Ladies and gentlemen, welcome to the Q4 2023 report conference call and live webcast. I am Sandra, the Chorus Call operator. I would like to remind you that all participants have been 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 so much, and hello, everyone. This is Guido, CEO of Sobi. We are delighted to welcome you into the fourth quarter and full year 2023 conference call for investors and analysts. Overall, we can say that we are pleased with our performance in 2023, and the year has exceeded our expectations. We posted this presentation to sobi.com earlier today, and with this, let's go to slide number 2. We would like to remind you, as per usual, of the forward-looking statement, and unless otherwise stated, we like making comments that most related to the fourth quarter, full year performance in 2023 at constant exchange rate in SEK million. With that, please turn to slide number 3. Today, we plan to cover key aspects of our Q4 and full year report.
I'm joined by Henrik Stenqvist, our CFO, and Lydia Abad-Franch, Head of R&D and Chief Medical Officer, during the Q&A session by Armin Reininger, our Senior Scientific Advisor. We plan to review the presentation first and then have Q&A until around 2:00 P.M., Swedish time. For those on the phone, please join in the queue of these questions by pressing star one. We propose you ask only one question, maximum two at a time. Please turn to slide number 4. As said, we are pleased with the 2023 performance, which has been driven successfully executing on our strategies throughout the year.
15% growth in Q4 and 12% growth for the full year make us one of the fastest growing company in the rare disease space, and it is around 2 times faster than the expected growth for the rare disease market globally. EBITDA margin of 34% at the higher end of our guidance, but still allowed us to significantly invest into our future, foremost launches and pipeline progression. Strategic portfolio with our launch medicines, changing rapidly the composition of our company, progressing our pipeline. Just some highlights that I find particularly remarkable before Lydia leads you through the entire part is really the exciting phase II data and the nephrology indication of Aspaveli and the phase III data for SEL-212. We continue to build a leading rare hematology franchise.
The growth drivers were Vonjo in the second half of the year, continued growth of Doptelet and launch of Aspaveli. While we have a stable growth in our hemophilia franchise of 6%. In the second half of the year, we focused on the integration of CTI, which has taken some time, but we feel we have the right elements in place right now and look forward to bring Vonjo to an inflection point in 2024. Immunology growth reflected strong Gamifant sales, growing an impressive 59% in Q4 outside of China. This strong royalty revenues, obviously of Beyfortus, need to be outlined. Forward-looking, we have a very strong momentum in the Sobi business, and we are pleased to announce our guidance for 2024. We expect high single-digit growth and mid-30s for the adjusted EBITDA margin.
As usual, we are rather impressed by what we are doing than what we promise. We expect material growth for Vonjo, Doptelet, Aspaveli, Gamifant, and Beyfortus, while looking forward to making first steps with our launch of efanesoctocog alfa. Geographically, we foreshadow material growth from our international franchise. This growth will help us to overcompensate a potential negative evolution of synergies and the loss of the China Fosun business. Let's move to slide 5, performance review. And let's look at the overall performance a little bit more in detail. Our 15% growth in the quarter was both driven by hematology and immunology, especially our launch medicines. We saw very strong performance of our hematology franchise, with 21% growth in Q4. For the full year, we can see a solid growth across all regions.
Of note is a strong performance in the international region, when excluding the effect of Doptelet in China, we grew impressively 54% in the year. The increasing importance of our North American franchise will help us to improve EBITDA margins, even though part of the synergies revenues were exchanged against royalties, mostly related to Beyfortus. Let's move to slide number 6. Sobi's strategic portfolio has led to a very strong result and is primarily driven by our launch medicines and our royalty income from Beyfortus and efanesoctocog alfa in the U.S. The strategic portfolio will be our main driver of growth, also during the forthcoming years. We have built this portfolio on top of a strong foundational portfolio, which has delivered an impressive 6% sales growth last year.
Our legacy portfolio, consisting of synergies, manufacturing and Doptelet, China, will have a reduced importance over time. Please turn to slide number 7. The metrics visualizes our sources of growth. Current and future growth is driven by our strategic portfolio and launch medicines, as well as our royalty streams from Beyfortus and Efa. Our late-stage pipeline, consisting of SEL-212 and Efa, as well as the important indication expansions for Aspaveli and Gamifant, will become important elements for future growth. Internationalization will remain a key driver for Sobi. We have enabled the organization to process multiple applications in international markets in parallel, prepare international supply and deploy competitive commercial capabilities. Aspaveli, Doptelet, Zynlonta, Gamifant and Vonjo are examples of current and anticipated growth in new markets.
We are excited about the potential of efanesoctocog alfa, which had a very strong start in the U.S. under our partner, Sanofi, who stated Altuviiio is capturing 50% of switches in the total U.S. hemophilia market in its first year of launch. We look forward to bring this important medicine to hemophilia A patients in Europe. Filing is progressing well, and we expect a decision during the first half of the year. We are working on expanding the indication for Aspaveli, Zynlonta, Gamifant and of course, Vonjo. The new development projects for Vonjo are expected to be announced in due course. This puts Sobi into a new phase of sustained growth, driven by a NOBLE range of products built on a strong foundation of existing medicines. Let's have a look at Doptelet, slide number 8.
