Incyte Corporation (INCY) Earnings Call Transcript & Summary

Okay. All right. Let's get started with the next session of Citi's Global Healthcare Conference. It's my great pleasure to have with me the senior management of Incyte Corporation. We have the CEO, Bill Meury; and Pablo Cagnoni, the President of Research and Development. So gentlemen, thank you both so much for taking the time to chat.

It's nice to be here. Thank you.

Thank you. All right. Well, let's just kind of kick off the conversation, if we could, with Jakafi and just talk about the overall strategy in terms of Jakafi and what you're doing to drive growth in the company as Jakafi moves beyond the LOE, which obviously is widely expected and you're, of course, very well prepared to address.

Listen, our focus right now is, as you said, transitioning the business from Jakafi to a hem/onc I&I company and building a steeper growth curve post '29 with durable revenue, earnings and cash flow. I think there's 3 parts to the solution. The first one is our base business, our core business, excluding Jakafi, has the potential to be as big as Jakafi in 2029. So that's sort of part one. Part two is we have 7 late-stage pipeline projects that will layer on top of that core business. And just to break it down a little bit, in hematology, which is a central identity of the company, we're working on several targeted treatments for MPNs. 989, of course, we'll be presenting data in about a week, and we'll be moving that into Phase III in 2026. In solid tumor oncology, I think we've systematically and quietly built what could be a high-impact oncology program with G12D in pancreatic cancer, TGF-beta by PD-1 in colorectal cancer and CDK2 in ovarian cancer. And those programs are starting to declare themselves right now. And then I&I, we have an oral JAK inhibitor that's being developed for 3 different indications: hidradenitis, prurigo nodularis and vitiligo. And we don't have to be perfect with this pipeline. But if several of these projects are successful, it will contribute substantially to that base business I talked about. And then the third part of the solution is business development, which we would use to extend our core in 1 of the 3 verticals: hematology, oncology and immunology. And as I mentioned, we think about a profile where the company has the potential once we get past Jakafi to grow at, let's say, a 15% to 20% 5-year CAGR. We have multiple products, 3 to 5 products with revenue potential of $1 billion or more. And importantly, minimal LOE exposure at that point because the products that we're advancing through development right now have strong patents and long periods of exclusivity and then ultimately run a business with a healthy operating margin, call it, north of 30%. That's the profile we're building. I think there's a lot of substrate in the company. We don't have to be perfect, but we do have to execute, and that's where our focus is right now.

Okay. That's a very good setup. I guess maybe just a few questions on Jakafi, just to level set and then we can move on to the list of very interesting topics you outlined. So can you talk about the once-daily formulation and how that may help you and where that stands in terms of readiness for launch?

Yes. We expect to launch that in the middle of 2026. And you can look at analogs for these XR conversions. There's a long list of them, as you probably know. And the range can be pretty wide. It can be as low as 10% and as high as 50% or more. We estimate we'll convert 15% to 30% of IR patients to XR, a more convenient form. Let's take the midpoint of roughly 20%. So XR has the potential to preserve almost $0.75 billion in Jakafi sales as we go through the 2029 period. Two things drive conversion. Well, 3 things. First, you have to have a good product, and it is a once-a-day version. Second, you need a sales organization, which, as you know, ours is wired into the community, the medical community. And then you have to achieve formulary coverage at a price that makes sense for the PBMs and health plans and makes sense for Incyte. And I believe we can do that. And that will be an important contributor to the sort of base business as we transition away from Jakafi.

And beyond the convenience of the once-a-day, is there more to the pitch? Or is that the essence of it? Or is there some -- are there additional benefits like, for example, less side effects or other aspects that are helpful?

Yes. The approval will be based on bioequivalence data. So it's really for a symptomatic condition like MF or PV or GVHD, compliance is important. And so this is simply moving from twice a day to once a day.

Okay. All right. Well, you mentioned 989 in your earlier comments. So maybe we could start there. Tell us a little bit about this target, this mutant CALR antibody. What is the significance of that? And you mentioned the data is coming this weekend. I'm not sure the exact time, but I'll be at ASH, so I'll check it out. So just tell us a little bit more about how you see that opportunity.

Okay. Pablo, do you want to take that?

