Okay, great. All right, let's get started with the next session of Citi's Global Healthcare Conference. It's my great pleasure to have with me the senior management of Incyte Corporation. We have the CEO, Hervé Hoppenot, and Pablo Cagnoni, the president of research and development. Gentlemen, thank you both so much for taking the time to chat.
Nice to be here.
Nice to be here.
Thank you. All right, you know, let's just kind of kick off the conversation, if we could, with Jakafi, you know, and just talk about the overall strategy in terms of Jakafi and what you're doing to drive growth in the company as Jakafi moves beyond the LOE, which obviously is widely expected and you're, of course, very well prepared to address.
Listen, our focus right now is, as you said, transitioning the business from Jakafi to a Hem/Onc I&I company and building a steep growth curve post 2029 with durable revenue, earnings, and cash flow. I think there's three parts to the solution. The first one is our base business, our core business, excluding Jakafi, has the potential to be as big as Jakafi in 2029. That's sort of part one. Part two is we have seven late-stage pipeline projects that will layer on top of that core business. Just to break it down a little bit, in hematology, which is the central identity of the company, we're working on several targeted treatments for myeloproliferative neoplasms. 989, of course, will be presenting data in about a week, and we'll be moving that into phase III in 2026.
In solid tumor oncology, I think we've systematically and quietly built what could be a high-impact oncology program with G12D in pancreatic cancer, TGF beta by PD1 in colorectal cancer, and CDK2 in ovarian cancer. Those programs are starting to declare themselves right now. In I&I, we have an oral JAK inhibitor that's being developed for three different indications: hidradenitis, prurigo nodularis, and vitiligo. We don't have to be perfect with this pipeline, but if several of these projects are successful, it will contribute substantially to that base business I talked about. The third part of the solution is business development, which we would use to extend our core in one of the three verticals: hematology, oncology, and immunology.
As I mentioned, we think about a profile where the company has the potential, once we get past Jakafi, to grow at, let's say, a 15%-20% five-year CAGR. We have multiple products, three to five products with revenue potential of $1 billion or more, and importantly, minimal LOE exposure at that point, because the products that we're advancing through development right now have strong patents and long periods of exclusivity, and ultimately run a business with a healthy operating margin, call it, you know, north of 30%. That's the profile we're building. I think there's a lot of substrate in the company. We don't have to be perfect, but we do have to execute, and that's where our focus is right now.
Okay, that's a very good setup. I guess maybe just a few questions on Jakafi, just to level set, and then we can move on to the list of very interesting topics you outlined. Can you talk about the once-daily formulation and how that may help you and, you know, where that stands in terms of readiness for launch?
Yeah, we expect to launch that in the middle of 2026. You can look at analogs for these XR conversions. There's a long list of them, as you probably know, and the range can be pretty wide. It can be as low as 10% and as high as 50% or more. We estimate we'll convert 15%-30% of IR patients to XR, a more convenient form. Let's take the midpoint of roughly 20%. XR has the potential to preserve, you know, almost three quarters of a billion dollars in Jakafi sales as we go through the 2029 period. Two things drive conversion. Well, three things. First, you have to have a good product, and it is a once-a-day version. Second, you need a sales organization, which, as you know, ours is wired into the community, the medical community.
You have to achieve formulary coverage at a price that makes sense for the PBMs and health plans and makes sense for Incyte. I believe we can do that, and that'll be an important contributor to the sort of base business as we transition away from Jakafi.
Beyond the convenience of the once-a-day, is there more to the pitch, or is that the essence of it, or are there some other additional benefits, like, for example, less side effects or other aspects that are helpful?
Yeah, the approval will be based on bioequivalence data. It is really for, you know, a symptomatic condition like MF or PV or GVHD, compliance is important. This is simply moving from twice a day to once a day.
Okay. All right, you mentioned 989 in your earlier comments, so maybe we could start there. Tell us a little bit about this target, this mutant CalR antibody. You know, what is the significance of that? You know, you mentioned the data's coming this weekend. I'm not sure the exact time, but I'll be at ASH, so I'll check it out. Just tell us a little bit more about how you see that opportunity.
Good. Pablo, you want to take that?
