Good morning, everyone. Thank you for joining us. It's my pleasure to introduce the Incyte management team. With me, I have Bill Meury, CEO, and Pablo Cagnoni, President and Global Head of R&D. To start here, Bill, could you give us an overview of where the company stands today, including your core franchises, Jakafi and OPZELURA, the pipeline priorities, and just-
Sure.
-how you're thinking about, big question-
Yeah.
-outlook and strategy for the company as we look to the next three years?
Sure. Big picture, we're transitioning Incyte from a single cornerstone product to what we believe will be a portfolio of growth drivers. We think about the business across three dimensions, as you know, hematology, oncology, and immunology. We also break the business down into three parts, a core business, a pipeline, and, of course, business development. When we look at our core business today, all the products ex-Jakafi, that business will finish this year in the range of about $1.7 billion, up 30+% versus prior year. It's relevant because by the time we hit 2030, the transition, we estimate that core business will be doing about $3 billion- $4 billion. Right now it's funding the pipeline, and it will set a floor. We look at the pipeline.
Today we have eight assets, including VGA039, the Star deal, that have the potential, on an unadjusted basis, to 2x the company. They're supported by 14 clinical studies, 15 clinical studies that will be underway in phase III. We don't have to be perfect here. The four assets that I think have a high PTRS will get approved and contribute meaningfully to the company are 989, our monoclonal antibody targeting mCALR, G12D, povorcitinib, and now VGA039 for von Willebrand disease. You don't need heroic assumptions, assuming we successfully complete the phase III programs, to get to a multi-billion dollar sales level with that group. You layer that right on top of the core business. Business development will be used just to simply strengthen, extend the core.
What happens is the pipeline becomes the core business, and we expect it has the potential to drive top quartile growth from 2029, 2030 out to 2030, 2035.
Could you touch on the business development side? You announced the transaction for Star Therapeutics yesterday. How are you thinking about BD from here and why Star? What are you solving for when you look at the overall pipeline, what are you adding?
Yeah.
As you go forward?
I'll start with your last question. What we're solving for is growth post-2029. When we looked at the Star deal, and I've said this a few times now, it was as close to a textbook example of the type of deal that makes sense for Incyte. It sort of checked all the boxes. First, it's novel. In other words, we're not dealing with incremental innovation. We're not in a situation where we're going to be maximizing marginal differences, or we're a late entrant. It has standard of care potential in von Willebrand disease. That's number one. Number two, it's in hematology. That's the central identity of the company. We have differentiated knowledge and capabilities there, and we have all the R&D and commercial infrastructure we need.
Number three, it has the potential to really move the needle in terms of our top line, and it could be highly growth and revenue accretive. It's in phase III, so the timing is right. We did a deal that was structured. The economics made sense for the seller, and they made sense for us. I think it's a good phenotype for the type of thing that we should be doing right now, very complementary to the business, the right risk-reward profile. We use only basically just over 20% of our go-forward balance sheet, so we still have flexibility going forward. Our view here is that we have a tight framework and criteria. If something is in the framework, we can act fast. If something's not, we're very comfortable being patient here, and that's how we're going to view it.
Great. Let's start with the myelofibrosis or the MPN business here. For Jakafi XR, you launched the drug last month, priced at parity with Jakafi, acknowledging your expectations that 2026 will primarily be focused here on formulary coverage. What are you seeing in these early days of launch? And what do you want to see over the coming quarters to give you confidence in reaching that upper end of your 10%-30% guidance range?
Yeah, it's a good question. As it relates to formulary coverage, I can provide an update. We're about 30 days in. Optum has added XR to formulary. CVS has added XR to formulary. 14 regional plans have added XR to formulary and four Medicaid states. As it relates to formulary coverage, we are off to a good start. Conversion or uptake for XR will be measured early and tied to formulary coverage. And we expect really a step change when you get to January 2027, and you're going to want to be converting at a point, a point and a half a month. That would be this working.
As it relates to what would get us to the upper end of the range, in which case we preserve north of a billion dollars in Jakafi sales, it starts with coverage and really just moving prescribers and patients to think about XR before IR. We have obviously a very large professional promotion effort in place. We cover all the major hematologist prescribers in the country. We also have a patient database, and we're able to communicate with Jakafi patients. As you know, with these launches, it's about execution. So far it's set up. If we're in the middle of our range, that's good. If we're at the upper end of the range, there's only upside in that.