Sure. So just to remind everyone, 989 is our mutant CALR antibody. We developed that internally based on our understanding of the biology of MPN, which I think is one of the many strengths of Incyte of the discovery organization. The molecule entered the clinic about 2 years ago and at EHA in June of this year, we presented data for the first time in patients with essential thrombocythemia. About 25% of the patients with ET are mutant CAR positive. MF is about 35% of the patient. So the data showed very clearly at EHA, a rapid normalization of platelet counts in patients with ET, which is the key goal of therapy in this disease is to normalize the platelet count. That leads to improvement in terms of rate of thrombosis and/or bleeding that are related to some of the interventions that are used in patients with ET. The drug was also well tolerated. At the time of the EHA presentation, only one of the patients had discontinued due to an adverse event. So we're very happy with the initial efficacy and safety that we showed. That data set is going to be expanded at ASH next weekend. 3 abstracts that are going to be presented in more detail have been made public. In ET, an update on incrementally more patients, longer follow-up, showing consistently that the results that we presented at EHA are evolving well. In other words, normalization of platelets, well tolerated, minimal side effects, minimal discontinuations due to adverse events. We're also going to present for the first time data in myelofibrosis, which obviously is a critical component of the strategy. The abstract shows very clearly that 989 in patients that are either ineligible, intolerant or did not respond to Jakafi produces, I would say, impressive effects in SVR35, shrink in the spleen, symptom improvement and very importantly as well, anemia improvement in more than half the patients. Anemia responses that it's either an increase of hemoglobin more than 1.5 grams or conversion to transfusion independency. We also have data in the abstract that will be updated at the meeting, combining 989 with Jakafi in patients that are suboptimal responders after at least 12 weeks of therapy with Jakafi. And again, in that group of patients, there's improvement in terms of spleen response, there's improvement in symptoms as well. Now a very important part of the story is in the third abstract, which is translational data from both studies that show convincingly that 989 not only leads to clinical benefit, as I described, but it has a disease-modifying effect. What does that mean? It means that in the compartments where these diseases are, which is the bone marrow and the peripheral blood, there's a reduction in the mutant CALR-positive megakaryocytes in the marrow, early progenitors in the blood as a result of which the VAF, the variable allele frequency goes down in these patients. That is telling us that 989 is fundamentally reducing the burden of the disease. In turn, when that happens, the normal clone, the wild-type clone is increasing, which is why the anemia is getting better and these patients are overall improving in a number of ways. All this picture will be made more clear next weekend. We'll have these 3 presentations I described, and we'll also have an investor event where we'll go over this into more detail. I believe that is on Sunday afternoon.

And I would just add, if we can replicate the data that we produced in Phase I and Phase III, 989 has the potential to replace Jakafi, both in ET and MF in total.

Yes, that was sort of getting to my next question. So yes, so you haven't specified what -- you mentioned both the post-Jakafi setting, you mentioned the combo. You didn't specifically mention frontline in what you said, but I think that's got to be in the strategy somewhere?

So yes, of course, it's ongoing already. We are treating naive patients. We're randomizing to 989 versus 989-Jakafi. The data will not be presented next weekend, that data will be presented at some point in 2026. It's an important part of the strategy. You will see, however, in the single-agent cohort that we're going to present at ASH, there's a group of patients that were put in 989 because they are ineligible for Jakafi. Those are Jakafi naive patients. And you will -- it's a small group, small sample size, but you will see that data at ASH next weekend. And it will give you an idea of what the drug can do in first-line, even though it's arguably a first-line population with a little bit worse prognosis because it's ineligible for Jakafi, which probably means they are anemic or thrombocytopenic. But you'll see that data.

And the -- but then getting to sort of the bigger strategy as far as where you would initiate a Phase III, would it be sort of a multipronged strategy where you go into some more -- one or more of these settings? Or of course, you've got the IRA considerations in terms of staggering. So talk a little bit to the extent you can base it.

