Good morning, everyone. Thank you for attending Jefferies Healthcare Conference. My name is Kelly Shi, one of the senior biotech analysts here. Please join me in welcoming Christiana Stamoulis, CFO, and Pablo Cagnoni, Head of R&D and President of Incyte for this very session. Welcome both.
Thank you. It's good to be here.
Before we dive into the commercial products and some specific programs, I wanted to take a step back and start with a high-level overview of Incyte's vision. What are the key areas of focus for Incyte right now, and what is the forward strategy for the company? Thank you.
Thank you, Kelly. It's good to be here. Thank you, everyone, for attending. Our focus at Incyte going forward is in three broad therapeutic areas that we've been expanding over the past several years. When you look at our strategy, it has been to continue to expand the use of Jakafi in myeloproliferative neoplasms and expand our presence in myeloproliferative neoplasms, which we believe is a really important pipeline of potential products there. In terms of a near term, we have our BET inhibitor, which has been in clinical testing now for some time, and we intend to disclose additional new data at ASH this year and to give clarity on the pivotal program for our BET inhibitor. That's in the relatively near-mid term in expanding the use of and expanding the options for patients with MPNs, particularly myelofibrosis.
More importantly, the longer term in MPNs is our advancing in the clinic of our mutant CALR antibody and our V617F small molecule inhibitor, both of which are in the clinic, and for both of which we will have data next year. And these two are very important because they're a fundamentally different way to treat myeloproliferative neoplasms. We are an emphasis on a potential functional cure for patients with MPNs. So that's pillar number one of our strategy, which also includes, I should say, graft-versus-host disease, for which Jakafi has become a very important part of the treatment for those patients. And obviously, the approval of Axatilimab Niktimvo and the near-term launch of that is an important part of the strategy as well. The second pillar of that strategy is our inflammation and autoimmune disease strategy.
Obviously, our first entry there with Opzelura for patients with atopic dermatitis and vitiligo, and we have a very important pipeline of programs there with pivotal data, first pivotal data for povorcitinib in hidradenitis suppurativa next year, as well as two proof-of-concept trials for povorcitinib in patients with chronic spontaneous urticaria and asthma later in 2025 as well. That will be followed by pipeline of products as well. In oncology, specifically in hematologic oncology, we disclosed data this year of tafasitamab, a pivotal trial in patients with follicular lymphoma. We're going to disclose the details of those results at ASH later this year, and next year, we have another pivotal readout for tafasitamab in patients with first-line DLBCL, together with data for our KRAS G12D program, as well as our TGF-β receptor II PD-1 bispecific, so overall, we continue to have a very full pipeline of programs.
We continue to be on track to what we said earlier this year, to have more than 10 potential launches for 2030 with a well-diversified, novel, and a number of first-in-class and potentially best-in-class programs. And as I should have mentioned, at ESMO, we disclosed for the first time data for our CDK2 inhibitor in patients with ovarian and endometrial cancer. And we intend to initiate pivotal trials in 2025 as well for that program. So that's another very important event for the oncology pipeline.
Very exciting time. Maybe let's start with Jakafi to dig deeper. So in Q3, you raised the full-year guidance now at $2.74 billion-$2.77 billion. Could you talk about the driving factors for the new guidance and how we should think about Jakafi's growth in the out years and where the long-term $3 billion peak sales projection stands now?
So when you look at Jakafi throughout the year, the performance has been very, very strong, with growth driven by demand across all indications. PV is leading the growth, is the primary growth driver. But we continue to also see growth coming from GVHD, as well as MF. We had indicated that we were expecting MF to be pretty stable, and we are actually seeing continuing growth this year. So the performance has been very strong, and that's what led to us raising the guidance for the full year. We expect PV to continue to be the main growth driver, driven by data. The MAJIC-PV study data that we reported last year has been the main driver of the growth that we are seeing. The data indicated that there is benefit in getting on therapy early on, survival benefit for patients.
We believe that's one of the key drivers behind the growth that we are seeing. The guidance that we have provided for the year puts us on the trajectory to getting to that $3+ billion in peak sales by 2028.
Fantastic. And there has been a good amount of investor focus on your LIMBER initiatives. And Pablo already touched on BET inhibitor a little bit. And we're also interested in ALK2 data. Maybe we can talk about how you envision these programs continue to build up the Jakafi-centered MF franchise.
