Incyte Corp (INCY) September 2026 Conference Transcript

All right. Good morning, everyone. Thanks for joining us for the next fireside discussion. My name is Derek Archilla. I'm one of the senior biotech analysts here at Wells. I'm very excited to have the next company here, Insight. From the company, we have Bill Murray, CEO, as well as Pablo Cagnani, global head of R&D, if that's right. All right. But gentlemen, so a lot of changes at Insight from last year when you started as CEO, Bill. So maybe just talk a little bit about a year in the seat, priorities, and then we can kind of go through some of the key growth drivers here.

Yeah, thanks, Derek. At the beginning of the year, we laid out a framework for how to think about the company. And I think there's really two simple parts to our plan, to our strategy. The first one is we have a core business, XJackify, and how we should be judged on that core business is maintaining a double-digit growth rate for the next five years. And by 2030, we think that core business, which sets the floor for Insight in many respects, is going to be up $3 to $4 billion. Product launches is what will continue to drive our core business. And I think we are on track to do that. And you see that each quarter as we report on the performance of Opsalora and Nick Timbo and Monjuvi and Zinus. And then part two is really executing against the pipeline. And that will drive the recovery. Our aim is to have a business post-29 that can grow at a 15% to 20% five-year kegger. And if you look at the unadjusted peak sales potential of the pipeline, you know, you could see a business. We have to we don't have to be perfect, but we have to be successful. That has about eight to ten billion dollars in top line potential. When you look at the pipeline, there are we have three therapeutic areas, as you know, hematology, oncology and immunology. There are five assets that I think have a high PTRS and will drive 80% to 90% of that recovery. In hematology, we have 989, our monoclonal antibody for MF and ET, which is in phase 3, and we have la tarsapart, which is a bleeding disorder, which we acquired at the beginning of the year. In oncology, we have a G12D inhibitor, frontline PDAC, which is in phase 3, and TGF beta by PD-1 by specific and frontline MSS CRC, which is also in phase three. And then, of course, we have povacitinib in immunology. And that's where our focus is right now. And this is an execution test. We have to convert phase three studies into FDA approvals and those approvals into revenue earnings and cash flow. And it's a two-part story. Business development will be used to supplement what we have internally to start therapeutics deal for Latar Sabartis, I think a textbook example, the type of deal that makes sense for Insight. We have a clear framework for doing deals. We have criteria. If a deal meets those criteria, we act quickly. If it doesn't, we're comfortable being patient. And I think that framework makes a lot of sense for recovery.

Perfect. Good segue. So let's kind of talk about, you know, these kind of five growth assets that, you know, you're pointing to, And maybe starting with 734 in G12D, just because ESMO is coming up. And maybe, you know, Bill or Pablo, if you can kind of set expectations on what we should kind of be seeing, you know, in that data set. And what gets you confident to build around and really invest around this, given a lot of the competition that's out there? Pablo, go ahead.

So it's a really important program for us, as Bill highlighted. And I think ESMO will be a very important meeting for all of you to understand why we're so excited about 734. What you're going to see are a couple of really important data sets. First, it's going to be a combination with two types of chemotherapy, GEMNAV and fulfirinox, in patients with previously untreated pancreatic cancer. That's our lead indication. We haven't shown mature data in combination with chemotherapy, so this is going to be very important. will be efficacy, will be a comprehensive update on the safety, including discontinuations, interruptions, dose intensity, et cetera, which I think everybody would like to see. The efficacy data is maturing very well. Importantly, we will not have yet a mature PFS, quite honestly, because we don't have enough events, not enough patients have progressed, but we'll have a landmark analysis that will give an idea of the durability of these responses. So very, very important data set to de-risk the frontline phase three study that is ongoing in patients with pancreatic cancer in combination with chemo. That study is ramping up very quickly globally. We'll have more than 150 sites open at its peak, and we're very optimistic on the enrollment rate and how that study is going. So that's sort of the corners from the foundational part of the G12D program. In addition to that, we will show data in combination with Erbitux in patients with late-line colorectal cancer. If you remember, Erbitux in those patients have a single-digit response rate. We're very, very enthusiastic about the data that we've seen in combination with a G12D agent. We'll show that data. We're having regulatory conversations with the agency to design a Phase III study in late-line colorectal cancer of our G12D in combination with Erbitux. So a very important part as we continue to expand the franchise into a different tumor type. Two more important things, or three, that we're not going to show data yet, but are important to keep in mind how the program is evolving. We are very interested in moving into adjuvant pancreatic cancer, a very important area for patients because they can drive a lot of benefit and obviously an important part of the market. We have combined also with Fulfuri and Arbitux in frontline colorectal cancer. That will not be at ESMO, but it's evolving very, very well. And the final point is we're going to give you an idea of the combination strategy. We realize that G12Ds combine well with other targeted agents, and that's also something we're building. So you'll see pancreatic and colorectal data, and you'll get an idea of how we're expanding the program going forward.

