Ladies and gentlemen, welcome to the Sobi Q3 2022 report. Throughout the call, all participants will be in Listen-Only Mode, and afterwards there will be a question and answer session. I will now hand over to the company.
Thank you so much. Hello everybody. This is Guido Oelkers, CEO of Sobi. We'd like to welcome you to the 1/3 1/4 2022 report and conference call for investors and analysts. The presentation was posted to sobi.com earlier. With this, maybe we can just do the second Slide. Slide 2 has the usual safe harbor statement.
We'll be making comments on our performance using constant exchange rate or CER, and numbers used in Swedish krona for the 1/3 1/4 of 2022, unless stated otherwise. Comments will mostly relate to the 1/3 1/4 performance. Please turn to Slide number 3. This is the agenda, where we plan to cover all key aspects of the results today. We plan to review the presentation first and then do a Q&A until around 2:00 P.M. Swedish time or Central European Time.
We want to be respectful of your time, as this is a busy day with other companies reporting as well. If you keep questions short, we will try to keep our answers short too. For those on the phone, please join in the queue for questions by pressing zero one. We propose you ask only one or 2 questions at a time, many thanks.
In speaking order, I'm joined by Henrik, our CFO, Anders, our head of R&D and Medical Affairs and Chief Medical Officer. For questions later, we will also have Armin, our Senior Advisor, for Scientific and Medical Affairs as well here. With this, please turn to Slide number 4. Starting off, I'm pleased that Sobi continued to perform well with sustained progress in support of the outlook for 2022.
Revenues decreased by 6% in the 1/4 at constant exchange rate, but increased by 6% at actual rates. This performance reflected a higher base such as COVID sales and with Kineret and our phasing of Doptelet sales to China, coupled with some clawbacks for lockdown Europe. In the year to date, revenues were up by 9%, fully underpinning the full year outlook.
We saw commercial execution across the board. Launch medicines which mainly Doptelet outside China, Aspaveli and Gamifant combined advanced by 22%. In hematology, hemophilia continued relative stability. Doptelet continued as a major contributor with sales up 77% outside China, and Aspaveli continued a good launch. In immunology, the performance was impacted by COVID in the comparative period.
Kineret is now rebased with no COVID sales, and Synagis did not have the same early start as of last year. Gamifant was softer following a good second 1/4. While we continue to invest for growth, we saw slower growth in selling and even some small step back in R&D and medical costs. As a result, the EBITDA margin landed at 31%.
The partner continued to progress with the first efanesoctocog alfa regulatory submission and U.S. priority review. There was a U.S., EU positive regulatory opinion for loncastuximab tesirine, a Kineret regulatory submission in China and an approval in Brazil. We expect increased pipeline news flow in 2023. With the performance today, we confirm the outlook for 2022.
Before I continue, I would like to thank all colleagues in Sobi for the work and commitment to the company and the focus on providing innovative medicines that transform lives of people with rare and debilitating diseases. Moving to the disease area, Slide 5, and geographies, we saw growth in hematology driven by Doptelet in all geographies outside China, while immunology was held back by lack of COVID-19 sales for Kineret, the later start this year to the RSV season for Synagis, and softer 1/4 from Gamifant.
From a geographical point of view, we saw higher growth in Europe from Doptelet and the launch of Aspaveli. Growth in North America was impacted by Synagis and the rest of the world by Doptelet sales to China, which is more an artifact due to the phasing of our sales to our partner, Zuellig.
On the topic of rest of world, we were pleased to have concluded an exclusive distributor agreement in Japan with Asahi Kasei Pharma in September, something we cover a little bit later today. With this agreement, we enter the second biggest pharmaceutical market from a commercial point of view and in support of the 2 medicines under regulatory review there.
Turning to Slide 6, with a specific attention to hemophilia, we saw continued relative stability. This performance is spot on the commitment to continue stability in all of 2022 and into next year. The Elocta decreased by 5% while the patient growth was up in single digits. There was growth, as mentioned, in this patient and higher factor consumption, but it was more than offset by, in the 1/4, retrospective clawbacks and price.
We also estimate that factor consumption is now back at Pre-pandemic level. Alprolix advanced by 2% driven by growth in patients, but slightly offset by the unfavorable country mix. We are pleased by the stable performance overall and stay focused on opportunities ahead. Please turn to Slide 7. Doptelet had another strong 1/4 with some impact from phasing of sales to China. Excluding China, sales grew by 77% on strong US performance and strong growth in Europe.
