Incyte Corporation (INCY) Earnings Call Transcript & Summary

Great. Well, thank you, everyone, for joining us at our 2021 Goldman Sachs Healthcare Conference. I'm Salveen Richter, biotechnology analyst at Goldman Sachs. And we're pleased today to have Incyte Pharmaceuticals with us. With us, we have Herve Hoppenot, Chairman, President and CEO; as well as Christiana Stamoulis, CFO. With that, Herve, I'm going to turn it over to you to make any opening comments, and then we'll jump to questions.

Okay. So yes, good morning. Thank you for inviting us to present here. So it's obviously a very busy time for Incyte, as we speak today. It was a very successful year in term of growth of revenue over the past 18 months. In 2020, Jakafi grew at 15% to $1.94 billion in the U.S., the rest of the hematology/oncology portfolio grew at 46%. The royalties we are getting from Tabrecta, ruxolitinib outside of the U.S. and baricitinib grew at 28% and reached our number that is meaningful to us of around $400 million. And we have now 6 different sources of revenue and have the potential to grow even further this year. In term of clinical success, obviously, the big events of the past few months are the 3 product approval in the U.S. with Pemazyre being approved also in Europe and Japan, Monjuvi and Tabrecta also in the U.S. from Novartis. The next few weeks are really about the multiple launches that we are doing in the U.S., Europe and Japan. And on top of it, we have 3 regulatory submission under review at the FDA. So it's ruxolitinib cream for atopic dermatitis; ruxolitinib in chronic GVHD, we'll speak about that in more details; and retifanlimab, our PD-1 antibody in SCAC. And then at the EMA, there are 2 submissions under review: 1 for Monjuvi, tafacitamab in DLBCL; and 1 for retifanlimab in SCAC. And we also have announced very important positive results from the CITADEL program for our PI3-kinase delta and in vitiligo recently for RUX cream. So a number of events and news flow that we were speaking about over the past months starting to become concrete and now moving to the next phase, which would be approval and then launching them. When we look at the future now more than just a few months, but a few years ahead, I mean there is one big component, which is our MF, PV, GVHD franchise. So it's a program we call LIMBER where we are working on improving the clinical profile of treatments available for patients with each of these diseases. It's starting with XR, ruxolitinib XR, which is a formulation of ruxolitinib QD. And it has been published recently, the bioequivalence study of XR with RUX. So that could be something that would be submitted early next year and could be approved at the end of next year. And a number of combination program with PI3-kinase delta. So we are already in Phase III with 2 Phase IIIs ongoing and accruing now and 2 new mechanisms that we are combining with ruxolitinib, one is ALK2, which is very important to manage anemia for patients with myelofibrosis; and the other one is a BET inhibitor we are also combining with ruxolitinib to improve the efficacy of ruxolitinib for some of the patients with myelofibrosis. In term of earlier portfolio, there are a number of programs ongoing, including IV and oral PD-1, PD-L1 products that we have in early stage of development; and a number of target, including some new target like the adenosine program with the A2A/A2B inhibitor under CD73; our AXL/MER program; and MCL-145, which is a bispecific we are developing together with Merus. In addition to this oncology portfolio, we are literally launching Incyte dermatology. So it's based on the atopic dermatitis programs that we have published and is well-known and is under review by the FDA. And obviously, it will be followed by our vitiligo indication that we will be submitted -- submitting before the end of the year. So when you look at the entire picture, it's a number of moving parts, obviously, but it's a number of positive results that we have been able to generate over the past months. And now we are in the phase of translating that into approvals in Europe and U.S. and into an additional layer of revenue growth for the corporation, which, obviously, is very important because it gives us flexibility to leverage the P&L on one hand. As our revenue growing and the expenses growing at a lower rate, it will leverage the P&L and give us financial flexibility to continue to invest in R&D or in business development when it's needed. So I will stop here because there are a lot of aspect of the portfolio to discuss, but it's certainly a very exciting and transformative time for Incyte this year.

