Swedish Orphan Biovitrum AB (publ)

Ladies and gentlemen, welcome to the SOBE Q4 2024 report conference call and live webcast. I'm Sandra, the chorus call operator. I would like to remind you that all participants have been listened only mode and the conference is being recorded. The presentation will be followed by a Q&A session. You can register for questions at any time by pressing star and one on your telephone. For operator assistance, please press star and zero. The conference must not be recorded for publication or broadcast. At this time, it's my pleasure to hand over to Guido Oerker, CEO. Please go ahead, sir.

Thank you. Hello, everyone. This is Guido Oerker, CEO of Sobe. We are delighted to welcome you to the fourth quarter and the full year 2024 Conference Call for Investors and Analysts. We posted, as mentioned, this presentation to Sobe.com earlier today. Let's move to slide number two, forward-looking statement as per usual, unless otherwise stated, we will be making comments that most relate to the third quarter at constant, to the fourth quarter at constant exchange rate in the million Swedish krona. Today, we plan to cover the key aspects of the Q4 report. I'm joined by Henrik Sundqvist, our CFO, Lydia Bart-Franzsch, our head of R&D and chief medical officer. We plan to review the presentation first and then have Q&A until around 3.30 Swedish time or Central European time. For those on the phone, please join in the queue for questions for pressing star 1. We propose that you ask only one or two questions at a time. Let's move to the beef. This is our overview on the performance of Q4. We are very pleased with the performance of the portfolio in the fourth quarter and overall for the full year. The full year was announced a few weeks ago. Our internal expectations with 26 billion SEC in revenues representing 90% growth at CER. And the full year adjusted EBITDA was 36%. In the quarter, we saw growth at 8% and adjusted EBITDA margin was 34%. This reflects a very strong performance across the portfolio. Please bear in mind that the RSV impact by Fortis had very strong quarters in Q3 and Q4. Synergies in Q4 2023 was also extremely significant. Hence, there was a negative variation in the underlying business In Q4, excluding RSV, has been growing over 20%. Hematology growth was driven by continued growth of Doctolet, Asper Valley, and the launch of AlteWorks. There has been a strong interest in AlteWorks in just the first half of this year on generating 300 million sec in the quarter. We continue to build the launch of Wondro and see consistent quarter-on-quarter progress and we are continuing to build awareness around the product and the unmet medical need in myofibrosis treatment. In immunology, it is reflected very substantial, obviously, as mentioned, by Fortis Royalty Income in both in Q3 and Q4. In terms of the pipeline, our progress continues with the filing of GAMI Fund in the U.S. for HLH-MAS in Stills disease, and we are happy to announce that we have also submitted ASPR Valley in Europe for C3G and ICMPGN. We look forward to continuing the discussion with health authorities and bringing these important medicines to patients in these disease areas. We have very strong momentum, as you can see, in the SOVI business, both commercially and in development. And 2025 will be a busy year with multiple filings ongoing. preparing the organization for a number of new launches whilst we bring SOBI to the next level. With that in mind, our outlook for 2025 is that we expect revenue growth at high single-digit at CER and adjusted EBITDA margin at mid-30s, reflecting the investment that is necessary. Let's move over to the overall business growth. Let's look at, and this is the next slide, let's look at the overall performance in more detail. Can you move to the next slide here? Our growth of 8% in the quarter was driven primarily by hematology sales, while strong by Fortis royalty income was not able to offset Synergy's negative evolution. We saw a very strong performance in hematology with 22%. Overall, the full year, all areas delivered strong performance with hematology growing 24% and immunology 11%. In the second half of the year, the U.S. business was impacted by the loss of synergies, as already mentioned, but Gummy Fund and Kinoet have grown strongly throughout the year. Europe saw a strong growth of 14% for the full year, reflecting the launch of Altovox and other strategic growth products. In the US, we saw, as mentioned earlier, the impact of synergies, and international is continuing its robust growth with 14% in 2024, while if you take away the Fosun effect, it has grown actually at 43%. When you think about the composition of our portfolio, regional portfolio, It just shows that our internationalization strategy that we laid out in 2017 is now showing the fruits when you just think about the composition of North America, including the Bifortis royalty and this very dynamically growing international business. Let's move to the next slide and go a little bit more deeper. Focusing a bit more on the portfolio in 2024, we have seen a strong momentum across the portfolio with already significant contributions from the AltaWalk launch. We are starting to see an impact on Alokta as expected from AltaWalk. However, we have seen 30% growth across the hemophilia franchise in 2024. Dr. Laird showed continuous growing demand across all regions with 58% growth in 2024. and Asper Valley continued to grow double-digit in 2024 with 76% growth. We do expect increasing competitive pressure from orals in 2025, but in those markets where we have seen this, where we are facing this competition, the product has shown good perseverance in these markets so far. Bonjour continues its sequential