Incyte at Jefferies London: Strategic Shift to Diversification

On Tuesday, 18 November 2025, Incyte Corporation (NASDAQ:INCY) presented its strategic vision at the Jefferies London Healthcare Conference 2025. CEO Bill Murray and Head of R&D Pablo Cagnoni outlined Incyte’s transition from a Jakafi-focused firm to a diversified player in hematology-oncology and inflammation. While the company is optimistic about its future growth, it faces challenges such as the looming loss of exclusivity for Jakafi in 2029.

Key Takeaways

• Incyte aims to diversify beyond Jakafi with a robust oncology and inflammation portfolio.
• The company plans to launch seven mid-to-late-stage projects by 2029.
• A 15%-20% compound annual growth rate is targeted post-Jakafi loss of exclusivity.
• The mCALR program is pivotal in Incyte’s hematology strategy, with promising data expected.
• Strategic acquisitions and internal R&D are key to maintaining competitive advantage.

Operational Updates

Incyte’s leadership highlighted a three-pronged approach to navigate the impending loss of Jakafi’s exclusivity:

• Continued strong performance of the core business, aiming to match Jakafi’s size by 2029.
• Launch of seven mid-to-late-stage pipeline projects by 2029.
• Stringent cost management to maintain healthy operating margins.

The mCALR program, a cornerstone of Incyte’s hematology strategy, is expected to deliver significant updates at the upcoming ASH meeting. The program targets diseases such as myelofibrosis (MF) and essential thrombocythemia (ET), with data indicating potential superiority over existing treatments.

Future Outlook

Incyte is committed to expanding its solid tumor oncology portfolio. The KRAS G12D inhibitor and the TGF-β PD-1 bispecific are at the forefront of this effort, with first-line trials planned to capitalize on competitive advantages in pancreatic and colorectal cancers.

In the dermatology sector, povorcitinib is poised to be a key growth driver. Expected to submit a New Drug Application in early 2026, povorcitinib offers a promising oral treatment option for immune-mediated skin conditions.

Q&A Highlights

During the Q&A session, Incyte’s leadership stressed their agnostic approach to internal R&D versus external business development, focusing on strategic fit and potential returns. The acquisition of Prelude’s JAK2 V617 VAF inhibitor underscores this strategy, aiming to provide comprehensive treatments for myeloproliferative neoplasm patients by the next decade.

Regulatory interactions are ongoing, with the company seeking to incorporate novel endpoints in future trials to enhance the robustness of their data.

In conclusion, Incyte’s strategic pivot aims to position the company for sustained growth post-Jakafi. For further details, readers are encouraged to review the full conference call transcript.

Full transcript - Jefferies London Healthcare Conference 2025:

Clara Dunn, Biotech Analyst, Jefferies: All right, good morning. Thank you, everyone, for joining Jefferies Healthcare Conference in London. My name is Clara Dunn, one of the biotech analysts here at Jefferies. Sitting next to me, we have the Chief Executive Officer from Incyte, Bill Murray, and the Head of R&D, Pablo Cagnoni. Thank you very much for joining me for this discussion. Welcome.

Bill Murray, Chief Executive Officer, Incyte: Nice to be here.

Pablo Cagnoni, Head of R&D, Incyte: Thank you. Good to be here.

Clara Dunn, Biotech Analyst, Jefferies: Bill, let’s start from the big picture. You’ve been in the CEO role for six months now. Tell us how you’ve enjoyed your time since joining and how your initial vision is coming to life.

Bill Murray, Chief Executive Officer, Incyte: Good afternoon, everyone. It’s good to see you. It’s been busy. Great company, great culture. I think strong organizational DNA, and most importantly, which is one of the reasons I joined, just a lot of substrate in terms of meaningful product flow over the next several years. In terms of the vision, our focus right now has got to be on one thing, and that’s transitioning Incyte from essentially a Jakafi company to a high-growth, hem-onc and INI business. We are hyper-focused right now on three verticals or areas: hematology, more specifically MPNs, blood cancer; second, solid tumor oncology; and INI. In hematology, I think we have an opportunity or a window of opportunity to transition that market from nonspecific symptomatic therapies to mutation-specific targeted therapies.

In solid tumors, we’ve systematically, strategically, and quietly, up until ESMO, developed what could be a high-potential oncology portfolio across ovarian, pancreatic, and colorectal, and then in INI, it’s a franchise play. Ultimately, what we’re trying to do is build a glide path to high growth and durable revenue and earnings and cash flow out into the future. 2026 is going to be about executing five phase three programs across those three areas.

