Incyte Corporation Price & Performance (INCY)

I'll now hand the call over to Herve. Thank you, Greg, and good morning, everyone.

First quarter of twenty twenty five was very important for Incyte. Not only because of the good performance of the commercial portfolio, but mostly because Q1 twenty twenty five puts us on a great trajectory for long term growth with the continuous expansion of OPSELLORA, successful launch of TIMRO, and the successes of the product studies in HS and proof of concept study in CSU. The financial performance was very strong, with growth above 20% in both product and total revenues, Our cash position at the end of the quarter reached $2,400,000,000 On the commercial side, Nick Timbo's successful launch is one of the four planned launches for Incyte in 2025 in The US. On the R and D front, we report significant progress so far this this year with several key data positive readout, extra bioequivalents for proof of concept data in chronic spontaneous urticaria for PoVo, and Phase III results for oxolitinib crib in prurigo nodularis and povocitinib in HS. In Q1, product revenue grew 26%, with total revenues increasing 20% year over year to 1,050,000,000.00 This growth was driven by the ongoing demand for Jakafi and ObsEloa and the initial launch of Nictimvo in third line chronic GVHD.

Moving to Slide seven and the first quarter commercial performance for Jakafi. Jakafi net product revenue in the first quarter grew 24% year over year to $7.00 9,000,000 Total patients increased 10% when compared to the same quarter in 2024. Due to strong demand and the expected continued growth of Jakafi, we are raising the full year 2025 net product revenue guidance to a new range of 2,950,000,000.00 to $3,000,000,000 Turning to Slide eight. I'm looking at Jakafi weekly by indication during 2023, 2024 and the first quarter of twenty twenty five. As you can see, unit growth remains robust across all three indications. Myelofibrosis showed growth again this quarter, while the most significant increase seen in polycythemia vera. We expect PV to become the largest contributor for Jakafi over time, supported by the data from the MAGIC PV study, which underscores the benefit of early intervention with Jakafi, and its impact on thrombosis free survival. Moving to Opsilor on Slide nine. Total Opsilora network revenue in the first quarter were 119,000,000 up 38% when compared to the same quarter last year, driven by continued growth in The U. S, contribution from Germany and France, and the more recent launches in Italy and Spain.

In The U. The annual prescription prescription trends 2024 and the first quarter of twenty twenty five as shown on the right of Slide nine, reflects continued growth of OPSELLORA for both atopic dermatitis and vitiligo. Effective March 1, Optum Premium added OPSELORA to their preferred formulary, which means OPSELORA is now preferred on two out of the three big PBM national formularies. This change has enhanced our commercial coverage from 86% to 94%.

On Slide 10, and our newest commercial product, Nictimvo, NYK TIMVO is the seventh product commercialized directly by Incyte after Jakafi, Opsilora, Iclusiq, Pemazyre, Montjuvie and Zenith. This novel medicine launched at the January for patients with third line chronic graft versus host disease addresses an important medical need and it has significant long term growth potential. After two months of commercialization, Nictimvo net product revenues in the first quarter were $14,000,000 driven by high patient need and strong commercial execution, along with our partner Syndax. We are seeing positive early launch metrics with with widespread product awareness and interest. 95% of top BMT centers have used Niktympo and 70% of all BMT centers have ordered. Nictimvo is the first anti CSF1R antibody approved to target the inflammation and fibrosis associated with chronic GVHD, and we are already seeing the impact it is having for patients giving us increased optimism for the long term potential of this product, as it is moving to earlier line of treatment. On Slide 11, a reminder that 2025 will be pivotal year for Incyte, with numerous defining catalysts set to create a significant inflection point. The launch of Nictimbo has already shown strong initial success, and we are preparing for three additional launches this year.

Collectively offering important near term revenue potential. We plan to initiate at least three Phase III study and we anticipate that seven early stage programs will generate informative data. These developments have the potential to transform our company. Finally, before I turn the call to Cristiana, would like to address the topic of tariffs. Seven years ago, we started the strategy to establish dual sourcing for key insight product with the goal of having a backup FDA or EMA approved facility in case of technical issues. This approach is giving us today flexibility for key products to manufacture in The U. S. The U. S. Market and for Europe from Europe for ex U. S. Therefore, we expect the impact to Incyte Of Any Potential Tariffs On Pharmaceuticals To Be Minimal. Finally, Our Exposure To China is now limited to some starting material for some of our drugs, and we currently hold inventory of starting material to support our forecasted supply needs, over a multiyear period. And have alternative sources of supply of starting materials that we could consider moving to if needed. Now I will hand over the call to Cristina for the financial update.

Thank you, Herve, and good morning. In the first quarter of twenty twenty five, we delivered total revenues of $1,050,000,000 up 20% versus the same period last year. Total product revenues of $922,000,000 in the first quarter represent an increase of 26% year over year. Driven by strong demand growth for Jakafi and Opsilura, as well as initial contribution from the commercial launch of Nick Timbo during the quarter. Turning to Jakafi on Slide 16. Jakafi net product revenue was $7.00 $9,000,000 for the first quarter representing 24% growth. Versus the first quarter of twenty twenty four. Pay demand increased 10% versus the prior year period, reflecting continued growth in all indications. Net product revenue growth also reflects a positive gross to net impact from the removal of the Part D coverage gap liability under the inflation Reduction Act and Incyte's Phase in participation in the Part D initial and catastrophic phases partially offset by growth in 340B. As a result of Jakafi qualifying for the small biotech exception, Incyte's participation in the Part D coverage is limited to 1% in both the initial and catastrophic phases in 2025. We expect this gross to net favorability for Part D to be limited to Q1 and for the remaining quarters in 2025, we expect the Part D coverage liability to be in line with 2024.