Doptelet had a very strong Q4, excluding China, with 59% growth and 62% for the full year. There were no Chinese sales to China during the second half of 2023. Sales growth was driven by increased uptake in the U.S. and ongoing launches in Europe and international. In the U.S., there's a continued positive evolution of new patients, new prescriber and higher market share and duration of treatment. There's also an accelerated growth in Europe and international markets driven by ongoing launches. We expect this positive trend to continue even with our China sales. We launched Doptelet in Japan in the second half and expecting future growth. Let's turn to slide number 9, Aspaveli.
The launch of Aspaveli continued well in the quarterly sales of SEK 186 million, continuing a solid launch trajectory. We have launched 27 countries across Europe, International and Canada. Product has material growth opportunity in the existing market and new launch countries. The recent positive CHMP opinion on first-line therapy offers opportunity for broadening the usage in various markets. It is fair to say that the expected development of Aspaveli into nephrology will open a much larger opportunity than the existing indication. We presented positive phase II results in C3G and IC-MPGN at the ASN conference in Q4 last year, and we look forward to seeing the VALIANT phase III trial study results during the second half of 2024. Let's move to Vonjo, slide number 10.
Vonjo sales were 322 million SEK in the quarter, in the Q4, with continued launch process progress and already contributing 706 million SEK in revenues for 2023. Q4 saw the highest number of new patients starting treatment since launch, reflecting initial positive results of the integrated sales force post the CTI acquisition, and we are therefore very confident to have the right elements in place for a stronger trajectory in 2024. We experienced a minor decrease in Q4 versus Q3, related to a negative new patient evolution during the transition period in Q2 and Q3. This effect may still mildly influence our Q1 numbers, even though we expect a positive evolution of leading indicators. Our positive outlook for the product was confirmed by recent market research.
The NCCN-updated NCCN guidelines, recommending the use of pacritinib as a potential treatment option in patients with mild fibrosis, also associated with anemia. We're expecting material growth by penetration and duration of treatment, driven by a differentiated mode of action and strong clinical data. So please turn to slide number 11. In hematology, our foundational business, continues to be underpinned by stable hemophilia growth at 6% in 2023. We expand the leading presence of Elocta and Alprolix to more patients in new territories. This confirms the community's confidence in this treatment, and has been able to overcompensate for price developments that we experience, particularly in Europe. For Elocta, we see continued growth in patients, geographic expansion and favorable phasing of deliverables, deliveries.
Government interventions compress prices in various European markets, while we see a positive evolution in demand and patient expansion in Europe. As a result, Elocta grew 6%. Alprolix grew also by 6%, with patient growing, offsetting unfavorable pricing development. Let's turn to the next slide, number 12. Turning to immunology in Q4, the new dynamics of the RSV market showed material growth of Beyfortus. We received $890 million in Q4 in royalties from the U.S. sales of Beyfortus, contributing significantly to our overall growth. On the other hand, this positive evolution negatively affected Synagis, that also had reduced sales due to the late start of the RSV season. In summary, the composition of our RSV franchise has positively evolved and was ahead of last year's exceptional performance, and in terms of top and bottom line.
We expect this dynamic to continue in the 2024-2025 RSV season, with a significant shift to Beyfortus. Please turn to slide 13. Immunology is also doing well, with growth of 10% in the quarter and 9% for the full year. As a franchise with Gamifant, we saw the continued significant sales increase since Q2, with SEK 497 million in Q4. This is the result of an enhanced go-to-market model, more experience with Gamifant, and recent publication of new data, reinforcing the belief of interferon gamma in this setting. We see increased interest from both existing and new physicians and new prescribers. Given the experience with the product, the initial dosing has been increased, and duration of treatment has been prolonged.
All this has contributed to a very strong three-quarter performance for Gamifant, and full year sales of more than SEK 1.6 billion. Kineret, as anticipated in July, with the COVID effect being washed out in H1, Kineret has returned to normal growth, as there is an elevated interest in the IL-1 mechanism. Growth is driven by the U.S. and Europe. Sales grew by 11% in Q4. With this, I would like now to refer to Henrik, our CFO. Please, Henrik, continue.
Thank you, Guido, and hello, everyone. Please turn to slide 15, and the key financials for the fourth quarter in 2023. So looking at the bars to the left, we see the consistent trend in hematology, similar to last quarter, with contribution to growth from Doptelet outside of China, Elocta, Aspaveli, and the addition of Vonjo. In immunology, Gamifant continues its strong momentum with over 100% year-on-year growth at CER. Synagis sales declined due to later start of the RSV season, as well as the launch of Beyfortus. And the Beyfortus royalties of SEK 890 million mostly compensated for the lower Synagis sales in the quarter. Over to the table on the right, revenue reached SEK 6.8 billion, and that was the highest quarter ever, as reported in SEK, as we continue to grow our strategic portfolio.