Clara Dunn, Biotech Analyst, Jefferies: As you mentioned, Jakafi has been really the cornerstone for Incyte for the past years. Sorry, I have to ask this question, so let’s just get it out of the way early. It’s a loss of exclusivity. How are you thinking? How are you planning to really navigate that through your kind of life cycle management in your MPN franchise, and especially with your mCALR program as well?

Bill Murray, Chief Executive Officer, Incyte: Yeah, it’s a good question. We’re not going to cut our way through or buy our way through 2029. I think we get through it three ways. First is our core business has to continue to meet or exceed expectations. And our core business today, excluding Jakafi, should be as big as Jakafi in 2029. All right? That’s number one. Number two, we have seven pipeline projects that are in mid to late stages of development, and those will start to launch in the 2029 period. Third, we’ll control our cost base and manage our expenses. And what that means is streamlining in areas that we can, and at the same time, making sure that we don’t underfund any critical initiatives that compromise future growth.

There is enough substrate here so that when we look at in the future, post-Jakafi, we see a business that has the potential—I do not expect anyone to take my word for it—but has the potential to grow at a 15%-20% CAGR. A business where we have, instead of one product north of a billion dollars today, Jakafi, we could have three to five products north of a billion dollars. Just as importantly as those two things, LOE exposure of only 15%-20%, as opposed to where we are today, which is much higher, and healthy operating margins.

Clara Dunn, Biotech Analyst, Jefferies: All right. Maybe let’s directly turn to your mCALR program. I mean, investors are watching very closely ahead of the ASH update this year. Maybe at a high level, just tell us, why is this program so important and meaningful for patients with myelofibrosis and in ET as well, which folks might be less familiar with?

Bill Murray, Chief Executive Officer, Incyte: Yeah, I’ll make a few comments and then ask Pablo to talk about it too. First of all, hematology is the central identity of the company. This is an outlier opportunity. Now, it hasn’t fully declared itself, but we’ve de-risked the program with phase one data that we presented in abstract form, and we’ll have more data at the ASH meeting. There are no targeted treatments available for blood cancer, MPNs, MF, PV, and ET. Very different than in other cancers where you have targeted treatments. We’ve produced meaningful data that shows that 989 is a superior approach—no head-to-head data yet—but is a superior approach to the standard of care in MF and to the standard of care in ET. And this business has the potential to at least replace Jakafi.

Where we are right now is to convert phase one results into a phase three trial and an FDA approval. I just asked Pablo to just make a few comments about the data and how he sees it as a transplanter.

Pablo Cagnoni, Head of R&D, Incyte: Let’s first agree on what we’re going to see at ASH. We showed, just to recap a little bit of what happened over the past six months at EHA five months ago, we showed data in ET. We showed very clearly that 989 was well tolerated by patients, and it basically normalized, not reduced, normalized platelets in almost all the patients that were treated, despite the fact that data was at a range of doses in a phase one study. We also saw significant reductions in VAF, which is arguably a lagging indicator of the fact that the drug is basically reducing the burden of the disease, and we can elaborate further. At ASH, we’re going to have three abstracts, or we put out three abstracts, and there will be presentations accordingly. One, updating the ET data, a little bit more data.

There’s a little bit more data in the abstract than EHA, but there will be a little bit more data at ASH, again, showing consistently that there is normalization of platelet count together with reduction in the burden of the disease. There are a couple of different measures to establish that. We will then have a translational abstract, or we have a translational, that gets into more detail into what 989 is doing to the bone marrow, to the immature CALR-mutated population in peripheral blood, as well as VAF. This comprehensive understanding of why 989 is so important for patients, going back to Claire’s question, which is, is it disease-transforming targeted therapy as opposed to a nonspecific cytotoxic? The third data set, which I think is the one you’re most eagerly awaiting, is MF. Obviously, there’s a lot of data in the abstract.

I think directionally, that’s the data you’re going to see. You’re going to see more data at ASH consistently showing that single agent 989 leads to substantial reduction in the spleen size, improvement in symptoms, improvement in anemia, and the disease-modifying aspect, again, reflected not just in VAF, but most importantly, in reducing the number of mutated megakaryocytes in the bone marrow and reducing the number of immature mutated cells in peripheral blood, both of which are leading indicators of the disease-modifying aspect of 989, which is why we think it’s such an important medicine for patients and eventually for the business.

Clara Dunn, Biotech Analyst, Jefferies: And then when we see the ASH data in December, what kind of benchmarks should we look at? Maybe you have your own Jakafi, Jakafi, and then there are other approved JAK inhibitors as well. What is the most relevant benchmark here?