quarter-to-quarter growth, and I will cover it in more detail. Kineret grew at an impressive 24% in Q4, driven by growing interest in the IL-1 mechanism in multiple settings, some phasing and some gross-to-net adjustments. For Globby Fund, we are happy to have filed in secondary HLH indication, and we see, and this will mean obviously an inflection point for the product, as it will significantly broaden the overall potential for the product. By Fortis continued its strong demand as seen in Q3, and with Q3 and Q4 reflecting the peak of the RSV season. Let's move to the next slide. And on the next slide, you can see our portfolio approach of today's and tomorrow's breadwinners. You know, while the foundation business is very resilient and has shown 6% growth, you know, this used to be essentially the DNA of Sobe. Today it is 50% of revenues, while the other half is on the right hand, where you have a nice blend of catalysts that allow us to transformation of Sobe and investing into our pipeline and into our strategic growth product and the new royalty streams from Bay Fortis and also Etuvio help on this list to go out. And when you look at the strategic growth product, they have grown very substantially. So they are 35% today, including the royalty stream is basically half of this portfolio. And this half was 55% in Q4. And then we have on the left, in the left, And this is for us obviously super important as we have a significant product that will determine the future of SOBI. So we received fast break designation for GAMIFUND in secondary HLH in Q2. And we have now submitted the filing package as indicated in December. For CEL 212, we are continuing the submission to the USF TV and we will complete the filing before Q2. We had the positive readout of Asper Valley in nephrology, and we have now submitted the filing to EMA and look forward to receiving the CHMP decision later during the year. At the same time, we continue building on our geographic footprint with launches of Asper Valley, Doctylert, Celonta, Gamifund, and Vonjo. This puts SOBE into a new phase of sustained growth driven by new products, execution in our development, on our development commitments, and we have an exciting launch in progress with Altuvox and two substantial indications in our hands with Asper Valley Nephrology and NASP in chronic refractory gout, which we will now prepare in 2025. Let's move to Altuvox. We are very pleased with our first half year on the market with Altuvox. Altuvox has seen a rapid adoption in Germany, and our market share in Haemophilia A in Germany has grown for Elocta and AlteVoc by 15 percentage points, essentially in the first five and a half months after launch. Our Haemophilia A sales grew as a consequence in Q4 at 9%. To date, in Germany, we have seen around 50% of the switches from Elocta, while the others are coming from competitive products. And the last three months clearly favor that we are taking significant more share from competition. We look forward to bringing this important medicine now to more markets in Europe and other Thobe territories in 2025. Let's move to Kaspar Valley. As you have seen, we had very strong sales evolution of Asper Valley in P&H. However, the main part of this franchise future is clearly related to Nephrology. And we are very pleased to have submitted the filing package for Nephrology of Asper Valley in EU after an impressive readout in 2024. The combination of very significant reduction in proteinuria, clearance of C3 staining from the kidney, and a high percentage of patients, and the stabilization of EFGR at such an early time makes the potential of this medicine that we were bringing to patients. For us, this product is fantastic. really right at the heart of what SOBE is about, given the fact that many of those patients are kids, and to prevent them from progressing to end-stage renal disease, we feel is an obligation and mission. We look forward to working with the regulatory authorities to move this forward and parallel with rebuilding the internal infrastructure and nephrology and prepare for the launch. we believe that Asper Valley has the potential to become a blockbuster product for Sobeys. Let's move to Bonjo. Bonjo sales were 460 million SEC in the quarter with 27% growth at constant currency and 6% quarter-on-quarter growth showing continued momentum with the product. Growth is primarily coming from They're labeled below 50,000 platelet population, and we are continuing to work to expand the use according to the NCCN guidelines in myofibrosis. We have recently hired a new U.S. chief medical officer, Jamie Friedman, who is a HEM-ONC specialist who is leading our medical organization in the U.S., and we're expecting further impulses from him to help us to expand the product. We are continuing to roll out our strategy to increase awareness of the product and the unmet medical needs with the NCCN guidelines and recommendations. The second pillar of our strategy is to bring Bonjo to patients outside of the US this year, and we will launch in selected markets which will follow the FDA label. and ultimately going to bring it to Europe and Japan, and Japan once we have the Pacifica trial concluded. The next step is to broaden the use, and we have initiated a Phase II study in Vexus, an area with currently no approved treatment, which Lydia is going to cover in her presentation. And we have also made an important strategic step to form a research collaboration to get CMML on label. And this is also another demonstration that we stand by the product. We want to further develop the product and bring it to the level that we earlier indicated when we consummated the transaction. On this note, I'd like to head over now to our CFO, Hendrik Stenqvist.