In the US, we saw more new patients, new prescribers, and higher market share, and also longer duration of treatment. We believe market share gains come mostly from injectable competitors. In Europe, Germany remained as the biggest driver, but also countries with recent reimbursement decisions have started to accelerate. This bodes well for 2023 performance.
In China, we started providing details last 1/4 and saw the anticipated phasing with a higher comparison in the 1/3 1/4 last year. The fourth 1/4 will provide a lower comp. Please turn to Slide 8. The launch of Aspaveli continued to progress well with sales of SEK 49 million in the 1/3 1/4. We have launched in the UK, Germany, and France, and parts of the Middle East, with earlier intermittent sales in a few countries.
We increased to approximately 65 patients on commercial supply by end of September, a nice step towards the goal as a 3-digit number by year-end. This progress was quite remarkable given the situation in Europe during the latter summer months. Please turn to Slide 9. Turning to immunology, Kineret sales were impacted by the lack of sales for COVID-19, but other indications continued to provide growth.
This growth will be more visible as Kineret completes the rebasing in early 2023. Gamifant sales were soft following a strong second 1/4. The decrease was driven by patient mix, i.e., a lower proportion of heavier patients than in the comparable period, as well as a fewer new patients. As we look ahead, the life cycle of Gamifant becomes more important.
Later, Anders will discuss some new data on Gamifant for this 1/4. We also expect new data at ASH at the end of 2023 for the ongoing phase 3 study. Please turn to Slide number 10. Last in the immunology is Synagis. We saw the RSV season start a little later than in 2021, but still a good start compared with historic levels.
While U.S. RSV infections have continued to increase, so we continue to expect a 2022/2023 season that follows a pattern closer to a normal season than in 2021. I will now hand over to Henrik for the financials. Please go ahead, Henrik.
Thank you, Guido, and hello, everybody. If we please turn to page 12, and I will now take you through the key financials for the 1/3 1/4 of the year. Starting with the top line, we're showing 5 quarters of revenue here. We've already covered Year-On-Year changes, but sequentially, revenue in the 1/3 1/4 was higher than the second 1/4, also when adjusting for currency, and this is mainly driven by synergies.
In hematology, we've reached a new higher level due to the strong Doptelet performance. Turning to the profit and loss on the right, and this is at actual rates. As expected, we saw slower growth in revenue in the 1/3 1/4 than earlier in the year, but it developed in line with our outlook, as communicated in connection with Q2.
Gross profit developed more favorably than revenue, mostly driven by a favorable product mix coming from relatively lower share of Doptelet sales to China that carry a lower margin than the rest of the business. The gross margin was also positively impacted by FX effects, so the gross margin ratio therefore ended at 77%, and that was up from 75%.
Selling and admin expenses increased by 1% at constant exchange rates when adjusted for amortization, while R&D expenses decreased by 3% due to phasing of study costs. As a result, the EBITA margin was 31%, same as in Q3 2021. There were no items affecting comparability in this 1/4, and we don't anticipate any further restructuring in 2022.
For details on items affecting comparability in the Year-To-Date period, you can, please look at page 3 in the Q3 report or the appendix to this presentation. Earnings per share for the 1/4 ended SEK 1.52, down by 5%.
Operating cash flow was strong in the 1/4 at SEK 780 million, offsetting the investment in the loncastuximab tesirine license, so that our leverage remained at about 1.5 times at the end of the 1/4. Will you please turn to Slide 13, and I will continue with the financial outlook for the full year, which is revenue growth at constant exchange rates and adjusted EBITDA margin.
As you will have seen, we leave the previous guidance unchanged, which means that we expect revenue to grow by a mid to high single digit percentage at CER, and potentially towards the higher end of that range. For clarity, revenue growth was 9% in the Year-To-Date period, which implies a relatively stable fourth 1/4 at CER compared to Q4 2021.
In terms of the margin, we continue to anticipate an adjusted EBITDA margin in the low thirties, percentage of revenue, including, as before, the cost effects of the license agreement from July for loncastuximab tesirine in hematology. This implies an expected increase in operating expenses compared to the average of the previous quarters of this year.
