Our first question today is coming from Marc Frahm from TD Cowen.

Congrats on the strong quarter commercially. Maybe this is mostly for Pablo. Just on the kind of CALR program and your regulatory discussions, can you maybe just review kind of what the major questions are still kind of awaiting resolution on that trial design in MF? How much of that is the endpoint, whether you can include something like anemia and some sort of composite versus how much of that is still outstanding dose selection work for particularly the type 2s? And might, on that latter part, that take a little bit longer for type 1s versus type 2s and lead to kind of different trial initiation time lines?

Marc, thank you for the question. So when we think about the regulatory path in MF, there's basically 2 paths, right? One would be the standard, which I think we all know about, which would include SVR35 and TSS50 as endpoints, or an alternative one, which will include other endpoints. And let me spend a minute on why we think the second is important to discuss with FDA -- we thought and still think it's important to discuss with FDA. 989 presented a completely novel mechanism of action, as we all know. And on top of delivering benefit, as we saw in the EHA data update that we provided, on top of delivering benefit on SVR35 and TSS50, it delivers an extraordinary benefit on improving hemoglobin levels in these patients. Most of the patients treated, whether it's first or second-line MF, show increases in hemoglobin that are clinically significant. In addition to that, there's clear evidence of what we discuss as disease-modifying evidence, including reduction of malignant megakaryocytes in the bone marrow, reduction of malignant progenitors in peripheral blood, et cetera. So when you put all that together, we thought, and still believe, it's important to have a constructive dialogue with the FDA to see how we can incorporate some of these endpoints that reflect the benefit patients receive from 989 and that reflect the mechanism of action of 989 that they need to be reflected in the clinical trial design. We have initiated those conversations with FDA. They're going well. They've been constructive. And as soon as we complete those, we will give you clarity on what the regulatory path will be first in second-line MF, which we intend to start this year. And then as a result of that, we'll continue the conversation with the agency on first-line MF, which we will initiate next year. At this point, our intention is to conduct a study in MF in all-comers, type 1 and non-type 1 patients. Potentially with a differential dosing strategy, not quite like in ET, because in ET, we have a dose escalation. The rapid normalization of platelets in ET allows you for a rapid dose escalation. In MF, we would start type 1 and non-type 1 patients at 2 different dose levels instead of doing the dose escalation. But that's where we are today with the planning of the study.

Our next question today is coming from Eric Schmidt from Cantor Fitzgerald.

Maybe a higher-level strategic question for Bill and team. Given you've just done the Vega acquisition, how are you feeling about the breadth and depth of your pipeline? Do you have more capacity? And is there some sort of a target R&D as a percent of sales level that you might want to be spending at as we go into the Jakafi expiration?

Yes, it's a good question, Eric. A couple of things. As it relates to business development and frankly, R&D, our job is to keep this product line and pipeline moving. And so I think you can never underestimate attrition in any business. And so we are actively looking at potential opportunities that meet or check the same criteria that Vega did. And I think that we have a very clear framework for doing business development. When we see opportunities that meet certain strategic and financial criteria, we can act quickly. Alternatively, if we don't, we're comfortable being patient. As it relates to R&D as a percentage of sales, I'd make a couple of comments there. We're not pursuing growth, one, at all costs. Alternatively, or on the other hand, we're not solving right now for a fixed margin percentage. What I will tell you is if there's any margin compression in this business, let's say, as we get to 2029, there'll have to be a clear and positive correlation with materially increasing the risk-adjusted value of our pipeline. And right now, every line item in our P&L is either absorbing, offsetting or directly funding the growth strategy. As you know, in SG&A, we're funding product launches. And as it relates to R&D, 80% of our investment is concentrated on what we think are really smart investments. And if any of the investments that we're making, if the facts and circumstances around those investments change or performance is not what we expected, we stop making those investments. And as we get closer and we have more clarity on our pipeline, where I think we're set up very well right now. I think when you look at the pipeline, there's 4 assets that have a high PTRS and the potential to deliver outsized returns. That's povorcitinib, 989, G12D and VGA039. Now that's not to say that there's not value in TGF-beta x PD-1 or CDK2, but the 4 assets I just mentioned have the potential to move Incyte way beyond Jakafi, which is ultimately what we're solving for. And so to wrap it up, 12 months of margin compression to set up 10 years of revenue and earnings growth, I think, is a smart calculation, and that's what we look at every day.

Our next question is coming from Tazeen Ahmad from Bank of America.