Why couldn't it be higher than the range you've given?
When you're dealing with an XR conversion, remember, there's new patients and there's current patients. IR makes a great deal of sense for new patients. When you're moving someone off of a drug, IR to XR, when they're a current, that takes a little bit more time. I think there's a certain amount of inertia in the market that you have to recognize. Now, you can solve for that with a lot of activity, and I think that's what we're going to try to do.
Great. Should we expect you to disclose sales or other metrics over the near term?
Yes. We'll provide an update on formulary coverage, prescriptions, and you will see the sales. Right now, we have about $10 million- $12 million in sales today. I think by the end of the year, that number could be in the range of about $50 million-$75 million.
Right. Pablo, turning over to you on the mCALR program here. That program remains the primary focus from a pipeline perspective and revenue replacement strategy. Ahead of the upcoming presentations at EHA, walk us through where the program stands today and your level of confidence in successfully bringing this to the market in both the second-line and first-line settings in MF?
Certainly. We will have an update at EHA, as you pointed out. We'll have an update on the ET population, an update on the MF population, and a translational update as well. When you look at overall what this program is, let's start with ET. We'll present an update to probably around 100 patients at EHA. I think what consistently we're seeing is very high rates of complete hematologic response, regardless approximately 70% or so. Patient in Type 1 patients, that number is even higher. It's probably around 90%, and it's lower in patients with non-Type 1 mutation. We've known that now for quite some time. Very importantly, the safety profile of 989 continues to be very clean. A lot of patients, almost all the patients are still on drug. It's a very low percentage of patients that had to discontinue.
In second-line ET, we have alignment now with FDA, and we're in the process of launching the first pivotal trial for 989. I'm highly confident that in second-line ET, when you look at the historical numbers for post-hydroxyurea interventions in the 30%-40% complete hematologic response, and not a lot of them with durability. The data that we've shown for 989 gives me a lot of confidence that this medicine will have a positive second-line ET trial, and eventually we'll get it to market. The goal here is execution in second-line ET, getting that off the ground, and enroll as fast as possible. On the MF side, you have data in the abstract, and we'll update it during the meeting, and there's two separate important messages there.
In this update, it's not a true frontline population that will be updated at ASH at the end of the year. What you'll see is post-Jakafi or post-Rux patients and a group of patients that were what we call ineligible for Jakafi. Let's start with the first one. We have SVR35 rates that we reported before, stranded approximately the same percentage points here. They're lower, but overall, the data looks consistent what we've shown in the past. Importantly, the anemia data continues to get better. When you think about what 989 does, which is basically normalizing the hematopoiesis in these patients, basically suppressing, eliminating the malignant clone, allowing the benign, the wild-type cells to grow back. That's why the anemia continues to get better. It's getting in the 60% range or so, which we think is pretty impressive in this pre-treated patient population.
The other thing you're going to see is that in the SVR35 rates are very high, that gives us a lot of data that we'll have later this year about the possibility to accelerating the development of 989, both in second-line MF and first-line MF as well. In second-line MF, we're already in the process of starting conversations with FDA in order to build a new framework, a new regulatory framework for these patients, which will be a composite endpoint, which will incorporate some of the things we're talking about, including some aspect of this normalization of hematopoiesis represented by anemia. We'll see how those conversations go. If we need to go with SVR35, I'm confident we can get the trial design with a high probability of success anyway based on the data that we already have.
The next step is, as quickly as possible, once we have all the data in-house for the first-line MF population, is to launch the first-line MF trial, which we probably will initiate early in 2027. That's the goal. By this time in 2027, probably earlier, we'll have three pivotal trials ongoing with 989. Second-line ET, second-line MF, and first-line MF. That's the goal.
Got it. If XR could get you to a billion at the high end of the range. What does mCALR give you in terms of revenue replacement of Jakafi?
Yeah, it's a good question. We'll take ET and MF, which both can contribute equally to what's called the peak sales potential of this product. In ET, the best way to think about it, there's 20,000 people with the mutation and ET. Half of them, roughly 50%, are not fully responding to hydroxyurea, not because it's not a really good cytoreductive agent, but because people can't get to the therapeutic dose due to toxicity. That's 10,000 people. At biologic pricing, let's call it $250,000 a year. That's a $2.5 billion TAM. What percentage of that segment does 989 get? If it gets all of it, then it would be a $2.5 billion opportunity. If it gets half of it, we still have $1 billion + coming from ET.