I think a key takeaway, and what Pablo just talked about, is we should be judged when it comes to G12D. I think the data are very competitive, and you'll see that at ESMO, is on systematic expansion, so that this moves from or transitions from a single asset story to a franchise. And that type of breadth is how we extract as much value out of G12D as anything else.

I mean, I guess when you think about the need to be differentiated, you know, as you said, you believe the data is very strong and we kind of know where that competitive benchmark is. But maybe talk to the development strategy as you kind of outline, Pablo, how you can differentiate around that and ultimately maybe be first in areas. And then just to follow up to that is, you know, how do you think the market evolves commercially?

Like, again, with the options that will be out there? so i think when i look at the kras g12d space right i think it's fair to say that there's two two companies us and our main competitor that are ahead of the pack let's call it that when it comes to executing frontline pancreatic cancer i think one area different and i think when you see the data at esmal hopefully you will agree with us that i think getting into who is two percentage points higher or lower on response rates or nausea, or I don't think it's a very productive use of time. I think you'll see that the two programs, the two drugs are basically comparable, and I think that's okay. In terms of who's going to finish first in pancreatic cancer, I think, again, we're neck and neck, and the two studies are likely to finish pretty close to each other. So for us, the differentiation here is going to come by combination strategy, and that's That's why we think colorectal cancer is very important, because I think we have generated data that you'll see at ESMO that is fairly mature, showing that we can combine with Herbitox, and we can really significantly improve the response rate of single-agent Herbitox in late-line colorectal cancer. And then taking that, which is in itself an important market, and moving that to front-line colorectal with Herbitox and chemo is a really important area of growth for the program. So that's the approach we're taking. Obviously, the combinations are going to come as well, but the key for us in this point is to accelerate as much as possible colorectal cancer. We think it's a critical area of differentiation from our competitors.

And as you think about kind of the opportunity from a TAM perspective or commercial opportunity, like I know, Bill, you were saying last night, kind of like framing out, you know, this kind of GI oncology, like where do you think that, what could that be? What could that look like?

Well, and we know the size of the PDAC and CRC markets. In PDAC, G12D is about 40%. If you look at CRC, it's roughly 15%. You know, you could estimate a TAM of $7.5 to $10 billion just in the United States. I firmly believe, and precedent proves this, that this will be a multi-asset, multi-billion-dollar category. You know, you look at other areas of oncology like HERD2 and BCR-ABLE and PD-1 and CDK-4-6 and EGFR, there are first generation, second generation, third generation, multiple lines of therapy, multiple tumor types, and multiple combinations. Right now, as you and I have talked about, there's only two companies in late-stage development with a G12D inhibitor in phase three, and that's Insight and, of course, RevMed. And so I believe that we're set up to build a vertical inside of Insight that has the potential to be as relevant and as big as our hematology business, which in many respects is the central identity of the company. And executing against the plan that Pablo just talked about is the priority. And if we focus on that, this will help drive the recovery of Insight post-2029.

Continuing to move on down the list of assets here. So we talked a little bit about TGF Beta as well. So I guess how does this fit in and ultimately part of that CRC story as well and maybe even the combinability of you know G12D and TGF-beta but you know maybe a little bit more higher risk but maybe you can kind of give us your sense of like how we should be thinking about that program in the portfolio.

