval for omalizumab, which is a prespecified threshold change after oral food challenge. We are activating sites in the U.S. Canada and Australia. And actually, it's important to point out that omalizumab is not approved in food allergy outside the United States. Top line data is expected in the first half of 2027, and I'm happy to report that the ramp of the study, while early, has met our expectations, and we are very much on track for delivery of top line data in this time frame. I wanted to dive a little bit more into the trial populations and powering assumptions of prestlgE. Of the 100 patients that we're targeting to enroll. 75 of those patients will be omalizumab eligible, meaning that they'll fall under the category that based on their IgE and weight, this is the primary analysis population with the goal to demonstrate statistically significant efficacy on par with omalizumab. This is powered to detect a 50% placebo-adjusted effect size at 90% confidence. We're also, though, very interested in exploring the omalizumab ineligible patient population. And we've actually separated this population into a subgroup. This is a 25-patient plus subgroup. We have the ability to increase that to 40 patients. It is not powered, but the goal is to demonstrate trends of efficacy in this population. Because these patients have no option, really, we think the bar for success is lower. And that's why we're looking for any trends of efficacy, which we think would be quite exciting. So let's move from food allergy to chronic spontaneous urticaria. We were very excited last year to report results from Jeyou Phase II study in patients with chronic spontaneous urticaria. These results showed that both the Q8 week and Q12 week are demonstrated comparable efficacy and safety to omalizumab that was dosed every 4 weeks. And in fact ozureprubart -- or both ozureprubart arms showed numerically superior efficacy to omalizumab on both the UAS7 score as well as the Complete Response Score, or UAS7=0 sort across all time points reported. Notable was that the 12-week arm, which is represented by a single dose demonstrated numerically superior efficacy to omalizumab and out to week 16. This is quite notable because the single 300-milligram dose of [ OZU ] was essentially equivalent to four doses of omalizumab. Speaking to the durability of this modified agent. Ozureprubart was well tolerated with no drug-related SAEs or discontinuations and no AEs of special interest, including anaphylaxis. We plan to present additional efficacy and safety data from the study, along with our partners, Jeyou at a future medical conference. These positive data, we believe, support moving directly to pivotal Phase III studies. Jeyou and RAPT plan to approach regulatory authorities this year in our respective territories. And both companies are planning to initiate our Phase III trials this year. Overall, the data support a best-in-class profile across multiple indications, including CSU, food allergy and other allergic disorders. Let's dive into the data in a little bit more detail. This is the design of the Phase II trial performed by Jeyou in China. This is a randomized, double-blind, active-controlled study of ozureprubart in adult patients with Chronic Spontaneous Urticaria that were inadequately controlled by H1 antihistamines. The primary endpoint was the change from baseline in the UAS7 score at weeks 8, 12 and 16, and the secondary endpoints reported were the UAS7=0 or complete response, the ISS 7 and the HSS 7 score. Additional endpoints will be presented at a future medical meeting. 135 patients were enrolled in this study, allocated 1:1:1 with roughly 45 patients per arm. And this study was enrolled entirely in China. The Q8-week arm of ozureprubart of 300-milligram was dosed at week 0 and week 8. The Q12-week arm was represented by a single dose at week 0, but there were no additional doses, including at week 12 in this arm. Whereas the omalizumab arm incorporated 4 doses at weeks 0, 4, 8 and 12. Top line data was reported after this part of the study, and there's an additional 16-week follow-up part of the study off of drug, which will be reported at a future medical meeting. This is the subject disposition. There were 170 patients screened, 137 patients randomized. I think the key point here was that there was a very low discontinuation rate with completers above 90% in every arm. And the reasons for discontinuations were expected, including withdrawal of consent, noncompliance and for personal reasons, but not related to AEs. This is important to share with you. These are the key demographics and baseline characteristics of the study. I think what's important to point out here is that the mean UAS7 score at baseline was 29 roughly across arms, representing a severe patient population and all other parameters were well balanced among groups. In addition, roughly 10% of patients had prior exposure to omalizumab. These patients were required to have a 4-month washout and also could not have discontinued omalizumab due to efficacy reasons or due to AEs. These baseline characteristics are very similar to studies run in Western countries. And you can see here that the translatability across Asian and Western trials are very strong, particularly for this mechanism of action. So let's show some of the efficacy data from the study. Both ozureprubart Q8 week as well as the single dose at ozureprubart shown here as Q12 week showed rapid reductions in the UAS7 score from baseline. At week 12, you can see that both arms showed a roughly 22-point change on the UAS7 score, which was numerically superior to omalizumab at 18.5%. The level of efficacy continues to extend. And even the single dose in the red bar here showed continued numerical superior to omalizumab. To put this in perspective, omalizumab typically shows a roughly 18 to 20-point change at week 12. So the performance of omalizumab was very similar to studies run in the U.S. as well as other European countries. Looking at the UAS7=0. This is the patients who achieved complete response meaning no hives and no itch score. You can see that there was a roughly 32% change at week 8. And week 12, you began to see separation between the ozureprubart arms and omalizumab. With a 37% to 39% of patients achieving the complete response versus 24% and of omalizumab patients. What was very exciting and interesting is that this level of efficacy continued with now 43% to 46% of patients achieving a complete response relative to 33% of patients on omalizumab. These results compare very favorably to historical data and suggest that there's potential for numerical superiority in this population. This is the safety summary ozureprubart was well tolerated with no drug-related SAEs or discontinuations and no AEs of special interest. The TAEs were well balanced across groups. And there were no new safety findings beyond what was expected from omalizumab. So this is the milestone slide, we're very excited over the next couple of years. The prestlgE food allergy Phase IIb study is ramping up and we are on track to deliver top line data in the first half of 2027. In addition, we're generating additional PK/PD data from the CSU trial ahead of initiating our Phase III trial in chronic spontaneous urticaria. Our partner, Jeyou, is planning to present data from their asthma study. and then initiate Phase III trials in CSU and in asthma in their territories before the end of the year. So with that, I'd like to thank the absolutely amazing team at RAPT. I'd like to thank our partners, including Jeyou, for their support and the amazing collaboration that we have with them. and for the investigators and patients that are participating in our studies. So with that, I'd like to thank you all and open up for Q&A.