Sure. Just to remind everyone, 989 is our mutant CalR antibody. We developed that internally based on our understanding of the biology of MPNs, which I think is one of the many strengths of Incyte, of the Discover organization. The molecule entered the clinic about two years ago, and at EHA in June of this year, we presented data for the first time in patients with essential thrombocythemia. About 25% of the patients with ET are mutant CalR positive. MF is about 35% of the patients. The data showed very clearly at EHA a rapid normalization of platelet counts in patients with ET, which is the key goal of therapy in this disease, to normalize the platelet count. That leads to improvement in terms of rate of thrombosis and/or bleeding that are related to some of the interventions that are used in patients with ET.
The drug was also well tolerated. At the time of the EHA presentation, only one of the patients had discontinued due to an adverse event. We are very happy with the initial efficacy and safety that we showed. That data set is going to be expanded at ASH next weekend. Three abstracts that are going to be presented in more detail have been made public. In ET, an update on incrementally more patients, longer follow-up, showing consistently that the results that were presented at EHA are evolving well. In other words, normalization of platelets, well tolerated, minimal side effects, minimal discontinuations due to adverse events. We are also going to present for the first time data in myelofibrosis, which obviously is a critical component of the strategy.
The abstract shows very clearly that 989 in patients that are either ineligible, intolerant, or did not respond to Jakafi produces, I would say, impressive effects in SVR35, shrink in the spleen, symptom improvement, and very importantly, as well, anemia improvement in more than half the patients, anemia responses, that it's either an increase of hemoglobin to more than 1.5 grams or conversion to transfusion independency. We also have data in the abstract that will be updated at the meeting, combining 989 with Jakafi in patients that are suboptimal responders after at least 12 weeks of therapy with Jakafi. Again, in that group of patients, there's improvement in terms of spleen response. There's improvement in symptoms as well.
Now, a very important part of the story is in a third abstract, which is translational data from both studies that show convincingly that 989 not only leads to clinical benefit, as I described, but it has a disease-modifying effect. What does that mean? It means that in the compartments where these diseases are, which are the bone marrow and the peripheral blood, there's a reduction in the mutant CalR positive megakaryocytes in the marrow, early progenitors in the blood, as a result of which the VAF, the variant allele frequency, goes down in these patients. That is telling us that 989 is fundamentally reducing the burden of the disease. In turn, when that happens, the normal clone, the wild-type clone, is increasing, which is why anemia is getting better, and these patients are overall improving in a number of ways.
All this picture will be made more clear next weekend. We'll have those three presentations I described, and we'll also have an investor event where we'll go over this into more detail. I believe that is on Sunday afternoon.
Okay. I would just add, if we can replicate the data that we produce in phase I and phase III, 989 has the potential to replace Jakafi, both in ET and MF in total.
Yeah, that was sort of getting to my next question. Yeah, you have not specified what you mentioned, both the post-Jakafi setting, you mentioned the combo. You did not specifically mention frontline in what you said, but I think that has got to be in the strategy somewhere.
Yeah, of course, it's ongoing already. We are treating naive patients. We're randomizing into 989 versus 989 Jakafi. That data will not be presented next weekend. The data will be presented at some point in 2026. It's an important part of the strategy. You will see, however, in the single-agent cohort that we're going to present at ASH, there's a group of patients that were put in 989 because they are ineligible for Jakafi. Those are Jakafi naive patients. You will, it's a small group, small sample size, but you will see that data at ASH next weekend. It will give you an idea of what the drug can do in first line, even though it's arguably a first-line population with a little bit worse prognosis because it's ineligible for Jakafi, which probably means they're anemic or thrombocytopenic. You'll see that data.
Then, getting to sort of the bigger strategy as far as where you would initiate a phase III, would it be sort of a multi-pronged strategy where you'd go into some of more, one or more of these settings? You know, of course, you've got the IRA considerations in terms of staggering. You know, talk a little bit to the extent you can.
Yeah. No, it's a very important point. Let me take a step back for a second. Our goal, stated goal, is by the end of the decade, early next decade, is to have a targeted therapy for every patient with MPN, ET, MF, and PV. This is the first step. You're right. We're not going to sequence initiation of trials. They're going to be a little bit staggered because the data in ET became clear faster, so that's moving a little bit faster. We are, 2026 is a year where we're going to implement one or more phase III trials in ET and MF with 989. The first one will be second-line ET. Again, we have all the data we need to make that decision. Regulatory interactions have started. That will be implemented as early as possible in 2026.