I wanted to maybe ask one quick one about the announcement you made last week about your global collaboration with Halozyme to use their ENHANZE drug delivery technology to help with 989. Can you maybe give us a little bit more color on what exactly you'd like to improve? And when you think this could move into clinic and we could start to see data using this technology?

Thanks, Tazeen. Pablo, why don't you set up where we are with the program overall and then get into Halozyme?

Certainly. I think let me remind you a couple of points that we've made, which are really important about this program and the subcu development. We have completed healthy volunteer work, and we are right now with the subcu -- existing subcu formulation in patients with MPNs. That's the status of the program. We have a clear path here to continue that program forward and by optimizing the existing formulation and the existing subcutaneous device for infusion, which is not a wearable. As we discussed before, this is something that patients will have to apply for 15 to 20 minutes every other week to deliver the desired dose. That path is clear. We have discussions with FDA on a bridging strategy for that path that I just described. We thought it was important to continue to add optionality to this program. As you can imagine, the conversations with Halozyme have been going on for quite some time before signature of the agreement. And they're not related in any way to any data that has emerged from the ongoing subcutaneous development. We thought it was important to have an additional option to improve flexibility and potentially to improve the patient experience when it comes to subcutaneous formulation administration of 989. So that's basically the plan we have in place. We're executing on the existing subcu plan with the existing formulation, and we're adding another option now with the ENHANZE technology.

Our next question today is coming from Faisal Khurshid from Jefferies.

Can you set expectations for the G12D update that you're going to have at ESMO? And can you possibly give us some more perspective on how you think about competitive positioning and how you see your opportunity to differentiate within the class?

Great. Pablo, do you want to take the first part of the question?

Certainly, thank you for the question. So when we think about 734, our G12D inhibitor, I think we are convinced we have in our hands a highly selective, highly potent novel medicine that combines well with existing standard of care, which, in first-line pancreatic cancer, is chemotherapy, either FOLFIRINOX or gem/nab. In that context, when we think about the development plan, our goal was to accelerate as much as possible development in first-line pancreatic cancer in combination with those 2 chemotherapy regimens. What we will do at ESMO is provide approximately 50 patients' worth of data, half and half with gem/nab and FOLFIRINOX, with a fair amount of maturity showing you where we are on efficacy and safety in that context. We think that's a really important derisking for the first-line pancreatic cancer strategy that we're pursuing. Now the first -- the Phase III study in first-line pancreatic cancer is ongoing. As far as we know, based on public disclosures, we are neck and neck with our competitors. We don't think we're behind, and our team is executing on that as fast as possible. Now let me add a little bit more context on the program because I think it's important, the breadth of how we're looking at this program in other indications. We're going to present data as well at ESMO of combination in colorectal cancer. We think that is a really important indication for G12D inhibitor. There's 2 basic ways to do it is late line in combination with EGFR inhibitors and in early lines in combination with chemotherapy and EGFR inhibitors. We'll show some of that data as well at the ESMO meeting. So when you start thinking about our G12D program, if things go well and the data that we present continues to derisk the program, you should think about it in a number of different -- in a couple of different tumor types and in a couple of different lines of therapy, specifically in pancreatic cancer in first line in combination with chemotherapy and potentially in the adjuvant setting as well. And in colorectal cancer in late line in combination with EGFR inhibitors and potentially in earlier lines in combination with chemotherapy and EGFR inhibitors. So we'll talk about it at ESMO. We think the data we're going to present is a significant derisking event for this program in first-line pancreatic and potentially in colorectal cancer as well. Thank you for the question.

And I would just add to what Pablo said as it relates to competitive positioning. I think it's unlikely that pancreatic cancer becomes a winner-take-all market. You rarely see that in oncology. I think, generally speaking, oncologists resist dependence on a single treatment. And so this is not, I believe, an either/or calculation. Populations are different. There's various combination strategies that can be put in place. And I think at the end of the day, this will become about sequencing and matching the right drug with the biology. We believe a selective G12D inhibitor will be used first in G12D patients and then a nonselective later. But there, again, it's not either/or. And what we do know is there's only 2 companies right now in Phase III studies with the first targeted G12D treatment in pancreatic cancer. And so whether you're first or early, this, for Incyte, can be a real needle mover. And I think when you look at the data that we'll share at ESMO, you'll be reassured about the activity of this compound in terms of response rates as well as durability of response.

Our next question today is coming from Jay Olson from Oppenheimer.