The plan in MPNs, myeloproliferative neoplasms, is, as I said very briefly in my introductory remarks, in the near term, we will have the bioequivalence data for ruxolitinib XR. That's a once-a-day formulation of ruxolitinib, which we think is important as a lifecycle management strategy. And potentially, as we move forward with combinations, it could be well leveraged, we could be able to leverage that for combinations with our BET inhibitor. The second part of the story is to expand the near-term or near-medium-term options for patients with MPNs. As I mentioned, our BET inhibitor, which we presented before, what we believe are very compelling data in terms of symptom improvement and spleen reductions, and in some patients, hemoglobin improvement as well. We intend to move that into pivotal trials in 2025.
We'll provide more details of that during or after the ASH conference, which is coming up in December. During the earnings call in the third quarter, we mentioned that ALK2 inhibitor, at this point, the data hasn't been compelling enough for us to decide to move forward with pivotal trials. We're going to provide an update to that. At the same time, we provide an update of our BET inhibitor. So that's sort of a near-medium-term strategy. And then the big part of the story, as I mentioned, is our two really differentiated ways to treat MPNs with a mutant CALR antibody for patients with mutant CALR, mutant CALR, MF, and ET, which are about roughly 30% of the patients. And then our V617F inhibitor, which is a dramatic difference for patients with PV.
90%+ of those patients are positive for the V617F mutation, and obviously, patients with MF as well, with a lower percentage. So the reason why those are important is, even though Jakafi does improve overall survival in patients with MF and thrombosis-free survival in patients with PV, and those have been two really important contributions to the management of those patients, we believe that our mutant CALR antibody or V617F inhibitor potentially can lead to what we define as a functional cure. And what we mean by that is the ability to selectively reduce or eliminate the malignant clone in patients with different MPNs. And if we're able to do that, we can really get a level of benefit for patients that is different, at a different level that we've been able even to observe here with Jakafi.
How we develop those programs, single-agent combinations, that will emerge over the next 12- 18 months. And we intend to present data, clinical data for those programs for the first time next year. And we think it's a very, very important part of the strategy. We've been the company that has really changed the face of myeloproliferative neoplasm treatment over the past 10 years. And we intend to do that again with our mutant CALR and V617F programs.
Maybe focus on BET inhibitor for the moment. Could we discuss at a high level how could a BET inhibitor development strategy be different in the backdrop of another BET inhibitor's delayed FDA filing?
Certainly. So we are aware, obviously, of what's going on with our main competitor, with pelabresib. That does not change our strategy at this point. In fact, we believe now we may, depending on what ultimately happens with that program, we may have the opportunity to be first-in-class with our BET inhibitor. It's difficult to compare side-by-side double-blind randomized phase III data with open-label phase I-II data, which is what we have with our BET inhibitor. But we really are very happy with what we see in terms of symptom improvement, spleen reductions, the effect on hemoglobin, and the safety profile of BET inhibitor. And we think the ability to dose continuously might be beneficial to patients when it comes to symptom improvement. So our strategy hasn't changed. We'll update the data later this year, and we intend to move forward with the pivotal program.
Great. Maybe we can also touch upon the ruxolitinib XR development and also the timeline for the future steps.
XR is part of the life-cycle plan for ruxolitinib. The idea here is, again, to demonstrate bioequivalence with a once-a-day formulation compared with a twice-a-day formulation. If we are able to demonstrate that, that will lead to an approval of an XR formulation, that will become, for us, the default formulation for patients, for new patients started with myelofibrosis and PV on Jakafi. We believe that's going to be an important part of the strategy as the LOE of Jakafi twice a day comes in at the end of 2028 in order to continue to smoothen that curve by basically initiating every patient on XR once that or try to initiate every patient on XR once that new formulation is approved.
In addition, if we combine Jakafi XR with our BET inhibitor, both are once a day, that simplifies the potential combination there, whether it ends up being a copackaging strategy or a co-formulation strategy, simpler if we have a once-a-day formulation for Jakafi.
Fantastic. And also great news to see Niktimvo get approved recently in chronic GVHD and how's the launch preparation for Q1 launch. And you already guided. And can you also discuss on the expansion opportunity on top of what's in the label?
So I'll start with the launch update. As you indicated, we received the FDA approval for Niktimvo earlier this fall. We are well-established in GVHD with Jakafi. We have great knowledge of the space. We have existing expertise and capabilities. And all these we will be able to leverage for the commercialization of Niktimvo, which we expect to be in the first quarter of the year. So very well prepared and a significant leverage of what we have already in place.