Reported growth was 14%, and that corresponded to 15% at constant currencies. The adjusted gross margin in the quarter was 80%, compared to 78% in the same period last year. The improvement is mainly due to having no low-margin Doptelet sales to China in the quarter. The gross margin was also improved by royalties from Beyfortus, but was somewhat offset by lower Synagis sales, which is another high-margin product for us. The adjusted EBITDA margin reached 38%, below last year of 41%, and this is explained by the increase in operating expenses in the quarter. As a reminder, the CTI business was not included until Q3 of this year, and in addition to Vonjo costs, the higher spend in marketing and sales related to the launches of Doptelet and Aspaveli, and pre-launch activities for efanesoctocog alfa.
The increase in R&D spend relates mainly to Vonjo and efanesoctocog alfa. For efanesoctocog alfa, we are running additional phase IIIb studies and also ramping up medical affairs and making geographic expansion efforts. The non-recurring costs or items affecting comparability of some SEK 80 million in Q4 relate to the ongoing integration following the CTI acquisition. We expect some further non-recurring costs in coming quarters, but at a lower level compared to Q4. For further details on items affecting comparability in the quarter, please see page 3 in the Q4 report. Operating cash flow in the quarter was just above SEK 1 billion, bringing net debt at the end of the quarter to SEK 19.3 billion, corresponding to a net debt to EBITDA ratio of about 2.5. As a reminder, we completed the SEK 6 billion rights issue in Q3.
If we go to slide 16, and the financial outlook for the full year 2024, for revenue growth at constant exchange rate and adjusted EBITDA margin. So as we heard, for 2024, revenue anticipated to grow by high single-digit percentage at CER and adjusted EBITDA margin to be in the mid-30s% of revenue. Expect the main drivers of growth in 2024 to be the uptake of Vonjo and including, of course, the full year impact. The launch products Doptelet outside of China, Aspaveli, Gamifant and royalties for Beyfortus. Pending approval, Efa alpha will launch in Germany in the second half of 2024, with most other markets coming in 2025, following the customary reimbursement processes on a country-by-country basis. This makes 2025 the main launch year for Efa alpha in our markets.
On the other hand, we do not expect any sales of Doptelet to our partner in China in 2024. Doptelet sales to China in 2023 were almost SEK 600 million. In addition to the usual uncertainty in the timing and severity of the RSV season, we do expect that the successful uptake of Beyfortus will have an impact on sales of Synagis next season. The guidance on EBITDA margin in the mid-30s% reflects a slight increase in margin from 2023. Just as with revenue, we will have the full year impact of Vonjo in 2024 in both SG&A and R&D costs. In SG&A, we will continue with a strong launch support for ongoing launches and also increase the investment into the launch and pre-launch of Efa in Europe, as well as continued geographic expansion.
In R&D, we will increase our efforts related to studies and the ramp-up of medical affairs activities for Efa, as well as the filing preparations for SEL-212. The continued investment in bringing our assets to approval and launching them successfully are, of course, critical for unlocking the long-term value of these assets. With the outlook covered, I will now hand over to Lydia. Thank you.
Thank you, Henrik. Hello, everyone. Let's start with the pipeline milestones on slide 18, please. So we hit quite a few R&D milestones in the quarter. There are three notable developments for Aspaveli. In nephrology, we are making good progress. The VALIANT study, our pivotal phase III clinical trials for pegcetacoplan in C3G and IC-MPGN, was fully recruited in December, and we are looking forward to the data. In November, we presented the positive phase II novel results at the American Society of Nephrology. We are very confident about the potential of pegcetacoplan for these indications in nephrology. There are currently no approved targeted therapies that can prevent or reverse renal injury and failure for C3G or primary IC-MPGN. As the only complement target therapy that can block the main pathophysiologic driver for these conditions, pegcetacoplan has a convincing mechanism of action.
For PNH in Europe, CHMP issued a positive opinion for pegcetacoplan use in first-line treatment. We terminated the phase III study for C3G as part of realigning our joint activities with our partner, Apellis. We are facing recruitment challenges due to availability of alternative therapeutic options that limited the number of patients eligible for this study. Important to note is that there are no safety concerns, and efficacy has not been evaluated due to the blind design of the study. For Vonjo, the National Comprehensive Cancer Network issued new guidelines in December. Importantly, a new section on myelofibrosis-associated anemia is now part of the guidelines, and pacritinib is included as an option for all aspects of management of patients with MF-associated anemia. This NCCN update further supports pacritinib's potential role in treatment of a broad range of MF patients.