I think Pablo does an excellent job of describing the scientific hypothesis behind TGF-beta by PD-1 which you know we're in a one-of-one situation one of the largest wide open white spaces and oncology it's a higher risk program but if we're right it could have a profound impact on the future value of the company and i'll let pavel talk about the hypothesis i think he's spot on so dgf beta is arguably the second most important mechanism of tumor evasion in solid tumors the obviously pd1 pd1 axis is the key and we figure out how to drug that now for the past 15 years the challenge is if you give it systemic DGF beta inhibitor is

systemic toxicity and those have been tested multiple times antibodies and small molecules traps don't work as well because catching enough like and to make a difference is problematic so those have been ineffective instead of toxic so what our team did is come up with a completely different idea which was take an antibody against the TGA beta receptor two, only one, which we think it's the most important one, and attached to it, anti-PD-1 arm. Now, the TGA beta receptor two antibody only engages when PD-1 is fully engaged. So what that does is basically drives the biospecific to the key side of action, which is the tumor microenvironment. And in the phase one study, what we've seen mostly up to doses of 900 milligrams were PD-1-related side effects, which you would expect. I mean, is that at the end of the day, I would call it a better PD-1. Very little, if any, TGF-beta side effects. Now, if you exceed the doses, there's a point where you start to get a little bit of that, but that's not the dose we're taking for further development. So that's the scientific concept. The data that we've generated, which is in hundreds of patients, we have now well characterized the safety of this molecule, is in patients with late-line colorectal cancer, MSS colorectal cancer, including more than half the patients with liver meds, a very clear evidence of single agent activity, which you don't see with anti-PD-1s. Anti-PD-1s have been tested in MSS colorectal. The response rate is zero. And we showed a 15% response rate, including more than half the responders were patients with liver meds, and the responses were quite durable. That was the data that really set up the chain of events of where we are today, which is we decided then to combine it with chemotherapy, which we've done, combination with Falfox-Bev, and then we started generating a larger data set, which you will see at ESMO in frontline MSS colorectal and combination with Falfox-Bev. In parallel with that, we took what is, you know, I would say a risky approach. We launched a phase 3 study in frontline colorectal. High risk, high reward. That study is going very well. It is expanding globally, rapidly, and you will see at ESMO the data that we have now in hand that hopefully helps significantly de-risk the program. A 40-plus patient data set, frontline colorectal MSS, including about two-thirds of the patient's liver meds, and the response rate, and some idea on the durability. Again, not a lot of progressors yet in combination with FALFOX BEP. So that's the data that we've generated. And probably with that, we're doing a couple of other things. We're combining with a G12D inhibitor. That's a very intriguing combination. When you have two novel drugs that work well, you try to see if you can give them together. That work is ongoing. And we're moving the TGF beta program also into the adjuvant setting in colorectal cancer, which we think is also a very important indication for patients and a big market. If you take patients with surgically resected MSS colorectal, you give them chemo. So after chemo, patients that have circling tumor in RNA have a very high risk of recurrence. We think we can fix that by giving them a TGF-beta by PD-1 in combination with chemo. So that's the plan for TGF-beta. We also have data in other tumor types. We won't talk about that at ESMO. We want to focus on most of the GI cancers at ESMO.

When would we learn more about potential other areas or other tumor types that you'd want to, you know?

I would call it first half of next year. We generate some more proof-of-concept data. We have presented some of that. We show data in ovarian cancer, head and neck and lung, 20 to 30% response rate, including post-PD-1. So clearly the drug is active in other settings. And the question now is the development plan, and we are laying the foundation for that, and you'll see more next year. Gotcha.

Maybe shift gears to 989, so this is one, you know, basically helping replace, you know, the current, you know, business with Jacoby and myelofibrosis, MPN. So, you know, we should get a couple updates, but you know the main one around kind of the phase three for MF so maybe just talk about you know some of the options that are on the table there and I know with a more targeted therapy like this that you know could be disease modifying your push to the FDA is maybe more novel endpoints but where do you think will that out in terms of that relative to more traditional endpoints I'll set it up and let Pablo expand first and we've talked about this there's a base case scenario here.