This relates to various activities, such as the inclusion of spend related to the new product, loncastuximab, the timing of study costs, for example, emapalumab study 14, and the timing of CMC development costs for SEL-212, to name a few. With the 2022 outlook covered, I will now hand over to Anders for the pipeline. Thank you.
Thank you very much, Henrik. Hello, everybody. I will now take you through the pipeline highlights and update on research and development in Japan. Please turn to Slide 15. The pipeline saw continued progress over the summer and early autumn. Efaneseptocog alfa achieved regulatory submission and priority review in the United States, and the first patient dosed in another phase 3 study for Aspaveli, this time in CAD or cold agglutinin disease.
Loncastuximab received a positive regulatory opinion in the European Union. Kineret was submitted for regulatory review in China in a second indication of Still's disease. Finally, Brazil approved Orfadin in HT-1, hereditary tyrosinemia. Orfadin was first approved in 2002 in the U.S. and in 2005 in the EU, showing Sobi's commitment to global formulary access for patients with rare diseases. With that, please turn to Slide 16.
On loncastuximab, the EU CHMP issued a positive opinion for the treatment of relapsed or refractory diffuse large B-Cell lymphoma, a debilitating disease in hematology. In addition, new data was shared on the medicine from safety Run-In of the LOTIS-5 phase 3 study. This study combines loncastuximab with rituximab, an Anti-CD20 monoclonal antibody widely used in B-Cell diseases. No safety signals were observed.
Early efficacy data from safety Run-In showed an encouraging 40% complete responses and a complete response rate with an overall response rate of 75%. New data were also presented on Gamifant from a long-term Follow-Up study. All patients had previously been part of a phase 2 study assessing Gamifant in the treatment of MAS or macrophage activation syndrome associated with systemic juvenile idiopathic arthritis.
13 of these 14 patients did not experience any MAS episodes, and no new safety signals were observed. The data support the ongoing phase 3 EMERALD study with data due in the first 1/2 of 2023 from the cohort in Still's disease. We also anticipate more data on Gamifant at this year's ASH meeting, which will happen in December.
Please turn to Slide 17. One of Sobi's strategic priorities is to go global. Japan is a key market and the second-largest pharma market in the world with high need in rare diseases. We have been building a global hub for research and development and medical affairs in Japan, and we can access local expertise and presence needed for getting medicines approved in the country.
We have been able to attract senior people from global and Japanese companies, and about 20 in total. There are currently 2 medicines under regulatory review, Doptelet and Aspaveli, with other medicines and indications to follow. These are the first Sobi medicines ever in Japan. To help commercialize these medicines, we have entered a distribution agreement with Asahi Kasei Pharma Corporation, previously the distributor of C5 medicines in Japan.
Asahi will augment the Sobi capabilities in Japan and help provide medicines in rare diseases. Please turn now to Slide 18. As we look ahead to the pipeline news flow in the remainder of this year and all of 2023, we expect news flow to increase. There are 3 main items left in 2022, with 12 more items planned for next year.
In the first 1/2 of 2023, we will see efanesoctocog alfa read out the second phase 3 and initiate the EU regulatory journey. In Japan, we also anticipate the first approvals for Doptelet and Aspaveli. Gamifant will read out a new phase 3 study as discussed earlier, and we will see the phase 3 program for SEL-212.
In the second 1/2 of the year, data readouts will convert to regulatory submissions, and we anticipate regulatory decisions in China for a couple of medicines. With that, thank you very much for your attention and for the opportunity to talk about science and pipeline in Sobi. With this, I'm happy to hand back to Guido, who will now conclude.
Thanks, Anders. Please turn to Slide number 20. In summary, I'm pleased that Sobi continue to perform well with sustained progress in support of the outlook for 2022. The pipeline continued to deliver, as Anders has pointed out, and with efanesoctocog alfa regulatory submission and US priority review, there was the EU positive regulatory opinion for loncastuximab tesirine, the Kineret regulatory submission in China, and Orfadin approval in Brazil.
We expect increased pipeline news flow in 2023, as pointed out earlier. We now go to Q&A. For those on the phone, please remember to press zero one to ask a question. Can I please remind everyone to limit questions to one or 2 to be fair to all other callers? Thanks in advance.
If it works, perhaps we can take the first question from the conference caller.
Thank you. Ladies and gentlemen, if you have a question for the speakers, please press zero one on your telephone keypad. Please keep to one to 2 questions per person, then re-enter the queue to ask any remaining questions. The first question comes from the line of Christopher Uhde from SEB. Please go ahead.