Over the course of the year, we'll move forward with second-line MF and first-line MF as well. This precise timing depends a little bit on having the necessary data to have the conversation with FDA about the dose selection and about the safety. Second-line ET and second-line MF are pretty straightforward. It's single-agent 989. Control arm is well known. In ET, it's probably best available therapy. In MF, it's best available therapy. There's a range of medicines that have been approved, none of which work very well. First-line MF, there's two different options. It's either single-agent 989 or 989 plus Jakafi, or a three-arm study with both, with a Jakafi control arm. As Hervé pointed out, when you look at the data in the abstract, in a population that is mostly Jakafi exposed, the data already looks very promising as a single-agent, stacking very well with Jakafi in first line.
We need more data, but that's basically going to be the evolution in 2026 on how these trials are going to be rolled out.
How are you competitively positioned with this particular target? Are you unique in having this construct, or are there others that are doing things with slight variations?
As far as we know, there's a recent announcement. There's one competitor. It's not in the clinic yet, so I would say three to four years behind. We have a strong lead. This is a space we know well. We need to execute. We need to execute flawlessly and rapidly. If we do that, we're going to be in good shape. You know, the drug works. The data presented today, I would argue, is compelling. We just need to roll out those phase III trials as fast as we can.
Okay. All right. We look forward to seeing that, and we'll check out the detail you mentioned on the Jakafi ineligible. Quickly on ruxolitinib, the Opzelura, the cream, if we could ask a few questions there, you know, just talk about the growth of the product and how you see it evolving. You know, where do you see the most uptake?
Yeah, as a base case on a global basis, Opzelura finished the year at roughly $650 million in sales. Over the next five years, it has the potential to grow at a 10% CAGR, so 2x this business between now and 2030. There will be three sources of growth. First is just increased penetration of the U.S. market. There is, as you probably know, a migration from topical corticosteroids to nonsteroidal topicals. Opzelura, having one of the larger prescriber bases and extensive formulary coverage, is a big beneficiary of this market growth, which I think will finish the year at roughly 20%. That's number one. Number two, we could get potential indications for HS and PN for Opzelura. That's number two. Number three is international growth.
We expect to get an approval for Opzelura in moderate AD in Europe in the middle to the end of 2026. If you take a look at the results from the moderate AD study, it was true AD with Opzelura. They were pretty remarkable. We had 70% of people achieve an EASI-75. 60% of people had itch relief at eight weeks. I think 30% of people had itch relief in two days, and 15% had itch relief in 15 minutes. It is arguably the most effective topical on the market, both in the United States and internationally. That European business will be an important driver of the overall growth of this product between now and 2030.
That submission is based on what set of data? Is it the U.S. data that you're doing additional studies to support the Europe work?
The recent data that Hervé mentioned was designed specifically to address the European market. It is a population of moderate atopic dermatitis patients that are considered eligible for DUPI in Europe. We run the study specifically in that population that we hope will lead, obviously, not just to approval, but to favorable reimbursement in Europe.
Okay. You would expect the typical pathway, the CHMP opinion in sometime in the first half of next year approximately?
Middle of next year.
Middle of next year. Okay. Okay. Do you speak about the split in terms of the revenues on those different indications on vitiligo versus AD?
Yeah, roughly right now it's 60-40.
Okay.
As I mentioned, in AD is the larger market, growth being driven by the migration of steroids like we talked about. You know, the key with Vitiligo is medicalizing the condition. We have done an excellent job at capturing those patients with Vitiligo who are seeking treatment. The key to success in that market, and this usually takes more time, is to increase the diagnosis and treatment rate, which is an ongoing process. We have a fairly sizable consumer campaign in place. I would expect that split to stay 60-40 with both indications, both in the United States and internationally, contributing meaningfully to the sort of double-digit growth rate that we talked about.
I assume that kind of growth you talk about, the 2X-ing by 2030, 10% CAGR, is that in factor in some of the competitors? Because there are some other products that are novel mechanisms that are topicals, I believe, like the PDE4 inhibitors, for example. Do they factor that in clearly?