Yes. No, it's a very important point. Let me take a step back for a second. Our goal -- stated goal is by the end of the decade, early next decade is to have a targeted therapy for every patient with MPN, ET, MF and PV. So this is the first step. And you're right, we're not going to sequence initiation of trials. They're going to be a little bit staggered because the data in ET became clear faster. So that's moving a little bit faster. But we are -- 2026 is a year where we're going to implement one or more Phase III trials in ET and MF with 989. The first one will be second-line ET. Again, we have all the data we need to make that decision. Regulatory interactions have started. That will be implemented as early as possible in '26. Over the course of the year, we'll move forward with second-line MF and first-line MF as well. This precise timing depends a little bit on having the necessary data to have the conversation with FDA about the dose selection and about the safety. Second line at ET and second-line MF are pretty straightforward. It's single-agent 989 control arm is well known in ET best available therapy. In MF is best available therapy, a range of medicines that have been approved, none of which work very well. First-line MF, there's 2 different options. It's either single-agent 989 or 989 plus Jakafi or a 3-arm study with both with the Jakafi control arm. As Bill pointed out, when you look at the data in the abstract in a population that is mostly Jakafi exposed, the data already looks very promising as a single agent, stacking very well with Jakafi and first-line. So we need more data, but that's basically going to be the evolution in 2026 on how these trials are going to be rolled out.

And how are you competitively positioned with this particular target? Are you unique in having this construct? Or are there others that are doing things with slight variations?

As far as we know, there's a recent announcement. There's one competitor is not in the clinic yet. So it's, I would say, 3 to 4 years behind. So we have a strong lead. This is a space we know well. We need to execute. We need to execute flawlessly and rapidly. And if we do that, we're going to be in good shape. The drug works. The data presented today, I would argue is compelling. We just need to roll out those Phase III trials as fast as we can.

Okay. All right. So we look forward to seeing that, and we'll check out the detail you mentioned on the Jakafi ineligible. So quickly on ruxolitinib, the Opzelura, the cream, if we could ask a few questions there. Just talk about the growth of the product and how you see it evolving? Where do you see the most uptake?

As a base case, on a global basis, Opzelura finished the year at roughly $650 million in sales. Over the next 5 years, it has the potential to grow at a 10% CAGR. So 2x this business between now and 2030. There will be 3 sources of growth. First is just increased penetration of the U.S. market. There is, as you probably know, a migration from topical corticosteroids to nonsteroidal topicals. And Opzelura having one of the larger prescriber bases and extensive formulary coverage is a big beneficiary of this market growth, which I think will finish the year at roughly 20%. That's number one. Number two, we could get potential indications for HS and PN for Opzelura. That's number two. Number three is international growth. We expect to get an approval for Opzelura in moderate AD in Europe in the middle to the end of 2026. And if you take a look at the results from the moderate AD study was TRuE-AD with Opzelura, they were pretty remarkable. We had 70% of people achieve an EASI75 60% of people had itch relief at 8 weeks. I think 30% of people had each week -- itch relief in 2 days and 15% had itch relief in 15 minutes. And so it's arguably the most effective topical on the market, both in the United States and internationally. And that European business will be an important driver of the overall growth of this product between now and 2030.

And that submission is based on what set of data? Is it the U.S. data that you -- or did you do additional studies to support the Europe work?

So the recent data that Bill mentioned was designed specifically to address the European market. There's a population of moderate atopic dermatitis patients that are considered eligible for Dupi in Europe. And we run the study specifically in that population that we hope will lead, obviously, not just to approval, but to favorable reimbursement in Europe.

Okay. So you would expect the typical pathway, the CHMP opinion in next -- sometime in the first half of next year or approximately?

Middle of next year.

Okay. Okay. And do you speak about the split in terms of the revenues on those different indications on vitiligo versus AD?

Yes. Roughly right now, it's 60-40. So as I mentioned, in AD is the larger market, growth being driven by the migration of steroids like we talked about. And then on the vitiligo side, the key with vitiligo is medicalizing the condition. And we've done an excellent job at capturing those patients with vitiligo who are seeking treatment. But the key to success in that market, and this usually takes more time is to increase the diagnosis and treatment rate, which is an ongoing process. We have a fairly sizable consumer campaign in place. I'd expect that split to stay 60-40 with both indications, both in the United States and internationally contributing meaningfully to the sort of double-digit growth rate that we talked about.

And I assume that kind of growth you talked about the 2x-ing by 2030, 10% CAGR, does that factor in some of the competitors? Because there are some other products that are novel mechanisms that are topicals, I believe, like the PDE4 inhibitors, for example, do they -- you factored that in clearly?