Lastly, the year over year comparison of net product revenue includes a 7% positive impact due to less destocking in the first quarter of twenty twenty five versus the first quarter of twenty twenty four. At the end of Q1 twenty twenty five, Jakafi inventory levels were within normal range. Turning now to Oceleura on Slide 17. Net product revenue for the first quarter was $119,000,000 representing a 38% increase year over year. U. S. Net product revenue of $95,000,000 was up 20% year over year, driven by a 24% increase in pay demand partially offset by a reduction in channel inventory. Channel inventory levels ended the quarter within normal range. Ex U. S. Net of product revenues of $23,000,000 were driven by continued uptake in Germany and France, as well as the recent launches in Italy and Spain. Turning to Slide 18. As in prior years, Opselura first quarter results reflect the typical seasonality we see in the first quarter of each year driven by the reset of insurance plan annual deductibles in The U. S. As well as holidays and other events that negatively impact Scripps. Turning now to other hematologyoncology products, on Slide 19. Net product revenues for the first quarter were $94,000,000 representing a 30% increase year over year.

This is primarily driven by the commercial launch of Nictimbo during the first quarter of twenty twenty five, which contributed $14,000,000 in net product sales. Growth from ONJUVY in the first quarter of the year primarily reflects a full quarter of Incyte recording net product revenues in The U. S. Versus two months of net product revenues in 2024 a result of the acquisition of the exclusive U. S. Rights to Montjuvy that closed in February 2024. Moving on to Slide 20 and our operating Total GAAP R and D expenses were $437,000,000 for the first quarter. An increase of 2% year over year driven by continued investment in our late stage development assets offset by the timing of certain expenses which favorably impacted Q1 twenty twenty five. Moving to SG and A. Total GAAP SG and A expenses were $326,000,000 for the first quarter, representing an 8% year over year increase primarily driven by timing of consumer marketing expenses, [indiscernible] and certain other expenses. Finally, total ongoing operating expenses in the fourth first quarter of twenty twenty five increased 6% year over year compared to a 20% increase in revenues during the same period leading to further increase in operating leverage and margin.

Moving on to our guidance for 2025. We are increasing our full year guidance for Jakafi from a range of $2,925,000,000 to $2,975,000,000 to a new range of 2,950,000,000.00 to $3,000,000,000 We are reiterating our full year guidance for Opselura our other hematologyoncology products, COGS R and D and SG and A. For R and D, our guidance excludes the impact of the recent deal we signed with Genesis, which is expected to add $15,000,000 to our full year R and D spend. I'll now turn the call to Pablo for an R and D update.

Thank you, Cristiano, and good morning, everyone.

As we highlighted a year ago and we summarized on this slide, we remain on track to deliver more than 10 high impact launches by 02/1930 from programs across the portfolio. In the next few slides, I would like to provide an update on two of these programs. The phase two proof of concept study of povorcitinib in patients with chronic spontaneous urticaria and an update on the Phase III results for povircitinib in patients with hidradenitis suppurativa. We're delighted to announce the policy top line results for the Phase two study evaluating povircitinib in patients with chronic spontaneous urticaria. The study met the primary endpoint at the seventy five milligram dose of change from baseline in the Urticaria Activity Score summed over seven days or US seven, at week twelve. Treatment with porcitine was well tolerated, with no new safety signals observed. These results open the door to a potentially new treatment option for over three hundred thousand patients with CSU are inadequately controlled on antihistamines. We're pleased with this proof of concept result. Which will be presented on upcoming medical conference. And we will be engaging with regulatory agencies to determine next steps as we plan a pivotal study for poresitinib.

In patients with CSU. Just a few weeks ago, we presented the results of the phase three studies STOP HS1 and STOP HS2 evaluating povircitinib in patients with moderate to severe HS. The studies showed statistically significant and clinically meaningful improvements in HiSCR at both doses in both studies. Slides twenty five and twenty six summarize updated results through eighteen weeks of follow-up in these two studies. As a reminder, patients on placebo were allowed to cross over at week twelve and were randomized to either forty five or seventy five milligrams of lovastatin. As illustrated in the chart, for those patients who started on povircitinib in STOP HS1, the number of patients achieving high score increased from one hundred and seventy six at week twelve to two hundred and three by week eighteen. Among the patients who crossed over from placebo to receive either povastatin forty five or seventy five milligrams high score of week eighteen improved from twenty eight point six on placebo to fifty seven point one and fifty seven point eight, respectively. Importantly, for the crossover patients, the number of responders increased from fifty eight to one hundred in just six weeks, demonstrating once again the rapid onset of benefit produced by polarsentan in patients with HS.

Similar findings are observed in STOP HS1 summarized on this slide. For those patients who started on povastatin, the number and proportion of patients achieving high score continues to increase from one hundred and sixty four patients at week twelve to a hundred and seventy seven patients at week eight eighteen.

Among the patients who crossed over from placebo, receive either poresitinib forty five or seventy five milligrams high score of week eighteen improved from twenty nine point seven percent on placebo to fifty eight percent and fifty five point two percent, respectively, while the number of those achieving high score increased from sixty to ninety nine. This week eighteen results from both stop ages one and STOP HS two clearly show that the response rates in the povastatinib arms continue to increase over time, and perhaps more importantly, demonstrated doubling of the responses in patients initially randomized to placebo after they were switched to either poresitinib dose level.