You do. It's not a, you know, it's not a winner-take-all market. If you were dealing, for example, in a category where the growth rate on the year-over-year basis was neutral or a category that was so well established that was declining, it may be a market share battle. There are plenty of patients out there that can benefit from Opzelura as well as these other topicals. I would say this, it's really tough to beat the data that we've produced on Opzelura, but I don't see it as a fight to the death. Our projection is taking into consideration that there are alternatives. I think one of the real strengths of Opzelura is we have almost 20,000 prescribers in the United States. That is a prescriber base that isn't matched by any other topical.
We also have extensive formulary coverage, both on the commercial side as well as on the Medicaid side. I would not say we have a moat around this business, but the fundamentals of Opzelura are in a very strong position. We just need to execute, and we should not be impacted negatively by competition. They will have plenty of opportunity too.
You're doing a very good job on the DTC because I see the ads on CNN. You know, my phone probably is plugged into the TV, so it knows I'm a biotech analyst.
Just make sure you go to the pharmacy and get some and pay full price.
Then moving on to other topics. Tropovo, there you're preparing to submit very soon to the EU, yes? Can you just talk about the steps there and then, you know, what the pitch is as far as a strong statement on efficacy for HS?
Great. You want to talk about the EU submission?
Sure. The EU submission is in. So.
It's in. Okay.
Yeah, it's in. That's done. Now we're working on the submission for the U.S. If you remember, we said earlier this year we needed 52-week safety data. It was requested by FDA for the initial submission for povorcitinib. Basically, it was about waiting for that. The submission will go in in early 2026. We're going to request prior review. We may or may not get it. Depending on that, the approval will be late 2026 or early 2027, followed by the launch. That's HS. As you know, we think we have a very strong data set here. It's going to be, you know, the oral convenience of povorcitinib. Aside from what we think are very competitive results on HiSCR50, 75, 90, and 100, what povorcitinib does very well is a very rapid pain improvement and very important reduction in number of flares.
When you look at the data from broad databases, patients with HS, the number one complaint is pain. About 80-85% of patients have some degree of pain. Povorcitinib basically shows that when you have long-term follow-up, 60% or 70% of the patients have either no pain or minimal pain on povorcitinib. We think that's going to be a really important differentiator from our competitors. The goal now is to get the U.S. submission in as soon as possible. Obviously, the team will prepare for the launch.
Okay. If you could maybe just talk a little bit about the market and the untapped opportunity in HS, you know, how big a product do you think povorcitinib could be if everything goes according to your projections?
Yeah, look, I think there's a feasible path to north of a billion dollars across HS, PN, and vitiligo. I believe HS has the potential to be the largest. There's a lot of estimates out there on the size of the HS market. You know, based on epidemiology data, we see that number as a base case at about 5 million people who are eligible or would be eligible for an advanced therapy, whether it's an oral, systemic, or a biologic. The question is, what percentage of these patients can we capture as part of the introduction of povorcitinib? You know, it's largely a category that's being managed by antibiotics on one side and by IL-17 and TNF alpha. TNF alpha is on the other side. Our strategy is to capture patients at two critical inflection points: after a biologic, but before a biologic, or post-biologic.
That is what our data set is in, in both pre and post-biologic patients. As Pablo said, the numbers across the board on skin clearance and pain are very good. We had a DT100 draining tunnels 100 clearance of 50%. This is a very, very good product. Layer in prurigo nodularis. That is an itch disease. You could argue it was made for JAK inhibitors. If you look at our phase II results in terms of itch relief, roughly 50% of patients achieved it on the NRS4, which is really impressive. Again, a rapid onset of effect. You start to see separation between povorcitinib and the control group in about 10 days. That will be an important contributor to sales.
The PN market is a little smaller than the HS market, but there's still, you know, probably a $2.5 billion-$3 billion category for advanced systemic therapies. On vitiligo, the key there is it opens up roughly half the market, patients who have a BSA of greater than 5%, where a topical like Opzelura is just a little less practical. You know, this will be about getting the data into the market, promotion, securing formulary coverage, you know, basic launch, launch execution. We start probably in the first quarter of 2027, assuming a standard review with povorcitinib for HS.
