Ladies and gentlemen, welcome to the Sobi Q4 2024 Report Conference Call and Live Webcast. I'm Sandra, the Chorus Call operator. I would like to remind you that all participants are in listen-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 Oelkers, CEO. Please go ahead, sir.
Yeah, thank you. Hello, everyone. This is Guido Oelkers, CEO of Sobi. 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 Sobi.com earlier today. Let's move to slide number two. A forward-looking statement as per usual. Unless otherwise stated, we will be making comments that mostly relate to the fourth quarter at constant exchange rate in millions of Swedish krona. Today, we plan to cover the key aspects of the Q4 report. I'm joined by Henrik Stenqvist, our CFO, Lydia Abad-Franch, 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 by pressing star one.
We propose that you ask only one or two questions at a time. Let's move to the brief. 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 were SEK 26 billion 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 quarters had very strong quarters in Q3 and Q4. Synagis in Q4 2023 was also extremely significant. Hence, there was a negative variation. The underlying business in Q4, excluding RSV, has been growing over 20%.
Hematology growth was driven by continued growth of Doptelet and Aspaveli and the launch of Altuviiio. There has been a strong interest in Altuviiio in just the first half of this year on generating SEK 300 million in the quarter. We continue to build the launch of Vonjo and see consistent quarter-on-quarter progress. We are continuing to build awareness around the product and the unmet medical need in myelofibrosis treatment. In immunology, it is reflected very substantially, obviously, as mentioned, by Beyfortus' royalty income in both Q3 and Q4. In terms of the pipeline, our progress continues with the filing of Gamifant in the U.S. for HLH-MAS in Still's disease. We are happy to announce that we have also submitted Aspaveli in Europe for C3G and IC-MPGN.
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 Sobi business, both commercially and in development. 2025 will be a busy year with multiple filings ongoing, preparing the organization for a number of new launches while we bring Sobi to the next level. With that in mind, our outlook for 2025 is that we expect revenue growth at highly single-digit, 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? Yeah.
Our growth of 8% in the quarter was driven primarily by hematology sales, while strong Beyfortus' royalty income was not able to offset Synagis' 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 Synagis, as already mentioned, but Gamifant and Kineret have grown strongly throughout the year. Europe saw strong growth of 14% for the full year, reflecting the launch of Altuviiio and other strategic growth products. In the U.S., we saw, as mentioned earlier, the impact of Synagis, 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 Beyfortus 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 Altuviiio launch. We are starting to see an impact on Elocta, as expected from Altuviiio. However, we have seen 30% growth across the hemophilia franchise in 2024. Doptelet showed continuous growing demand across all regions with 58% growth in 2024, and Aspaveli 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, we are facing this competition, the product has shown good perseverance in these markets so far. Vonjo continues its sequential quarter-on-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 Gamifant, 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. Beyfortus 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.
On the next slide, you can see our portfolio approach of today's and tomorrow's breadwinners. While the foundation business is very resilient and has shown 6% growth, this used to be essentially the DNA of Sobi. 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 the transformation of Sobi and investing into our pipeline and into our strategic growth product. The new royalty streams formed by Beyfortus and also Altuviiio help on this side. When you look at the strategic growth product, they have grown very substantially. So they are 35% today, including the royalty stream. It's basically half of this portfolio, and this half was 55% in Q4. Then we have on the left, in the left.
This is for us, obviously, super important as we have very significant products that will determine the future of Sobi. We received fast track designation for Gamifant in secondary HLH in Q2, and we have now submitted the filing package as indicated in December. For SEL-212, we are continuing the submission to the U.S. FDA, and we will complete the filing before Q2. In Q3, we had the positive readout of Aspaveli 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 Aspaveli, Doptelet, Zynlonta, Gamifant, and Vonjo. This puts Sobi into a new phase of sustained growth driven by new product execution and our development on our development commitments.