Maybe to start here. Product diversification has been a focus for Incyte as you stand today with Jakafi and Pemazyre and Monjuvi and a potential approval for ruxolitinib cream in the current pipeline. What is your overall outlook I guess for the business here? And maybe you could just touch on business development and what your considerations are with regard to assets or technologies that you're looking to potentially bring into the portfolio.

So note, the overall picture is that we have an internal -- we have a portfolio today, even before business development, that is generating a very high level of growth for the next year. So it's not like we are -- we have to buy new asset because the internal growth is not there. At the same time, and we have discussed it with the Board multiple -- in multiple occasions, we are generating cash. So we are cash flow positive. We have around -- for the end of this year, it will be around $2 billion in cash. And we believe it is the right time in the cycle of the organization to continue to acquire what could be growth potential in the years '24, '25, '26. So it tells you what it could be. I mean there are products who would be at a sort of a bulk proof-of-concept or early Phase III type of stage. And there are assets that could be complementing our oncology-hematology portfolio and/or maybe our dermatology or autoimmune portfolio. So we have been -- we are looking at these opportunities. But at the same time, there is also one of the -- I mean the priority, in fact, for us, is the delivery of the value of our internal assets that are already fairly -- there are many of them in -- coming in the next few months. So there is no urgency, but it's obviously something that we will do if we see the right opportunity for the right price.

What do you think investors are missing on the story?

The way we look at our own portfolio is obviously what I was describing, is establishment of a meaningful hematology/oncology portfolio of products beyond Jakafi. Each of them may be relatively modest in size. When you look at the mega blockbuster, it's -- pemigatinib is not part of that. Maybe PI3-kinase delta in lymphoma is not a mega blockbuster by itself, but when you start taking Monjuvi plus pemigatinib plus PI3 delta plus pemigatinib and all of that is under review. So it's sort of relatively short term. What you end up is with a meaningful portfolio made of all of these components. And it's very synergistic from the commercial standpoint. So it's sort of from the P&L standpoint, it's working very well. The second piece, and that's the one where we need to demonstrate and show the results, is about LIMBER. Because obviously, everybody is looking at the growth of Jakafi. And we -- as we described it, it's a franchise that could be growing north of $3 billion in the U.S. And what we believe is that between now and 2028, we will have a transformation of that portfolio, which will be first with XR formulation. And then with the different combinations we are working on, and we believe some of them or all of them will be providing a medical, clinical benefit to patients that does not -- is not provided by Jakafi alone. So it's a true improvement for patients suffering from myelofibrosis. And that sort of transformation of the Jakafi portfolio into -- or Jakafi into a portfolio of product addressing the different needs of patients like patients suffering from anemia, patients suffering from suboptimal response on Jakafi, each of these subgroup of patient could be addressed with one of the combination we are developing. So that's the 2 component for hematology/oncology. I think then there is a question of how big could our dermatology franchise become over time. And I must say it's something that is still relatively difficult to quantify because when we look at the number of patients who will be potentially eligible for RUX cream both in atopic dermatitis and vitiligo, it's a very large number. So there is a lot of variability on how big it could be. So that's, for us, the 3 components, is built the non-Jakafi onco portfolio of products that would be meaningful. We place Jakafi in myelofibrosis, PV and GVHD and build a new revenue stream with a dermatology portfolio that could be fairly or very large.

So starting with Jakafi, you've noted as of your earnings call kind of a return to pre-COVID levels and new patient starts in March. Has this continued? And maybe if you could touch on the trends you're seeing across the different indications where the key drivers of growth are coming from.