It is the preferred agent for its indication patient population of intermediate or high-risk MF patients with platelet counts below 50,000. It's also noted as a potential option for high-risk patients with higher platelet counts. Finally, Kineret received its first approval in China, to which I will come back to on the next slide, please. Looking ahead, we have a lot of news to share. 2024 will be the year to launch efanesoctocog alfa. We believe that we have convincing and strong data and are preparing for the anticipated E.U. decision. The process has been going smoothly so far, and we answered the 120 questions and received certification for the device. We are also preparing for important U.S. submissions.
First, for SEL-212 in chronic refractory gout, for which Sobi now has the full responsibility after taking over the Selecta team in November to keep the submission preparations on track. We are still aiming to file with FDA in the first half of 2024. Later in the year, we will receive the full data from the Gamifant Still's cohorts from the MAS study. This will enable us to file in secondary HLH for macrophage activation syndrome in Still's disease in the second half of this year. Lastly, we continue our geographic expansion with anticipated Chinese decision for Doptelet in ITP and submission in Japan. After receiving the FMF and CAPS indications for Kineret in China last year, we're also looking forward to the Still's indication, which is the most significant of the three.
As you can see, we are taking the momentum from 2023 and accelerating further in 2024. With that, I would like to hand back to Guido. Next slide, please.
Yeah, thank you, Lydia. We are pleased with Sobi's development, as pointed out, during Q4 and the full year. You know, as we outlined, we saw 15% for the quarter growth, 12% for the full year. You know, this reflects a strong performance of our launch medicines and foundational business in all regions. In addition, obviously, we received a strong contribution from Beyfortus. Our R&D pipeline progressed with key milestones for efane soctocog alfa, Aspaveli, and Doptelet. We have a strong momentum in the business and look forward to a successful 2024. With that said, let's move to the question and answer session, and maybe the operator takes over.
We will now begin the question and answer session. Anyone who wishes to ask a question may press star and one on the touchtone telephone. You will hear a tone to confirm that you have entered the queue. If you wish to remove yourself from the question queue, you may press star and two. Questioners on the phone are requested to use only handsets and eventually turn off the volume of the webcast. Anyone with a question may press star and one at this time. The first question comes from Yang Eun from Jefferies. Please go ahead.
Thank you. I have a question on Vonjo first. So, understanding that there is a integration phase that impacted the growth in Q4, but Q4 sales are lower than Q3, so you didn't see the integration issue in Q3. And despite the fact that you have, but you had about 22% new patient starts in Q4, I'm just wondering why Q4 sales became lower than Q3. And was there any impact from GSK launch? And another question is on hemophilia A royalty exchange rate with the Sanofi. It could be that I must be mistaken, but my understanding was that the royalty rate on Altuviiio was negotiated to 8% range, a high single percentage range from 12% on Eloctate.
Was it a renegotiated range, or was it from the start that it was 8%?
Yeah, thank you, Eun. Maybe we start with Vonjo. I mean, basically, you know, where we are right now with Vonjo, given the fact, you know, that we have a stronger propensity to, you know, this more severe patients with platelet counts below 50,000. What we have right now, and obviously, you know, also the way the product is used in the treatment algorithm, we have a shorter treatment period than other JAK inhibitors. This is basically, you know, right now it turns out that this is, you know, impairing obviously sales, but it's also an opportunity when this is corrected, particularly now with the new guidelines. But what it means is that essentially, you have an average duration of treatment of eight months.
With this, you lose, you know, you, if you don't have replenish your new number of patients on time, then this has an effect, obviously, over time on the patient buildup. We haven't seen this that much in Q3. That's correct. But we have seen it more in Q4, which you guys has an accumulated effect of Q2 and Q3. And, you know, when we modeled this one out and tried to really get to the bottom of this. So whilst, you know, I would agree, I mean, if it was the other way around and we didn't wouldn't have seen the patient growth in Q4, then I would have agreed with your suggestion that maybe this is related to GSK.
But as we have seen the uptake in Q4, I mean, I'm not saying that we are completely free from the GSK effect, but you know, it is right now, it's more, it has more to do with our, you know, to be honest, probably CTI took our eye off the ball in Q2, and you know, we had quite a bit of, you know, we needed, there was a bit of a cultural alignment that needed to happen, and quite a few people actually left as you know, also to deliver the synergies that we wanted to have. So that's really behind this. And then, sure enough, we also clarified that we could improve the messaging, create more clarity here.
But all of this has been all achieved, agreed, you know, and the, and the team has a, you know, a very clear target audience. So I think what you see has more to do with us, and we, we had to do our housekeeping. You know, sometimes in life you wish, you know, you could, you could compress life into a spreadsheet and just extrapolate. Sometimes that's not the case. And let's say we, we just have to accept that we now need to give this team a bit of time. But, but, you know, from what we have, what we understand, we are in a good way, and we should be able to demonstrate growth from here. Yeah.
With regard to the royalty agreement, maybe, Henrik, you share your views, what has been agreed.
Yeah. Can you repeat the question?
Sure. So the exchange royalty rate with the Sanofi-
Yeah.
My understanding was that the Eloctate is about 12%, you know, both ways. But-
Yeah.