Thank you, Guido. And hello, everyone. Please turn to slide 12. We will now take a look at some key financial metrics for the quarter. In Q4, our revenues of $7.4 billion meant that we exceeded $7 billion of revenue in an individual quarter for the first time, while also making significant progress on our pipeline assets. Revenue growth for the quarter was 8% at constant currencies, and we delivered an adjusted beta margin of 34%. For the full year 2024, we achieved revenues of 26 billion corresponding to a growth of 19% as outlined in our early announcement, as well as an EBITDA margin of 36% in line with guidance of adjusted EBITDA in the mid-30s. So if we look at the bar on the left with revenues by quarter and business area, we see the solid growth in hematology of 22% in the quarter driven by all adopted hemophilia On the other hand, Immunology experienced a decline of 12% in the quarter as a result of the much lower sales of synergies and the facing of Bay Fortis royalties this year, with a clearly larger share of royalties in Q3 than in Q4. Referring back to the table on the right, the adjusted gross margin of 78% in the quarter compared to 80% in Q4-23. Royalties in general were net positive to our gross margin in the quarter, but offsetting this was the loss of Synergist sales. Synergist was a high margin product with significant sales in Q4-23. Gross margin was also negatively impacted by other product mix items, but to a lesser degree. The adjusted EBITDA margin reached 34% compared to 38% last year. The drop of 4 percentage points was due to Two percentage points lower gross margin, as already discussed, and higher OPEX driven by our investments in pipeline and launch products. Looking at the operating expenses for the quarter, we observed an 11% growth at CER compared to the same period in 2023. SG&A, excluding non-recurring items and amortization, increased by 10% at CER in the quarter. driven by launch and pre-launch costs for Altevoxt, Asta Valley Nephrology, DASP, and Bonjo. We've managed to partly offset the impact of these activities on the SG&A line through savings in the synergies organization, as we have reported in prior quarters. R&D expenses increased by 13% at CR, excluding non-recurring items, mainly due to post-approval activities for Altevoxt, and development programs in Gamifund, Bongeo and Sylvonta. The operating cash flow for the quarter increased by 67% to 1.8 billion, benefiting from less capital tied up in receivables from synergies than a year ago. And if we turn to slide 13, we see on the right-hand side of the slide that net debt went from 16.9 billion at the beginning of the quarter to 15.2 billion, corresponding to that EBTA ratio of 1.6 times. And to the left, we see the debt reduction of more than 4 billion during the year and the leverage journey from 2.5 to 1.6 during the same period, driven by the improvement in EBTA and strong cash flow. Please turn to slide 14. And we will now discuss the financial outlook for the full year 2025. And as usual, this outlook is based on revenue growth at constant exchange rates and adjusted EBITDA margins. For the full year 2025, we anticipate revenue to grow by a high single-digit percentage at CR and an adjusted EBITDA margin in the mid-30s percentage of revenue. On the revenue guidance, we look forward to continuing to launch Altevox into new markets in 2025, growing the Himophilia A franchise, as well as continued progress with our existing commercial portfolio. We expect a continued strong contribution from day four to three, although this is a factor where we do not control the outcome ourselves. In regards to our EBITDA margin guidance, we will continue to invest in our pre-launch assets, specifically NASP and ASPA Valley in Nephrology. In R&D, we will also continue with post-approval studies for Altavox and the new studies for Bonjo in Paxos and CMML, as well as major registrational efforts for ASPA Valley, Gambit Fund, and NASP. With the outlook covered, I will now hand over to Lydia. Thank you.