Yes. The 3 indications are growing. So that -- they don't grow exactly at the same reason. Sometimes it's very difficult to know precisely between MF and PV because the coding are not always very accurate. But what we see is that over a period of time, we have a growth in MF, PV and GVHD. So the 3 of them growing. The growth rate we have in GVHD is higher than PV, is higher than MF. So that's the ranking of the growth rate, but the size of the indication is larger for MF, followed by PV, followed by GVHD. So the growth is inverse of the size, which is not surprising. We see the new patient flow normalizing, and we showed that at the quarterly call where it was a return close to what we had or, in fact, slightly above what we have in 2019 and, obviously, now very much higher than what we had in 2020. And that trend is continuing. It's not -- when we do the calculation of how large it could be without COVID, in fact, I don't think we are back there because there is still a number of patients who are not diagnosed. And that's a sad story of what's happening now in -- or what has been happening over the past 15 months in the U.S. is that a number of cancer patient did not -- were not diagnosed or were not treated. But when we look at the number of treated patients, we are still lower than what we think it should be, but it's now north of what it was in 2019. So it's back to normalization.

And you announced this morning that the FDA has extended the sNDA review for chronic GVHD to allow more time to review for additional data. Just maybe you could just help us understand what the nature of the request was.

So it's a randomized Phase III study at REACH3 that has been presented. So it's a very robust set of data. And the FDA relatively late in the process asked us for additional patient-level data that was provided to them. And as it was provided to them, they asked for more time to review it and to make sure they will integrate it into their review. So that's what happened, in fact, yesterday night. So it's -- it happened to us also when we did the submission for acute a few years ago where there was a 3-month delay. So it's not ideal, but it's a relatively short delay that I think is important for the FDA to have all the components that they need to have to write the label.

Great. And then how are you thinking about the incremental add to the Jakafi opportunity with this indication? I mean do you -- is there off-label use already in this population? How should we think about that?

The -- so there is a little bit of an overlap between acute and chronic. I mean 70% of chronic patients had some form of acute GVHD before chronic. So there is not only off-label, but there is an overlap of the population. We know some physicians are using Jakafi in the treatment of chronic GVHD already. It's difficult to quantify. What we know is that there are probably around 10,000 patients in the U.S. suffering from chronic GVHD. So it's a fairly large number. The flow of patient is more limited. It's like probably between 2,000 and 3,000, but the pool of patients existing is relatively large. And we know that many of them are not treated with Jakafi. So what we anticipate is that as we get formal indication, it will give physicians an easier path to using Jakafi for chronic GVHD. So it should be helping continue growing the Jakafi franchise in the U.S. at a rate that we have seen historically. Last year was 15%, the year before was around 20%. So it's -- we have been in this sort of high-teen, low 20% growth. And I think chronic GVHD will be -- the approval in chronic GVHD would be important to maintain the growth rates that we have seen.

And you talked about the long-term strategy here for myeloproliferative disorders. And Jakafi looks like it's on track to be over a $3 billion peak sales drug, as you've guided to. When you think about the steps to maintain your leadership position, could you talk about, one, the life cycle management strategy with LIMBER and the different approaches and where you think the greatest potential to extend the franchise would be; and two, if there's anything else we should be thinking about?

So -- yes. So the first step is the introduction of the new formulation of Jakafi. So it's once-a-day formulation. It's important not just because once a day is more practical than twice a day. I mean it's true, but it's also important because it's a different PK profile. And you know, the twice-a-day Jakafi has 2 peaks when, in fact, the once a day has a very much smoother PK profile. And we are not exactly -- we have not demonstrated the clinical benefit of that, but it has a different -- certainly a different effect. But more importantly, a lot of the progress in the treatment of MPN is coming from combination therapies. And they are the one we are developing. So it's ALK2, PI3-kinase delta and BET as of now. But it's also other companies developing BCL-X and BCL2 inhibitors. There are a number of mechanisms that are combined with Jakafi. So for -- and most of them, if not all of them, as of today, are once a day. And when you combine 2 oral products in cancer, it's really important. It's not a small thing to have 2 once-a-day product because if not, there is obviously a risk of problems or mistake. So that's the first step, is saying we can improve over Jakafi as it is today, the clinical profile of Jakafi. In term of efficacy, there are a number of patients who have suboptimal responses to Jakafi and in term of safety where there are a number of patients who cannot take the full dose of Jakafi because of anemia mostly or thrombocytopenia or some other potential effects that Jakafi could have. So what we are looking at is, on both aspects, better safety leading to higher dose intensity or better efficacy when Jakafi response is not good enough or over time when it's starting to fade. And that is I think the future of the franchise where, first, we have XR being introduced potentially at the end of 2022; and then we have a number of combinations that will be once a day, once a day. And then we could potentially develop, and we are working on it, fix those combinations that then can be used for subgroups of patients who are in a certain type of suboptimal response or suffering from some type of toxicity. So the way I see it is a fragmentation of the franchise into subgroups of patients, which may also help grow the franchise more than it -- we could do with Jakafi alone and will give us, obviously, a life cycle for the entire franchise that goes far beyond 2028. So that's what we are working on. We made a very good progress over the past 12, 15 months. And I think we'll start seeing the effect of that in '23, '24 when first we get XR, and then we get the result of the studies we have ongoing.