You do. It's not a winner-take-all market. If you were dealing, for example, in a category where the growth rate on the year-over-year basis was neutral or a category that was so well established that was declining, it may be a market share of battle. But there are plenty of patients out there that can benefit from Opzelura as well as these other topicals. I would say this, it's really tough to beat the data that we've produced on Opzelura, but don't see it as a fight to the death and our projections take into consideration that there are alternatives. I think one of the real strengths of Opzelura is we have almost 20,000 prescribers in the United States. That is a prescriber base that isn't matched by any other topical. We also have extensive formulary coverage, both on the commercial side as well as on the Medicaid side. And I wouldn't say we have a moat around this business, but the fundamentals of Opzelura are in a very strong position. We just need to execute, and we shouldn't be impacted negatively by competition. They'll have plenty of opportunity, too.

Well, you're doing a very good job on the DTC because I see the ads on CNN. My phone probably is plugged into the TV. So it knows I'm a biotech analyst.

Just make sure you go to the pharmacy and get some and pay full price.

So then moving on to other topics. So to povo, there, you're preparing to submit very soon to the EU, yes. So can you just talk about the steps there? And then what the pitch is as far as a strong statement on efficacy for HS.

Great. Do you want to talk about the EU submission?

Sure. So the EU submission is in. So...

It's in. Okay.

It's in. So that's done. Now we're working on the submission for the U.S. If you remember, we said earlier this year, we needed 52-week safety data was requested by FDA for the initial submission for povo. So basically, it was about waiting for that. The submission will go in early 2026. We're going to request priority review. We may or may not get it depending on that. The approval will be the late '26 or early '27 followed by the launch. So that's HS. As you know, we think we have a very strong data set here. It's going to be the oral convenience of povo. And aside from what we think are very competitive results on HiSCR 50, 75, 90 and 100, what povo does very well is a very rapid pain improvement and very important reduction in number of flares. And when you look at the data from broad databases, patients with HS, the #1 complaint is pain. About 80%, 85% of patients have some degree of pain. And Povo basically shows that when you -- at long-term follow-up, 60% or 70% of the patients have either no pain or minimal pain on povo. So we think that's going to be a really important differentiator from our competitors. So the goal now is to get the U.S. submission in as soon as possible. And then obviously, the team will prepare for the launch.

Okay. And if you could maybe just talk a little bit about the market and the untapped opportunity in HS. How big of a product do you think povo could be if everything goes according to your projections?

Yes. Look, I think there's a feasible path to north of $1 billion across HS, PN and vitiligo. I believe HS has the potential to be the largest. There's a lot of estimates out there on the size of the HS market. Based on epidemiology data, we see that number as a base case at about $5 billion, people who are eligible or would be eligible for an advanced therapy, whether it's an oral systemic or a biologic. And the question is what percentage of these patients can we capture as part of the introduction of povorcitinib. It's largely a category that's being managed by antibiotics on one side and by IL-17 and TNF-alphas on the other side. Our strategy is to capture patients at 2 critical inflection points. after antibiotic, but before a biologic or post-biologic. And that's what our data set is in, in both pre- and post-biologic patients. And as Pablo said, the numbers across the board on skin clearance and pain are very good. We had a dt100, draining tunnels 100 clearance of 50%. And so this is a very, very good product. Layering in prurigo nodularis, that's an itch disease. You could argue it was made for JAK inhibitors. And if you look at our Phase II results in terms of itch relief, roughly 50% of patients achieved it on the NRS4, which is really impressive. And again, a rapid onset of effect. You start to see separation between povo and the control group in about 10 days. And so that will be an important contributor to sales. The PN market is a little smaller than the HS market, but there's still probably a $2.5 billion, $3 billion category for advanced systemic therapies. And then on vitiligo, the key there is it opens up roughly half the market patients who have a BSA of greater than 5%, where a topical like Opzelura is just a little less practical. And this will be about getting the data into the market, promotion, securing formulary coverage, basic launch execution, and we start probably in the first quarter of 2027, assuming a standard review with povo for HS.

And -- but you'll have 2 important data sets, if I'm not mistaken, next year, Phase III data sets for vitiligo and for PN.