Thank you, Henrik, and hello, everyone. So we start with the pipeline milestones on the next slide, please. We kept advancing our pipeline projects, hitting important milestones in the fourth quarter. The very positive phase three data for us, PAVELI in C3G and ICMPGN was presented at the ASN Kidney Week in October as an oral presentation during the high impact clinical trial session. And very importantly, as you have heard, based on this data, we submitted the EU application for a label extension to EMA this week. We're also launching a phase two clinical trial for Bonjo in Vexus syndrome after receiving the IMD from FDA. And I will come back to this in a minute. We also submitted the Gamifam supplemental BLA to FDA for the treatment in HLH mass in a serious disease. and the SYNLONTA LOTUS-5 study is now fully recruited. With this phase three study, we are confirming the conditional EU approval, and we plan to extend the indication from third line therapy to second line in combination with rituximab. All of these show our ambition to drive innovation for patients and extend the reach of our medicines. Next slide, please. In December, we submitted a supplemental biologic license application for igamifan for the indication of HLH macrophage activation syndrome in Stills disease to FDA. HLH mass, a form of secondary HLH, is a rare systemic auto-inflammatory disorder for which there is currently no approved therapy. It is a life-threatening complication of a Stills disease where patients can experience intense systemic hyperinflammation and even multiple organ failure. Emapalma neutralizes interferon gamma and blocks the expression of inflammatory cytokines, which drives the hyperinflammation of HLH mass. The application is based on the pool analysis from two clinical trials presented at ACR in November, which show that Emapalma rapidly controls things and symptoms of HLH mass. 85% of patients achieve complete response at any time during the study, And the median time to achieve an overall response was below three weeks. These two clinical trials which evaluated emapalumab are the first completed prospective clinical trials in this rare disease patient population. With a potential U.S. approval later this year, we hope to provide patients with HLH mass in a still disease the first approved medication for this potential fatal condition. Next slide, please. Thank you. And speaking of first, we're launching the first randomized clinical trial in VEXA syndrome. Paxys will be a randomized phase two study to assess the safety and efficacy of Bonjo in this disease, which currently has no approved therapy. An IMD to study this indication was granted in December, and we're planning to start activating sites soon. Vexa syndrome is caused by an acquired gene mutation and manifest in a wide range of auto-inflammatory symptoms across the entire body. It has first been described in 2020 and therefore has a potentially high number of undiagnosed patients. The causative mutation has a prevalence of approximately 1 in 4,000 males over age 50 in the United States. There is no standard treatment available for patients with Vexus syndrome that may require high-dose steroids to control their inflammation. While JAK inhibitors and cytokine blockers offer some efficacy, they do not target root inflammatory pathways, and they may even worsen cytokines. Acretinib is a JAK2 inhibitor that additionally targets NF-kappa-beta-mediated inflammation via R1, and inflammatory anemia via ACDR1. Due to this unique profile, pacretinib could be both more effective and safer than other therapies that have been used to treat PECS. Next slide, please. We are very proud of what we have achieved in 2024, hitting major milestones. Altivoc was approved by EMA with a strong positive reaction by physicians and patients. As Paveli's EU label in PNH was expanded to first line, and we got very promising data in C3G and ICMPGN. We continue to grow Docteles rich in region international. We submitted the supplementary BLA for Gamifan HLH mass to FDA. We initiated the FDA rolling submission for NASP, and Kineret is another good example of our lifecycle management and geographic expansion. Next slide, please. Looking ahead, we will be busy with the submissions to the major regulatory agencies, FDA, EMA, and PMDA, for our key assets, Gamifan, Aspavelli, and NASP. In the U.S., the focus will be on the approval of Gamifan for HLH mass instills disease and on finalizing the NASP rolling submission for chronic respiratory gout. In Europe, the focus will be on the approval of Aspavelli in the nephrology indications, C3G and ICMPGN. And in Japan, we will be submitting three dossiers, Aspavelli for the nephrology indications, Gamiton for HLH mass in STILs disease, and Kineret for STILs disease. And with that, I would like to hand back to Guido. Thank you very much.

Yeah, thank you, Julia. As you can sense, you know, we are very pleased with Solvig's development in 2024. We saw significant top-line growth of 19%, driven by a positive lead was driven positively by growth in our portfolio, particularly related to our strategic growth portfolio, that has grown at 87% in 2024. Our R&D pipeline has shown tremendous progress with the approval and successful launch of AltaWorks in Europe, the filing initiation of NAS in Chronic Refractory Gout in the US, and include for the filing of GAMI Fund in the US in secondary HLH, continued in February by our filing of Asper Valley Nephrology. These open tremendous opportunities for SOBE in the coming years, and we are actively preparing these new launches in 2025, continuing the expansion of ongoing launches with our strategic growth portfolio. We have a very strong momentum, We have a lot to do in our pipeline development, and we look forward to this journey with our colleagues and stakeholders across the globe. And as you can sense, the outlook is a reflection of this work. And also, as you know us, we are not the guys who want to impress you by what we forecast, but more by what we are doing. and and we have a lot on the plate we need to do a lot because we are blessed by a fantastic pipeline in this regard i like now to refer to the q a session you will now answer your questions for those on the phone please remember to to press star one to ask questions and i can please can i please remind you to limit your questions to one or two to be fair to other callers thanks in advance and let's proceed, please. I go back to the operator.

Thank you. We will now begin the question and answer session. Anyone who wishes to ask a question may press star and one on the telephone. You will hear a tone to confirm that you have entered a queue. If you wish to remove yourself from the question queue, you may press star and two. Questions on the phone are requested to disable the loudspeaker mode and eventually turn off the volume of the webcast while asking a question. In the interest of time, please limit yourself to two questions only. The first question comes from Mattias Heggblom from Handelsbanken. Please go ahead.

Thank you so much, Mattias Heggblom from Handelsbanken. Two questions, please. So, before Disroid is made up a third of your 2024 EDITA project, And in light of a potential competitive launch by Merck ahead of the 25-26 RSV season and the 100% margin contribution a royalty stream provides, I was curious how you incorporated that potential competitive launch into your 2025 guide. Does guidance include that Merck launches and grabs a fair share of the US market season one? And as a consequence, before this royalties have now peaked in contrast to what consensus models or what is baked into your guidance. Secondly, investors appear to expect that Sobe will host a CMD later this year and perhaps provide 20-30 revenue targets. Is that fair assumptions, or are you more likely to do selective deep dives on select assets rather than host a full-blown CMD? Thanks so much.