Thanks, Brian. I'll ask the first couple of questions, but there will be an opportunity for folks in the audience to get their questions and to just raise your hand and you'll get a mic. So Brian, just wanted to ask where you are on site initiation and what will be kind of the geographic breakdown of the Phase IIb food allergy study?

Yes. It's a really good question. So we're planning to open sites in the U.S., Canada and Australia. Just to give you a little bit of color there in the OUtMATCH study, there were 12 sites that were run from this CoFAR group. I think what's very exciting is that all of those sites are participating in our trial, which is great to see. We've also opened sites outside of the U.S. really for the reason that the launch of omalizumab in food allergy has gone probably better than anyone expected. And so because omalizumab is not approved outside the U.S., we think there's going to be potentially a greater pool of patients available for clinical trials. So it's still hard to predict the breakdown in terms of enrollment. We definitely expect to have omalizumab eligible patients in the U.S. But as a mitigation measure as a backstop, we have sites planned in Australia and in Canada to make sure we have enough eligible patients. The ineligible patients, there's a very high unmet need. We don't think there's going to be a large problem enrolling those patients.

And you reiterated your guidance for top line data from the Phase IIb in the first half of 2027. How should we think about -- you mentioned in your comments that enrollment is going well. But how should we think about this enrollment curve as you come in initiating sites and things of that nature?

Yes. I think what we can say now is that the level of investigator interest and patient interest is high, and that's translating well into the accrual curve. As you know, typically, these things tend to ramp up over time as more and more sites get online. But we're very much tracking with what our projections would suggest to get to that first half of 2027. Of course, we may try to translate that investigator interest, if there are additional sites that wish to participate. We're going to be very open to that to accelerate enrollment.

Questions from the audience?

You shared very nicely the data in CSU with the sort of on dose equivalent being almost the equivalent of 4 doses of omalizumab. In food allergy, I guess, the levels of IgE are higher, so how confident are you did extrapolate that dosing paradigm from CSU to food allergy? .

Yes. That's a really good question. So in urticaria, as you know, it's a flat dose of 300-milligram every 4 weeks. And that was largely based on the overall goal for omalizumab to target this level of free IgE that's been consistently to show efficacy across multiple indications. It's a sort of magic 25-nanogram per mL target. The 300-milligram Q4-week dose regimen, we know is probably not without some issues, right? We know that roughly 20% to 30% of patients on that dose do end up in the real world getting up-dosed due to inadequate efficacy. And I think that speaks to the fact that, that one size doesn't quite fit all. In contrast and food allergy, there is that dosing table, which is really designed to titrate each patient individually based on their IgE level as well as body weight. And I think that has led to the very high response rates that you saw in the OUtMATCH study. So I think that's the advantage of having that dosing table, which is now you can properly address patients even with very high levels. The issue with [ OMA ], of course, is that the potency in PK is limited. So they're not able to address every patient, whereas [ OZU ], we think can. All that being said, though, I think there are probably ways to simplify the dosing table. This is certainly something that the FDA is thinking about quite a bit. And so can we reduce the number of categories? Right now, it's like over 300 to something more manageable or even switch to weight-based dosing and eliminate the need to measure baseline I think those are all possible. Our plan is to gather the data from the Phase IIb study, look at every covariant and see if we can come up with something that is a lot more manageable for phase III.

Additional questions from the audience? In the back.

Congrats on the progress. Can you comment on the disruption from an [ MOA ] standpoint, you mentioned disruption of existing binding of IgE to Epsilon receptor 1. Is that a differentiation from OMA in your view? And if so, what are the clinical implications of that disruption?

Yes, it's a really important question. So just to be transparent, omalizumab also disrupts that complex, and it's not a surprise because too ozureprubart actually shares the identical epitope with omalizumab. We think the advantage of this is that there's much less risk and a very high probability of technical success. Because we're essentially mimicking the same mechanism of action that's been well proven across multiple indications. In contrast, we know that other attempts at making next-generation IgE have failed partly because we believe they use a nonoverlapping or a nonidentical epitope omalizumab. So we think that this molecule was designed in a way that enhances drug-like properties, potency and efficacy, we'll not -- while providing the highest probability of technical success.

One of the key questions that we get a lot is just the translatability of China-specific data and CSU to not just CSU global study, but also FA global study.

Yes. I think -- omalizumab, I think, has shown particularly for this epitope that the translatability between Chinese patients and Western patients is quite good. We saw that in the CSU study where the baseline characteristics and the performance of omalizumab is nearly identical to what's been seen historically for those studies. In addition, when you look at the labeling of omalizumab across different territories, including in China, the dosing, safety and PK/PD are nearly identical across labels. So we've heard from the regulatory -- the regulators that I think there's significant appreciation that this is a well -- a translatable mechanism across age, sex and also ethnicity. In fact, we were able to move directly from a healthy volunteer study that Jeyou performed directly going into Phase IIb study in food allergy. So I think the FDA certainly has recognized that translatability there. And we would expect that to translate also to CSU.

Any final questions from the audience? Thank you, Brian.

Thank you all.