Second line, MF, conventional endpoints. That's SVR35, TSS50. We'll collect information on anemia with a focus on type 1, although we'll study non-type 1. And then there is an ideal scenario, you could argue, which is we convince the FDA that a composite endpoint makes sense given the attributes of 989. It's a more complete way to look at the benefit of the product in in MF base case we get conventional endpoint with a focus on type 1 and we turn the composite endpoint into a key secondary and then continue our conversations with the FDA as it relates to a composite endpoint which could be relevant to a first-line program or to our next-gen antibody we'll provide an update on the third quarter call we have not finalized the protocol but those are the two paths the same two paths we talked about several months ago we know that with the conventional endpoint in a base case scenario that 989 is going to be best available therapy if you look at the data from our phase one so we were very confident about that when you go into the frontline setting what's going to be relevant is the data we share at the end of the year which is we'll have data in monotherapy and combination therapy with with ruxolitinib roughly 50 or 60 patients split two-thirds one-third model therapy in combination and those data are going to help instruct what are our approaches in the frontline setting if the data in our ash update looks like the data from the jack and eligible cohort that we shared in the middle of the year at eha we have a real line of sight even on conventional endpoints to going into a frontline study and we'll provide as complete an update as we can at the third quarter call. Gotcha.

I mean what do you think you know those types of that composite endpoint and the disease modify like what does that afford you kind of down the line and how do physicians really start to you know understand that and where we're going versus kind of like the more blanket jack approach getting to more targeted therapies because there's gonna be a learning there.

Yeah yeah it's look when you introduce a new mechanism you need to understand what that new mechanism does for patients we don't think as you are 35 and TSS 50 are the best way to understand what 989 does for patients with a math quite simply and you know those endpoints were tailored for jackify and that was the right thing to do at the time but when you look at the data that we presented and we'll present more of that later this year, the normalization of hematopoiesis, which is what 99 does in this patient, is not reflected in SVR35 or TSS50. And we think it should be. Now, the conversation with FDA will be important, as Bill outlined, and whether we get there soon or we get there a little bit later, honestly, it doesn't really matter. The first step is to get this drug available for patients on the market. We have a way to do that, both in ET and MF, using conventional endpoints. The second step of the journey is to really convince the FDA to redefine the regulatory landscape for patients with MF. And I think we have a way to do that. I do think they're going to be receptive. They may need more data. We'll generate the data, and I think we're going to get there.

I guess when you think about the opportunities across MF and ET for 989, so maybe can you help quantify those in light of the fact that it is being delivered IV, But you guys do have a very, you know, kind of robust program to get to sub-Q. So kind of marry all that together.

Yeah, we expect when we launch for ET that within six months, plus or minus, we'll have an on-body device available. So you go from taking, for example, hydroxyurea once a day for the rest of your life to a twice-a-month injection, which I think is much more convenient. And I think in order to penetrate the ET market, we're going to need the on-body device. And then, of course, that would be available for MF. You know, when you look at the size of these categories, just to combine it, there's roughly, let's call it 20,000 people with a CalR mutation that either have ET or MF. So you're looking at a market that's north of $5 billion. And the question is, how much does a monoclonal antibody targeting CalR get? I don't think it takes heroic assumptions to pencil out a peak sales estimate where 989 across MF and ET in CalR-mutated patients could be as big as Jackify. That is this working. You know, if you think about the ET market, they've been using hydroxyurea for four decades. It's not an easy drug to dose. It has warnings and precautions, grade three AEs. If there's one thing you can say about 989, in addition to being at least as effective as hydroxyurea, it is a very safe antibody. And for patients with EET that are diagnosed at 40 or 50 years of age, and half the patients in our study were that young, they're going to live with this condition for the rest of their life. And all you're doing with hydroxyurea is treating it like you treat a fever with Tylenol. You're not doing anything to the underlying disease. And so I think there'll be a shift in ET from platelet counts to disease modification. And half the people on hydroxyurea get a partial response, which means residual symptoms, residual thrombotic resists, and residual risk of transformation, although that is low. And then on the MF side of it, we know that there's a therapeutic squeeze with Jackify and Jack inhibitors. If you increase the dose, you control the symptoms, but you cause anemia. If you don't increase the dose, you avoid the anemia, but you have symptoms. And 989 goes to the one flaw of JAK inhibitors. And so I think that the potential here is real. And the most important thing is for us to get it out, even in the second line, in both conditions. And the hematology community is going to reshape how they use the two current standard of cares, hydroxyurea and obviously the JAK inhibitors, namely JAK and fine.

