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

Welcome, everybody, to the 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, Malcolm Kuno and Rati Pinge. Our next presenting company is RAPT Therapeutics and presenting on behalf of the company is CEO, Brian Wong. Brian?

Great. Thank you, Anupam, for that kind introduction. And before I begin, I'd like to thank the organizers of the conference, giving us the opportunity to present the reinvigorated RAPT Therapeutics story. And I'd like to thank you all for your attention today. RAPT's mission is to discover, develop and commercialize transformative therapies for high-value autoimmune and inflammatory diseases. And I'm very excited to announce that we recently expanded our pipeline through the in-licensing of a new asset called RPT904 from Jemincare, a leading pharmaceutical company in China. RPT904 is a half-life extended omalizumab or Xolair bio-better with the potential, we believe, to transform the therapeutic landscape of food allergy and CSU or Chronic Spontaneous Urticaria. Based on the design of RPT904 and the clinical data to date, we believe that 904 has a best-in-class profile with more convenient dosing and therefore, greater compliance, which should be a very attractive option for patients, health care providers and payers. From the RAPT perspective, we plan to initiate a Phase IIb study in food allergy in the second half of 2025 with data expected in the first half of '27 and in addition, we expect to initiate a Phase II or a Phase III study in CSU next year. Based on extensive market research, we expect $5.5 billion approximately in U.S. peak revenue for FA and CSU combined. Our partner, Jemincare, is currently in Phase II in 2 indications, CSU and in asthma. And I'm very happy to report that their enrollment is going faster than expected. And both the top line data for both studies are expected this year in the second half of the year. Following on 904 is our next-generation oral CCR4 antagonist, that we believe has the potential to fill a high unmet need for a safe oral option in a range of Th2-driven disorders. We expect to select a preclinical candidate in the first half of this year and anticipate entering the clinic in 2026. Finally, the company is well funded with a cash runway expected through multiple clinical catalysts, including the Phase IIb top line data in food allergy. This is the pipeline chart. You can see that 904 is in multiple Phase II indications. Our oncology program tivumecirnon just completed its Phase II study, we're happy to report that it demonstrated clear efficacy in a range of solid and liquid tumors, including non-small cell lung cancer. And we're currently in partnership discussions to continue the development of tivumecirnon. So let's dive into RPT904, its value proposition and its positioning in food allergy and in CSU. So as many of you know, omalizumab has been a very successful drug for a range of allergic disorders, including asthma, CSU and chronic rhinosinusitis. Recently, omalizumab was approved and it is emerging as a blockbuster in a large and growing food allergy market. There are approximately 17 million food allergy patients in the United States, of which 50% have experienced a severe reaction leading to over 3 million ER visits per year. And to the approval of omalizumab, the treatment has been dominated by inconvenient approaches, including food avoidance, and single allergen desensitization, namely oral immunotherapy or OIT. Omalizumab is the first and only FDA-approved therapy to reduce allergic reactions to multiple foods as shown in the Phase III OUtMATCH study, which was the basis for approval. And the launch has been incredibly successful with 30,000 food allergy patients on omalizumab after only 2 quarters post the launch. Despite omalizumab early success, in our market research, payers and prescribers are very enthusiastic about RPT904's profile, given its increased convenience compliance, which should lead to better patient outcomes as well as decreased burden on the health care system. We tested a target product profile of efficacy similar to omalizumab as well as equivalent safety. But instead of omalizumab Q2 week or Q4 week dosing, we tested Q8 week or Q12 week dosing subcutaneously. Based on this target product profile and using Q8 week is the more conservative targeted profile, prescribers that were expected to use RPT904 and approximately 16% of their moderate to severe food allergy patients. Omalizumab biosimilars are expected to launch by the time RPT904 is on the market with an expected 30% to 40% erosion in price. Payers, given the positive reception to this target product profile would support a 30% premium over omalizumab biosimilars and based on these assumptions and based on the total addressable market of around 2 million food allergy patients, we estimate $4.5 billion in peak U.S. sales for food allergy alone. Moving on to CSU. We believe this indication offers additional commercial upside. CSU affects over 1 million patients in the United States, and over 40% of those patients or around 400,000 are not well controlled with antihistamines. Omalizumab is the only approved biologic in CSU after the failure of antihistamines. And therefore, we believe that 904 is positioned to be the preferred choice