We previously reported a greater differential in favor of polarsitinib in patients previously treated with biologics, with an average placebo adjusted difference in high score of nineteen one percent for povastatin forty five milligrams and eighteen point three percent for povastatin seventy five milligrams in the pooled analysis for stop HS one and stop HS two. Slides twenty seven and twenty eight show that this is true regardless of the type of biologic being considered. Either anti TNF or anti l seventeen agents. Shown on this slide is the high score by prior anti TNF therapy placebo subtracted high score of 13 to 23% in the different arms of these two studies. On slide 28, we see the high score by prior and IL-seventeen therapy with a placebo subtracted high score of five to 25% in favor of povastatinib. Treated patients. In all, the totality of the data presented clearly demonstrates that patients with HS have the potential to benefit from povircitin therapy regardless of whether they have received treatment with a biologic, and regardless of the type of biologic they received. We're pleased by the positive data that Paul was sending continues to generate. With positive phase three data for HS, positive Phase II proof of concept data previously presented for vitiligo, prurigo nodularis, and now CSU, poresitinib solidifies itself as a potential new medicine across several indications in development.

We're executing a broad development plan and anticipate additional proof of concept data for asthma to be available in the second half of twenty twenty five. We continue to evaluate additional opportunities for proracitinib and plan to share these updates in the second half of twenty twenty five. As mentioned by Herve, 2025 will be a pivotal year for Incyte. With over 18 key milestones, including four new product launches, four pivotal trial readouts, at least three phase three study initiations, and seven proof of concept study results. As you can see on slide 32, we have achieved several of these milestones with the launch of Nictimbo, bioequivalency data for ruxolitinib extended release, phase three data for ruxolitinib cream in pyrrigonodularis, and povirsitinib in hygienitis suppurativa, as well as the Phase II proof of concept data for CSU. We look forward to sharing additional updates on these milestones over the course of 2025. I will now hand the call over to Herve. For closing remarks.

Yes, thank you. Before we close the presentation, following Pablo's update on Povo data in HS, I would like to comment on the HS market twenty twenty seven in The US. When PoVo will be launched. It's a fast growing market where there are more than 100,000 diagnosed patients with moderate and severe HS who do not yet receive advanced systemic therapies. The illustration on slide 32 reflects the group of patients on systemic therapy. There are around 3,000 patients who are not eligible for injectable treatment with biologics, as research shows that ten to fifteen percent of eligible diagnosed HS patients are not receiving injectable therapy for practical, financial, reasons or at the patient's request. POVO will be the only oral treatment approved in the pre setting, and we anticipate this segment to grow significantly in the years following the approval of povercitinib. In 2027, Novo will compete for the 16,000 new biologic eligible patients started on systemic therapies that year, in dark blue on the graph, with a competitive product profile based on an oral treatment with high high score, durable responses, fast pain relief. The largest segment at launch in 2027 will be the group of patients, who have received biologic treatment including anti IL-seventeen and require a new option for lack of good disease control.

We estimate that group at twenty seven thousand patients, or around one third of the pool of seventy four thousand patients, on biologics that year. This is equivalent to an estimate of average biologics treatment duration of three years. In this patient population, as Pablo has presented earlier, povastatinib efficacy profile is unique, and will drive the early adoption curve.

Overall, these estimates show that porosity porvastatinib will be potentially targeting forty six thousand HS patients in 2027. With the longer term data shown today for new patients with efficacy data maintained in the post biologic setting, we see HS as an important contributor to the total potential of povercitinib with vitiligo, prurigo nodularis and now CSU as the subsequent indication.

To recap, we are we have delivered a very strong commercial execution in the first quarter in both Oncology and in dermatology. The successful launch of Nictimvo demonstrates that there is a clear need for new treatments in GVHD, giving us optimism for the long term potential of Niktympo. This quarter is when we confirm that PoVo will be potentially launched in 2027 for HS with positive data on all primary endpoints in both Phase III studies a competitive profile in treatment naive and post biologic HS, and now proof of concept in CSU. This result reinforced povastatin potential as a multibillion driver of future growth for our company. Our pipeline continues to advance with short term deliverable for three additional launch launches in 2025, Wrox XR in 2026 and good progress of the earlier project. And importantly, we have multiple upcoming and catalysts remaining in 2025, which will further shape our trajectory. And create additional value. Operator, that concludes our prepared remarks. Please give your instructions and open the call for Q and A. Certainly. We'll now be conducting a question and answer session. If you'd to remove yourself from the queue, please press 2. The interest of time, we ask you to please ask one question then return to the queue.

Once again, that's 1 to be placed in the question queue, and please ask one question then return to the queue. Our first question today is coming from Michael Schmidt from Guggenheim. Your line is now live. Hey, good morning. Thanks for taking my questions. I had a question on Jakafi where PV, as you mentioned, is now the most important growth driver for the product. You know, capturing about one third of sales. And can you talk a bit more about your expectations for how much of that is driven forward by new patients versus continued use of the drug by patients on therapy. And secondly, there was some recent positive announcement of Phase III data of a cidin mimetic in PV. As an add on to standard of care. How do you expect that potential approval to impact potential use of Jakafi going forward? Thanks so much.

Hi, Michael. Mohammed here. Thank you, for the question. Let me just address the PV. Growth drivers first.