Congrats on all the progress, including closing the Vega deal. Based on everything you've learned, including feedback from KOLs at ISTH, can you comment on the potential for latarcibart to expand beyond VWD? And eventually, do you think latarcibart can be the next Hemlibra?

Jay, thank you for the question. I'm going to turn it over to Dave Gardner and let him make a few comments.

Yes. Thanks, Jay. Yes, we did get very favorable feedback, both from KOLs and importantly, from the patient advocacy channel as well at ISTH. A lot of the discussion was around the impressive clinical profile thus far from latarcibart. But a secondary discussion did emerge around the treatment of bleeds and the urgency to use better prophylaxis to prevent bleeds in a broader set of patients. So coming out of ISTH, absolutely, we are emboldened by the feedback that if we deliver on the target product profile, there is potential to deliver a transformative Hemlibra-like opportunity to these patients.

And Jay, if you think about it, there is a hemophilia A-like population in von Willebrand. And that is a sizable pool of patients who are severe frequent bleeders. And if 039 comes out of Phase III, like David said, with a substantial reduction in the annual bleed rate and a good benefit/risk profile, adoption in that group, which could be almost 10,000 people, would turn this into one of the largest products Incyte would have. The most important thing for us to do right now is execute this Phase III program, maintain the quality of the data and then, of course, get it approved. But all of the substrate is there for this to be a large product.

Our next question today is coming from Derek Archila from Wells Fargo.

So given Niktimvo's IPF data, Phase II data is going to come from Syndax later this year. I know you guys have an opt-in. So just wondering if you could walk us through kind of the decision framework, what sort of data thresholds may trigger an opt-in, how you kind of communicate that decision? And just remind us of the split on the development cost if you decide to proceed.

Great. Thanks for the question. Pablo?

Yes. Derek, thank you for the question. The disclosure of the data, since they're conducting the study, will be done by Syndax. It will not be done by us. Obviously, they'll share the data with us. We'll discuss the results. And depending how clear they are, it will take a little bit longer or not to make the decision to pursue the indication together with Syndax. When it comes to the existing agreement, it's the same type of agreement we have for other indications, both in sharing development costs and sharing economics. So there's no difference. And when it comes to the opt-in, I just want to make clear that if we decide to opt-in, there's nothing to prevent us from doing so. So we really look forward to hearing the data from our colleagues at Syndax, but they will be the ones releasing those results.

Thanks for the question, Derek.

Our next question today is coming from Andy Chen from Wolfe Research.

This is Jason taking in for Andy. And I just wanted to ask, how well is the Jakafi XR conversion tracking along your internal metrics so far? And do you know when payer reimbursement might kick in? And when -- which specific earnings will this specifically impact the most?

What was the second part of the question?

And when payer reimbursement might kick in and which of the earnings coming up will this impact the most?

Great. Go ahead, Pablo -- I mean, Mohamed, why don't you go ahead and comment on that.

Yes. Thanks, Bill, and Jason, thanks for the question. Look, like we mentioned earlier this year, we're focused on accelerating XR formulary access because that will serve as the basis for demand growth, and we're well on track to achieve that goal of 50% to 70% formulary coverage by the end of the year. So to answer your question specifically, when will payer reimbursement kick in? It has kicked in. And like Bill mentioned in the prepared remarks, several major payers have already moved and put XR on formulary. We've already seen demand start to pick up. And if by the end of the year, let's just say December, we exit the year with XR maybe representing somewhere between 3% to 5% of our demand, that will put us somewhere in that $40 million to $50 million range that Bill mentioned in the prepared remarks, and that puts us well on our way to that 10% to 30% conversion before Jakafi LOE. So we're very pleased with the access so far. The market access team has done a really nice job of getting us and putting us in a position for demand generation to accelerate later in 2027.

Our next question today is coming from Matt Phipps from William Blair.

Nice execution in the quarter. Pablo, you mentioned the totality of the data did not support continue to develop 058 for the V617F indication. Over the past year, it seems like the issue has really been around the bioavailability of this drug and being able to achieve the target coverage. So were there other factors, as you changed the formulation of things, that move -- that contributed to this totality of the data? And can you just remind us on the time line for moving that backup program into the clinics and how you're thinking maybe about the internal program versus the Prelude option?