Pablo Cagnoni, Head of R&D, Incyte: Look, we can, I’m sure everybody in the room has their favorite benchmark. If you look at second line MF, you always have to be careful when you look at comparables to look at the right eligibility criteria for patients in different studies, right? The data in the abstract, an SVR 35 with 30% with reduction in symptoms and improvement in anemia over 50% of the patients, there’s no precedent for that kind of data in this same population. This is a phase one population, patients are treated at a range of doses. The higher doses tend to have shorter follow-up, so they had less time to work. Let’s keep that in mind. The most recent approval in second line MF is Momelotinib. Depending on the Momelotinib trial you look at, it’s between 7% and 22% SVR 35.

I think the difference there is basically the patients that were enrolled in one study versus the other. For the combination data with 989, we need more time. The data that we put out in the abstract confirms that the two drugs can be combined safely in patients with MF, and in a population of patients that achieved a ceiling on the benefit of Jakafi, there’s still room for improvement when you add 989 in terms of spleen and symptoms as well. That data needs to evolve a little bit further, but we’re very confident in the direction it’s going. The data that we don’t have yet, but we’ll have next year, is in naive patients. We are enrolling that cohort now. We’re treating previously untreated MF with 989 alone or 989 in combination with Jakafi. We’ll have the data in 2026.

That’s the data that will inform the first line MF trial.

Bill Murray, Chief Executive Officer, Incyte: Just to add to the benchmarks, if you look at ET for a second, in the abstract, the complete hematological response was 73%. If you look at real-world efficacy data with hydroxyurea, it’s between 25% and 50%. It is pretty clear. If you look at the MF side, if you look at the label for Jakafi, the SVR 35 is between 28% and 40%, and our abstract is at 30%. On anemia response, as Pablo said, if you look at the Jakafi label, obviously there’s no anemia response. There’s actually grade 3 anemia in about 34% of patients. It is just a fundamentally different data set and approach.

Clara Dunn, Biotech Analyst, Jefferies: Besides SVR 35 and TSS 50, I mean, for folks who might be less familiar, you’re also reporting VAF reduction as well. Maybe just tell us a little bit about the significance of VAF reduction and how should we interpret VAF reduction in terms of clinical benefit?

Pablo Cagnoni, Head of R&D, Incyte: Yeah. The first point I think anybody has to remember is VAF is a lagging indicator of what’s truly going on in terms of reducing the burden of the disease. Okay? The reason is, when you think about it, what’s truly going on here is that there’s an abnormal population of cells in the bone marrow that are CALR mutated megakaryocytes. There’s a spillover of mutated early progenitor cells in peripheral blood. These two populations are generating the malignant cells in MF and ET. Reducing those, it’s critical. That’s what 989 does. As a result of reducing those over time, you will see decreases in VAF. VAF is easier to assess. It’s just a peripheral blood sample, it’s simpler, but it’s a lagging indicator of what’s truly going on when you give 989 to patients with ET and MF.

We showed at EHA that this seems to be a correlation, maybe not hard established correlation yet, but a correlation directionally between reduction in VAF and complete hematologic response. That was data we presented a few months ago. We are seeing in almost all the patients with MF a certain reduction in VAF. The magnitude is smaller than we’ve seen in ET. I think it needs more time. It needs more time because the starting VAF in MF patients is higher and because the residual wild-type clone, the benign cells, are smaller in MF. That flip, that ratio, takes longer to occur. As long as we reduce the source of the disease, bone marrow and CD34 positive peripheral blood population, over time, the VAFs will continue to come down, and that’s what we expect to happen.

Clara Dunn, Biotech Analyst, Jefferies: Maybe talk about your timeline to start pivotal development. I think you touched on a little on your recent earnings update as well. Any regulatory interactions related to potential trial design and any possibility of using a composite endpoint, including VAF reduction as well?

Pablo Cagnoni, Head of R&D, Incyte: Our most urgent trial now is second line ET. It is pretty straightforward. The design is simple. You have seen the data at EHA. We think we have a medicine that is superior to anything that has been tested in second line ET patients. That design, we have already started conversations with FDA, and we will finalize the design and start that in 2026. I assume at this point, to be clear, that the approval is going to be based on conventional endpoints such as hematologic response. We will have a conversation with FDA about incorporating VAF in some capacity. Maybe it is a key secondary endpoint. I think it is important to inform treatment decisions, but while directionally, it seems that lower VAF leads to better hematologic outcomes, I am not sure the data are ready for the FDA to accept that as an approval endpoint, just to be clear.