The team is doing a really nice job, today, executing on our PV strategy, educating the marketplace on the importance of treating PV earlier with Jakafi, which results in reducing the risk of thrombosis And because of that, we're seeing actually new patient growth as well as patients continuing on therapy. So the drivers for growth for us in the future will be a combination of both new patient starts as well as persistency within that. And then from the phase three data that you're mentioning, look. I think know, first and foremost, it's always good to see new treatment options available for patients. That said, the agent that you're referring to is currently being studied in combination with other agents. We think that that's going to be used generally in combination with Jakafi and others. And Jakafi, on the other hand, remains you know, the only FDA approved JAK inhibitor for PV after HU. Failures or intolerance that addresses both hematocrit and disease progression. That's a really unique profile for us that we think continues to put us in a really competitive leading position. Thanks again for the question, Mike.

Thank you. Next question today is coming from David Lebowitz from Citi. Your line is now live.

Thank you very much for taking my question. In terms of povo for chronic spontaneous urticaria, ultimately, where do you see it fitting? Is this something that would be, before moving to biologics such as, Xolair, and other therapies, but after things like the anti the antihistamines and montelukast, or do you see it more competing directly with the post Xolair crowd?

So let me let me take that that question. So, look, I think that as you know, most of the patients, more than half the patients fail not only conventional antihistamines, but by next generation antihistamines and high dose And those patients we believe, will benefit from having an oral option to manage their chronic spontaneous urticaria. So I think it will be both populations. I think it will be a patient preference to some extent. Some patients will prefer to try another oral, like policidinib, before trying a biologic. Other patients, particularly perhaps those with high IgE, which are about half the patients will prefer to try biologic first. Those patients still have a very high failure rate. And they could be treated with over a significant alternative after that. So I think we will potentially address both patient populations.

Thank you. Next question is coming from Andrew Barron from Leerink Partners. Your line is now live.

Thanks and congrats on the new Povo HS data. I know placebo patients crossed over in this trial, but what would you have expected the control arm to do based on historical data Are you guys gonna continue following these patients beyond eighteen weeks? Then you also suggested in the press release that there may be increased activity in naive patients crossing over from placebo Was this the data that you shared in the presentation in patients that have received a prior biologic? Or were these true naive patients?

Good morning, Andy. So a couple of points to address your your questions. Yes. We will continue to follow the patients. For efficacy and safety up to fifty two weeks. So as you know, we're not gonna provide an update every few weeks. But there will be future updates on the maturity of the data both for efficacy and safety from the two studies. I think we wanted to provide an update now because our study was analyzed at week 12, which was a little bit earlier than other studies from competitors. So we wanted to show longer from the from both treatment arms and particularly important in this case, the crossover arm which show how quickly the placebo patients improve when they're crossed over to povastatinib. I think that when it comes to naive versus biologic exposed, I think the important point is the overall, the two studies met the primary end both studies in both dose levels. And that's, I think, important to remember. We wanted to give clarity on the post biologic use because we think that, as Herve highlighted, is one of the areas where povastatin could have a very important role for patients. And so the clarity that he worked very well regardless of prior biologic use and regardless of the type biologic.

We thought it was an important thing to remind everyone of.

Thank you. Next question is coming from Tazeenah Mogg from Bank of America. Your line is now live.

Hi. Good morning. Thanks for taking my I just wanted to get an update on one of your pipeline assets namely the Kallar compound You had guided the data for this calendar year. Is that still the plan? And if can you just give us a little bit of guidance on what level of data to expect? Thanks.

This is Pablo. I think you're asking about the, mid monoclonal antibody. We promised date in 2025, and we will present data this year. It will be a substantive amount of data. We have doses escalation. We're gonna have a range of doses. We're gonna have data in ET. And data in myelofibrosis, and we will present clinical endpoints as well as early data on VAF variability of fraction burden over time. So I think you should expect a reasonable number of patients with a range of doses that will be presented.

Thank Next question is coming from Salveen Richter from Goldman Sachs. Your line is now live.

Hey. Great. Thank you. This is Matt on for Salveen. Maybe just a follow-up on that last question. Could you share any more details terms of how we should assess the kind of curative efficacy potential? For KALAR. And then kinda just walk us through what is, like, the base case in terms of [indiscernible] Mono Versus A Jakafi Combo. And Then If I Could Just On Tariffs, It Seems Like You All Are Well Positioned From A Manufacturing Perspective. Is There Anything You Guys Can Share In Terms Of Where IP Is Based And How Much Profit You Book In The US? Thank you.

Let me take the first part of the question on on [indiscernible] So I think that the data for [indiscernible] with ET and MF. Obviously, we would like to change treatment paradigm in these patients. And over time, we would like to see evidence of disease modification That could take time, but we would like to see early on there's a decrease in the allele burden in these patients.

And that's an important part of this study.

However, the immediate benefit for patients or in the near term will be the classic signs and symptoms of this disease, is blood counts, symptoms, etcetera, both in ET and MF. So what we intend to present is a comprehensive data package addressing both sides of that the clinical endpoint as well as allele burden reduction. And over time, we expect a sustained and more pronounced effect in these patients as we continue to treat them with the antibody.

And on the on the on the tariff question, so as I said, I mean, we have manufacturing available for each of the products in Europe and in The U. S. So that gives us basically an opportunity to supply The U. S. Market from The U. S. And therefore, there is no tariff eligibility there. Regarding IPs, the ownership of the patents for our key product is in The U. S. Thank you. Next question is coming from Brian Abrahams from RBC Capital Markets. Your line is now live.