And assuming completion of the 12-month stability data for the extended-release formulation, should we assume approval by year-end next year or shortly thereafter? And help us understand what proportion of patients or -- and which patients would be likely to switch over to this formulation.

So yes, the timing is right. I think the stability will be -- the stability data will be available early next year. It's a 10-month review. So it could be approved at the end of '22. I think it's difficult to describe which patient should stay on the twice a day versus the once a day because the once a day is more -- as I said, is more practical. So I think it will be a question of new patients maybe will have the tendency to be put on the once a day. For the existing patients, it may be more complicated to switch. But over a period of time, our view is that once a day will become the norm for using ruxolitinib in MPNs and GVHD.

And then for your combination therapies, which one do you think would be most impactful there?

So it's a very interesting question. I think -- so the delta program has 2 Phase III studies ongoing. One is the first line. So it's a high bar because a lot of patients are doing well on Jakafi alone. So comparing to Jakafi alone makes it difficult to do better than that, but I think it's an important study to do. So it's ongoing. And we have a second study in suboptimal responders to Jakafi. So it's a different population. It's a population where patients are treated with Jakafi and are not doing well enough on Jakafi alone in term of symptoms or spleen size. And we are comparing Jakafi to Jakafi plus PI3-kinase delta. And that's Phase II that you have seen published. And what we believe is that we can improve meaningfully the outcome in term of efficacy by adding PI3-kinase delta. It will be the same thing we would be doing with the BET inhibitor when we have the dose and schedule in combination with Jakafi, which is something we plan to have by the end of this year. And so that's the efficacy aspect. It's important because there are probably 40% of patients treated with Jakafi who are doing very well on Jakafi alone. So there would be no need to go into that type of combination but obviously, the other 60% could benefit from it. On the safety aspect, and that's the ALK2 programs that we have ongoing, it is being tested. But what we anticipate is that we'll be able to maintain the dose intensity of Jakafi by adding an ALK2 inhibitor to Jakafi. And that would have an effect on efficacy -- on safety, obviously, with the rate of anemia, but on efficacy because we have shown, together with Novartis, there were a number of publications showing that maintaining high-dose intensity of Jakafi has an effect on the efficacy of the treatment. So it's another angle where there is a better safety leading to better efficacy. So I think both can coexist. In fact, the 3 program can coexist for different subgroups of patients, and that's what we are working on now. And we have other programs that we are working on still at the preclinical level to add new mechanism that could be useful also for patients with myelofibrosis or polycythemia vera.

So moving over to the dermatology franchise here, the next key catalyst is the PDUFA for a topical RUX cream in atopic dermatitis. How are you thinking about the profile of use for patients, the amount, the duration of use, constant threat of abuse? What has research suggested there?