We’re going to try to incorporate in some capacity. That’s ET. We’re not convinced about the need of a trial, of a pivotal trial in first line ET. We think that with 989 approved in second line ET, the pressure to switch patients from hydroxyurea, which is toxic and inconvenient and doesn’t really modify the natural history of the disease, probably the pressure to switch patients will be intense. We’re debating that. We’re not saying no, but it’s not an urgent need right now. MF, sort of the same. Second line MF is pretty straightforward. We have data in a population of ineligible, suboptimal, and intolerant to Jakafi patients, which is what we’ve been talking about. It will be a single agent 989 with a control arm incorporating best available therapies for MF. We think that’s pretty straightforward as well.

The one thing that there comes into play that is very important is anemia. More than half the patients in the abstract, as you saw, have anemia improvement, which is something that has not really been seen in patients with MF. We think that we will try to incorporate that in the endpoints for the trial. We think it is important for patients and it is important for treatment decisions. First line MF, we need the data from the naive patients with both 989 and the combination. We will have that data in the early part of 2026. Our goal in 2026 is to start more than one pivotal trial with 989. The most urgent one right now is second line ET.

Clara Dunn, Biotech Analyst, Jefferies: Got it. I also want to touch on the JAK2 V617 VAF. We recently announced the acquisition of Prelude’s inhibitor. I mean, what drove that decision, and how should we think about the position of that asset in the landscape of all the efforts you are making in the MF?

Pablo Cagnoni, Head of R&D, Incyte: Yeah. Our goal by the end of the decade, early next decade, is to have a new treatment for every single patient with a myeloproliferative neoplasm. Okay? That obviously, CALR, we discussed, 25%-35% of ET and MF, and then leaves V617F, which is almost all the patients with PV and the remaining MF and ET patients. We have a program in the clinic. We just introduced a new formulation because the previous formulation could not get to the right exposures that we predicted would be necessary to inhibit the target. The new formulation has been introduced. The thesis is very much alive. We believe, we’re convinced that inhibiting the pseudokinases in V617F in a selective manner will lead to good outcomes in patients with a V617F mutation.

Now, like with other programs, we have internal backup programs, and we’re constantly scanning the landscape to understand what else is out there that is potentially different from what we’re doing. We saw a series of compounds from Prelude, as you pointed out, and we thought it was important to have an option to acquire them if the data convinces us at the right time. That’s simply what’s going on. We’re pushing our lead program forward. We’re still standing our backups. This is another set of backups, basically, that are external to Incyte right now.

Bill Murray, Chief Executive Officer, Incyte: Just to put it in context, the targeted treatments we have in development today, as successful as Jakafi has been, it’s used in roughly 20,000 people. So only 20%, less than 20% of people with MPNs. We, of course, have work to do with both 989 and 617, but if we can successfully move these products forward, you’d cover an addressable market that’s about two to three times that between the small molecule and the monoclonal antibody.

Clara Dunn, Biotech Analyst, Jefferies: Got it. I’m going to go by chronological order. Maybe recently you also presented some data at ASH in solid tumor. Let’s discuss on that a little. I mean, for your KRAS G12D inhibitor in PDAC, maybe walk us through your key highlights there. Another exciting program is your TGF-β PD-1 bispecific, and you’re actually soon initiating phase three program in early 2026. Tell us what you’ve seen give you such strong conviction to have the program move forward very fast.

Pablo Cagnoni, Head of R&D, Incyte: Let me start with the second one. What we presented at ASH for our bispecific PD-1 by TGF-β receptor 2, arguably or not, is the best anti-PD-1 data ever presented in late line colorectal cancer, MSS colorectal. Okay? We showed response in patients with liver metastases and without. We showed long durational responses, and our response was about 15%, which may not sound like a lot, but in MSS colorectal in third, fourth line, there are three or four studies with nevo, pembro, atezolizumab, et cetera, 0% responders. We saw that signal, we think is real. We treated more than 100 patients, so it is not like we treated a handful of patients. It is a sizable data set that convinces us we have an active drug in late line MSS colorectal.

Instead of going line by line backwards like people tend to do in oncology, we decided to combine that PD-1 TGF-β receptor bispecific with chemotherapy and move straight into first line colorectal. We are enrolling that cohort to have clarity on the safety, which we established already, by the way. We established we can combine them. We’ll see what the response rate looks like. In parallel with that, we’re implementing a first line MSS colorectal trial in combination with chemotherapy and bevacizumab. We’re basically bringing three distinct mechanisms to the table. Obviously, chemotherapy is in the background. We’re giving these patients Avastin, so they get BEV plus PD-1 plus TGF-β. You’re bringing three additional mechanisms to the chemotherapy. We think that is a very strong thesis to advance that medicine in early line.