That's right. We'll have the vitiligo data set sometime in the second quarter and the PN data set sometime in the fourth quarter.

And how do you see those? I mean the expectation is based on the Phase II data, based on the strength of the data in HS that those are in good position to work? Or what do you need to see on those to be very confident in a strong profile?

Yes. I think if you -- look, we know what HS looks like, obviously. If you take a look at PN, if we can replicate or get close to our Phase II results, we have a real product there. And as far as I can tell right now, we'll be the only oral JAK approved for PN. Obviously, Galderma has done a really nice job with it Nemluvio. It's a category of patients where there's significant unmet need. And so that's the target. And then as it relates to vitiligo, we have a lot of experience in that category. I think our data are going to have to match what RINVOQ has and Pfizer has a product, too. But right now, all 3 programs, I mean, there's always sort of -- you got to get these Phase III studies done, but it's a somewhat derisked program in terms of what we expect from the product.

Okay. And just sorry for a basic question since we don't formally cover you at the moment. Povo, so that's not something that you could use as a Jakafi replacement in those settings. Is that correct? It wouldn't -- there's a reason for that.

It's a selective JAK1 inhibitor.

Okay. So it just wouldn't work.

Jakafi is a JAK1/JAK2 inhibitor. It's interesting because the JAK2 effect obviously is more relevant to MPNs. The JAK1 effect provides a broad anti-inflammatory effect, which is one of the reasons why Jakafi improved symptoms so quickly. But povo was designed specifically as a JAK1 highly selective, highly potent inhibitor, arguably the most selective JAK1 inhibitor out there. And on top of that, and we've shown this recently, has very high concentrations in the skin. The PK of povo in the skin basically replicates the curve that you see in plasma, which is one of the reasons why we think it works uniquely well in some of the diseases we're discussing.

Okay. I'm glad I asked for that clarification. All right. And now for one that we are very familiar with since we cover Syndax, Niktimvo, axatilimab. So that launch has done exceptionally well. So maybe just tell us a little bit more about how you're investing in that asset and where you see the growth. Obviously, there were royalty partners that were very interested in that asset and have made a big bet, just on the third-line opportunity, let alone the other work you're doing in the earlier lines. So maybe you could kind of walk us through your strategy overall for the program.

Yes. The launch has gone extremely well, as you said, partnership with Syndax has been excellent. We'll finish the fourth quarter annualizing north of $200 million in sales. So that is a very, very good start. I think Niktimvo is differentiated in several ways. First, mechanistically, it targets CSF1R Second, it covers macrophages and fibrosis. Third, very high response rate. And I think fourth and importantly, what we hear more from BMT centers every day is that it retains its activity after Jakafi or in a heavily pretreated population. One of the most encouraging findings since the launch is that 70%, 80% of people who were started on Niktimvo in February 2025, the launch month, are still on therapy. And so that persistency is probably the most concrete evidence of how the real-world experience is standing up to the clinical trial experience where the results were very, very strong. If you look at the adoption curve over the past 12 months, it looks like it's right on top of Sanofi's Rezurock. It is a new launch. It can be unpredictable. It's still early, but we like everything that we see right now. I think the broad organ control that it provides, liver, lung and skin is also a differentiator. And so we're really leaning into this. And it's an important product for Syndax, of course, and it's a very important product for Incyte.

Okay. And do you want to talk a bit about the studies that you're pursuing in the earlier lines. There's a few, the steroids and then with Jakafi?

Sure. So we're doing 2 -- the goal here is to move Niktimvo to first-line treatment of patients with chronic graft-versus-host disease. That's where the bigger gains for patients are going to be and obviously, it's a much bigger market. We're going to present at ASH next weekend data from the combination -- safety data from the combination of Niktimvo with Jakafi. That's a very important first step to show that these 2 drugs can be given together. That was the first step that we set out to do, and that will be followed by randomization to move this to first line. And when you talk to transplant physicians, they tell you one of the key things they want is a steroid-free regimen for these patients. You have to remember, chronic GVHD is usually in the setting of prior acute GVHD, which is also managed in part with steroids. So these patients are on steroids for long periods of time and getting them off steroids is a key goal. So we have high hopes for this regimen, combination of the 2. There's mechanistic reasons why they should work well together. One is more T cell directed. The other one is obviously CSF1R antibody. So that's an important part of the story. The other is a more traditional approach, which is to take the most commonly used drug in first line, which is steroids and combining with Niktimvo. That Phase III study is also ongoing. Those 2 will potentially be the way we expand the label into first-line use.