Certainly. Thank you for the question. I think you captured the key point there. It was not just about bioavailability. It was not just about exposure. We think the new formulation showed promise, and we will continue to escalate. When we started to look at the emerging data and what we look at, as you can imagine, is obviously the PK that you just pointed out to as well as the safety and efficacy that is emerging from a particular program. And we look at that in the context of other programs that we have in-house and that we have been advancing preclinically over the last couple of years. And when we put all that together, it just made no sense to continue to develop 058. The next-generation programs have moved along very, very well. We're really excited about what the data looks like preclinically. We will provide an update preclinical data later this year just so you have clarity on what the differences are between this program -- this new program and 058. And we're looking to basically file the IND in the relatively near future. I won't give you a precise point in time right now, and we'll provide an update later this year when we present the data, but it's reasonably close to an IND filing. On the Prelude agreement, we -- obviously, those programs are managed by Prelude. In terms of updates, they can provide them. The lead is in the clinic, and there are other programs that we discussed with them that they're advancing through different stages of preclinical development. We will sit down with them and discuss the current data that they have. But in terms of providing further updates than that, that should be done by Prelude since they are their programs at this point until we opt in.

Thanks for the question, Matt.

Our next question today is coming from Evan Seigerman from BMO Capital Markets.

I want to touch back on some of the data at ESMO, specifically on 734. As you prepare to present the PDAC and CRC data later this year, what benchmark should we use to judge success? And how much -- how would you frame your conviction in this asset versus kind of the competitive profile that we had talked about earlier on this call?

Thanks for the question, Evan. Pablo?

Certainly. Thank you for the question, Evan. So when we -- the way I think about it is as follows. So the first thing, we initiated a Phase III trial in pancreatic cancer in combination with chemotherapy, as you know, with 734, and we've shown very little data other than ASCO GI last January. So we thought it was very important to have an expanded cohort of patients, as I mentioned, about 50 patients, about half and half with each type of chemotherapy with some maturity in order to derisk this program and generate more conviction around that first-line indication. When you look at benchmarks, there's 2 sets of benchmarks here. One is existing chemotherapy, and that's pretty clear. There's a number of publications with response rate in the 30%, 40%, 45%. And then there are our competitors, which have presented some data as well in combination with chemotherapy. As we put the data at ESMO, we'll discuss it in more detail. But we think potentially, we have a best-in-class agent here in combination with chemotherapy in frontline pancreatic cancer. We'll discuss those results and then hopefully, will be the level -- you'll share our level of conviction around that program. When it comes to colorectal cancer, obviously, that's a smaller data set, but we'll have data in combination with Erbitux that we also think potentially starts to show signs of being a best-in-class agent to combine with an EGFR inhibitor in patients with colorectal cancer, which we think it might be an underappreciated opportunity for G12D inhibitor that we intend to pursue.

Our next question today is coming from Michael Schmidt from Guggenheim.

I had one on the PD-1 TGF-beta asset, 890. Pablo, I guess, what is your level of conviction that this could succeed in frontline colorectal cancer? How is that positioned longer term in the CRC space relative to other emerging therapies, including amivantamab or ivonescimab, which are in Phase III? And then how do you think about other opportunities for this agent longer term?

Thank you for the question, Michael. Okay. Let's start with frontline colorectal cancer. What we know today is that TGF-beta receptor 2 x PD-1 antibody generated what I would describe as the best single-agent activity ever reported for a PD-1 therapy in patients with MSS colorectal, particularly in patients with liver metastases. That led to an acceleration of that program, we generated in combination with FOLFOX-bev, that first showed it was tolerable and then showed increasingly a level of responses and durability that convinced us that was the right path forward. So what we're going to show at ESMO is a pretty large data set with a fair amount of follow-up that we believe supports the frontline strategy with FOLFOX-bev. We're fully aware of the competitive landscape. I think the difference here, and both approaches might work, Michael, but I think the difference is bevacizumab is a very important drug in patients with colorectal cancer. And when you give a PD-1 x VEGF, you cannot give full dose bev. By giving the TGF-beta receptor 2 x PD-1, we can give with a full dose bevacizumab, which we believe could potentially be a differentiating feature. Data over time will decide which one of those approaches is better and both might be successful. So that's point number one. The second is we've generated data also in combination with bevacizumab alone. Some of the data might be presented at the meeting as well, and we believe also continues to show the potential of TGF-beta receptor x PD-1 in colorectal cancer more broadly. When it comes to other tumor types, as you know, we've done some work in other tumor types. I'm not sure we're going to have time for an update on that at ESMO. We want to focus at ESMO on the 3 things that I discussed in my prepared remarks: G12D in pancreatic and colorectal, TGF-beta x PD-1 in colorectal and 667 in patients with ovarian cancer now in combination with bevacizumab, which we also think it's an important update, derisking the maintenance study that we're conducting in that program.