Thank you, Mattias, for your questions with regard to you know, before this margin. I mean, obviously, you know, we do our best possible judgment and based also, you know, we follow here some of these guidelines and, you know, you probably listened in to what Sanofi was outlining last week. I mean, just bear in mind, let's say that obviously our royalties, relatively speaking, are going to grow as a percentage of sales And yes, we basically based it on what we think, you know, without having had any direct discussions with Sanofi, to what we think their prospect is. And we are recognizing that a formidable competitor is coming in, but we also recognize that the product has very strong, that Byfortis has very strong data in terms of real-world evidence. and in terms of primary endpoint versus the product. So we don't see now a Cassandra scenario for this royalty stream. So we have recognized this in our guidance. As far as the CMD is concerned, we were thinking about it, but we have actually a lot to share. So as opposed to now having one CMD and we may end up there, but Our current thinking is more to have a sequence of events and deep dives where we want to update the audience on different items, definitely related on a pipeline, but also, for instance, related for sure at the right time to watch on how to think about these new indications and other products. This is probably more what we want to do. as opposed to having one event and, you know, providing at the different time points when new data arises and new endpoints have achieved, that we basically provide an overview to keep you abreast. This is what we are doing. Thank you.

We have maybe a question. Sorry? A quick follow-up, if I could. Sanofi said they expect to grow global sales by Fortis, but they refuse to comment on USA, since you only have exposure to the US portion, any insight to how you expect that market to progress during 2025?

We have made certain scenarios and on that basis we have forecasted. I don't want to comment more on what kind of other data points we may or may not have. Thanks so much. Thank you.

The next question comes from Brian Balchin from Jefferies. Please go ahead.

Hey, thanks. Just the one question on margins. So clearly 2025 margin guide of mid-30s factors in the build-out of AstraZeneca nephrology and NASP in CRG. But then you look at the 2026 consensus, margins are stepping up to 40%. So Guido, it'd be great to get your thoughts on that step up into next year, just how we should be thinking about margins going forward. Thank you.

Yeah, thank you. I mean, you know, we were happy already to provide guidance for this year. And obviously customary is that we provide guidance for next year at the same point of time in a year later. But, you know, when you think about this business and why, you know, and I know that everybody wants us to, you know, to have higher margins. But realistically, we have, when you think about it, three products very near term in the pipeline. two of them extremely material to the future of the company. We have two products in the growth phase and, you know, Altobox being now commercialized all Europe and then also internationalized in our territory, you know, during the next, let's say, 12 months. And then you have one, Joe, where we shared your vision that we want to embark on labor expansion and new indications. This is a lot for the size of the company. In fact, the opportunity in terms of scale is probably, for the size of company we are, is a massive work. That's the reason why we look at the royalty income and the income we derive from our foundation products as a source, as a unique opportunity to catalyze this. But some of these building blocks and these expenses on a relative scale, A, because the company grows, B, because some of the expenses will come down, should allow us to have margin expansion. To what extent this will yield now to result in 2026? I think we have obviously certain assumptions, that will be premature. I mean, I think we, at this point of time, we want to demonstrate that we can be proud of our results in 2025. And as I said, we want to shine by results, not by forecasts. Thank you. I think that may give you some color, at least one. Thank you. Maybe next question.

The next question comes from Harry Gill from Bernberg. Please go ahead.

Thanks for taking the questions. I have a couple on hemophilia A, please. So given the strong Altuvox launch in Germany, Just wondering how you're thinking about your target market share. You've given the 30% to 40% range, but should we now sort of consider that you're aiming for the higher end of that range and perhaps it's 35% now a reasonable floor? And then I know you've talked about considering Altuvox and Locta as a single heme affiliate A franchise. So just wondering, do you think you can grow this franchise as a whole by double digits consistently over the next few years? Thank you.

Thanks for your question. As you can see, the market share evolution has been very impressive. Granted, this is only Germany, one part of the franchise, and we want to make sure that this becomes a European and then an international launch very soon. Basically, the data and the evolution that we have seen, when you think about it, 15 points more in five and a half months is is really impressive. And I think, you know, any data point that we have a good start also in Switzerland and, you know, once we got the regional approvals in Spain, we also look forward to material sales there. So I think, you know, the data, probably our confidence in that range has increased because, you know, the product gets in a significant pull from, from the patient community, from the physicians, and the feedback we got from patients is, and also physicians, is very positive in terms of how it affects the daily life in terms of I feel better, experience less pain. So all of these assumptions that we hoped for and that we saw initially from the trials, it's coming true. And we see that we are by far, you know, we are really at the early start, we think that these ideas are transferable. So, clearly, we are probably more in the higher end of the range as far as our expectations are concerned. I think this gives you probably some color. I don't want to be now setting out as a singular number, I think, but higher end, I think, should give you some direction. Next slide. Next question.

The next question comes from Christopher Ode from SEB. Please go ahead.