Hi, everyone. This is Nevin on for Brian.

Just a quick question on Ophtholura. It's been the contribution to of atopic derm and vitiligo to one q for Opsilurin. How do you how do you kinda see that moving forward We've heard from some physicians that access to AD can to be a hurdle. So how how are you currently working to improve some of access to Absaluran AD?

Yeah. The two part question.

Is Matthew. I'll take the first part on the contribution of AD versus, Vitiligo. Right now, we we see the the split to be pretty as both indications are growing at pretty much a similar pace. In terms of access to a d the future, there are two components of it that we're working on. One, is the formal reposition that we have, particularly on the commercial plan. And as Herve mentioned before, as of March 1, we had Optum Premium moving from no cover for ObsEleura to preferred position. That brings us not just two out of three major PBMs in their preferred position, but also, as Herve mentioned, more than 90% of on commercial plan covered. The other area of work that we're doing, and we're receiving initial positive feedback on improvement, the AC ACPs and their office staff see on the accessibility to ObsElla is on the patient service that we offer. So we continue to work on both fronts. To make sure that the feedback and the easy to access Obsolura feedback continues to improve in in the coming quarters.

Thank you. Our next question today is coming from Jessica Pfeif from JPMorgan Chase. Your line is now live.

Hey, guys. Good morning. Thanks for taking my question. Curious if you could update us on how the company is thinking about capital allocation and business development. Do you want to see the rest of this year's pipeline readouts play out before making any moves there? And with the stock back in the fifties, is another ASR on the table? Thank you.

Let me take that. I mean, the the the big picture on capital allocation is obviously our internal pipeline success and or lack of. So the evolution of the internal pipeline is driving a lot of the way capital is allocated. You can imagine with seven proof of concept events happening each of them can lead to a phase three program, and therefore, it will be utilizing a large portion of our R and D budget. So that's the first capital allocation is in our R and D. In term of external business development, we spoke about it. We would be like we have done recently with Genesis, looking at our research partnership or very early products where we have an interest on the side, like preclinical or very early clinical. Sort of partnership, and we continue to look for that. And regarding future strategies in term of share repurchase, I cannot comment on that.

Thank you. Next question is coming from Mark Fromm from TD Cowen. Your line is now live.

Hi. Thanks for taking my question. Maybe a couple of follow ups just on some of the earlier topics.

On the the CalR update, would you would you expect to be able to talk about kind of next steps and whether you know, you think there's a pivotal path forward yet? Or is it the state likely to maybe not quite be that level of maturity? And then on the, on the updated HS data, just the potentially better efficacy in the 17 experienced patients is obviously provocative. Any ideas as to how you can kind of prospectively identify these patients that may do very well on a JAK relative to an 17 to maybe help them avoid months of what might be ineffective IL seventeen therapy?

Hi, Mark. This is Pablo. On CALAR, we'll certainly discuss next steps when we present the data.

We always try to do that. That's why we wait to have a reasonable number of patients. And some follow ups so we can tell you what we're planning to do next. So you should expect a conversation on that to happen when we disclose the caller data. On your the second part or your second question, you know, it's it's hard to tell at this point. I think that we will look more depth at the data that we have, which are two large positive phase three studies, to see if we can identify any specific baseline characteristics that predict for better results But it's gonna be hard to figure it out, ahead of time which patients are more likely to respond to an IL-seventeen than to a JAK inhibitor.

Think Herve highlighted very clearly where do we think that patients are more likely to benefit or to use a JAK inhibitor. From the start of therapy. And in a proportion of patients, that will happen after now seventeen or after until TNF. But it's gonna be hard to identify those patients ahead of time.

Thank you. Next question today is coming from Dipram Pohit from Morgan Stanley. Your line is now live.

Hi. Good morning. Thanks for taking our questions. Following up on immune calor questions, we actually had a similar one for the JAK two b six one seven f I program.

Just wanted to see what level of update we can expect this year for that program and also kind of what what you might be able to communicate on next steps there once we have that dataset. And then secondly, guess revisiting Rux XR, just wanted to get an update on where that program stands, what next steps are, and how you would see that moving forward.

Assuming you know, positive update from the FDA there?

Thank you.

So on June, that program is if you remember, is behind the mutant cholera antibody program because we started in healthy volunteers. We had to do some work on the formulation. So it started to be tested in patients later than the mutant cholera antibody. So the update that we provide which we intend to do this year, may be a smaller number of patients, than the mutant cholera antibody. Still gonna discuss what the next steps out of that time, but the the the extent of the update could be more limited. Let me hand it over to Steven to talk about where we are with the rux XR program.

Yeah. Thanks. On the extended release, as we communicated earlier, this year, the key component that we had to achieve was to meet bio equivalence, which we did and we have in writing from the regulators that, that was achieved. What follows is to, lay down stability and complete that towards the end of this year and then immediately file that response towards the end of this year.

It's a response to a CRL. The timeline clock on that from a regulatory point of view is six months. So we expect approval for XR should that all go well by the middle of next year.

Thanks.

Thank you. Next question is coming from Kripa De Veraconda from Truist Securities. Your line is now live.

Hi. This is Alex on for Kripa.

In reference to the slide of the HS market, with the 46,000 eligible patients that could be treated by PoVo, Is that a snapshot of the current market and when we think about penetration into the different segments there, is it equal penetration? That you see Pogo going into for all the three different segments? Or does some stand out more than others? And how do you see the landscape evolving, in the future?