Our plan for Axatilimab is to move to earlier line therapy in patients with chronic graft-versus-host disease. The current approval is in third-line plus, as you know. We believe that's a really important new option for patients with chronic graft-versus-host disease. I think it's important to understand, patients with chronic GVHD, a lot of them are cured of their primary problem due to the transplant, and they're dealing with this chronic complication. There's a lot of cycling through different medicines over time the way these patients are managed. We believe that there's two things based on interactions with KOLs that are really important for these patients. One is to be able to combine Axatilimab with steroids in first-line treatment of patients. We intend to do that. We're moving in that direction.
And the other thing that has been particularly important for treating physicians is a steroid-free alternative for patients with chronic graft-versus-host disease in early lines of therapy. So we are initiating a randomized phase II study in combination with Rux for first-line patients. And we think that's hopefully going to be the long-term best therapeutic options for most patients with chronic graft-versus-host disease. So those studies are moving well, and we fully intend to expand the label of Axa in the next few years.
Great. Now moving to a very important development front, dermatology and immunology pipeline. So maybe we can dive directly into the two key component drugs Opzelura and povorcitinib. One focused question from investors is the HS readout next year from two phase III trials. And maybe you can help us to set an expectation. What kind of efficacy safety profile could secure a role in the HS market, which we believe continues to grow? And how do you think about the oral regimen relative to other novel agents, for example, IL-17A and F?
So povorcitinib has the first pivotal readout next year, in addition to the two proof of concept randomized phase IIs that I mentioned in CSU and asthma. So obviously, our HS program with povorcitinib is very important. We presented what we believe very strong randomized phase II data, strong HiSCR 50, 75, 90, and a 29% HiSCR 100. Also rapid response in terms of pain alleviation in these patients, which is a significant problem for patients. All that with what we believe was, and we presented this several times, a clean safety profile. So we believe we have currently, based on randomized phase II data, comparable data to biologics in a pill. That's basically been our position. And if we replicate that in the phase III, we think we're going to have a very competitive program.
Obviously, there's an increasing competition in the HS space, but we believe if povorcitinib replicates its phase II profile, which has been pretty much something that has happened in HS over the years, phase III data tends to track reasonably well with randomized phase II data. If we do that, we think we have a very competitive program here and a really good treatment options for patients with HS, and again, emphasizing the potential for HiSCR 100 over an extended period of time together with a rapid improvement in symptoms and the convenience of a pill, we think that's going to be very important for patients.
What do you think about the market potential in HS for povorcitinib?
We have not provided guidance in terms of the size of opportunity that we see for povorcitinib yet. We believe that is a significant opportunity. Right now, HS tends to be underdiagnosed. There are numbers floating out there as to the size of the market being $5+ billion . We believe that both as patients start getting diagnosed, but also as there are more therapies and entrants in the space, it will help grow the market from where it is today.
Great. And povorcitinib is set for moderate to severe HS patients. You also have Opzelura to pursue mild to moderate different subgroup of HS patients. And the phase III trial you guided the primary endpoint is now using stringent HiSCR 75. Curious what drove this decision and how would you think about the success possibility for phase III?
So at AAD in March of this year, almost a year ago, we presented randomized phase II data for Rux cream in patients with mild to moderate HS. We thought that data was very strong. And what we did over the course of the year was discuss with FDA what would be the design of a potentially pivotal trial. And we wanted to make sure the agency agreed on the use of HiSCR 75 in order to reduce the impact of placebo potentially. So because you're talking about patients with mild, a lot of them are going to be mild disease, some early moderate disease, if you use HiSCR 50 and you have a strong placebo effect in those patients, you can potentially erase the difference with an active arm. So we wanted to have a more stringent endpoint.
We think HiSCR 75 is the right endpoint for these patients. Agency agreed. We're in the process of launching that study. And we think we're going to then have the option for patients to really treat the whole spectrum of HS, from patients with really mild early disease to patients with very severe disease that need rapid alleviation of pain and potential for almost complete clearing of the lesions, which is something we think that povorcitinib can provide. So having both programs, a topical for mild, early moderate patients and a pill for patients with moderate to severe disease, we think it's going to be a really, really important strategic advantage.
Great. And for Opzelura, what is the current split of prescriptions between two approved indications? And what would be the ideal split in the future and also your commercial strategies along with that?