in the frontline setting due to its improved compliance and convenience compared to OMA. In fact, this less frequent dosing is a very strong driver and prescribers suggest that even efficacy below that of omalizumab would still be attractive given its more convenient dosing. However, just to be clear, we believe that RPT904 will drive very similar efficacy to omalizumab. Based on these assumptions, we estimate $1 billion in peak U.S. revenue in CSU. So let's talk about RPT904's design and its attributes and why we think it's the best-in-class bio-better. So Jemincare took a conservative approach to enhance the half-life of omalizumab, improving drug life properties while retaining the clinically validated epitope. Using omalizumab as a starting point, they introduced the well-established YTE mutation into the Fc domain, which should extend its half-life. In the variable region, they performed affinity maturation remove post-translational modification sites to improve manufacturability and stability and also performed additional framework humanization to reduce the potential for immunogenicity. There's a very strong patent position and freedom to operate with loss of exclusivity in 2021, excluding any patent term extensions or additional formulation or device patents. So this should translate to what we feel is a best-in-class profile for an anti-IgE option in food allergy. Similar to omalizumab 904 shares the clinically validated epitope which should greatly increase the probability of clinical success. And like omalizumab, this should be active against multiple allergens. In contrast to omalizumab, we believe that the convenience of Q8 or Q12 week dosing with the ability to access high IgE and high weight patients will set this apart from Xolair. In addition, the food allergy table for omalizumab is quite complex, and there's an opportunity to simplify this, which should be attractive to prescribers and health care providers. So let's talk about the data and how this data supports RPT904 as the best-in-class -- potential best-in-class anti-IgE antibody, and in addition, how we are projecting doses in our food allergy study. This is Jemincare's Phase I healthy volunteer design. It's a double-blind, placebo-controlled, single ascending dose study of RPT904, which Jemincare calls JYB1904 along with an omalizumab comparator in healthy Chinese subjects. Objectives were tolerability, safety, immunogenicity, PK and PD. All active agents were dosed subcutaneously and subjects were followed for 24 weeks to account for RPT904 as long half-life. 5 dose strains of RPT904 were study from 75 milligrams to 600 milligram, and omalizumab was dosed at 150 milligrams, so a direct head-to-head comparison could be performed with 904 at 150 milligrams. The results of the study suggest that 904 has a longer half-life with superior pharmacodynamics compared to omalizumab. On the left shows the pharmacokinetics at 150 milligrams of 904 demonstrating a 60-day half-life compared to omalizumab's 26-day half-life. This increase in half-life of over twofold is very consistent with the YTE alterations and other therapeutic antibodies. In addition, on the right, you can see that in a head-to-head comparison that RPT904 shows deeper and more sustained reduction in free IgE. One caveat to mention is that the comparisons of Absolute free-IgE to other trials is not possible, given that Jemincare did not use the same free-IgE assay format as Novartis and Roche. However, we will be performing additional PK/PD work, both in healthy volunteers and in patients using the more standard assay so that additional comparisons can be made and doses could be further refined for Phase III. So the results are quite encouraging. How do these data translate into our dose projections for food allergy and other allergic indications. To start, I need to first describe the omalizumab food allergy dosing table, which is shown here. It is quite complex, and it's based on well-established PK/PD models along with validated target free-IgE levels. Based on body weight and baseline IgE, patients are allocated to 1 of 8 dose strengths between 75 and 600 milligrams and either Q2 or Q4 week dosing resulting in 13 different dosing regimens. Of note, 30% of patients approximately are excluded from the Xolair label due to high weight and/or high IgE levels, and that's shown in the black triangle. Our approach for dose projection was to follow the Novartis and Roche example and use the Phase I PK data with well-established omalizumab PK/PD models to estimate dose and dose frequencies as a function of both body weight and IgE levels. And the results are shown here. So you can see on the left, an example of a free-IgE simulation. This is a 20-kilogram hypothetical subject of estimated 6 years of age with a baseline IgE of 300 IUs per mL. The approved omalizumab dose based on the table is 150 milligrams Q4 week, and that's shown in the black dark line where you can see it does reduce free-IgE below the therapeutic threshold of 25-nanogram per ml. When we simulated Q8 week which is shown in the light gray line, you can see that omalizumab no longer is able to achieve therapeutic levels of free-IgE. In contrast, RPT904 at 150 milligrams a Q12 week is able to reduce free-IgE well below the therapeutic threshold. We