Maybe I mean, and Mateo can can complete the response. The way the slide was, was really to give you a picture of 2027. So it's when Provo will be launching. And the idea is to show that in fact, there is three different segments that are part of where Pogo could fit and would be competing. One of them, the first one, is for patients who don't want to get injection for many reasons, but and that's not a nothing. It's around ten to fifteen percent of new lead diagnosed patients who are moving to systemic therapy today. We have research on that. So that's the top line that's the top segment it will start at around this ten percent to fifteen percent, which is three thousand patients. And obviously, as the other piece, which is the dark blue in the graph, is evolving, is a place where newly started patients who are eligible to biologics, and that's where basically, the competition will be between starting with the biologic versus starting with PoVo. And I think that will take time. So at the beginning, we will be dealing with patients who are not eligible for injectable therapy and a lot of patients who are basically coming out of the pool of existing biologic treated patients And what I wanted to say with this slide is that that number is, in fact, the largest of the three.

And that's a place where, as you have seen the data from Pablo was speaking about on the prior biology exposed patients, we think the first pool of patients treated with PoVo will be there. In addition to the 3,000 early patients. So the light blue and then over time, dark blue, which is the newly studied patient on systemic therapy, will be evolving to oral treatment when people are comfortable with the profile of PoE. So that's what we are trying to say, that there is a market with biology exposed patients. There is a small segment who don't want to receive injectable and then over time, we will be gaining share in the third segment, which is the newly treated patients.

I can complement on a couple of comments on the evolution of, the landscape. As Arve said, we are already seeing now in 2024 and beginning of twenty five, quite a dramatic in the churn of patients that go from 17 to DNFs and and vice versa. And we see that continuing grow all the way to set twenty twenty seven when we expect to come with Volvo. And and beyond. And that's actually the segment in terms of penetration that we see the highest unmet need from the very beginning. So we're very confident in the market growth that we see in front of us. For Povo.

Thank you. Next question today is coming from Matt Phipps from William Blair. Your line is now live.

Great. This is Madeline on for Matt. Thanks for taking the question.

Related to POVO and CSU, how does the efficacy profile you're seeing compare to the profile with MRG p r x two inhibition. And does the positive data with PoVo change your view on the potential to develop backup x two antagonist programs? Thanks.

So we'll discuss how the data compares with the data sets once we show the data later this year. I think that related to the X2 program, we have no intention on restarting this program. We're very happy with the results of Poe and CSU. Think this proof of concept is very important for Povent for patients with CSU, and we intend to advance to pivotal studies. We'll talk about the details of the data later this year.

Thank you. Next question is coming from Ash Verma from UBS. Your line is now live.

Hi.

Thanks for taking my question. So I had a on Manjavi, just on these Phase three in the first line and refractory DLBCL would be be in the front mind studies. Just if you can share what are your expectations here in these studies in terms of the efficacy that would be great. Thanks.

Yeah. Thank you. It's Steven. So, you know, tafasitamab now obviously has positive data in relapsedrefractory large B cell lymphoma, and that indication is approved. And then more recently at ASH last year, the IN MIND study in follicular lymphoma with really outstanding efficacy in terms of, you know, hazard ratios, etcetera, and now waiting the first line study to report out. It's event driven. It's a large study. And we've guided to having data potentially in the first half of this year as soon as we have sufficient events. Should that be positive, we would be moved very rapidly to complete a submission package and get it across the finish line. Line. But we really like the way, the c d nine antibody is shaping now as it moves sort of forward in, as I said, relapsed refractory follicular and now potentially in first line. And with more and more evidence, accumulating that c d 19 expression is not affected by treatment with this antibody. It's maintained. And so people can, for example, use CAR T directed against CD 19 after the therapy. So it's a profile that we're becoming, you know, increasing encouraged by. Thanks.

Thank you. Next question is coming from James Shin from Deutsche Bank. Your line is now live.

Good morning, guys. Thank you for the question.

Maybe one for Steve and Pablo. For the week eighteen telvirsenib update, it looks like about half of the placebo patients crossed over Did these crossover patients experience rapid pain reduction from the week like, we saw in week twelve? And if I recall, around thirty six to thirty seven percent of the placebo patients were put [indiscernible] Can you give us a breakout of pre and post biologic for these placebo crossovers? Thank you.

Yes. No, thank you. It's Steven. I'll take that question. Pablo may add comments. To what he had in his prepared remarks. We thought this was a really important update to reiterate what Pablo said. To demonstrate drug effect.

Because, you know, once you have that twenty eight, twenty nine percent placebo rate at week twelve, then introduce those patients to either the forty five or the seventy five, you can see in in six weeks, you know, this dramatic twenty to thirty plus percent absolute improvement in his car rates. And that really demonstrates the drug effect of placebo versus active drug there. So that's really, really encouraging.

What's more is because of the market breakdown that Herve illustrated, in the different eligible potentially eligible populations, whether it's naive or biologic exposed, again, we thought it was important to illustrate the data in biologic exposed patients both to TNF alpha inhibitors, IL-seventeen, potentially to both and again demonstrate their, you know, really encouraging and potentially even better activity in those populations as demonstrated by the data.

You're absolutely right. About, one third, thirty five percent to forty percent of patients on the whole of biologic exposed, So the majority of the population sixty percent plus is is naive. That's an important population to study. It was really important for Europe, in terms of getting reimbursement there as well. So we the breakdown in the naive versus experience, we didn't tease out directly, but you can indirectly work it out. And, again, activity is shown across the board.