You will have two important data sets, if I'm not mistaken, next year, phase III data sets for vitiligo and for PN.
That's right. We'll have the vitiligo data set sometime in the second quarter and the PN data set sometime in the fourth quarter.
How do you see those? I mean, the expectation is based on the phase II data, based on the strength of the data in HS, that those are in good position to work? What do you need to see on those to be very confident in a strong profile?
Yeah, I think if you know what HS looks like, obviously. If you take a look at PN, if we can replicate or get close to our phase II results, we have a real product there. As far as I can tell right now, we'll be the only oral JAK approved for PN. Galderma has done a really nice job with it and Nemluvio. It's a category of patients where there's significant unmet need. That's the target. As it relates to vitiligo, we have a lot of experience in that category. I think our data are going to have to, you know, match what Rinvoq has, and Pfizer has a product too.
Right now, all three programs, I mean, there's always sort of, you got to get these phase III studies done, but, you know, it's a somewhat de-risk program in terms of what we expect from the product.
Okay. Just sorry for a basic question since, you know, we don't formally cover you at the moment. Povorcitinib, so that's not something that you could use as a Jakafi replacement in those settings. Is that correct? There's a reason for that.
It's a selective JAK1 inhibitor.
Okay. It just wouldn't work.
No. Jakafi is a JAK1, JAK2 inhibitor.
Yeah.
It's interesting because the JAK2 effect obviously is more relevant to MPNs. The JAK1 effect provides a broad anti-inflammatory effect, which is one of the reasons why Jakafi improves symptoms so quickly.
Yeah.
Tropovo was designed specifically as a JAK1 highly selective, highly potent inhibitor, arguably the most selective JAK1 inhibitor out there. On top of that, and we've shown this recently, has very high concentrations in the skin. The PK of Tropovo in the skin basically replicates the curve that you see in plasma, which is one of the reasons why we think it works uniquely well in some of the diseases we're discussing.
Okay. I'm glad I asked for that clarification. All right. Now for one that we are very familiar with since we cover Syndax, Niktimvo, axatilimab. That launch has done exceptionally well. Maybe just tell us a little bit more about how you're investing in that asset and, you know, where you see the growth. You know, obviously, there were royalty partners that were very interested in that asset and that have made a big bet just on the third line opportunity, let alone the other work you're doing in the earlier lines. Maybe you could kind of walk us through your strategy overall for the program.
Yeah, the launch has gone extremely well, as you said. Partnership with Syndax has been excellent. You know, we'll finish the fourth quarter annualizing north of $200 million in sales. That is a very, very good start. I think Niktimvo is differentiated in several ways. First, mechanistically, it targets CSF-1R. Second, it covers macrophages and fibrosis. Third, very high response rate. I think fourth, and importantly, what we hear more from BMT centers every day is that it retains its activity after Jakafi or in a heavily pretreated population. One of the most encouraging findings since the launch is that 70-80% of people who were started on Niktimvo in February 2025, you know, the launch month, are still on therapy.
That persistency is probably the most concrete evidence about how the real-world experience is standing up to the clinical trial experience where the results were very, very strong. If you look at the adoption curve over the past 12 months, it looks like it is right on top of Sanofi's Rezurock. It is a new launch. It can be unpredictable. It is still early, but we like everything that we see right now. I think the broad organ control that it provides, liver, lung, and skin, is also a differentiator. We are really leaning into this. It is an important product for Syndax, of course, and it is a very important product for Incyte.
Okay. You want to talk a bit about the studies that you're pursuing in the earlier lines? There's a few, the steroids and then with Jakafi.
Sure. We are doing two. The goal here is to move Niktimvo to first-line treatment of patients with chronic refluctuous disease. That is where the bigger gains for patients are going to be, and obviously, it is a much bigger market. We are going to present at ASH next weekend data from the combination, safety data from the combination of Niktimvo with Jakafi. That is a very important first step to show that these two drugs can be given together. That was the first step that we set out to do, and that will be followed by randomization to move this to first line. When you talk to transplant physicians, they tell you one of the key things they want is a steroid-free regimen for these patients. You have to remember, chronic GVHD is usually in the setting of prior acute GVHD, which is also managed in part with steroids.