We have an exciting launch in progress with Altuviiio and two substantial indications in our hands with Aspaveli in nephrology and SEL-212 in chronic refractory gout, which we will now prepare in 2025. Let's move to Altuviiio. We are very pleased with our first half year on the market with Altuviiio. Altuviiio has seen a rapid adoption in Germany, and our market share in hemophilia A in Germany has grown for Elocta and Altuviiio by 15 percentage points, essentially in the first five and a half months after launch. Our hemophilia 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. The last three months clearly favor that we are taking significant share, more share from competition.
We look forward to bringing this important medicine now to more markets in Europe and other Sobi territories in 2025. Let's move to Aspaveli. As you have seen, we had very strong sales evolution of Aspaveli in PNH. 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 Aspaveli 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 eGFR at such an early time makes the potential of this medicine that we are bringing to patients. For us, this product is really right at the heart of what Sobi is about, given the fact that many of those patients are kids.
To prevent them from progressing to end-stage renal disease, we feel it's an obligation and mission. We look forward to working with the regulatory authorities to move this forward. Parallel, we're building the internal infrastructure in nephrology and prepare for the launch. We believe that Aspaveli has the potential to become a blockbuster product for SOBI. Let's move to Vonjo. Vonjo sales were 460 million SEK 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 the labeled below 50,000 platelet population, and we are continuing to work to expand the use according to the NCCN guidelines in myelofibrosis. We have recently hired a new U.S. Chief Medical Officer, Jamie Freedman, who is a hem-onc specialist who is leading our medical organization in the U.S.
We are 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 need with the NCCN guidelines and recommendations. The second pillar of our strategy is to bring Vonjo to patients outside of the U.S. this year, and we will launch in selected markets, which will follow the FDA label, and ultimately want to bring it to Europe and Japan once we have the pacritinib trial concluded. The next step is to broaden the use, and we have initiated a Phase II study in VEXAS, an area with currently no approved treatment, which Lydia is going to cover in her presentation. We have also made an important strategic step to form a research collaboration to get CMML on label.
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 hand over now to our CFO, Henrik 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 SEK 7.4 billion meant that we exceeded SEK 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 EBITDA margin of 34%.
For the full year 2024, we achieved revenues of SEK 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 of Doptelet hemophilia, Vonjo, and Aspaveli. On the other hand, immunology experienced a decline of 12% in the quarter as a result of the much lower sales of Synagis and the phasing of Beyfortus royalties this year, with a clearly larger share of royalties in Q3 than in Q4.
Referring back to the table on the right and the adjusted gross margin of 78% in the quarter compared to 80% in Q4 2023, royalties in general were net positive to our gross margin in the quarter, but offsetting this was the loss of Synagis sales. Synagis was a high-margin product with significant sales in Q4 2023. 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 2 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 observe 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 Altuviiio, Aspaveli in nephrology, Synagis, and Vonjo. We've managed to partly offset the impact of these activities on the SG&A line through savings in the Synagis organization, as we have reported in prior quarters. R&D expenses increased by 13% at CER, excluding non-recurring items, mainly due to post-approval activities for Altuviiio and development programs in Gamifant, Vonjo, and Zynlonta. The operating cash flow for the quarter increased by 67% to SEK 1.8 billion, benefiting from less capital tied up in receivables from Synagis than a year ago.
If we turn to slide 13, we see on the right-hand side of the slide that net debt went from SEK 16.9 billion at the beginning of the quarter to SEK 15.2 billion, corresponding to a net debt to EBITDA ratio of 1.6 times. To the left, we see the debt reduction of more than SEK 4 billion during the year and the leverage journey from 2.5 to 1.6 during the same period, driven by the improvement in EBITDA and strong cash flow. Please turn to slide 14. We will now discuss the financial outlook for the full year 2025. 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 % at CER and an adjusted EBITDA margin in the mid-30s % of revenue.