Got it. And again, these are a must-win for you guys and kind of NPNs and, you know, just because Jacobi and what you have there, but can you just talk about, you've talked about another mutant KLR antibody, you've talked about a TCE, so like maybe just reinforce your commitment to, you know, this space and the options that you're looking at in the pipeline. Yeah, go ahead.

We are the company that basically built the Philadelphia negative NPM space. Over the past 15 years, first in MF, then in PV, Jackify has created this, you know, through the ability to help patients, created this significant business. Our goal now is to go after the entire group of patients with NPMs. All MF, all ET, all PV. the first step in that direction is 999 as Bill outlined we're confident that we're going to be first to market for a color antibody now the next step is we have to be at best with color antibody that's the next generation program we'll introduce you at the right time but it basically optimizes every property of 999 more potent almost equipotent for type 1 and type 2 but much more potent overall and longer half-life and you'll see some of the data in the relatively near future in parallel with that we have a TCE we have D cell engager CD3 by color that studies in dose escalation will have data in 2027 we think it could be an important part of the story for certain patients with MF that don't respond or respond poorly to a to its regular color antibody the next step of the story is B617F we had a program we discontinued it because we didn't think it will clear the bar in terms of optimal efficacy the new gen next generation v6 and 7f inhibitor is a much much better molecule and you will see data at the right time as well but that will be introduced in the clinic in the very very near term so by doing this we are committed to the space and we're committed to going after to find a solution a targeted therapy disease modifying therapy for every single patient with an NPN by the end of the decade and we think that plan is on track.

And you also have a couple shots on goal with 617F right with Prelude as well.

We do thank you for bringing it up so we have a we have an internal program that I just mentioned it will be that IND will go in relatively soon and then we have a collaboration with Prelude there's an option deal the option vests in 2027 it's not just one program the lead molecule is in the clinic already but they have other backups that are moving through the system. We're going to get to see all the data that they have, and then we'll make a decision. We don't play favorites. The best drug will win. Our goal is to win in V617F inhibitors. We think we can do that because we understand that biology very well, and we have the right models in-house to understand that biology very well.

So that's why the best of those molecules will be advanced and development you know the biggest shift i would say over the last six months at insight as it relates to i would say our two most important therapeutic areas hematology and gi oncology is they're moving from single asset stories to franchise plans in other words we had a walk before we ran 989 we had to get it into phase three and the same thing with g12d but they have in single asset, single study, single indication plans, but you're seeing over the next six to 12 months, it'll become clearer that we're going after breadth as it relates to both those programs and systematic expansion. I think that's how you extract as much value out of these two very novel compounds as we can.

Well, let's segue into VGA 039, because again, this is another potential franchise play as you just talked about. So I guess what really, like, was attractive about this deal and certainly the asset in your wheelhouse because of the hematology, but, you know, what gets you excited about Von Willebrand's?

Yeah, I'll make a couple comments and let Pablo expand on it. If you look at a neighborhood right next to Von Willebrand's, it would be hemophilia A. And Hemlibra is now a standard of care for hemophilia A patients. It went from replacement therapy to once-a-month injection to provide protection against bleeding. Von Willebrand's, all they have is replacement therapy. Replacement factor degrades over time, requires frequent infusions, and only a very small percentage of patients with von Willebrand's disease are receiving prophylaxis therapy because it's not convenient, and there's peaks and troughs when you're given replacement factor. There's a segment of von Willebrand's disease that looks like hemophilia A, severe frequent bleeders. That's 7,000 to 10,000 patients. And when we look at a protein S modulator, it's a system-level correction. It's restoring thrombin under a bleeding challenge, but not increasing thrombotic risk materially. And we thought this, VGA039, could be, to von Willebrand's disease, exactly what Hemlieber was for hemophilia a phase one data is a limited data set but we saw significant reductions in bleeding the entire biomarker package was very very supportive and there was a clear regulatory path to be the first prophylaxis once a month treatment for von Willebrand's which doesn't exist today and it was a perfect adjacency to our current NPM business and so the deal made sense strategically and operationally and obviously financially too and I think Pablo can talk a little bit more about the scientific hypothesis