Altuviiio started with the 12%, but you were negotiated recently, and we went down to 8%. So question to you-
Yeah.
... is that was it renegotiated down to 8% recently, or was it 8% from the start? On Altuviiio.
It was 8% from the start. You know, it was not only a royalty that was negotiated. We made an early opt-in to the product.
Mm-hmm.
It was a larger deal than only the royalty terms.
Yeah. And you and I can very well remember-
Sorry.
When we announced this deal, we actually clarified this with 8% and 9%. Nine, that we pay, eight that they pay us. And we clarified that, you know, by the expanded market share that you would expect for Afa on the total earnings side or revenue side from royalties, we should be, we should have a positive.
Thank you.
Sorry. Good.
The next question comes from Charlie Maybury from Morgan Stanley. Please go ahead.
Hi, thanks very much for taking my question. Charlie Maybury, from Morgan Stanley. I guess firstly, just back to Vonjo. I guess it would be interesting to hear your thoughts on how the debate actually is playing out on the market in terms of the relative importance of thrombocytopenia and anemia, because I appreciate that you're on the NCCN guidelines for both, but obviously you're the preferred regimen for thrombocytopenia and momelotinib is preferred in anemia. So just thinking about-
Mm.
The dynamics would be really helpful. And then I don't know if you can, but I think following the conversation we've been having today, if you could sort of help give any assurances on the level of growth we should expect, maybe through 2024, and how much of sort of the long-term revenue opportunity for the product you believe is in MF versus other indications outside of MF, I think those factors would all be very helpful. Thanks very much.
Yeah. You know what I mean, you know, our, our ambition for 2024 is, is unchanged. Yeah, we, we want to make this an important medicine. When you look... When you think about the market, you know, and, you know, basically, and you segment it, and let's assume, you know, you segment it according to two dimensions, hemoglobin level, and you say, okay, anemic below 8-10 grams per deciliter, and then thrombocytopenic below 100,000, then that segment below 100,000, irregardless whether you are anemic or not, is more than 65% of the market. Yeah. And this is where we believe we have, a positive preference share, based on market research and also now confirmed with the, with the guidelines.
Granted, guidelines is not label, but, you know, the, and I think the main topic is when you are a cytopenic patient, and there's a large group, obviously, of, JAK inhibitor-treated patients who are not getting a full dose, and, and if they don't get full dose, they don't get full effect. And the dosing is related to, you know, also to the, to the mechanistic effect of JAK1 inhibition. We are JAK1 sparing a JAK2 inhibitor. So, you know, logic would suggest that, that basically, why would you use another JAK1 inhibitor if, if basically you're underdosing because, of, the mechanistic effect in the first place? Yeah. And that basically, you know, makes us quite confident. You know, obviously, proof is in the pudding. I mean, I get it, yeah.
You know, that, you know, I could have also lived with a higher number for Q4. Very straightforward. Let's say, but, you know, but I think, you know, you, what you can sense is, you know, we, we, we think that we have the right product in our hands, and we will, you know, make this a very significant product also with this year, and there's, and nothing has changed this. I, I don't think we have set out, any specific target for the product for this year, but that this will be a material product, let's say, you know, until... And you have seen the expectations, you know, we, we, you know, we will think that, you know, that, this product will, will be an important contributor this year. Period. This is... Does this give you some flavor?
Maybe, Armand, you can, because, you know, historically you have done quite a few interviews with some of the KOLs. You know, maybe you can give some color how you see the topic, thrombocytopenia versus anemia.
Yeah, happy to do so. Thank you very much, Charlie, for your question. I think it's a really important one, because the way we look at this, and there's also discussions that we have a lot, anemia clearly affects the well-being of the patient, their fatigue and other things. But if you look at the real heavy outcome, that is life expectancy, this is much less driven by low red cell counts, but clearly determined by the low platelet counts.
And if you look at that aspect, and if you see that Vonjo really has positive effects, even in the worst patient group, with platelet counts below 50,000, but has not only good effects on the platelets, but as well on the anemia, we feel strongly that we have shown in the worst patient group that this drug, our drug, Vonjo, is really helping those patients, and that should also be the case in the ones with higher platelet counts. So for us, we feel that if you compare the different aspects, particularly from the outcome and life expectancy, we feel that we have a great product. It's not a direct comparison that exists, but we feel that only looking at the anemia part doesn't give justice of what the patients truly need, and that is more than just improving anemia.
Cool. Thank you very much.
Thank you. Maybe we go to the next question.
The next question comes from Neil Alexander from Deutsche Bank. Please go ahead.
Hi, how's it going? It's Neil Alexander from Deutsche Bank. Thanks for taking my questions. So question on RSV. We're seeing consensus forecast a 35% decline in 2024 and then a 30% decline in 2025. And, you know, we're seeing Beyfortus doing well in the U.S. so far, with Sanofi commenting that they expect Beyfortus to be blockbuster product. So question is, do you feel the 30%-35% decline in Synagis over the coming years is reasonable to assume? And that's the first question. And then just the second question is a quick one. Q4 2023 SG&A came in ahead of consensus estimates. So it'd just be good to get a feel of how we can expect the SG&A to trend going forward. Thanks.