On the revenue guidance, we look forward to continuing to launch Altuviiio into new markets in 2025, growing the hemophilia A franchise, as well as continued progress with our existing commercial portfolio. We expect a continued strong contribution from Beyfortus royalties, 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 Aspaveli in nephrology. In R&D, we will also continue with post-approval studies for Altuviiio and the new studies for Vonjo in VEXAS and CMML, as well as major registrational efforts for Aspaveli, Gamifant, and NASP. And 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 Aspaveli in C3G and IC-MPGN 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 are also launching a Phase II clinical trial for Vonjo in VEXAS syndrome after receiving the IND from FDA. And I will come back to this in a minute. We also submitted the Gamifant supplemental BLA to FDA for the treatment in HLH, MAS in Still's disease. And the Zynlonta LOTIS-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 Gamifant for the indication of HLH macrophage activation syndrome in Still's disease to FDA. HLH MAS, a form of secondary HLH, is a rare systemic autoinflammatory disorder for which there is currently no approved therapy. It is a life-threatening complication of Still's disease where patients can experience intense systemic hyperinflammation and even multiple organ failure. Emapalumab neutralizes interferon gamma and blocks the expression of inflammatory cytokines, which drives the hyperinflammation of HLH MAS.
The application is based on the pooled analysis from two clinical trials presented at ACR in November, which showed that emapalumab rapidly controls signs and symptoms of HLH/MAS. 85% of patients achieved 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/MAS in systemic disease the first approved medication for this potentially fatal condition. Next slide, please. Thank you. Speaking of first, we are launching the first randomized clinical trial in VEXAS syndrome. PAXIS will be a randomized Phase II study to assess the safety and efficacy of Vonjo in this disease, which currently has no approved therapy.
An IND to study this indication was granted in December, and we are planning to start activating sites soon. VEXAS syndrome is caused by an acquired gene mutation and manifests in a wide range of autoinflammatory 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 one in 4,000 males over age 50 in the United States. There is no standard treatment available for patients with VEXAS syndrome, though it 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 cytopenias. Pacritinib is a JAK2 inhibitor that additionally targets NF-kappaB-mediated inflammation via IL-1 and inflammatory anemia via ACVR1.
Due to this unique profile, Pacritinib could be both more effective and safer than other therapies that have been used to treat VEXAS. Next slide, please. We are very proud of what we have achieved in 2024, hitting major milestones. Altuviiio was approved by EMA with a strong positive reaction by physicians and patients. Aspaveli's EU label in PNH was expanded to first line, and we got very promising data in C3G and IC-MPGN. We continue to grow Doptelet reach in region international. We submitted the supplementary BLA for Gamifant, HLH, MAS 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, Gamifant, Aspaveli, and NASP.
In the U.S., the focus will be on the approval of Gamifant for HLH, MAS, and Still's disease and on finalizing the BLA rolling submission for chronic refractory gout. In Europe, the focus will be on the approval of Aspaveli in the nephrology indications, C3G and IC-MPGN. In Japan, we will be submitting three dossiers: Aspaveli for the nephrology indications, Gamifant for HLH, MAS, and Still's disease, and Kineret for Still's disease. With that, I would like to hand back to Guido. Thank you very much.
Yeah, thank you, Lydia. As you can sense, you know we are very pleased with Sobi's development in 2024. We saw a significant top-line growth of 19%, 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 Altuviiio in Europe, the filing initiation of SEL-212 in chronic refractory gout in the U.S., and in Q4, the filing of Gamifant in the U.S. in secondary HLH continued in February by our filing of Aspaveli nephrology. These open tremendous opportunities for Sobi 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.
Also, as you know, we are not the guys who want to impress you by what we forecast, but more by what we are doing. We have a lot on the plate, and we need to do a lot because we are blessed by a fantastic pipeline. In this regard, I'd like now to refer to the Q&A session. We will now answer your questions. For those on the phone, please remember to press star one to ask questions. Can I please remind you to limit your questions to one or two to be fair to other callers? Thanks in advance. 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. Questioners 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 Häggblom from Handelsbanken. Please go ahead.