Thanks.

Thank you. Next question is coming from Salim Syed from Mizuho Securities. Your line is now live.

Great. Thanks for the question, guys. Just maybe one for me on Niktinbo, actually. So pretty good beat. This quarter. Just curious if you can maybe comment on just some of the dynamics with the $14,000,000 of sales. Was there anything there particularly one timer that we should be aware of and then kinda related to that with the j cut going effective for 01/25, how much of a tailwind has that been kind of through the through the month of April? Thank you.

Hi, Saleem. Mohammed here again. Thank you for the question. Yeah. Look. So let me just start by saying we're very pleased with the launch performance so far. Our team has done a really effective job of driving broad and productive of Nicktimbo.

As you heard earlier in the prepared remarks, 95% of our top accounts are using Nicktembo 70% of all target accounts are already using Nicktimbo. And from a onetime perspective, there isn't really much there. We're seeing that, penetration and productivity continue. As you'd expect, Nicktymbo this early on is used primarily in that fourth line plus patient. And there's obviously a bolus of patients with an urgent need for these new treatment I think that's where you're seeing the Kimbell's rapid uptake really take hold. The great news, though, is that these patients are seeing a rapid response that's very favorable, which is going to naturally encourage providers to use Niktembo earlier in treatment And then the last thing maybe I touch on from a onetime perspective as you know, we have a generous, EAP program In the first quarter, only fifty percent of those patients moved on to, paid drug, and the other fifty percent or so will come in q two. And then, you know, as you would expect when a new product is launched, there's certainly an inventory dynamic that you see in q one.

So about, you know, a third of our sales in q one is also coming from some inventory build, but we expect that to be stable for the rest of the year.

Thank you. Our next question today is coming from Gavin Clark Gardner from Evercore ISI. Your line is now live.

Hey, guys. I just wanted to quickly follow-up on the tafa first line Phase III DLBCL trial.

Believe on the slides, you noted the data got moved to the second half of this year. I I think, Steven, you may have noted data was still in the first half potentially.

Just wanted to confirm the latest guidance, and also clarify if a 0.73 hazard ratio from Pilevi's trial is a reasonable benchmark. Thank you.

Yes, Gavin, it's Steven. It's always tricky with event driven studies to be precise, as you know, and when data will ultimately come, especially when spans, you know, a quarter change. But you can read in the marks, you know, from my remarks that we expected sometime soon, we're getting close to the required events. To trigger the analysis. What will then follow is database closure, clean in, independent review of radiology, etcetera.

So it may it may track a a little later. We see and that could be a positive thing if those obviously, delay of events is due to to activity.

You know, I think the the polyvi effect in first line diffuse large B cell lymphoma is probably in the ballpark of a reasonable benchmark because it's the similar population of the more severe people with this disease. So the IPI, higher scores in terms of prognostic index. And it was just to remind everyone, you know, the first positive study increasing cure rates in first line diffuse large b cell lymphoma in a long time obviously, with the 79 mechanism. We're really interested now in dual inhibition of nineteen and twenty. We've shown data just to be repetitive in relapsedrefractory follicular, and now we'll see what the first line data shows. You know, we will announce because of the materiality of this data, you know, as soon as we have have it available, and we're waiting for those events.

Thanks.

Thank you. Our next question today is coming from Olson from Oppenheimer. Your line is now live.

Hey. Thanks for taking the question, and congrats on all the progress. For your CDK two inhibitor, what are the key data points we be looking out for in your ASCO update, and, what are the gating factors to starting the phase three study in ovarian cancer? Especially if you could talk about the companion diagnostic and how that's progressing? Thank you.

So thank you for the question.

So what you what you will see at ASCO is an incremental update. In the you remember, we presented a very comprehensive dataset at ESMO last year, and ASCO will provide a little bit more data, more follow-up in some of those patients. I think more importantly, to the second part of your question is, we are in process of implementing the pivotal trials in platinum resistant ovarian cancer. That's moving forward. Are moving forward with the diagnostic, as well. That's advancing very well. And we are, conducting a combination, a phase one study in combination with Beva cizumab, which is necessary to launch the platinum sensitive ovarian cancer study. All those things are moving forward as we speak.

Thank you. Our next question today is coming from Kelly Shi from Jefferies. Your line is now live.

Good morning. This is Clara on for Kelly. Congrats on the update and the initial launch performance.

Performance of So for Neopinglo, I wonder if you can could share some key physicians feedback whether [indiscernible] or rather off naive patients such as Sephoine how you expect this dynamic to evolve over time? Well, apologies if I missed it, but what's the time line for approval if she has regulatory submission?

Yeah. So The question was about ResiWalk and where it's used on the launch.

Yeah. Thank you, Claire, for the question. Let me take the Nitemvo piece, and then I'll pass the timeline for Povo HS.

To Pablo and Steven.

As I mentioned, know, Niktymbo when when introduced in such an unmet need of that currently exists, we're currently seeing it used in you're really primarily in the fourth line plus patients. As as you would expect, there's a bolus of patients with GVHD late stage that have an urgent need for a new treatment option, and that's where I think Myktymba will make an impact as soon as it gets introduced.

Like I also mentioned, the great news, though, is that we're seeing these later stage patients respond very favorably. Customer feedback has been very positive.

With some sharing that they're seeing Nectimbo really demonstrate its rapid and broad efficacy profile. That was seen in clinical trials in practice, and that will naturally, move Nictimbo earlier line.