Another way to think about it is 5,000 people in the United States have the mutation and are resistant to hydroxyurea, which is a negative prognostic indicator. You probably get most of those. Again, you kind of get to a billion dollars, multiple roads there. That's half the product. The other half is MF. I think the most important point of what Pablo said is that we're very encouraged. We can't call it yet. We'll know more at the end of the year at ASH with the frontline performance of 989. When it's used earlier, it does better, especially in a Type 1 population. Type 1 patients are 75% of MF. There's 10,000 people with the mutation and MF. That's a $2.5 billion segment. If you're in the front line, you get more of it. If you're in the second line, you get a little bit less.
Either way, I think both indications can get 989 into that $2 billion-$3 billion range. That would be a real success for us.
That's great. Pablo, going back to you here. You have an end of phase II meeting with the FDA later this summer to discuss the potential for a new composite endpoint for a pivotal phase III here in second-line MF. Walk us through the strategy here and how critical this is to phase III success in both the second-line and front-line? And what the implications for the field and competitors are if the FDA does move forward with this, and does it really set a new bar here?
The argument here, which I think it's important to understand, is the reason why SVR35 and TSS 50 are there is simply because 15 years ago, 16 years ago, it was clear that Jakafi was very good at shrinking spleens and improving symptoms. They were put there, and everybody has had to use those endpoints in MF since then. While 989 does shrink spleens and improve symptoms, and we've shown that data very clearly at EHA and ASH last year, it has a completely different mechanism and a different impact on this disease, which the term to summarize that I've used is it normalizes hematopoiesis. That's basically reflected in a dramatic improvement in anemia that we've seen that, again, we reported at ASH last year.
When you take that into account and about the fact that anemia, it's a better correlate of long-term survival in these patients that SVR35, you really reach a point that you say, well, it's time to figure it out how to incorporate this knowledge into a novel endpoint. This is, by the way, data has been generated independently of us. It's been published by a group of experts showing that other factors than SVR35 and TSS50 have better correlates with long-term survival in MF patients. That's the argument that we put together. Obviously, the data has been published. There's support from the scientific community, both in the U.S. and in Europe, about really redefining how these medicines are approved. If we can't get there with FDA, I'm confident an SVR35, TSS50-focused trial is still a trial we can win.
When you look at the comparable data in second-line MF in patients with no washout from Jakafi, the SVR35 to momelotinib in that group of patients is 7%. We've been reporting rates around 30% now since ASH last year, and you'll see another update on Saturday. That's still a trial we can win. We just think it's important to change the regulatory paradigm. If we have to stick with SVR35 and TSS50, we'll do that and still think we're going to have a way to run a positive trial.
Just on a related point, we've been monitoring the impact of mCALR on VAF, which has been fairly modest thus far in MF. At which time point should we expect to see this meaningfully improve, and how critical is it to the drug's long-term success?
Let's remember what VAF tells us and what it doesn't tell us, because I think it's really important. VAF in peripheral blood is basically taking a pool of cells, a highly heterogeneous cell population, and measuring the frequency of the variable, the different wild type and the mutated allele in that population. It's a ratio, and the important point there is in MF, the wild type population is smaller, so changing that ratio with a small population takes longer to grow. It's harder. Second, it's going to be a lagging indicator to what's going on in the bone marrow. In addition, VAF measures cells that are CALR mutated positive, but thrombopoietin receptor negative, and those cells are not affected by the antibody. They have to die on their own. They're not malignant, they don't lead to the disease, and they have to die on their own.
When you put all that together, we think over time VAF will continue to improve, but is a much lower indicator of what's going on. What we pay a lot of attention, and we'll update this at EHA, is the megakaryocytes in the bone marrow, which are the source of the disease. We measure CALR-mutated megakaryocytes and wild-type megakaryocytes, and we're seeing a shift. The mutated ones are going down, the wild type are going up. We look at immature cells in peripheral blood, CD34+ CALR-mutated cells in peripheral blood, and we again see those going down. The third, we see normal red cell progenitors in the bone marrow going up. All that is telling us the right things are happening. We look at VAF, the magnitude may be modest, as you pointed out, but almost all the patients are pointing down in that waterfall.