Thank you so much, Mattias Häggblom from Handelsbanken. Two questions, please. So Beyfortus royalties made up a third of your 2024 EBITDA in light of a potential competitive launch by Merck ahead of the 25-26 RSV season and the 100% margin contribution that 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 U.S. market season one? And as a consequence, Beyfortus royalties have now peaked in contrast to what consensus models or what is baked into your guidance? Secondly, investors appear to expect that Sobi will host a CMD later this year and perhaps provide 2030 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 Beyfortus' margin, I mean, obviously, we do our best possible judgment. And based also, we follow here some of these guidelines. And you probably listened into 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.
Yes, we basically based it on what we think without having had any direct discussions with Sanofi to what we think their prospect is. We are recognizing that a formidable competitor is coming in, but we also recognize that Beyfortus has very strong data in terms of real-world evidence and in terms of primary endpoint versus the product. We don't see now a catastrophic scenario for this royalty stream. 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 our pipeline, but also, for instance, related for sure at the right time to wonder on how to think about these new indications and other products. So this is probably more what we want to do as opposed to having one event and providing the different time points when new data arises and new endpoints have achieved that we basically provide an overview to keep you abreast is what we are doing. Thank you. We have maybe quick question.
Sorry? A quick follow-up, if I could.
Sanofi said they expect to grow global sales of Beyfortus, but they refused to comment on U.S. sales since you only have exposure to the U.S. 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. And 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, yeah, thanks. Just the one question on margins. So clearly, 2025 margin guidance in the 30s factors in the build-out of Aspaveli 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 just get your thoughts on that step up into next year and just how we should be thinking about margins going forward. Thank you.
Yeah, thank you. I mean, 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 when you think about this business, and why, and I know that everybody wants us 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 Altuviiio being now commercialized all Europe and then also internationalized in our territory during the next, let's say, 12 months.
And then you have Vonjo, where we shared your ambition that we want to embark on label expansion, new indications. So 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, will allow us, should allow us to have margin expansion to what extent this will lead, will yield now to result in 2026. I think we have obviously certain assumptions, but that will be premature.
I mean, I think 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, Brian. Thank you. Maybe next question.
The next question comes from Harry Sephton from Berenberg. Please go ahead.
Thanks for taking the questions. I have a couple on Hemophilia A, please. So given the strong Altuviiio launch in Germany, just wondering how you're thinking about your target market share. You've given the 30%-40% range, but should we now sort of consider that you're aiming for the higher end of that range and perhaps is 35% now a reasonable floor? And then I know you've talked about considering Altuviiio and Elocta as a single Hemophilia 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.
Yeah. No, thanks for your question. I mean, 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. So basically, the data and the evolution that we have seen, and when you think about it, I mean, 15 points more in five and a half months is really impressive. And I think any data point that we have a good start also in Switzerland. And once we got the regional approvals in Spain, we also look forward to material sales there.
So, I think the data we have probably increased our confidence in that range has increased because the product gets a significant pull from the patient community, from the physicians. And the feedback we get from patients 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 through. And we see that we are by far, and we are really at the early start, but 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. Yeah, I think this gives you probably some color.
I mean, I don't want to be now setting out a singular number, I think, but higher-end things should give you some direction. Next slide. Next question.
The next question comes from Christopher Uhde from SEB. Please go ahead.
Yeah. Hi, thank you for taking my questions too, please. First, just 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. I mean, is there some indication you can give 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. Is that a factor when you are guiding on the margins, or do you tend to exclude that?
My second question is on Altuviiio. 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-Elocta factor VIII switches? Thank you.
Yeah. Let's start with the long-term margin and R&D expenses. I mean, historically, what we said is that R&D expenses is a floor probably around for the kind of model that we are running, 13%-15%, that's a range, yeah. In a very important year, that's the upper limit, but normally, probably we are at the lower end given the fact that we obviously insource innovation. That's roughly where we are in this range, but we obviously, as you will see also during the later part of the year, we really want to make a difference.