Yeah. Hi. Thank you for taking my questions, too, please. First, just, you know, coming back to that 2026 margin and, I mean, noting that some of the R&D investments are obviously going to take a little time to kick off. I guess a few trials yet to be put in. How, I mean, is there some indication you can give, you know, on sort of a long-term floor for R&D? And also as it relates to the margin going forward, you've been on pause for a little while for BD and M&A. You know, is that a factor when you are guiding on the margins or do you tend to exclude that? And then my second question then is on Altevox. Can you give us a sense of the demand in markets you've entered outside Germany And what proportion of switches are non-factor therapies versus what are non-ELACTA factor VIII switches?

Thank you. Yeah. So let's start, you know, with the long-term margin and R&D expenses. I mean, historically what we said is, you know, that R&D expenses, there is a floor, you know, probably around for the kind of model that we are running you know, 13 to 15%, that's a range, yeah. And in a very important year that, you know, that's the upper limit, but normally probably we are at the lower end given the fact that we obviously insource innovation. You know, that's roughly, you know, where we are in this range, but, you know, we obviously, you know, as you will see also during the later part of the year, we we really want to make a difference. This is a very strong team under the leadership and that have demonstrated now, you know, to execute in line with expectations. And as far as M&A is concerned, we have excluded this simply because we don't know what comes our way and what kind of profile you're going to find. And then it's very difficult to model this. But, you know, we are very mindful of the sensitivities on on margins in today's environment. So for us to unload things now that would mute our earning expectations is very difficult undertaking and it would need a lot of conviction to do this. And as regard to how to work switches, I mean, what we see here is, you know, as an example of Germany that, you know, at the beginning it was majority locked up, and now it's a vast majority, as I pointed out during the presentation, is driven by competitive products, including non-factor products. So we try to be democratic and take from everybody.

Thanks very much.

Thank you.

The next question comes from Eric Hultgaard from Carnegie. Please go ahead.

yes hi uh two questions if i may uh first on vonio could you give us an update on the ip status for vanio and the patent extension application if i remember it correctly the application was pending the time of the acquisition and was expected to be approved in 2024 so i may have missed it but I haven't seen an update on the matter. And then, secondly, on VONIO as well, and the Paxys study, is that, do you think, registrational, given the unmet medical need? Or should we sort of think that additional or phase three studies will be required as well? The opportunity within this indication compared to MS, if you could categorize that, that would be helpful. Thank you.

Yeah. You know, maybe, you know, I started with the IP status on Bonjour. I mean, our assumption hasn't changed, you know, that we have a 2034 protection, under 2034. And, you know, that obviously predicates a patent extension that, you know, based on my knowledge is not yet there, but we have not seen anything that would, you know, speak against this. And so I think it's more of a formality than an if. And with regard to Paxos, I mean, this is obviously a phase two study. Depending on the results, it will be, you know, hopefully a phase two B. I mean, Lydia, maybe you want to comment

Yeah, sure. So obviously, this is a dual finding study in a disease with a very high unmet medical need and no available treatments for patients. So depending on the magnitude of the effect, what we have agreed with regulators is that we will have the discussions to see if this could lead directly to a registration. What is positive is that we have started the discussions before in order to have a trial design that could meet all these expectations. But obviously, until we see the data and the results, we will not be able to finalize the strategy. But we are very eager on starting the trials activated, and also the physicians, the PIs are really eager in starting the recruitment.

So there's a lot of unmet medical need, Eric, and a lot of excitement that was, you know, expressed to us at ASH. And the size of the opportunity is very material. So it is not, you know, in MF you have around 17,000, 13,000 are treated by JAK inhibitors. Here you have patient population that are de facto, where there's no available treatment, effective treatment. is around 5,000 in the US. And for a company that potentially is the first into the therapy, this would be a very meaningful, very sizable opportunity. Thank you.

The next question comes from Gonzalo Artic from Danske Bank. Please go ahead.

Hi. Thank you for taking my questions. Two questions. First one is on Aspa Valley. Appellees mentioned recently that they will aim to initiate two new phase three studies in renal diseases in FSGS and DGS. So I was wondering, what is your plan here? Do you have any intention to join on that, given the strong data you saw in Valiant? Or, yeah, I haven't heard anything from that. from you guys. And the second question is on Cell 212. Based on the interactions you have had with clinicians, what is the feedback you get for a potential launch this year, beginning of 2026? Is it, I mean, because based on the way you have phrased it, it seems that you are more cautious in terms of that launch. So where do you see the initial patient indication? Is it in methotrexate intolerant or resistant patients, or are you planning to compete straight with Cristexa and Cristexa methotrexate? Thank you.