Mm-hmm. Yeah, thank you. I mean, you would expect, you know, with an increase of, of obviously of Beyfortus, in line with the guidance of, Sanofi, that this will affect us. And, and no matter, no matter what, let's say. But, you know, we-- I think a good indicator, because there's a bit of uncertainty. I mean, you know, we obviously have two factors that have influenced, you know, Synagis's performance in Q4. Also, when you think about now, the coming year. And the first factor was that the season started late, which basically didn't allow us to get enough doses, you know, administered.
Then the second reason was that, you know, obviously there was a supply, then in the end that I think, you know, was able, even though maybe not to be anticipated in the late stage of the quarter, which was then obviously, you know, consumed and obviously affected also our ability, you know, to sell Synagis. Now, the question is, you know, where will we land? I think, you know, that you will have to expect an effect on our business. You will have to expect, you know, just by the virtue that, you know, we have a certain group of patients now that are using the product.
There will be quite a few that will continue treatment, but it's clearly less, you know, than we had the year before on Synagis. That basically will affect us. To what degree will we be affected in the second part of the year, meaning the 2024, 2025 season? I can't tell you. This is a big part of the uncertainty. But what I can see is, you know, when you look at the dynamics of royalties from Beyfortus and our business, I mean, it's a bit like a yin and a yang. Yeah, and it is, let's say, you know, quite a view, quite beautifully offsetting each other. So, you know, we would not necessarily anticipate, you know, a decline of the franchise, definitely not in terms of profitability.
Yeah, so I think that's how we are thinking about it. But, you know, it is, you know, there is an asymmetric element with Synagis, where we obviously have higher sales with the Synagis patients than we get effectively than royalties from Beyfortus. So that basically creates a little bit of an uncertainty, and that's what basically also is included in our guidance. You know, so I hope that gives you a little bit, you know, of some perspective on this, yeah.
Then, on your question on the SG&A, I mean, Q4, in reality, most of 2023, the SG&A is, of course, a reflection of our five ongoing launches.
Mm.
So, we will, of course, continue in 2024 with, you know, strong launch support and also then, of course, intensify pre-launch and launch of EFRA. So, so that is what I can say about the trend in 2024.
Yeah. But I think it's, you know, and this is basically what you have seen also in Q4. We saw the opportunity to invest into our pipeline and into our launches, which I think, you know, this is what we are supposed to do and what we should be doing, building the company out for the future. But we are also recognizing the fact that, you know, that obviously people want to see profit improvement, and that is also incorporated as part of our guidance.
Brilliant. Thank you very much.
Thank you.
The next question comes from Alistair Campbell, from Royal Bank of Canada. Please go ahead.
Thanks so much for taking the questions. I guess two. First of all, you know, obviously we're now learning a lot more from Sanofi about Altuviiio's launch in the U.S. And I just kind of wonder, you know, from what you've seen, from those U.S dynamics, what do you think will be similar in Europe, and what do you think actually may be different as that molecule comes to market? And then another question, if I may sort of chance my, chance my luck a bit. If I look at the most recent consensus, it's got an EBITDA margin of about 43% by 2026. Now, clearly, we're trying to wrestle with the positive impacts from a significant Beyfortus royalty, against other things as well.
But just get a sense of how realistic do you think that margin level can be in terms of attaining that level by that timeframe? Thank you.
Yeah, thank you. I mean, you know, what can we learn from Altuviiio in the U.S? I think, you know, though obviously we have a larger relative franchise of Elocta, you know, so basically, I think, you know, what is... That, you know, may influence this, but, you know, what you can see is that there are certain EHLs and SHLs, you know, which clearly would be the natural sources of growth for Altuviiio. There will be also quite a few patients from Hemlibra that may want to switch back to factor VIII to Efa, simply because they're needing additional factor, or they want to benefit from additional protection.
And you know, so these will be, will be, but you know, structurally, when you think about it, where growth comes from, factor and Hemlibra, maybe structurally it may not be so dissimilar. Yeah, when we look at our, let's say, what then the share of Efa, of Elocta is versus the share in the U.S., you know, we'll figure it. But you know, I think you know that there's a certain amount that we're getting from short-acting and from long-acting, and then obviously also getting some share back from Hemlibra. And then you know, you will see how the momentum is built up, how the community is reacting. You know, patient experience, they will be typically very much shared within the community.
We know we have shared with you the anecdotal evidence, you know, from patients who are on the product, who really, you know, where the vast majority of patients who have been in the clinical trials definitely want to stay on the product because they have such a wonderful experience. So, so there's a lot of good things coming into this direction. And maybe later, because Lydia is just now actually at EAHAD, at the EAHAD conference, she can provide you maybe with some feedback on this. And then, just a snapshot on EBITDA. EBITDA is going to be a function on how much we are going to invest into our future, you know, obviously on the Beyfortus, and it basically also obviously how we are able to build up scale.