The current split is 55-45 between AD and vitiligo. We continue to see significant growth in both indications. What you are seeing also here is a growth in the number of refills per patient for vitiligo, which is what we are expecting, that eventually the number of tubes of cream used by a vitiligo patient will be significantly higher than that of an AD patient. In addition to the growth that we are seeing in the currently approved indications, we have filed for approval for AD Pediatric. Hopefully, we'll be in a position to commercialize in this indication next year. We expect this to be another significant addition to the opportunity in AD and represent at around 10%-15% of the total AD opportunity in terms of peak sales potential.
So you have, on one hand, an additional indication within AD that will help to continue to grow the AD indication. And on the other hand, you have a significant opportunity in vitiligo to both continue to penetrate and activate vitiligo patients to get on therapy, but also with adherence to increase the number of tubes used by a vitiligo patient. So there are drivers of growth in both indications.
Okay. Fantastic. And there is an overnight headline from Incyte on MRGPRX2 and MRGPRX4. Maybe for those who have not got time to digest the information, could you help us to lay out the details and what drove the decision and any alternative development in the future?
So what you're referring to is we became aware very recently of a toxicology finding, an in vivo toxicology finding with an MRGPRX2 program in the clinic that's called 262. And we decided, as a result of that tox finding, to pause enrollment in the CSU study and to communicate to FDA the findings of the tox. And now we will discuss with the agency what the next steps are. So just to be clear, the CIndU study and the atopic dermatitis studies were fully enrolled. The CSU study was almost fully enrolled. What we did was pause enrollment and obviously not adding new patients. Patients in the study will be told of the changes, and they can decide whether to complete dosing or not.
So what we need to do now is work with the agency and decide next steps for the program, which we will do as rapidly as possible. Importantly, what we disclosed as well is that we have backup programs for MRGPRX2. We intend to continue to move those programs forward at this point. And one thing that I want to emphasize is the pause in enrollment in the CSU study. It is not related to any clinical findings. This was an in vivo toxicology finding that we recently became aware, and we moved rapidly in order to communicate with the agency the findings.
Thank you very much for the details. And moving to oncology, as said, CDK2 inhibitor, you presented data at ESMO in ovarian cancer, which is a bit different from most of the CDK2 peers pursue a breast cancer opportunity. Maybe could you help us to understand what drove this decision and maybe more details on how is your development strategy in ovarian cancer in terms of pivotal trials?
So we presented data at ESMO, as you pointed out. We believe we have, at this point, based on presented data, a best-in-class and potentially first-in-class CDK2 inhibitor in ovarian cancer. So we presented data in platinum-resistant ovarian cancer and some data in endometrial cancer as well. We are doing work in breast cancer. We decided to accelerate ovarian cancer because we think we can be first in that indication. So the plan now is in 2025 is to initiate the pivotal program for a CDK2 inhibitor. So the options in ovarian cancer, and we'll provide more detail next year, are potentially platinum-resistant ovarian cancer. Obviously, it could be an accelerated approval in a phase II market or a randomized trial compared with chemotherapy.
But the more important opportunity for us, because of the really good safety profile we presented at ESMO, is to combine with bevacizumab, and that work has already been initiated, and move as quickly as possible to the maintenance setting in patients with platinum-sensitive ovarian cancer. So we're in the process of doing that, and we will give more details in 2025. But we fully intend to move forward with pivotal trials in ovarian cancer with our CDK2 inhibitor.
Last but not least, what do we expect for the next 12 months in terms of data catalysts and milestones? And also, where are you on the BD front?
We've been talking for the past 20 minutes almost that there's a lot of catalysts in 2025. Povo, HS readouts, proof of concept in CSU and asthma, Rux cream, and prurigo nodularis. We didn't have time to talk about that, and potentially the approval in atopic dermatitis. For MPNs, we're going to present data on our BE study for Rux XR, mutant CALR data, as well as 617F data. For our oncology pipeline, initiating our CDK2 pivotal program in ovarian cancer, as well as data potential on our G12D inhibitor and data on our TGFβR2 ×PD-1 inhibitor. For tafasitamab, which we recently reported a positive pivotal in follicular lymphoma, also the readout of our first-line DLBCL trial also in the first half of 2025. I've forgotten about anything.
On the BD front, as you hear, we have a very, very full pipeline. The priority right now is to continue to invest in pushing those programs forward. BD is more opportunistic. We have the financial ability and flexibility to do BD, but it's more opportunistic. The type of assets we're mostly looking at are assets that are earlier stage technologies and capabilities that could help us with our discovery efforts.
Looking forward to an event for 2025 for Incyte. Thanks both for this insightful discussion. Thanks everyone for attending.
Thank you.
Thank you.