So you saw the data was -- is very impressive because it's data that is showing a level of efficacy in atopic dermatitis that you find with biologics. And it's done with a topical formulation where the systemic exposure, and that was also recently published, is very, very, very low. And therefore, the risk-benefit ratio of using topical RUX is very unique. And that's a field where you have, on one hand, steroids. And we have no ambition to replace the steroids in some way. So we will be dealing with patients who have been exposed to steroids or TCIs in a topical form. And there are patients where the disease is of such a size that it can be treated topically instead of systemically. So it's -- really, the positioning, if you want to put it that way, is between steroids and Dupixent in that group of patients, which is it's millions. In fact, in the U.S. and where the benefit of RUX cream is very unique in term of profile, in term of itch relief, which is the goal of treatment at the beginning, is to quickly manage the itch effect of eczema. And the way RUX cream does it -- and it's not a surprise, we know the cytokine effect of JAK inhibitors. But doing that at the local level with a topical formulation is providing this unique profile of high efficacy, very rapid itch relief without system -- meaningful systemic exposure. And it's something from market research, from discussion with the dermatology community that is very attractive and fitting a relatively large patient population. The number of tubes of the cream used per patient, in our experience, and there is always a lot of variability, but it's around 3 per year per patient. As patients will be using the cream, then as the disease is subsiding, they will stop using it and then some time, it will come back a few months later. And that's the cycle that we have observed in our studies. So when we do calibration, we are -- that's what we are using, around 3 tubes per patient for atopic dermatitis. It's more around 10 or 11 for vitiligo.

And if your label includes a black box warning just given what we've seen with the JAK class, do you have a sense from your research with dermatologists how this would be viewed or the effect it [ may come out with ]?

It's -- I mean it is clear to every dermatologist that if you want the benefit of RUX cream over JAK, it's certainly better to use it as a topical formulation than as a systemic treatment from the question of JAK exposure. That is the question. What we have shown in our studies, in our data is that, in fact, with RUX cream, the systemic exposure is so low that the question about systemic side effect from JAK in that case is not really a problem. So I think everybody does understand that. After that, the way the FDA is dealing with labeling, frankly, is something that is ongoing. And there is nothing I can I can announce today, but it's also very clear to us and I think to physicians treating atopic dermatitis that having a topical formulation is a plus.

And just remind us where you stand in terms of launch readiness here, who the initial targets are and how quickly you can reach these high prescribers.

So we have 11,000 physician on the target list. They are physicians who are initiating prescriptions for eczema, atopic dermatitis in the U.S. and will be treating the type of patient I'm speaking about, who are not easily treated with OTC or steroid prescription but have sort of a recurring or a little bit more difficult-to-treat type of atopic dermatitis. So it's 11,000. We have a team already in place, in fact, ready to go. We were able to hire very experienced and talented group of people with experience in dermatology. So we are new -- Incyte, as a company, is new to dermatology, but the team we have in place is not new at all. They have done it with multiple companies. And frankly, it was a relatively easy process to attract talent in the field, in large part, because of the profile of the product because they heard about these products from their customers, and there is an anticipation. So the team is in place, ready to go, and we have a PDUFA date at the end of this month. So we are ready for the second half of the year to launch the product. And I think it would be -- I believe it will be very successful because all the market research we are getting is showing that the need for that type of profile, specifically the itch relief, the quickness, the speed at which itch can be going away, is something that is very unique and different from all the other creams, all the other topicals.

And Herve, you also announced positive data here for RUX cream in vitiligo. Just remind us what needs to be done ahead of the sNDA submission. And as you mentioned, it's a large opportunity, where do you think that initial kind of I guess low-hanging fruit population will stand there?

So the sNDA is being put together. The goal is to submit it in the second half of the year after approval in atopic dermatitis, obviously, as sNDA. The data, you saw the Phase II data. It has not yet been published, the full Phase III data, but what we said is that it's not dissimilar to what has been seen in the Phase II. So the end point is at 24 weeks. What was -- and it's a repigmentation end point. So it's a really disease-modifying effect. And it's very important. And you -- I don't know if you were able to follow it, but the FDA organized a meeting with vitiligo patient to speak about the medical need. It was a few weeks ago, maybe 1.5 months or 2 months ago. And it's absolutely clear is that there is suffering from vitiligo. It's mostly -- not mostly, it is maybe starting with the hands and the face where the most visible part of vitiligo are the most problematic. So I would say that would be where it will start of patients who want to first manage the most visible part of the vitiligo. And then I think what we have seen in our own studies is that as you see the mechanism working and the repigmentation taking place, patients plan to treat other parts of the body as they choose. But yes, I think the face and hands is -- will be the first -- maybe the patients with the highest medical need in some way will want to use the cream. I mean when you look at the Phase II follow-up, we did a follow-up. So 24 weeks was the primary end point. We had the 52 weeks, and we are showing that the proportion of patients improving continues to grow. And then we showed recently the 2-year end point, and we continue to see an improvement in the number of patient with up to 90% of repigmentation. So it's a really meaningful improvement in their vitiligo. And it's something that has a lot of impact on the life -- not just the quality of life, I mean the life of people suffering from vitiligo.