Yeah, thank you. So with regard to the two indications for Aspervilli in nephrology, you know, yeah, I mean, this is a partnership with Pellis. We had discussions with them on how to best partner you know that we have a mechanism in any case that allows us to opt in at the end of the phase three development. And, you know, we have discussions on how we can, because, you know, we are excited towards the opportunity of us pavilion and renal disease on nephrology. And as a consequence, you know, we have no update yet, but, you know, it's an ongoing dialogue with Appellus. And Appellus is a great partner in We are super excited, obviously, about nephrology. As far as SL212 is concerned, we have done various surveys, as you can imagine, and the idea is clearly that we provide an alternative to patients because when you think about the dosing, the corresponding treatments, that you need to undergo with folic acid, with methotrexate, and then twice a month with Bistexa versus, you know, our product is sure enough a space for a product like 0212. And, you know, we would be daring enough to say, you know, that we want to be a relevant alternative. And when you think about the, number of CKD patients who are suffering from this disease and patient groups who are also excluded from using methotrexate, we feel that there is a very material opportunity also to expand the market. And we gave guidance that we think that around 15,000 patients could benefit or should benefit from regulated urocase treatment. And, you know, and Christexa has probably around six and a half to 7,000 patients currently treated. So, you know, there's still a very significant blue ocean out there, but, you know, we will not, and we understand, you know, that, you know, we will not win at all, but the CELTA-1-2 for the patient has a very interest and for the physician is an interesting profile. So, you know, our conservatism is more, you know, we want to complete now submission and then, you know, we, but we are preparing success as we speak and, you know, and building, building the teams. So, you know, this, we will not be shy. Yeah. All right. Thank you. And then maybe we go to the next question.

The next question comes from Shelly Chen from Barclays. Please go ahead.

Hi. Thank you for taking my question. I have one on Aspen Valley. So we saw a slowdown of growth this quarter, and then you mentioned about in TNH. Can you please talk about your observations so far on Aspen Valley competing with these recently approved drugs? And would you expect them to take a big role towards the first-line treatments? And also, what's your view on the sales growth for 2025? Will we see some initial uptake from C3G and ICMPGN towards the very end of this year? Thank you.

Thank you. You know, we have seen some initial impact And, you know, in some of the markets where we were facing our competition, and that's what you see trickling through to a certain degree in Q4, and there's also a little bit of phasing in Q4. But, you know, for us, Asper Valley at P&H is clearly a double-digit growth product. And, you know, we have obviously significant growth still ahead of us, particularly also in international territories. I just wanted to outline that, obviously, the majority of our growth, if you think about when you can afford about looking out, you know, maybe five years, will definitely come from nephrology because the opportunity is so much larger and competition is less pronounced, and our data are so differentiated in nephrology, but the product is quite resilient, and this is What we can see, we can see also patients now switching back from oral treatment to Pexetacroplan also in PNH. So, you know, we are not giving up on PNH. So we think that we will have a good year ahead of us and obviously a more magnificent year than in the years to come with a significant opportunity. And to what degree we will see CCG and ICMPGN patients ahead of registration. We'll have to see. I'm sure there will be some requests in terms of early access, and we will have to treat this, obviously, using the appropriate standards as we do usually, but you would probably not be able to avoid it simply because There are desperate patients in need who look forward to protect themselves or in family situations to protect their children. That said, the data are so compelling, obviously. Thank you.

The next question comes from Victor Sandberg from Nordea. Please go ahead.

Yes, hi, thank you for taking my questions. So one question on gamifant. Before, there had been some uncertainty if the pool data from the open label and the MRL trials you have submitted to the FDA for getting it approved in secondary HLH is enough for the agency to make a decision on this indication. I guess now with more interactions, have you got more confidence that the data you have at hand is enough for the FDA to take a decision on this? And then secondly, I think a lot of the investor debate this morning was about your outlook on EBITDA margin in the mid-30s, with consensus being a bit higher here in 2025, especially as the guidance for 2024 set in the beginning of last year was a good indicator of the actual outcome last year, even if you have beaten your initial guidance quite often historically. But I just wanted to understand a bit more what kind of moving parts you expect for a beta guidance this year. What could get you in the high end of margin or even surpassing in 2025? Thanks.

Yeah. You know, first maybe about the confidence of secondary HLHV between us. If we wouldn't be confident, we wouldn't submit, yeah. But that doesn't mean we get certainty. I mean, Julia, you want to comment?

Yeah, sure. obviously we've been in conversations with FDA and and we are what in our submission package we have robust data from several studies and not only the Stadiosix and the Emernal but also from the Amethyst which is a historical control arm so we are providing FDA with everything that has been requested and and the conversation it's it's really a in a positive framework so that we are really confident that we will bring the products to patients with this high medical need. So, yeah, I think the level of confidence is high because we have a strong data to support the submission.