This is a very strong team under Guido's leadership and that have demonstrated now 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 we are going to find, and then it's very difficult to model this. But we are very mindful of the sensitivities on margins in today's environment.
So for us to unload things now that would mute our earning expectations is a very difficult undertaking, and we would need a lot of conviction to do this. And with regard to Altuviiio switches, I mean, what we see here is, as the example of Germany, that at the beginning, it was majority Elocta, 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 Erik Hultgård from Carnegie. Please go ahead.
Yes, hi. Two questions, if I may. First, on Vonjo, could you give us an update on the IP status for Vonjo and the patent extension application? If I remember it correctly, the application was pending at 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 Vonjo as well and the PAXIS studies, do you think registrational, given the unmet medical need, or should we sort of think that additional or Phase III studies will be required as well? And then maybe the opportunity within this indication compared to MS, if you could categorize that, that would be helpful. Thank you.
Yeah. Maybe I start with the IP status on Vonjo. I mean, our assumption hasn't changed that we have a 2034 protection until 2034. And that obviously predicates a patent extension that, based on my knowledge, is not yet there, but we have not seen anything that would speak against this. And so I think it's more of a formality than an if. And with regard to PAXIS, I mean, this is obviously a Phase II study. Depending on the results, there will be hopefully a Phase II B. I mean, Lydia, maybe you want to comment.
Yeah, sure. So obviously, this is a low-finding study and 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.
Yeah. So there's a lot of unmet medical need, Erik, and a lot of excitement that was expressed to us at ESH. And the size of the opportunity is very material. So it is not in MF, you have around 17,000, 13,000 are treated by JAK inhibitors.
Here you have a patient population that are de facto where there's no available treatment, effective treatment, with around 5,000 in the U.S. And for a company that potentially is the first into this therapy, this would be a very meaningful, very sizable opportunity. Yeah. And so it will be a yeah. Thank you.
The next question comes from Gonzalo Artiach from Danske Bank. Please go ahead.
Hi. Gonzalo Artiach from Danske Bank. Thank you for taking my questions. Two questions. First one is on Aspaveli. Apellis mentioned recently that they will aim to initiate two new Phase III studies in renal diseases, FSGS and C3G. So I was wondering, what is your plan here? Do you have an 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 SEL-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? 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 Krystexxa and Krystexxa methotrexate? Thank you.
Yeah. Thank you. So with regard to the two indications for Aspaveli and nephrology, I mean, this is a partnership with Apellis. 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 III development.
We had discussions on how we can because we are excited about the opportunity of Aspaveli and renal disease on nephrology. As a consequence, we have no update yet, but it's an ongoing dialogue with Apellis. Apellis is a great partner, and we are super excited, obviously, about nephrology. As far as SEL-212 is concerned, we have done various surveys, as you can imagine. 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 Krystexxa versus our product is sure enough a space for a product like SEL-212. We would be daring enough to say that we want to be a relevant alternative.
When you think about the number of CKD patients who are suffering from this disease and the patient groups who are also excluded from using methotrexate, we feel that there is a very material opportunity also to expand the market. We gave guidance that we think that there's around 15,000 patients who could benefit or should benefit from regulated uricase treatment. Krystexxa has probably around 6,500-7,000 patients currently treated. There's still a very significant blue ocean, I would say. We will not, and we understand that we will not win it all, but SEL-212 for the patient has a very interesting and for the physician is an interesting profile. Our conservatism is more we want to complete now submission, and then we are preparing success as we speak and building the teams. 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 Aspaveli. So we saw a slowdown of growth this quarter, and you mentioned about the competition in PNH. Just want to, can you please talk about your observations so far on Aspaveli 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 IC-MPGN towards the very end of this year? Thank you.
Thank you. We have seen some initial impact in some of the markets where we were facing our competition.