performed these simulations at multiple doses at 150, 300 and 600 milligrams Q12 week across the entire dosing table, every body weight category and every IgE band. And the results are shown on the right. We showed that RPT904 up to 600 milligrams at Q12 week could cover all OMA and many of the OMA excluded patients. There are a small fraction of patients of the highest body weight and highest IgE levels that may not be addressed by Q12-week dosing of 904, but could be readily addressed with Q8 week dosing. So let's turn to the clinical development plan and ours and Jemincare's Phase II trials. We modeled our Phase IIb proposed study very much off of the OutMatch Phase III study, which formed the basis of approval for omalizumab. The proposed study is a randomized, double-blind, placebo-controlled food challenge study of RPT904 as monotherapy in patients with moderate to severe food allergy. We expect to include children and adults starting in adolescents 12 and above, and then expanding to children 6 and above during the course of the study as safety information is gathered. We are expecting and including patients with at least 1 documented food allergy by skin-prick, lab testing, as well as food challenge. Patients are then randomized in a 2:2:1 allocation to a RPT904 Q8-week regimen in the 12-week regimen or placebo. 75 patients are expected to be enrolled in the study, and therefore, the allocation is 30, 30 and 15. After 20 weeks of therapy, there's a second oral food challenge and if patients reach a prespecified threshold for food challenge, they are considered responsive to the drug. We expect to enroll this trial primarily in the U.S. and EU and we expect 18 months from a steady start to top line data. This slide here shows how we are expecting to simplify the dosing regimen after randomization, if patients are allocated to the Q8 week regimen or the Q12 week regimen, then they'll be further allocated to 1 of 3 dose levels of the 150, 300 or 600 milligrams. We do plan to include patients who are currently excluded from the Xolair label, although we do expect to cap those patients. As I mentioned, additional PK/PD studies are planned in healthy volunteers and atopic subjects to help refine the dosing table for Phase III. So here are the Jemincare studies that are currently ongoing. Jemincare is focused on asthma and in CSU. In asthma, their Phase IIa study explores 3 dose levels of JYB1904 versus omalizumab with the primary endpoint being PK/PD in patients with moderate to severe asthma. This is a relatively small study of N equals 60 and is primarily used to refine the dosing for Phase III. If successful, Jemincare will move to a Phase III study next year. In a 1,000 patients with moderate to severe asthma, and this is a noninferior design versus omalizumab. The CSU Phase II is much more efficacy-oriented patients with a poor response to antihistamines will be allocated to either 300-milligram Q8 week, 300-milligram Q12 week of 1904 versus omalizumab at its approved dose of 300 milligrams Q4 weekly. If successful, Jemincare will move to a Phase III trial in 200 to 400 patients in a noninferior design versus omalizumab. As I mentioned, enrollment is moving more quickly than expected, and data from both Phase II trials are expected before the end of the year. So let's look at all the milestones put together. In the back half of this year, we expect to start our Phase IIb study in food allergy and have some initial data from our PK/PD studies in healthy volunteers. In addition, Jemincare's Phase II data from asthma and CSU should read out. If the CSU data are positive, there's a possibility that RAPT could initiate a Phase III study directly starting next year. In addition, we expect to have additional PK/PD study data from atopic patients in the first half of 2026. And finally, we expect the readout from our food allergy Phase IIb study in the first half of 2027. So let's turn to our next I&I asset, our next-generation CCR4 antagonist. Based on the data that we've gathered to date, we believe CCR4 remains a compelling target for a range of Th2-driven disorders. Our research teams are actively identifying the next-generation CCR4 antagonist with improved potency and additional safety margins. We expect to select the preclinical candidate in the first half of this year and enter the clinic next year. In addition, we plan to disclose data from the zelnecirnon Phase II trials at a targeted medical meeting as we get closer to the clinic. So finally, I'm very excited to highlight RAPT's expanded new pipeline. We're very excited about 904s ability to provide more convenient dosing for patients with greater compliance, which we should -- we believe should drive a high level of revenue from food allergy and CSU combined. We're expecting multiple catalysts in the next 3 years, including data from our food allergy study as well as potential initiation of late-stage Phase III studies in CSU. In addition, we're expecting data from Jemincare over the next few years, including Phase II data readout from both CSU and in asthma. So with that, I'd like to finish my presentation. I'd like to thank the amazing team at RAPT, our Board, our investors and, of course, all the patients who have enrolled in our clinical trials. And thank you for your attention.