These patients are on steroids for long periods of time, and getting them off steroids is a key goal. We have high hopes for this regimen, combination of the two. There are mechanistic reasons why they should work well together. One is more T-cell directed. The other one is obviously CSF-1R antibody. That is an important part of the story. The other is a more traditional approach, which is to take the most commonly used drug in first line, which is steroids, and combine it with Niktimvo. That phase III study is also ongoing. Those two will potentially be the way we expand the label into first-line use.
Okay. Have you provided any timelines on readouts for those? Or those are just booting up now?
The steroid one is ahead. We haven't provided any detailed timelines. I mean, these studies take, you know, chronic relapsing disease is not a super common disease. So enrollment sometimes takes a little bit longer than what we'd like. I would say towards the end of the decade, earlier, probably 2028, we'll have some of the data that we need to expand the label potentially. We'll give more clarity as the studies progress.
The key here is we have two shots on goal, because if one of those studies hits, you roughly two-x the addressable population. These are really important, important for the medical community too, that are looking to, as Pablo said, migrate from steroids.
What are the data points or proof points that would support working in those front line, either combination? How much evidence is there? I mean, it's a good design. The study should be run. I'm just curious what, where are you, you know, where are you getting the confidence that it's likely to work? Or is one more likely to work than the other?
It's a really good question. Look, I think it comes down to mechanism. In general, chronic graft-versus-host disease is a very complex disease biologically. We know that if you remove all the T-cells from a graft, you reduce dramatically or eliminate graft-versus-host disease. That's known. Obviously, the problem in that case is that you have increased risk of relapse. So the T-cell component of the story matters. Now, what the data from the AGAVE trial has conclusively shown is that there's an important component of the chronic manifestations, particularly fibrosis in some of the organs, that is driven by macrophages. And that is why Niktimvo is so important. In a way, by combining the two, and this is the best explanation I can give you today, since we have no clinical data, is we calm down the T-cell response that continues to damage tissues.
At the same time, with Niktimvo, we allow those tissues to heal by impacting CSF-1R. I think when you put those two components of the story together, mechanistically makes a lot of sense that the drugs will improve the treatment together.
Okay. You mentioned briefly Rezurock. I mean, that's a different mechanism, right? Like the read-through there, I assume the answer is not much read-through, but anything else you want to say?
I think, you know, I know what you're referring to. I think mechanistically, it makes a lot less sense to combine Rezurock with steroids or with Jakafi, right? Because you're sort of going after the same biology. It's not identical, but you're going after the same group of cells. I think combination with Niktimvo makes a lot more mechanistic sense, to be honest with you. I don't think there's a read-through from that.
Yeah. Okay. XUS, is there a plan? Or what is the thinking there?
XUS, we've been pretty open in the past that it was going to be really hard to get approval and reimbursement in Europe on the basis of AGAVE. The approval in Europe will have to depend on one of the first line studies.
Okay. Just like overall for this franchise, the profitability, can you talk about the profit margins? You mentioned the BMT centers. I'm also just curious, anecdotally, you know, what are you hearing in the field as far as the experience, given what you said before about the % that are staying on it for as long as they are?
Yeah, the reports from BMT centers are very, very positive. Even though it's a weekly, excuse me, twice a week, twice a month IV, it fits for most patients in their follow-up routines, labs, clinical visits, other supportive care that they may be getting. Tolerability is excellent. I think that sort of, you know, speaks for itself in the persistency rate. For those that aren't going to the centers, we have home care solutions, infusion center solutions. Everything we're hearing so far is very, very good.
Okay. You mentioned at the top of the hour, the solid tumor work. I want to make sure we have time to talk about both of those programs. Let's start with KRAS. You just had some phase I data, I think, at ESMO. Tell us more about the KRAS. You know, what's the exact mechanism? This is a G12D, but is it hitting the on-state, hitting the off-state, both? Talk about those details and how, and there are quite a few of these in development, you know, as you know. How do yours fit in?