And where do you stand in terms of partnerships? You've talked about looking at that for the ex U.S. commercialization.

Yes. The goal for -- so there is Europe and there is the rest of the world. For the rest of the world, we are looking at different partnerships that would be possible. Obviously, having the Phase III study in vitiligo, which just happened a few weeks ago, is very important because in many countries, in fact, vitiligo could be the first indication that our partners would seek because of the reimbursement system for atopic dermatitis is leading to a level of pricing that may not be compatible with a product like RUX cream. So there is, in many parts of the world, potentially a launch in vitiligo. And that could be also the case in Europe. So in Europe, we are looking -- after a fairly in-depth analysis, we are looking at Incyte leading the commercialization in Europe. It may not be that we will be alone doing it. So there could be a co-commercialization kind of mode in some countries or in different geographic areas in Europe. But from the revenue standpoint, Incyte will be booking the sales in Europe and will be leading the commercialization, pricing, et cetera. And we anticipate that it will be also vitiligo first. So the first indication will be vitiligo. So submission could be done in the second half of this year, leading to a launch a year later in Europe. So early '23 could be when we are launching the cream for vitiligo in Europe.

And how are the launches progressing for 2 of your other drugs, Pemazyre and Monjuvi? Pemazyre, I think there was a competitor that just entered the market. Just curious how that's playing out. And with Monjuvi, it's early days, but just how has the feedback from physicians and patients been?

So we launched both of them during the COVID period. As I was describing at the beginning, the cancer hospitals and clinic, specifically, we are very close to any type of in-person visits from us. So it was an interesting challenge. The launch of Pemazyre ended up being better than we were expecting. So that was interesting because the number of patients we have seen benefiting from Pemazyre was more than what the epidemiology was telling us it should be. So there is a lot of -- it's happening fairly often is that when you have a new target, like fusion, translocation or mutation, when a product becomes available, the number of patients being diagnosed goes up because physicians tend to test more of their patients. And there are some patients where cholangiocarcinoma was not diagnosed first, but where the mutation led to the diagnosis. So like unknown origin type of tumors that are reclassified as cholangiocarcinoma. So that's doing well. It has been very well tolerated. We see a duration of treatment that is more also than what we were expecting. So patients are benefiting from Pemazyre, and it's doing well. We are now launching in Japan and in Europe. So the launch on other parts of the world is taking place. Regarding Monjuvi, it was a little bit more complicated. It's an injectable product that requires a number of injection at the beginning of the treatment. So what we have seen is that the clinical profile of Monjuvi is very, very well received. Everybody can see -- and you saw it at ASCO just a few days ago. There was a publication of the 3-year data showing that the complete responders are, in fact, maintaining their response for a very, very long period of time, up to -- I think it was 40 months in the publication. So it's a very beneficial treatment, the only approved second-line treatment after R-CHOP. And obviously, because it's a chemo-free type of treatment, it has a tolerability profile that is better than using chemotherapy plus Rituxan, which is what a lot of people are still using as a second-line treatment. At the same time, access for patients to their oncologist and access for us to inform hematologists on how to use Monjuvi has been a challenge. So we really expect to see in the second half of the year an acceleration of the launch. It went okay, but it was not maybe as dramatic growth as what some -- we were expecting. And we think the second half of the year would be the time when, in fact, the actual launch is taking place with physicians speaking with our team on how to use the product and with patients coming for injection, which is a number of -- I think it's starting with 5 injection over the first 2 weeks. So it requires public transportation to come to the hospital. And you can imagine, in the middle of COVID, it was not the first choice in some way. And I think it's going to improve because the profile of the product is excellent in term of safety, efficacy and the duration of response. At the same time, we are also expanding the Monjuvi program in the first line. So that study is ongoing. You saw some of the data at ASCO. It's a very good, very high response rate when it's combined with R-CHOP. So that is ongoing. And we are also looking at different type of B-cell malignancies where it could be used. So it's a program where we think it has the potential on the clinical side to become very meaningful for IncyIncytet. The review in Europe is ongoing, and we are expecting the response to the review in the next few months.