Hi there. Thanks so much for taking my questions. I guess the first one is quick, just about geographic expansion that you mentioned. In terms of Orfadin, are you selling directly or via a partner? The second one is a bigger one more about R&D. Obviously appreciate the progress that you guys have been making and notably in Japan as you highlight. But I mean, it seems to me that the big sort of underlying weakness in Sobi is, you know, to the extent that there is one is in R&D where.
I'm wondering what steps have you taken to strengthen or are you taking to strengthen the organization and/or need to take. Sort of, can you elaborate on your strategy? I mean, is it because I think is what you're doing in Japan perhaps like providing a little bit of a roadmap for what you could do in Europe? I mean, is it that you need to add more people?
I mean, just basically because you got some delays for some products in the pipeline in terms of the program. Then finally, just related to that on costs. With these delays, does it affect the previous guidance on R&D to sales? Should we expect some shifting of costs to 2024?
Also the midpoint of your guidance of 13%-15% implies almost SEK 900 million in R&D for Q4. Yeah, that's it for me. Thanks.
Maybe I start with the easy bit of Orfadin. We have a partner and that allows us to book most of the sales in the invoice. That is maybe the easier bit. With regard to R&D, maybe Anders can talk about the improvement program, and then maybe we can provide some financials from Henrik towards the end. You know, I think if we can follow this flow, Anders, maybe you talk about some of the changes you're doing in R&D and.
Yeah.
How you view.
I mean, first of all, I would probably respectfully disagree that R&D is a weak spot. I've been here for 10 months now, and I must say I'm quite impressed by the caliber of scientists and operational people we have. I think the challenges I'm dealing with is to catch up with a very fast transformation and growth of our pipeline with a lot of successful deals recently and also our geographic expansion, which of course require to ensure that we match that with the agility and scalability that this fast-growing company require.
To do that, we have first of all kind of completed the integration of the companies we acquired by ensuring a consistent project-driven operating model with a core asset team, cross-functionally, commercial, Tech ops and R&D represented with senior leaders in charge of these programs. We are improving our planning process.
We are closely integrating between our global and U.S. medical organization, and we have scaled up our R&D investments in Japan to enter into that market. I feel very clearly we have had a couple of important studies that have not delivered exactly to the aggressive timelines we had. This is not the first time I have seen this during my 30 years in R&D.
I think we are working with some quite challenging indication areas with very rare diseases. Our EMERALD study has been delayed more than we wished, but fortunately, we have been able now by implementing additional measure both internally and in relation to our external providers. We can see that we now have very good traction with that study.
I'm pretty confident that we will deliver to the current timeline and to the timelines that Guido indicated in his presentation. I hope that answered your question, but I'm happy to take any Follow-Up questions.
Maybe with regards.
No. Thank you.
R&D expenses. Henrik, you want to comment?
No, Christopher, you're right that we do expect more R&D coming in in Q4 related to various activities as I mentioned before. We don't plan for pushing a lot of these costs into next year. There is no change to what we've said when it comes to the relation between R&D spend and revenues.
Very good.
I can just add this is kind of typical that you have a bit of a different periodic distribution of our R&D costs. This is nothing unusual, I would say.
Yeah. Very good. Thank you. Maybe we go for the next question because this was a more loaded one.
The next question comes from the line of Adam Karlsson from ABG. Please go ahead.
Hello. Thank you for taking my questions. I have one on the 2022 outlook and one on Elocta. First, though, on the unchanged 2022 outlook and what that implies for Q4. Henrik, you gave some flavor there, but just to clarify then, perhaps. We've only got 2 months left of 2022, so I guess my question is what the biggest uncertainties are that hold you back from dropping that mid-single digit part of the guidance.
Or is it more the case that you have a fair degree of confidence on where within that range you're heading, but you're just choosing not to formally change guidance at this point? And then also on the outlook, you added that excludes any potential share of losses and profits on nirsevimab.
After Sanofi seemed to submit their BLA, do you anticipate that there could be any share of losses already in 2022? That's my first question.
No. I mean, basically, you know, when you look at the outlook-
They do hear you.
They cannot hear us? Sorry. Yeah. Can you hear me? Sorry. We had a bit of a technical glitch here.
Yeah, I hear you.