we we love the program for you know I think Bill made all the points but just to maybe emphasize a couple of things great science it's on a completely novel way to treat a bleeding disorder right it's a modulator protein s which is a natural anticoagulant and so by modulating not reducing or depleting it, but modulating protein S, you don't create a procoagulant state, but you rebalance the coagulation cascade. And we know that because you normalize thrombin generation. You don't overshoot it. You don't increase D-dimer. You don't increase fragment. So it's very clearly rebalancing in a way, but more modulating protein S activity, okay? Second, the medical need is clear. von Willebrand's disease patients need something better than infusions two to three days a week in order to prevent their bleeding. The data package was very, very solid. And we think, because of the mechanism of action of modulating protein S, that can potentially work on all types of von Willebrand's disease. And in fact, the data set that we presented at ISDH in July shows exactly that the reduction in ABR annual bleeding rates was independent of type of on Willard run disease independent of type of bleeding independent of frequency of bleeding so very clear evidence across the board even though the sample size is relatively small so when we put all that together we really thought this was a perfect program to bring into the company the phase three studies and rolling very well the pivotal trials ongoing we have a very very strong agreement with FDA and the design of that study so we're very comfortable. It would be a global study. We think it could enroll ahead of schedule, perhaps, and we'll have data in the first part of 2029.

And beyond von Willebrand, where could you see this type of, you know, kind of more universal agent to expand into?

So there's, I think it's an important point because this is not a von Willebrand disease drug, right? It's not a factor replacement. It's really independent of that. So there are a number of areas that we're looking at. The first and most important one, I should say, is to do a study in prophylaxis, patients that are on prophylaxis today. The pivotal trial excludes those patients. Patients have to be free of prophylaxis for six months. It's an observation period, and then they enter the study when they start to be dosed for a year. So we need to do a prophy-switch study. patients that are on current prophylaxis from Willebrand, switch them to the Tarsivar VGA039 to make sure we can keep the control on bleeding that they had on the prophylaxis. I would argue that's the most important study for the program after the pivotal trial to supplement the label as well to supplement or support reimbursement, particularly ex-US. After that, the story gets a little bit more complicated because we don't have any preliminary data in the clinic yet. However, potentially, there are diseases like HHD where this could have a role. That's a disease where patients have severe bleeding particularly a lot of epistaxis is very common in those patients and arteriovenous malformations which also create a risk for those patients. There's an argument to be made that by modulating protein S you can again improve the coagulation the formation of that initial clot in this patient and that could really be very very helpful. There's a group of disorders called bleeding in disorders of a known cause that happen to be fairly frequent in bleeding disorders clinics, and there's a strong interest in also generated in that group of patients. So that's some of the ideas. I don't think we are planning to go into hemophilia right now. That seems a problem that is well addressed by current interventions, but those are some of the other ideas that we have. Got it, so more to come.

And then maybe the last couple of minutes, last but not least, POVO. You know, you got launches coming up, in HS, potentially, and other indications. So talk to us about how you think about that in the context of your I&I franchise.

Yeah, POVO is going to be an important launch for the company in 2027. It's under review at the FDA right now. We expect an approval in the first quarter of 2027. The current options for hydronitis, Superteva, which is one of the worst dermatological conditions you have, are completely imperfect. On one end, you have antibiotics and steroids, and on the other hand, you have the IL-17s, which have had a big benefit for a certain portion of patients. What POVO is going to be in HS is the first FDA-approved multicytokine inhibitor for a multicytokine disease. It's not like single cytokine IL-13-mediated AD or IL-23-mediated psoriasis. You have very impressive skin clearance data, very impressive pain data, pain relief data, which is the cardinal symptom of the condition. And there's one thing a JAK inhibitor does, and that's it works fast. It has a well-characterized safety profile, and it's an oral. Our view is that this drug is going to be used in both the pre- and the post-biologic setting, subject to a label for both populations, which is what we expect. I think there's going to be immediate trial and adoption of povacitinib. If it performs in the real-world setting like it did in the clinical trial setting, this will be a very important first indication per POVO. We'll follow it up with vitiligo and PN roughly a year later. I believe that this business has peak sales potential of at least a billion dollars in sales. These are product launches, as you know, Derek. And so our job is to execute this launch, and it will be fully funded and resourced. It'll be marketed right alongside Opsalora. Opsalora will have data in HS at the end of the year in the fourth quarter. It could create a really nice sequencing strategy of a topical to an oral. And right now we're heads down in terms of managing the program.

Well, we'll look forward to that. Thank you guys so much.

Great conversation.