We're seeing that the malignant clone is going away as represented by that. I think over time VAF should continue to get better. We're not too focused on VAF. I know there's a lot of interest in seeing that. I would focus more on what's going on in the bone marrow and what's going on in the peripheral blood progenitors.
Great. There's an expanding competitive landscape that's playing out within MPNs, including J&J and Daewon for mCALR and Lilly and Ajax on the JAK inhibition side, where we've seen more data, I guess, per the EHA abstract and expect to see initial data from the mCALR programs over the next 12 months or so. What are you monitoring most closely from a competitive perspective, and how are you thinking about differentiation and positioning relative to these assets?
I'll just make a few comments and let Pablo expand. What we're focused on right now is our programs, obviously. As Pablo said, we have an opportunity by the middle of 2027 to have three phase III trials. I think as it relates to the other monoclonal antibody, thoughtful antibody design, no human data. Not a lot to say there. As it relates to the opportunity that Type II JAK2, I think that it's an apples and oranges comparison. One's a symptomatic therapy, optimizing or maximizing spleen volume reduction and symptoms versus a potentially disease-modifying therapy. I don't think it's an either/or. I think in a CALR population, if we can replicate in phase III what we're seeing in phase I, we have a solid path to build a very important product for us.
As it relates to the T cell engagers, more advanced disease, and it could have a role, and we have to focus on ours, not J&J's. That's my view.
Just to complete a couple of points there. Look, our goal, as we stated last year, is by the end of this decade is to have a targeted therapy for every single patient with MPN. In order to do that, we need to execute on the current plan. We have the understanding of the space. We know this biology. We have the right team in place. We have these medicines that we've been talking about in the clinic and launching pivotal trials as we speak. We also have a number of next-generation programs that we're working on. We're going to continue to innovate in the space. We have the critical mass in place to continue to expand our presence in MPNs, and we will. Obviously, you always follow your competitors. You don't underestimate anyone, but our goal and our focus is to execute on the current programs.
Just the last one to round out the questions on MPNs here. Where does your mutant selective V617F program stand, are you seeing encouraging signals with new solid dispersion formulation, and when should we expect a go, no-go decision for this lead asset?
INCB160058 has been a challenging program. The first thing I would say is we remain absolutely convinced that this mechanism will work. If we hit V617F hard enough, we will get positive clinical readouts in patients with V617F mutated MPNs. The program has been challenging. We've been generating data. The data right now are not trending in the direction that we would love to see. We will reassess the program later this year, then we'll make decisions. We have next-generation programs that look much better, molecules that look much better than the lead. We also have the option agreement with Prelude. We're following, we're tracking their progress, and we can execute the option whenever we think it's the right time. We're unlikely to present meaningful data later this year, but we will continue to update you as the program progresses.
Bill, moving over to povorcitinib here, you have framed this opportunity as a $500 million-$1 billion peak sales outlook in HS across both pre- and post-biologic patients. Walk us through the launch strategy and how you plan to target both of these subpopulations? And what needs to play out to reach that upper end of the guidance range?
Yeah. We do believe, given the data set, which 70% is in a pre-biologic population and 30% is in the post-biologic patient population, that we can capture or garner utilization at both those inflection points. When you look at the data on povorcitinib and compare it to that of a biologic, you see HiSCR 50, 75, 90, 100, pain relief, draining tunnel clearance, flare control that rivals the IL-17s. I think it's indisputable. The one thing that a JAK inhibitor does is it relieves pain, I think perhaps as good or better, and it's definitely faster. There's no FDA-approved oral option. Someone gets put on or gets diagnosed with HS, they get an antibiotic or a steroid on one end, then they have to leap over to an IL-17. I think this will be an important treatment option for dermatologists and NPs and PAs.
The benefit-risk profile in HS, I think is very attractive. The most important part of what we're going to do at launch is to educate them on the data, of course, then garner utilization in both those places. You're talking about 150,000 patients who are diagnosed and treated, I think some estimates are higher, with HS that are not taking any advanced systemic therapy. There's only about 50,000- 60,000, which is growing on the IL-17s. HS is unlike IL-13-mediated AD or IL-23-mediated psoriasis. It's a multi-cytokine disease. JAK inhibitors are multi-cytokine inhibitors, so I think there's real potential here. The most important thing for us to do is to get trial at launch. If the drug performs in the real-world setting like it did in the clinical trial setting, I think it's going to be a needle mover.