Perfect. Yeah. With regard to the 2022 outlook, what are the main uncertainties? You know, there's always when you have with synergies, when you have a lot of the sales skewed to the last 1/4, as it always happens, you know, there's always a bit of uncertainty. I mean, the world, you know, is is obviously reasonably volatile.
Hence, you know, we did not feel that we have to get out of our way, but we are confident about our business. We have good momentum, as you can see. That's basically, you know. We are prudent, and hence, you know, we don't want to get ahead of ourself in in today's environment, which I think may be, maybe understood.
With regard to nirsevimab in 2022 will not have any effect on our business in doing this. I mean, the only thing we will do is we'll likely opt in, as you all know, that there is a milestone due. You know, that apart from that's it. Yeah. Maybe we then open this floor for other questions. It's a prudent approach to 2022-
Wait. No, that's good.
Yeah.
Understood. Thanks. I had another one on Elocta, but perhaps I jump back in the queue.
Yeah.
If we're keeping it to one.
Yeah. Good. Thank you.
The next question comes from the line of Eun Yang from Jefferies. Please go ahead.
Thank you. I have a question on nirsevimab. In the past, you guided as BLA filing in the fourth 1/4, but today is an acceptance. Question number one is, has it been filed already? Second question is to Henrik. You pay $175 million to opt in completely for nirsevimab. How is it gonna be treated in P&L for the guidance for this year? Thank you.
Thank you. I mean, I'm not sure that the nirsevimab is filed. I mean, not that I'm aware of. Maybe Henrik, you want to comment on the treatment?
Yeah. The milestone will be capitalized, so no material P&L effect this year.
Thank you.
Thank you. Next one, please.
The next question comes from the line of Viktor Sundberg from Nordea. Please go ahead.
Yeah. Hi, Viktor Sundberg from Nordea. My first question is on Elocta. You talk about this clawback in Greece and Italy. Is it possible to quantify that effect and how much that impacted sales in Q3, given that it maybe should be viewed as a one-off, perhaps?
Yeah, I mean, basically, you know, it's a mix of clawback and price. You know, this would have been a very stable business based on the patient growth. Price and patient growth or the impact of patient growth and volumes due to consumption would have offset each other. Basically, the clawback is a difference. I don't think we will be commenting any further on this.
Okay. Thank you. I also had another question. Thinking about guidance for next year, this might be a bit early, but how should analysts and investors think about the nirsevimab and Synagis dynamic for next year? I mean, if nirsevimab is recommended for all infants, I guess you might take a revenue drop in the second 1/2 of 2023 for Synagis. If we assume that you can keep some of that business, it might be business as usual.
Mm.
I'm just a bit curious how you're thinking about guidance for next year?
Yeah. I mean.
Taking into account Nirsevimab and its anticipated approval.
I mean, we will provide guidance as usual. For next year, we will provide guidance on the eighth of February in 2023. You know, basically, you know, there will be an effect obviously of nirsevimab. You know, as you can see, it's a broader indication.
Whether you know, the 1% of patients, a little bit more than 1% of babies is now gonna be the foremost target of Sanofi will have to be seen and whether it's clearly not enough to satisfy the growth needs. I think you know, there will be an effect. To what extent, I think we will probably provide some more profound thinking on the eighth of February.
We don't think that this is gonna be a Cassandra scenario that we are expecting. It is, as you said. If it affects us in a material way, it will be for the second 1/2 of next year.
Okay. Just a very quick final question here on inflation also. I see that you believe that you're insulated from inflation for this year in your report here. Could you perhaps elaborate a bit more on why that is and what in the supply chain would be most vulnerable to inflation and what is more protected? I just wanna get a feel for how to model this going forward.
Mm.
Thank you.
I mean, we are insulated in the, let's say, in our supply chain, because of the contracts that we have made and some of the savings that we have realized historically, for instance, in hemophilia by changing supply chain, and we are benefiting from this, and it always takes a while until this then makes its way into the COGS. Henrik, you want to comment on the topic of inflation in a broader way?
Yeah. No, but we don't see any material effects yet. As Guido said, our supply agreements are regulated through indexes. It takes some time, obviously, before it will hit the P&L. Remember that we are relatively profitable, so it takes really material increases to really have a material impact on the margin.
Mm.
When it comes to
Yeah
you know, to the rest, yeah, I mean, there will be inflationary pressures. We work quite hard on procurement activities, so we expect to be able to mitigate that to a large extent.