No, it's, so yeah, it's both on-off, but I just want to make sure we don't forget about the third of my solid tumor oncology children. We have a CDK2 inhibitor right now initiating pivotal trials in platinum and resistant ovarian cancer, and we intend to move it to maintenance after chemotherapy Avastin combination with Avastin. That's moving forward. That's on the basis of data that we presented last year at ESMO, and we've updated recently showing the competitive response rate in patients that are cycling E1 over expressors with platinum and resistant ovarian cancer. That's ongoing. You referred to the two programs we provide an update at ESMO. We have a KRAS G12D inhibitor. We show data at ESMO, both efficacy and safety that we think are very competitive. We are fully aware of the intensive competition in this space.
There's particularly one company that is ahead of us. However, what we have, our plan is to combine with chemotherapy, and we've done that work already, to show that we can combine our G12D inhibitor with both types of chemotherapy used in first-line pancreatic cancer, which are Gem/Nab or Gem/Abraxane and FOLFIRINOX. In the U.S., about 60% of the patients get FOLFIRINOX, 40% get Gem/Abraxane. Worldwide, that's about 50-50. We think it's important for physicians and for patients in the long run to have a G12D inhibitor that can be given with both main types of chemotherapy. That's our key difference. That trial will be implemented in early 2026. It's a race with our competitors for first-line pancreatic. We think we can execute well, and we think we have a differentiated plan here by being able to combine with both types of chemotherapy.
Obviously, first-line pancreatic is a very large market. That is the key, that is the central component of the strategy of our G12D. We have other things we are thinking about doing, particularly a combination with Erbitux, which we think could be important because we have seen no rash with our product as opposed to what some of our competitors have seen with PanRAS inhibitors. TGF beta PD1 is an interesting story because it is the only, at this point, as far as we know, TGF beta receptor 2 by PD1 bispecific. What we have done is we have designed this to block the TGF beta receptor 2 only in cells that express PD1. By doing that, we have so far eliminated the TGF beta-related side effects that have plagued TGF beta approaches in the past.
What we showed at ESMO was the best response rate ever reported with a PD-1, PD-1-like in MSS colorectal cancer. 15% of the patients responded, including those with liver mets. We are very excited about that data. We have combined the bispecific with chemotherapy with FOLFOX, bevacizumab, and we are moving straight to first-line MSS colorectal. We think that the paradigm of taking responses from late-line therapy, combining with chemotherapy in early lines with the PD-1 plus had been done before. We need to execute on that trial. We think that is an enormous market opportunity. Obviously, it is 80-85% of colorectal cancer patients. Gave you the very rapid blurb there where we are with solid tumors.
This is one where it both, it must bind both. That's the point. Is that right?
It has to bind PD-1 for the TGFβRII to engage. That is key because that way you only block the TGFβRII, the TGF beta, when PD-1 is present.
Right.
Ideally, you focus that into a microenvironment. When we showed the dose escalation data, if you exceed the recommended dose, if you get to 1,500 milligrams, then you start to see TGF beta-related side effects. Up to 900 milligrams every other week, you just do not.
Okay. And then, you know, the logical strategy question is, are these getting equal priority? Is one more of the favorite than the other? CDK2 sounds like you really like that one a lot too. You are already in phase III there, so.
I want to make sure we didn't forget that one. Look, I think CDK2 enters a very competitive space versus ADCs in ovarian cancer. We're aware of that. The efficacy that has been shown with ADCs has higher response rates than we have. We have the advantage of an oral and a very well-tolerated drug. We think it's important, particularly in maintenance, so we're executing on that plan. On the other two, it's about executing on pancreatic first line, colorectal first line. Those are the central focus. We're discussing whether there's a path to expand from that, but the focus right now is to execute on those two trials.
Okay. Just sort of last, you know, portfolio question. You've got a lot, a lot of, a lot of things going on and a lot of interesting assets. Is there a BB pipeline that you're looking at for other opportunities? Or you feel you have enough on the plate at the moment? What else can we look forward to?
Yeah, it's a good question. It'll be used to extend the core to supplement what we're doing internally. We'll be focused on hematology, oncology, and I&I. I think the most important part of BD is to have a good framework first and foremost, and then a lot of throughput so that when you do something, you know what the opportunity cost is and you know if it's right. It's about calling balls and strikes, essentially. It'll be part of it. Right now, we're focused on the seven projects we just spent time talking to you about.
All right. We will be at ASH, we will look forward to the data. Thank you both for joining.
Great. Thank you.
Thank you. Thanks, everyone.