Yeah, and with regard to the auto, before I hand over to Henrik, I mean, just bear in mind, Victor, you know, 2025 is a defining year for the company. You know, we have, when you think about, you know, to keep it simple for everybody, you know, in US dollar terms, you know, roughly the company is a $2.5 billion dollar business. Yeah, you know, at the Capital Market Day, you know, many, many years back now, we set out this vision of 25 by 25. Now it is 26 by 24, which, to be honest, is a big relief after We suffered a little bit for a couple of years from it. But having said this now on the earnings, I mean, we are launching two products. Yeah, the launch is two products. Where we said, Alterbox is a growth cluster. And Bonjo, the indications are out there, even though we owe you obviously more proof points that we can move the product into this direction. No questions. But, you know, we are confident. Then we have three products. One of them, we said, broke past the potential for us, but really. Cell 212, at the last earning call, we already indicated that there is absolutely no reason to revise our ambition for Cell 212 from this capital market. We said this could be a $500 million product. And, you know, when you look at, you know, the Latest report from Amgen on Christexa, you understand there's absolutely no reason to revise our ambition. If anything, once we have submitted, maybe we can think about it, what more is possible. And then we have secondary HLH, which would essentially double our opportunity as we previously pointed out for coming fund. This is a year where you don't want to make too many shortcuts and misses because it will be so important for the company to, again, change its layout totally, you know, and basically have much more material products in the year to come. And that is basically driving our cautiousness, but we understand, you know, that obviously today margins are important and, you know, and you know us a little bit, you know, we are not here to sit back and relax and spend frivolously. But we are a company that is building businesses and we will look for opportunities to improve this company as we speak. And we are not the guys who are typically giving guidance lightheartedly. So we are more on the conservative side. Maybe, Henrik, you want to comment what could influence guidance?

We obviously have a lot of opportunities to pursue this year, and we need to give justice to the opportunities that Guido mentioned. I'd also like to mention that margins are also a function of sales and sales growth. So, of course, the continued momentum here is very important, and there we have a high degree of confidence. Then maybe just to reiterate that obviously Bay Fortis is part of our P&L, and that's a factor that we don't control.

Yeah. So I think this gives us a bit of color. You know, I think if some of you are still up for it, you know, I think we should be open for at least one question. Two questions, yeah? We have two questions for those who want to stay. Yeah, please. Maybe next question.

The next question comes from Alistair Campbell from Royal Bank of Canada. Please go ahead.

Hi there. Thanks for fitting me in. To be honest, we've covered most of my questions, but if I could just have a follow-up on Vonjo and the PAXIS trial. Vexis is a disease area I'm frankly not very familiar with, but just to get a sense as you launch that study, given the biology of the disease, is that somewhere where you feel quite a high degree of confidence, or is this more of a sort of, well, it might work, let's give it a chance? I just want to get a sense of your confidence levels as you head into that trial. And then maybe just coming back to balance sheet, Guido, you obviously talked a lot about, there's a lot going on internally, but with the balance sheet strengthening, do you think you would be looking at new deals and new opportunities going into this year, or do you think the focus will be very much internal? Thank you.

Yeah, thank you. Maybe Lydia on the confidence on VEXUS?

Yeah, sure, so basically, we have very high level of confidence because of the unique kind of profile of Bonjo, as I've mentioned during the presentation. So this is something that could be very specific and targeted. And what was at the beginning just a scientific concept, we already got a proof of concept with some patients that have been treated, and we already know the efficacy and the high efficacy in those. Obviously, those are small and single center experience. And that's why we are running this clinical trial with this high level of confidence. So based on the mechanistic effect of Bonjo and based on the pre-existing proof of concept data available in the US in few centers.

Yeah. So obviously it's a new disease, time will tell, but the team as thought about this very carefully, and we have chosen very strong centers and a strong setup, so there's confidence. We probably even have a higher confidence or a higher probability of success in CMML, which is much more closely related to MF, and this is also not an indication that should be underestimated, and we can talk about it another time. And then as far as firepower is concerned, we are reviewing assets as we speak. But we are mindful of what we have on the plate today and we are very mindful on the earlier discussions on earnings. Last question. Thank you.

The last question comes from Liu Yifeng from HSBC. Please go ahead.

Right, thanks for taking my question. Just one on Bonjour, specifically on CMML, and you just talked about it. Could you give a bit of a color on the development timelines and, you know, when you're sort of planning to launch clinical trials and whether that's the trial has the registration or potential? How should we think of that in 2025 and 2096? Yes. Thanks.

Thank you.

Sure. So what we're starting right now, it's a research collaboration with the International Working Group. And so that's what, it's our first step based on the data that we see and on the results, we will be defining the path to registration. But again, based on the magnitude of the effect that we could see on the results. But what we're starting right now, it's a research collaboration.

Yeah. And you know, this research collaboration could lead you know, to a filing, you know, that is basically because, you know, there's a huge unmet medical need and it's a very significant patient population. I mean, today, you know, the epi data vary quite a fair bit, but even in conservative funds, you know, it's definitely worth our while. Yeah, so this maybe summarizes, let's say, our earning call. I would like to thank you for your attention and And please reach out to us if you have further questions. I mean, time is always running out. But we wanted to give you some color at least. Really like to thank you for your interest. And as you can see, we like this company and we like to build it. Thank you so much and look forward to catching up with you in the new course. Thank you.

Ladies and gentlemen, the conference is now over. Thank you for choosing Coral School and thank you for participating in the conference. You may now disconnect your lines. Goodbye.