That's what you'll see them trickling through to a certain degree in Q4, and there's also a little bit of phasing in Q4. But for us, Aspaveli and PNH is clearly a double-digit growth product. And 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 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 pegcetacoplan also in PNH. So 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 the significant opportunity. And to what degree we will see C3G and IC-MPGN 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. I think that's the data are so compelling, obviously. Thank you.
The next question comes from Viktor Sandberg from Nordea. Please go ahead.
Yep. Yes, hi. Thank you for taking my questions. So one question on Gamifant.
Before, there have been some uncertainty if the pooled 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 investor debate this morning was about your outlook on revenue 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 of what kind of moving parts you expect for EBITDA guidance this year. What could get you in the high end of margin or even surpassing in 2025? Thanks.
Yeah. So first, maybe about the confidence of secondary HLH. To be honest, if we wouldn't be confident, we wouldn't submit. Yeah. But that doesn't mean we get certainty. I mean, Lydia, you want to comment?
Yeah, sure. Because obviously, we've been in conversations with FDA, and in our submission package, we have robust data from several studies, not only the Study 06 and the MRL, but also from the AMITIS, which is a historical control arm. So we are providing FDA with everything that has been requested.
The conversation, it's really in a positive framework so that we are really confident that we will bring the product to patients with this high unmet medical need. Yeah, I think the level of confidence is high because we have strong data to support the submission.
Yeah. With regard to the outlook before I hand over to Henrik, I mean, just bear in mind, Viktor, 2025 is a defining year for the company. When you think about to keep it simple for everybody in US dollar terms, roughly the company is a $2.5 billion business. We are, at the Capital Market Day, 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. We had the launch with two products where we said Altuviiio is growth faster. And Vonjo, the indications are out there, even though we owe you obviously more proof points that we can move the product into this direction. No question. But we are confident. Then we have three products. One of them, we said, blockbuster potential for Aspaveli. SEL-212, as the last earnings call, we already indicated that there is absolutely no reason to revise our ambition for SEL-212 from this capital market. We said this could be a $500 million product. And when you look at the latest report from Amgen on Krystexxa, 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.
Then we have secondary HLH, which will essentially double our opportunity, as we previously pointed out, for Gamifant. 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 and basically have much more material products in the year to come. That is basically driving our cautiousness. We understand that obviously today, margins are important. You know us a little bit. We are not here to sit back and relax and spend frivolously. We are a company that is building businesses, and we will look for opportunities to improve this company as we speak. We are not the guys who are typically giving guidance lightheartedly. We are more on the conservative side. Maybe Henrik, you want to comment what could influence guidance?
Yeah.
So I mean, 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, Beyfortus 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. I think if some of you are still up for it, 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 Alastair 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. VEXAS is a disease with which I'm frankly not very familiar with. But just to get a sense, as you launched 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"? Just want to get a sense of your confidence levels as you head into that trial. And then maybe just coming back to balance sheets, 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. I mean, maybe Lydia on the confidence on VEXAS.
Yeah. Sure. So basically, we have a very high level of confidence because of the unique kind of profile of Vonjo, 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 Vonjo and based on the pre-existing proof of concept data available in the U.S. in few centers.
Yeah. So obviously, it's a new disease. Time will tell, but the team has thought about this very carefully, and we have chosen very strong centers and a strong setup. So there's confidence. We even probably 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, yeah, 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. Maybe next 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 Vonjo, specifically on CMML, and you just talked about it. Could you give a bit of color on the development timelines and when you're sort of planning to launch clinical trials and whether that's the trial has registration or potential? How should we think of that in 2025 and 2026? Thanks.
Thank you. Lydia?
Sure. So what we are 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 are starting right now, it's a research collaboration. Yeah.
And this research collaboration could lead to a filing that is basically because there's a huge unmet medical need, and it's a very significant patient population. I mean, today, the epi data vary quite a fair bit, but even in conservative part, it's definitely worth our while. Yeah. So this maybe summarizes, let's say, our earnings call. I would like to thank you for your attention, 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 due course. Thank you.
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