Okay. And have you provided any time lines on readouts for those? Or those are just booting up now?

We -- the steroid one is ahead. We haven't provided a detailed time lines. I mean these studies take chronic graft-versus-host disease is not a super common disease. So enrollment sometimes takes a little bit longer than what would like. I would say towards the end of the decade, earlier, probably '28, we'll have some of the data that we need to expand the label potentially. We need more clarity as the studies progress.

The key here is we have 2 shots on goal because if one of those studies hits, you roughly 2x the addressable population. And so these are really important -- important for the medical community, too, that are looking to, as Pablo said, migrate from steroids.

And what are the data points or proof points that would support working in those frontline either combination? How much evidence is there? I mean it's a good design that the study should be run. I'm just curious what -- where are you getting the confidence that it's likely to work? Or is one more likely to work than the other?

It's a really good question. Look, I think it comes down to mechanism. In general, chronic graft-versus-host disease is a very complex disease biologically. We know that if you remove all the T cells from a graft, you reduce dramatically eliminate graft-versus-host disease. That's known. Obviously, the problem in that case is that you have increased risk of relapse. So the T cell component of the story matters. Now what the data from the AGAVE trial has conclusively shown is that it's an important component of the chronic manifestations, particularly fibrosis in some of the organs that is driven by macrophages. And that is why Niktimvo is so important. So in a way, by combining the 2, and this is the best expansion I can give you today since we have no clinical data, is we calm down the T cell response that continues to damage tissues. But at the same time, with Niktimvo, we allow those tissues to heal by impacting CSF1R. I think when you put those 2 components of the story together, mechanistically makes a lot of sense that the drugs will improve the treatment together.

Okay. And then you mentioned briefly Rezurock. I mean that's a different mechanism, right? So like the read-through there, I assume the answer is not much read-through, but anything else you want to say?

Well, I think I know what you're referring to. I think mechanistically, it makes a lot less sense to combine Rezurock with steroids or with Jakafi, right? Because you're sort of going after the same biology. It's not identical, but you're going to the same group of cells. I think the combination with Niktimvo makes a lot more mechanistic sense, to be honest with you. So I don't think there's a read-through from that.

Yes. Okay. Ex-U.S., is there a plan? Or what is the thinking there?

Ex-U.S., we've been pretty open in the past that it was going to be really hard to get approval and reimbursement in Europe on the basis of AGAVE. So the approval in Europe will have to depend on one of the first-line studies.

Okay. And then just like overall for this franchise, the profitability, can you talk about the profit margins? And you mentioned the BMT centers. I'm also just curious, anecdotally, what are you hearing in the field as far as the experience given what you said before about the percent that are staying on it for as long as they are?

Yes. The report from BMT centers is very, very positive. Even though it's a weekly -- excuse me, twice a week -- twice a month IV, it fits for most patients in their follow-up routines, labs, clinical visits, other supportive care that they may be getting. Tolerability is excellent. I think that sort of speaks for itself in the persistency rate. For those that aren't going to the centers, we have home care solutions, infusion center solutions. So everything we're hearing so far is very, very good.

Okay. You mentioned at the top of the hour, the solid tumor work. So I want to make sure we have time to talk about both of those programs. So let's start with KRAS. You just had some Phase I data, I think, at ESMO. So tell us more about the KRAS. Is it -- what's the exact mechanism? It's -- this is a G12D, but is it -- the hitting the on state, hitting the off state, both. We'll talk about those details and how -- and there are quite a few of these in development. And as you know, so how does yours fit in?