Thank you, Brian. I just want to remind folks, there's 3 ways to ask a question, right? There's the old school way where you raise your hand, and I'll call on you. There's the question portal. You can submit your question here, and I'll ask it on your behalf or you can e-mail me and I will do it. So Brian, I just wanted to understand what the gating factors are for the IND filing here in the U.S. for 904. I believe that's anticipated here in the first half?

Yes. Great point. So obviously, we just signed the deal before Christmas. And so we're gathering all the information from Jemincare and documentation to file the IND so that we can initiate the food allergy study before the end of the year. Other than that, there are really no gating factors to file the IND and initiate the study.

I guess, how confident are you that the FDA will be comfortable with a healthy volunteer study that's based in China?

Highly confident. There are clear guidelines from the FDA in terms of using data outside of the IND from foreign clinical studies. We believe we filled those criteria. And we and all of our consultants, many of them who are ex FDA believe that there is a clear path to initiate the Phase IIb study based on data from Jemincare.

And then what specific feedback are you looking for on 904 Phase IIb design from the FDA, you had the trial schematic in one of the slides.

Right. It's a great question. So one of the key questions is to -- or the key goals of that interaction with the FDA is to align around the Phase IIb trial design. So we have a seamless transition to Phase III and that we're set up for pivotal studies post the Phase IIb study. So this would include patient population, dose and overall trial design elements.

Questions from the audience? How are you thinking about OMA generic entry? And what would your pricing flexibility be?

Great question. Maybe Rodney Young, our CFO, is here, and he's done a lot of work along with our Head of Commercial Adnan Rahman.

Yes. So we've -- we do assume there will be OMA biosimilar launched by the time we launch. When we did our primary market research and queried payers, what kind of price erosion they would expect for the biosimilar, you get a range about 35%, 40% price erosion versus the branded. So our assumption is by the time we launch the biosimilars will probably be at about 60% of branded.

Got it. And then you mentioned the CSU study. What would you have to see from the Jemincare Phase II study so that it would give you confidence to move forward with a company-sponsored study at RAPT?

Yes. So as I mentioned, Jemincare's Phase II study is comparing a Q8-week dose, 300-milligram, Q12-week dosing at 300-milligram versus omalizumab approved dose at 300-milligram Q4 week. And I think the expectation is that the efficacy should be on par with omalizumab. And based off of the efficacy level at the specific dose that could inform our Phase III study, for example, and which dosing interval to use.

Questions from the audience? Malcolm?

Yes. So there's 1 million CSU patients more than half our control. What does the -- what's the definition for Xolair [indiscernible] X number of flares per year, months [indiscernible]?

The question for the webcast is how do you define control in CSU?

Yes, that's right. So if patients after a number of weeks still have flares, despite high dose levels of antihistamine then they're eligible for a biologic, which in this case, is Xolair. And from our perspective, there are really no other biologics even DUPIXENT, which has shown some activity. But Xolair still appears to be the most active agent in that frontline setting. So we believe that 904 could essentially take some market share away from Xolair, but also expand the market for patients who no longer respond to antihistamines.

Questions from the audience? Yes, go ahead in front.

Can you talk about the competitive landscape from small molecules [indiscernible] in CSU.

The question is the competitive landscape.

So I am aware of CSU, there's competition, certainly. From a small molecule perspective, they're the CK inhibitors. Companies are developing these. There are, as you know, some on target AEs, including hematologic changes as well as cosmetic changes like hair color and so forth. So it's very likely that the small molecules will be positioned post Xolair or post an anti-IgE antibody, presumably post 904. There's also, as you're probably aware, I might butcher the name, but it's MRGPRX2 which are a small molecule, it's a GPCR that also is expressed on mast cells that's currently being developed in CSU as well. I am not aware though, of those agents being used in food allergy studies yet. And there may be more too, that I haven't mentioned.

I think you guys have $670 million in milestones to your partner. I think it's broken down. Is there any breakdown between clinical, regulatory and commercial?

Yes. Great question.

Yes. I mean those kind of information are always pretty well guarded. So what we can say is we wanted to have the milestones and the payments be fairly back-ended. So we can say that probably about 2/3 of those milestone payments are post -- are either approval or beyond approval.

Okay. And with the recent financing, just some of the key catalysts that are assumed within the runway?

Yes. So with the recent financing, our pro forma cash at the end of '24 was about $230 million, and we project that to provide runway well into the second half of 2027. So the key catalyst in that period is obviously the Phase IIb readout from our food allergy trial which would be in the first half of 2027. But also in that period, are the Jemincare data from Phase II, their Phase II CSU trial as well as their Phase II asthma trial. And we do expect to have our PK/PD data from healthy volunteers as well as atopic patients in that time frame as well.

Any final questions from the audience? All right. Thank you, guys.