We have also good data, very good data, in head and neck, lung, and ovarian. We’re trying to decide how actionable that data is, and we’ll give an update in the near future. That’s TGF-β. On G12D, we have data in mostly third line, a little bit second line, but mostly third, fourth line PDAC that convinces us that we have a very competitive agent. We have some low-grade GI side effects that we reported. We have shown that we can combine with chemotherapy, both with Gemcitabine-nab-paclitaxel and with FOLFIRINOX. Again, we decided to move as quickly as possible to first line. We’re fully aware of the competition. We think it’s a race to first line pancreatic cancer. We think our ability to combine with both types of chemotherapy that get used in first line pancreatic, it’s going to be an important differentiator.

Now, as with TGF-β, in parallel with initiating the phase three trial, we continue to track the response rate and the duration of response to make sure that with more data, we’re still convinced on the activity of that compound. If so, it will be a race to first line PDAC.

Clara Dunn, Biotech Analyst, Jefferies: When should we expect the next update from them?

Pablo Cagnoni, Head of R&D, Incyte: We haven’t decided exactly. I mean, everybody knows what the right meetings are in 2026. At some point during 2026, probably in the first half of that point, we’ll provide an update where these programs are. Our goal now is to initiate these trials as soon as possible.

Clara Dunn, Biotech Analyst, Jefferies: Got it. Maybe let’s switch to your dermatology and broad INI franchise. Bill, as your INI portfolio continues to expand, how should we think about the role you see INIs playing in your company’s overall growth? What’s kind of your forward strategy to develop this franchise further?

Bill Murray, Chief Executive Officer, Incyte: Yeah, the next step is povorcitinib, and we’ll have the only sort of franchise that consists of a topical to oral solution covering mild to severe disease, as well as local to extensive skin involvement. Povo mechanistically covers multiple cytokines. I think that is an advantage in a multicytokine condition like HS. I think it’ll be differentiated relative to an IL-17 or to a TNF-alpha. If you look at the data from our HS studies, we had rapid pain relief and skin clearance that was on par with biologics. Of course, it’s an oral, and I think there’s a treatment gap right now in HS that exists between oral or topical antibiotics and an IL-17 or TNF-alpha. It’s no different than what the position that Otezla occupied in psoriasis. The difference is povo is a high-efficacy option, and we expect to introduce it probably in early, early 2027.

It’s going to be an important part of the growth of the business. It may not be as big as our hematology business, but INI is valuable to us, especially in immune-mediated skin conditions. If we can add to that through our internal research or external business development, we’ll do that.

Clara Dunn, Biotech Analyst, Jefferies: What are the remaining steps for regulatory submission for povorcitinib in the U.S.? What are the other opportunities beyond hidradenitis suppurativa for povorcitinib?

Bill Murray, Chief Executive Officer, Incyte: Yeah, we expect to submit an NDA in the first quarter of 2026. We’re also running two phase three programs for prurigo nodularis and for vitiligo. In PN, that condition was made for JAK inhibitors. Itch is the defining symptom of the condition. We know they work, especially with Opzelura, extremely well on itch, and that’ll be an important driver of future sales and utilization of povorcitinib. For vitiligo, there’s a large portion of the vitiligo population that has BSA involvement of greater than 5% that is sort of not using topicals. It’s just not as practical. Povorcitinib is going to open up a larger portion of that market. I think Opzelura and povorcitinib will sit next to each other as a treatment solution for dermatologists.

Clara Dunn, Biotech Analyst, Jefferies: Great. For the last minute, Bill, I also want to ask, how do you balance your investment in internal R&D versus maybe external business development opportunities, and what kind of factors maybe tip the scale one way or the other for Incyte?

Bill Murray, Chief Executive Officer, Incyte: Yeah, it’s a good question. I think most companies have to be agnostic. We can’t have a bias towards internal or external innovation. We’re more interested in strengthening the portfolio and outcomes than the source of a deal. Every project, whether it’s internal or external, has to get put through a scoring system and ranked in terms of strategic fit and PTRS and rate of return. The pressure to fill pipelines is unforgiving. We look at anything and treat it the same.

Clara Dunn, Biotech Analyst, Jefferies: Great. That brings us to the end of our discussion. Thank you, Bill. Thank you, Pablo, for this discussion. Thank you for the audience online and in person for joining us. Enjoy the rest of the conference. Thank you.

Pablo Cagnoni, Head of R&D, Incyte: Thank you.

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