From a payer perspective, is there any hindrance to really kind of dominating that pre-biologic setting?
Yeah. I think usually what you worry about in this situation is prior authorizations and steps through, for example, a biosimilar or Humira. It's really difficult to mandate that type of medical exception if the label doesn't. It is important that we have a label that covers both the pre- and post-biologic setting. If it was to happen and there were drug utilization management measures put in place, they wouldn't be widespread. They wouldn't be universal. I think more and more cross-subsidization and bundling agreements are less and less effective given the push for transparency. Even on the PBM side, they want to manage their budgets on a line item by line item basis. I believe there's a price point in the end that we can charge that makes sense for the PBMs and the plans and makes sense for Incyte, and we'll manage that during the launch.
Speak to your confidence here for expansions into vitiligo and asthma and PN as you look to growing this product further?
Very high confidence in vitiligo. We have the data. I think the key there, whether it's AbbVie, Pfizer, or Incyte, is you have to medicalize vitiligo. It has to be perceived, understood as a chronic immune disorder, not an aesthetic or a cosmetic problem. That does take some time, but its prevalence is very, very high. We know, given our experience with OPZELURA, what it's going to take to commercialize povorcitinib for vitiligo. That could be a quarter of a billion dollars that you're adding on. There is a bull case there where it's bigger just based on the prevalence numbers, but I think you have to be clear-eyed about where that category is in terms of diagnosis and treatment. PN is an itch disease. We'll have those data at the end of the year.
There's one thing JAK inhibitors do well, and that's relieve itch, and they do it fast. I think that is of equal significance to povo rcitinib as vitiligo is. I think those two indications could be $500 million , maybe a little bit more. As it relates to asthma, wait for the data at the end of the year. It's not in our model.
Maybe just a final question here. You continue to sound very confident regarding the profile of your G12D KRAS program and PDAC post the data that we've seen, not just from you, but also from competitors in this space. What drives this level of confidence, and how do you see the drug existing within the landscape with other therapies?
It's an amazing time in pancreatic cancer research. I mean, the data from Revolution Medicines was pretty extraordinary. Now, when it comes to specifically inhibiting G12D mutations, we think we have what looks in our hands, whether you want to call it best in class, as good as anybody else in class. We can debate that when we show the data. What we've been doing over the past few months is, number one, we've been executing on putting in place a frontline phase III trial of our G12D in combination with chemotherapy, both types of chemotherapy, FOLFIRINOX and Gem-Nab in previously untreated pancreatic cancer. The trial is getting off the ground, excuse me, is already enrolling patients and is going quite well. In parallel with that, we generated data, two cohorts or a cohort of 50 patients, give or take, half with Gem-Nab, half with FOLFIRINOX.
We'll present that data at ESMO, assuming it gets accepted, and we'll have a fair amount of follow-up in order to give you an idea of not just the responses, but the durability. We're very happy the way that data are evolving. Hopefully, you will agree when we show it later this year. What we've also done is combine our G12D with Erbitux, which is something that daratumumab, axicabtagene, can't do because of the rash. We thought that angle in colorectal cancer was very important. We've also combined it with chemotherapy plus Erbitux. All that data as part of a potential expansion into colorectal cancer will be presented later this year as well. We're really excited how the program is trending.
We really like the way the data are evolving. You should expect not just continued evolution in first-line pancreatic, but also an expansion of the program to other indications.
Great. Maybe just one last question. Anything else I did not ask about that you want to highlight as you look forward here?
I think on Niktimvo, which has become a nice incremental growth driver for the company, we'll have data at the end of the year looking at Niktimvo in combination with Jakafi, which would result in a steroid-free regimen for patients with GVHD. I think that is an important outcome to watch.
Great. OPZELURA seems to be on track.
OPZELURA looks good. The AD launch in Europe I think will be important to keeping that product on a solid growth trajectory. Also, we have a study with OPZELURA in HS that will report out in the fourth quarter, and there's no FDA-approved topical treatment. It would be for mild to moderate disease. Our phase II study, the HiSCR 50 rate in HS was 79%. Vehicle was high too. The phase III study, we're using a HiSCR 75 endpoint. To have OPZELURA as a topical for mild to moderate and to have povorcitinib for moderate to severe creates a franchise and a sequencing strategy that could be very valuable.
Great. Well, with that, thank you so much.
Thank you.
I appreciate the time.