Nictimbo, you know, our perspective, has a key differentiator, which is the mechanism of action, which is completely different pathway than other approved agents.

Making Nictimvo, I think, a great addition and option to be used right after Jakafi in the third line. So whether it's it's, you know, in the third line now versus Resuroc or or or not, I think it's soon to be told, but we're really optimistic about the competitive profile and the customer feedback so far. And again, we're really optimistic about it being used earlier in line once providers and patients get more experience with Yeah. And, Kelly, in terms of the time line for the HS submission, obviously, you know, you've seen the efficacy data and the safety profile through week 12 and now through week 18 very clean. The key component of this is negotiating with the regulators as to how much of the safety they'll require the time of initial submission, versus the ability to supplement that as at the four month safety update. So our guidance hasn't changed. We wanna do it as quickly as possible. Towards the end of this year, tracking potentially into early twenty six at the moment. And we'll provide more precision on that when we have more precision. Thanks.

Thank you. Next question is coming from Schmidt from Cantor Fitzgerald. Your line is now live.

Great. Hi. This is Imogen on for Eric. Good morning, everyone. Two questions from me. The quick one on axatilamab. Could you comment on that 14,000,000 of what proportion of that is inventory? It looks like a really strong launch. So congrats. And then one question on Pogo and the HS and the, longer term data after week 12. Could you talk about how, you the dropouts were treated in that later section? And whether patients who took rescue medications like antibiotics in in the week 12 control period were then kind of added back in because I think that was part of the, nonresponder criteria. Thanks.

Hi. Imogen Muhammad here. Thanks for the question on nictimbo. In just the first couple of months, we're seeing about twenty percent to thirty percent of the of the sales so far is really made up of inventory. But as I mentioned, multiple accounts have already reordered.

That inventory level, continues to be stable. So that's what I would expect for the rest of the And then, Imogen, thank you. On the long term data, It's really interesting. So we obviously had a very conservative approach in terms of the analysis and the non responder imputation. And that anybody who discontinued for whatever reason was considered a nonresponder. First, a more modified approach, which some other competitors are using We will analyze both and at some point in time provide both. We expect the modified NRI actually to have slightly better numbers. Than the conservative approach we use. So thank you for that question. It's an important one.

Thank you. Next today is coming from Evan Seigerman from BMO Capital Markets. Your line is now live.

Hi. Malcolm Hoffman on for Evan. Thanks for taking our question. For Opsalora, you noted a slight reduction in inventory, which maybe dampened sales. Could you quantify the impact any further And then also, can you provide any additional commentary on how you've seen tube usage in The U. S. Progress? I know at the start of the launch, this was, highlighted as an expansion opportunity. Do you guys still think we could see more tube usage per patient over time? Thank you.

Hi, Malcolm. Miss Cristiana. Let me take the first part of the question regarding OXELURA and the inventory. I I mentioned in my prepared remarks, in The U. S, the net revenue growth was 20% with the paid demand growth 24%. The difference came from the reduction in inventory. The reduction in inventory was mainly because in given where the end of the year holiday happened took place this year, which was in the middle of the week.

Whole sellers bought before that. So it impacted Q4. And we saw that inventory level coming back down in Q1 of the year. As I mentioned, we look at the current inventory levels as within normal range and expect to continue to be pretty stable at those levels.

And I'll comment on the on the tube usage over time and what we expect We expect increased utilization overall in both indication. I think it's driven by two dynamics, our continuous prescription growth, which includes, obviously, additional new patients over time in both indication as well as the usage of the the tubes across the extensive patient population that we have built so far. And then to continue to close with that is the feedback that we continue to get from on the patient side, highest level of patient satisfaction of people that have used ObsEleura. And on the ICP side, we continue to see the willingness to utilize it more in the coming future. So when we put everything together, we expect higher utilization in the coming quarters. [indiscernible] Our next question is a follow-up from Michael Schmidt from Guggenheim. Your line is now live.

Hey. Thanks, for taking the follow-up. Just another one on on povastatin.

This this continued increase in high score 50, you know, out to week 18. Obviously, it looks very, very interesting. Did you observe a similar trajectory also for the high score 75 outcomes? And and the other question I had is just on your KRAS g twelve b inhibitor where I know you've guided to POC data later this year. Just wondering how you think about differentiation and the competitive landscape there just given we've seen some data recently at AACR. For taking the follow ups.

So Michael, I'll start on the 18. Obviously, we just showed for efficiency reasons the Hiscar 50 because that was the primary endpoint, and it's you know, we wanted to demonstrate that over time. We absolutely will have the others. As well, Hisco 75, etcetera. And the trend, I can say is similar. To your question. I'll hand it over to Pablo for your 12 d question.

So Michael, thank you for the question. As you know, KRAS inhibition continues to get increasingly competitive. I mean, I think there were 57 posters and presentations at AACR. And new data continues to be presented. We are very happy with the profile of our g twelve d inhibitor. That study is advancing very well, and we will have data to discuss with you later this year. I think at that point, we're optimistic that our profile is gonna be very competitive. We're advancing not only single agent, but we're starting combinations as well. So we'll have a broader conversation when we have the data. But so far, we're very happy with progress of that program, and we think we're gonna have a very competitive profile.

Thank you. We reached the end of our question and answer I'd like to turn the floor back over for any further or closing comments.

Thank you all for participating in the call today and for your questions. We will be available for the rest of the day for Thank you, and goodbye.

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.