You know, we unfortunately don't provide guidance at this stage beyond 2024. And, you know, but, you know, we understand that the more Beyfortus royalties we have, the more profitable the company becomes, and that the more it allows us to make those educated choices. But we want to build, obviously, the company out for long-term growth. And, then let's see, you know, where we stand at the end of the year, whether we have been conservative or we have been right on. But, you know, time will tell. But, you know, we want to make sure that we drive this for strong growth, despite obviously a few headwinds, yeah, that are quite material on the scale of Sobi.
Lydia, maybe you want to give them the, let's say, snapshot from, from EAHAD, as you are right now there.
Yeah. Thank you.
All the sentiments.
Yes. I think there is a lot of excitement here at EAHAD with Efa. We have six abstracts that have been accepted. One is an oral presentation on the pediatric data, because that's the piece that we will be publishing this year as well. So it's, it's generating a lot of interest in the community for, not only for the adult treaters that we have published the data, but it's also very highly respected by the pediatricians. And what we hear is that, that there is still very high interest due to the fact that, that for many factor is still fundamental, that the expected levels of protections are something that have, has never been able to be achieved. And the one sharing the expertise from the clinical trials is really positive.
So, I think that here in our territories, we will see switches from all the alternative treatment options that are currently available in the market, including factor and non-factor. Looking forward to having it approved and launched here.
Yeah. I think this gives you a bit of a flavor where we are. Maybe we go to the next question.
The next question comes from Christopher Uhde, from SEB. Please go ahead.
...Hi there, Chris Uhde. Thanks for taking my questions. So, I guess I'd just like to start on OpEx going forward. So, for 2024, does Q4 does the base there represent sort of a fully loaded SG&A that we can expect sort of going through 2024 on the existing portfolio? And then, when it comes to Synagis, are there any subgroups of patients where you're you've been more resilient to cannibalization from Beyfortus? And also, how much can working capital improve as Synagis declines? And then, lastly, on Vonjo, you've talked about you know, doing trials in the future, expanding Pacifica for one thing, looking at other indications and also combinations with other myelofibrosis drugs.
But you had the asset for more than half a year, and so far we haven't seen anything happening there. Have you changed your mind on this? And sort of as a, an aside to that, the anemia guidelines, a 2B recommendation, so it's not an easy ride for reimbursement there. Is that good enough, or do you need a trial? Thanks.
Yeah, maybe, you know, thank you. I mean, thanks for asking only one question, Christopher. Very much appreciated, let's say. But, you know, with regard to Vonjo, let's say, you know, let's start the other way around here, because that was quite loaded. You know, with Vonjo, we, you know, we have obviously, we are progressing quite a lot, but unfortunately, for competitive reasons, we can't tell you right now. But that's the reason why we set due course. Yeah. So it's- we haven't changed our mind, and the entity in guidelines is good enough for reimbursement. Yeah. And, let's say, and that basically, so hence, you know, we, I mean, obviously, it's, you know, we have to work for it.
It needs to be understood, but, you know, we, we think that this is, this was an important milestone for the company, for the product. Yeah. We stand fully behind this. Nothing has changed. Then we maybe with the SG&A side, Henrik, you want to take this?
Yeah. So on the question whether Q4 OpEx was fully loaded, I mean, and representative for 2024. Of course, there are ups and downs between quarters, but Q4 was for sure fully loaded. I can take also your question on you were expecting an improvement in cash flow when Synagis is switched to Beyfortus, and that's not really the case because Beyfortus, we get paid after the quarter, whereas in the case of Synagis, when we've been invoicing ourselves, we have collected money before that. But of course, Beyfortus is, relatively speaking, much more profitable and will from that point of view, generate a lot of cash.
Yeah. Does this give you... There was another element in your question? Sorry,
No, yeah, those are great answers. The last element on the Synagis was, are there any subgroups of the patients where you're seeing more resilience to cannibalization?
No, I think the subgroups is more driven by the profile at this stage of the physician. And there are some who are quite resilient and believe in the advantageous profile of the product and, you know, and want to see more evidence. And, you know, as we historically have said, with increasing evidence, obviously they accrue quite a lot of evidence, you know, by the number of patients that are now on the product, that basically, you know, may or may not change. But for now, we have quite a large group still supporting the product.
Thanks very much.
Good. Maybe we move to the next question. Thank you.
Yeah, and if we could keep to one question, please, because we have three people left on the line. We're running out of time.
The next question comes from Liu Yifeng from HSBC. Please go ahead.
Hello, thanks for taking my question. I have one on your RSV, specifically for your 2024 guidance and especially both on revenue and margins. I was just wondering how much sort of, you know, the share between Synagis and Beyfortus are you sort of penciling in from your implied, you know, margin and revenue? And secondly, on if I offer, you mentioned that you're doing additional phase III trial, and just trying to understand what does it differ from your current data package and what value does it add? Thanks.