Two very quick last question. So for -- Herve, for you, you have a number of early to mid-stage pipeline programs advancing. We didn't have time to go through all of them, but what are you most excited about? And then, Christiana, when you think about the guidance you've provided for this year and the impact from the COVID pandemic, endemic globally, how are you thinking about these various levers in your guide and confidence around the higher range of guidance?

Do you want me to go first, Herve?

Yes. Go ahead.

Okay. So let me touch on the guidance. The guidance that we provided for Jakafi at the beginning of the year, the $2.125 billion to $2.2 billion, accounted for several scenarios around the recovery for COVID in the second half of the year in terms of the depth of the recovery and the speed of the recovery as well as some additional sales from Jakafi in chronic GVHD. We will review the guidance based on our current expectations. So on that recovery, what we are seeing as well as this 3-month delay to determine if there is need to make any adjustments to the range. And if there is, then we will communicate it at the time of the second quarter call.

No. So the early pipeline, I mean we know there are a number of projects. So there is an adenosine project with CD73 and 2A/2B. It's a very interesting target because we know it's an immunosuppressive -- it's the most important immunosuppressive mechanism in the tumor. It's very difficult to address it, but we have this sort of dual approach of antibody against CD73 and a small molecule 2A/2B that is excellent in term of profile and the potential for us to combine PD-1 antibodies with CD73 and 2A/2B. I mean it's a sort of a unique opportunity that we have there. We have the oral PD-L1 program ongoing. Now we have more than 1 molecule. We have 3 of them in the clinic. It's something we have shown at SITC is, in fact, the mechanism is doing what it's supposed to do. So it's active. And the question for us is to find the right schedule and how to use it. So we have multiple opportunities to do that. It could be applicable obviously in multiple conditions where using an oral PD-L1 instead of an injectable antibody would be useful. And it has a unique property of being reversible, is that if you stop taking the drug, you can see obviously the biologic effect disappear very quickly, which is not the case with an antibody that can stay for a long period of time. So that's exciting. We have AXL/MER, which is a sort of a TAM inhibitor. So it's a thyro-sparing, AXL/MER-specific inhibitor. It has been slow because we were very careful in the dose escalation to start at a relatively low dose, but it's moving forward in an interesting way. And I think it could be important. And we have MCLA-145, which is a 4-1BB PD-L1 bispecific, that we are developing together with Merus. So it's a little bit -- you know, 4-1BB is an active mechanism, but it has its own issue in term of systemic and liver toxicities. So the idea here is to see if we can redirect the 4-1BB to the tumor and avoid some or all of the liver toxicity. And we don't know that yet, but it's certainly an interesting mechanism. So yes, there are a number of program in the early portfolio moving. And also some of the molecule like PI3-kinase delta, we spoke about myelofibrosis, but we have also a submission planned in lymphoma in the second half of this year. And we showed recently first data in hemolytic anemia where, in fact, it has a very interesting efficacy profile. And that's something we are planning also to develop. So there are multiple dimension to PI3-kinase delta that could make it a very important part of the portfolio.

Great. Well, with that, thank you so much. Really appreciate your time today. Thanks, Herve. Thanks, Christiana.

Thank you. Have a good day.

Thank you.

Thank you.