Our next question today is coming from Jessica Fye from JPMorgan.

Just wanted to confirm what the right way to think about Opzelura gross to nets is going forward. And also, can you just remind me of your regulatory plans for povo in vitiligo?

Great. Jess, I'll take the first part of the question and Mohamed or Suky can add. In simple terms, we were working with a gross to net in the low 60s. And with the settlement, now we're in the high 50s. And as I had mentioned at the start of the call, it just simply improves the gross to net profile and average selling price for Opzelura. We made a strategic decision at the beginning of the year to expand access, and there was an investment associated with that. And I can tell you, here we are 7 months later, and I think it was the right decision because when you look at the fundamentals of this business, which is basically volume growth, coupled with coverage, we're in a really good spot. Our job right now is to just manage this selling price as we get into '27 and '28. I think that pretty much covers it. And I think I can turn it over to Pablo or Steven to talk about the vitiligo regulatory plan.

Thank you for the question, Jess. The plan of vitiligo, after discussions we had with the FDA over the past year or so, is to submit right after the approval in HS with 2 years of safety data, safety follow-up in the vitiligo patients. So basically, as soon as -- the team is prepping the filing. As soon as we get the HS and we sort of collect the 2-year follow-up, we will submit that. So it's going to go in early next year.

Our next question today is coming from Salveen Richter from Goldman Sachs.

Could you speak to your target profile for the mCALR program 989 as we look to first-line data by year-end in both the mono and combo cohorts versus what you've established with Jakafi and the traditional endpoints of spleen and symptoms and maybe put this in the context of the composite endpoint that you're trying to create as well.

Great. Thanks for the question. Pablo?

Thank you, Salveen. So as I mentioned, and I won't repeat myself, early in the call, there's 2 regulatory paths here. One, traditional endpoints, as you alluded, with SVR35 and TSS50, and the conversations we're having with the FDA on second-line MF. Depending on the success of those conversations, some of those lessons may be applied to first-line MF or not. Our conviction here remains because of the data we presented in a small subset of JAK-ineligible patients, which is basically a JAK-naive population, which we presented at EHA and we will update later this year. We show pretty solid numbers in terms of SVR35 and TSS50, stronger in type 1 patients than non-type 1. But certainly, when you think about -- if you remember the EHA data, there were very few non-type 1 patients that have received a higher dose. And we do know those patients do need a higher dose. So when you put all that together, our conversations with FDA will complete the second-line MF conversations. Depending on that and whether we are able to advance a different endpoint or not, we will decide the regulatory path for first-line MF. As of today, our plan continues to be in first-line MF to develop 989 both as a single agent and in combination with Jakafi and both in type 1 and non-type 1 patients. That's still the plan.

Our final question today is coming from Mitchell Kapoor from H.C. Wainwright.

This is Matt on for Mitchell. And I guess in the same vein, could you help the stage -- set the stage for the 2H '26 treatment-naive MF readout? What would support advancing 989 monotherapy versus plus ruxolitinib or both? And how are you viewing the analysis of the incremental contribution of 989 in the combination arm?

Mitchell, could you just repeat the question, your audio broke up?

Yes, no problem. I was just asking if you could help set the stage for the treatment-naive MF readout. What would help support the decision to advance 989 monotherapy versus in combination?

Terrific. Thank you. Look, we have the JAK-ineligible cohort from EHA. So that's the first data set that we have, which is about 20 patients that showed what I would describe as strong SVR35 and TSS50 data. And as I mentioned to Salveen, maybe we needed more data at the higher doses in non-type 1 patients to sort of complete the picture. Later this year, we'll have between 50 and 60 patients worth of data with longer follow-up, both in combination with Jakafi and as a single agent, that's a randomized -- small, randomized cohort. And I think all that data put together is what's going to determine which path we go forward. Based on the emerging data that we have, our plan today is to develop 989 in frontline, both single agent and in combination and both in type 1 and non-type 1 patients. But obviously, the data that we're generating as we speak and that we will provide an update on later this year, we'll make the final determination there.

Thanks for the question, Mitchell.

Thank you. That does conclude our question-and-answer session. And ladies and gentlemen, that does conclude today's teleconference and webcast. You may disconnect your lines at this time, and have a wonderful day. We thank you for your participation today.