Yeah, no, we, I'm sorry, you know, that we, we have not provided, let's say the, you know, the, the breakout of Synagis and, and, and also now of Beyfortus. And, you know, you, you probably the best indicator on how we think about it, but we won't tell you is what, what some of you are saying about Beyfortus revenues next year in the U.S. And with regard to, you know, let's say this is the, the, with regard to ReFacto AF, this is more long-term safety and phase IIIb. And, and Lydia, you want to comment on this?
Yeah. So it's a phase IIIb trial that we are running in our territories to collect additional data focusing on physical activity, so patients will have physical activity trackers, and that will provide additional data that was not collected in a continuous way in the pivotal trials.
Yeah. But, you know, we are well on to it. Yeah. Good. Next question, maybe.
The next question comes from Viktor Sundberg, from Nordea. Please go ahead.
Yes. Hi, guys. One question here on Vonjo and your integration of CTI. Could you quantify or maybe guide for us the synergies here? Do you think the product here will be highly margin accretive going into 2024, for example, versus your mid-30s margin target for the combined sales of your products? I guess there's some overlap here between Dova and CTI. That's the reason for my question. And maybe just a very quick one on VALIANT also, start to read out here mid-2024. What's the commercial opportunity here, in your view, for that indication? Thanks.
Mm-hmm. Yeah, I mean, I start with, you know, we said accretive in 2024, for Vonjo, and we stick to it, yeah? And let's say it's not maybe massively accretive, but, you know, it's a very profitable product, and it will make a contribution, to the product, to the franchise. Henrik?
Yeah. Victor, obviously, since we are speaking about an uptake here, the accretion will be building during the year.
Yeah. So we know that we have work cut out, and we are not shying away from this. And, you know, we think we have enough what it takes to make this. With regard to VALIANT, this is obviously, you know, when you think about the number of patients, you basically have substantially more patients in the nephrology indication, as per VALIANT, than you have for PNH. And in addition, it's what we can expect is a two-horse race, given the effect, you know, and one of the diseases even called C3G, yeah. So no surprise that you would expect a C3 inhibitor having a very direct effect, and therefore, we are super excited.
And also, when you think about the deposit removal data, yeah, and you know, the images that were shown as part of the phase II, we are really excited about this. So we think that, first of all, a lower number of competitors. Secondly, a very direct way, and certainly, we think that the data we can also look forward to is maybe, maybe quite positive. Yeah.
Okay.
So that, that spurs our excitement. Thank you.
Yeah. Thanks very much.
And then maybe thank you. Next slide, next question, sorry.
The next question comes from Erik Hultgård from Carnegie. Please go ahead.
Yes, Harvey, thanks for taking my question. On Aspaveli, the opportunity in rare renal diseases. Can you talk a bit about how you see? Obviously, there is no approved therapy within C3G, but Novartis iptacopan announced positive headline data in, I think it was in November.
Mm.
So just curious to hear your thoughts there on potential differentiation, looking at sort of-
Yeah.
... earlier stage data, what we should anticipate there? Thank you.
Yeah, thank you. I mean, we basically look at this, at this market, from the following axes. It's pre/post-transplant and IC-MPGN and, and also the C3G. You know, we think that, you know, and basically what you have to believe in or what you believe in is, is you know, that by that time, you know, we have a new applicator that Apellis has launched in, in the U.S., for the, for the product that makes the administration of the product much easier and more convenient based on recent data points.
So we think that this device, twice a week, subcutaneous, will then, you know, we compared obviously with twice a day oral, and then basically you say, "Okay, what will be the compliance with the oral?" I mean, we have certain reference points, you know, on how compliant patients are with oral therapy in different settings. And you know, and obviously non-compliance could lead to complications. And you know, and hence, we think, you know, that there will be a fair share of physicians electing, you know, subcutaneous direct C3 inhibition, particularly as the data will stack up.
We're actually quite positive, you know, based on the phase II data, that we will show some strong data also in phase III, so that, you know, that this will be a strong alternative treatment option for physicians. You know, we have now quite a few patients early, also in early access, because it's there in such a desperate stage, and that we make product available, and we see really spectacular, you know, data from this. You know, we are really, you know, proof is in the pudding, but, you know, the opportunity is very material. You know, if you are, if you are... I think, you know, there may be a bias in the IC-MPGN patient potential and for also post-transplant.
So we may have there a strong target audience. Yeah, I think this gives you-
Thank you.
Thank you, Eric, and for your question. And so, guys, I think we are a little bit ahead of time. So sorry that we were a bit extensive, but, you know, as you can see, we don't feel sorry with 12% growth, yeah. And we are bullish about our future, and we try to delight and make sure that we, that we you know, we can live up to your expectations. Appreciate it, and wish everybody a great week. Thank you.
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