No, it's -- so yes, it's both on off. But I just want to make sure we don't forget about 1/3 of my solid tumor oncology children. We have a CDK2 inhibitor right now initiating pivotal trials in platinum-resistant ovarian cancer, and we intend to move it to maintenance after chemotherapy Avastin -- in combination with Avastin, so that's moving forward. That's on the basis of data that we presented last year at ESMO and we've updated recently showing the competitive response rate in patients that are Cyclin E1 overexpressers with platinum-resistant ovarian cancer. So that's ongoing. So you referred to the 2 programs we provided an update at ESMO. We have a KRAS G12D inhibitor. We showed data at ESMO, both efficacy and safety that we think are very competitive. We are fully aware of the intensive competition in this space. There's particularly one company that is ahead of us. However, what we have -- our plan is to combine with chemotherapy, and we've done that work already to show that we can combine our G12D inhibitor with both types of chemotherapy used in first-line pancreatic cancer, which are gem/nab or gem/Abraxane and FOLFIRINOX. And in the U.S., about 60% of the patients get FOLFIRINOX, 40% gem/Abraxane. Worldwide, that's about 50-50. So we think it's important for physicians and for patients in the long run to have a G12D inhibitor that can be given with both main types of chemotherapy. That's a key difference. That trial will be implemented in early 2026. It's a race with our competitors for first-line pancreatic. We think we can execute well, and we think we have a differentiated plan here by being able to combine with both types of chemotherapy. Obviously, first-line pancreatic is a very large market. So that's the key -- that the central component of the strategy of our G12D. We have other things we're thinking about doing, particularly combination with Erbitux, which we think could be important because we have seen no RAS with our product as opposed to what some of our competitors have seen with pan-RAS inhibitors. TGF-beta PD-1 is an interesting story because it's the only at this point, as far as we know, TGF-beta receptor 2 by PD-1 bispecific. And what we've done is we've designed this to block the TGF-beta receptor 2 only in cells that express PD-1. By doing that, we have so far eliminated the TGF-beta-related side effects that have plagued TGF-beta approaches in the past. What we showed at ESMO was the best response rate ever reported with a PD-1, PD-1 like in MSS colorectal cancer. 15% of the patients responded, including those with liver mets, so we're very excited about that data. We've combined the bispecific with chemotherapy with FOLFOX-bevacizumab, and we're moving straight to first-line MSS colorectal. We think that the paradigm of taking responses from late-line therapy, combining with chemotherapy in early lines with the PD-1 plus had been done before. We need to execute on that trial. We think that's an enormous market opportunity. Obviously, it's 80%, 85% of colorectal cancer patients. I gave you the very rapid blurb there where we are with solid tumors.

And so this is one where both -- it must bind both. That's the point. Is that right?

It has to bind PD-1 for the TGF-beta receptor arm to engage. And that's key because that way, you only block the beta receptor 2, the TGF-beta with PD-1 is present. So ideally, you focus that on the tumor microenvironment. And when we showed the dose escalation data, if you exceed the recommended dose, if you get to 1,500 milligrams, then you start to see TGF-beta related side effects. But up to 900 milligrams every other week, you just don't.

Okay. And then this -- the logical strategy question is, are these getting equal priority? Is one more of the favorite than the other? CDK2 sounds like you really like that one a lot, too. Well, you got already in Phase III there.

So I want to make sure we didn't forget that one. But look, I think CDK2 enters a very competitive space versus ADCs in ovarian -- so we're aware of that. The efficacy that has been shown with ADCs has higher response rates than we have. We have the advantage of an oral and a very well-tolerated drug. So we think it's important, particularly in maintenance. So we're executing on that plan. On the other 2, it's about executing on pancreatic first-line, colorectal first-line. Those are the central focus. We're discussing whether there's a path to expand from that. But the focus right now is to execute on those 2 trials.

Okay. And then just sort of last portfolio question. You've got a lot of things going on and a lot of interesting assets. Is there a BD pipeline that you're looking at for other opportunities? Or do you feel you have enough on the plate at the moment? What else could we look forward to?

Yes, it's a good question. It will be used to extend the core to supplement what we're doing internally. We'll be focused on hematology, oncology and I&I. I think the most important part of BD is to have a good framework, first and foremost, and then a lot of throughput so that when you do something, you know what the opportunity cost is and you know if it's right. And it's about calling balls and strikes essentially. And it will be part of it. Right now, we're focused on the 7 projects we just spent time talking to you about.

All right. Well, we'll be at ASH. We'll look forward to the data, and thank you both for joining.

Great. Thank you.

Thank you. Thanks, everyone.