I mean, as we reported also earlier, we will have Forward-Looking some significant relief on the change of supply in the case of Doptelet, which should help us as well.
Thank you very much.
Thank you. Maybe we open up for the next question.
The next question comes from the line of Sarita Sherpa from Morgan Stanley. Please go ahead.
Hi. Sarita from Morgan Stanley. Thanks for taking my question. The first is just on how we should be thinking about the sales trajectory for Aspaveli, particularly given the increasing competition in PNH from Iptacopan, and then as Iptacopan moves into new indications like C3G. Then secondly-
Mm
... on hemophilia. Sanofi has kind of previously highlighted that the hemophilia market could reach $13 billion by 2030, and 40%-50% of patients could stay on factor. To what extent do you think that new innovation in the Non-Factor space, so for example, Mim8 and next generation Hemlibra from Roche and Chugai, could impact the number of patients that stay on factor longer term? Thank you.
Thank you. We'll start with Aspaveli. You know, there obviously a lot will have to be shown. When you look at the landscape right now, I mean, we feel very good in our position with Aspaveli. We see some early signals. I mean, is this a vertical launch yet? No. Simply because it is a product, you know, that needs to go through a certain cycle and, you know, Armin will talk about also the competitiveness.
But you know, what we see is we have a product that has demonstrated very strong impact on hemoglobin levels, on anemic patients, as well as on Transfusion-Dependent patients based on the 2-pronged approach. We are confident, based on the medical profile, to take a significant share in this market.
Now, well, you know, more competition make it easier? Answer is clearly not. This is a very differentiated product that we feel we have in our hands, and maybe, Armin, you can talk to this how you see it from a medical perspective.
I'm very happy to do so. Hello, everyone. I do believe that the data that we have published so far in the PRINCE and PEGASUS studies show clearly that there's quite a dramatic improvement that you can achieve in prior treated patients, C5-Inhibited patients, as well as in naive patients. I think one of the reports that I was reading was fairly clear.
There are some magic words in the press release, like clinically meaningful and statistically significant. If you look at least at the little information that has been published so far, it is a more relaxed approach. For example, just to pick one, the sort of leaving the hemoglobin level unchanged, the margin that is given for pegcetacoplan is 2 grams per deciliter, while in the PRINCE study it was less than one.
I think there's a higher stringency in the data that we have looked at, as well as the real numbers of how many patients have really improved. If you look into those 2 studies, it is somewhere between 3-almost 4 grams per deciliter hemoglobin improvement and also LDH. I think we have fairly good hard facts that make us believe that we are definitely competitive.
Yeah. We are quite reassured by the feedback that we get from patients and from physicians when they have switched to pegcetacoplan.
Maybe just one more. It is not the clinical data, but more on a mode of action. If you really want to block the complement system, and I think infections and other challenges will really prove it, then a complete blockage of the alternative pathway is literally only done when you block at the C3 level and not if you block either factor B or D. Just of note.
Yeah. From this perspective, we believe that we will keep growing share, obviously benefiting from further internationalization of the product and obviously going through the cycle of building the funnel from, you know, identifying the patient then getting through vaccination and then ultimately bringing the patient on the product. And you know, don't forget, you know, in summer it's very difficult in Europe to switch patients.
The second question on
Yeah, the second question now is on hemophilia. There basically, what do we expect there? I mean, we think that factor treatment is still there to stay, particularly also because we look with efanesoctocog alfa at a product that has a very favorable profile and obviously blessed by very strong clinical data. We can see a lot of excitement in the community, whether it's patients or also physicians, and got very reassured by the anecdotal data that we got from patients and physicians who are participating in the trial.
Now, the question is how is this going to change now forward looking with new therapies ahead? There we think that we have a more optimistic perspective with regard to efanesoctocog alfa, given its profile and its ability to normalize more patients.
Armin, maybe you want to give a perspective from a scientific level.
Yeah. Since you mentioned next-generation bispecific antibodies, I mean, just of note also mode-of-Action-Wise, the limiting factor for the bispecific antibodies is Factor IX. I just saw an abstract yesterday that tried to increase Hemlibra, not the next generation, but tried to increase the Hemlibra dose.
There's literally, as to be expected and even published in Blood, there is no possibility to really get more effect by increasing the dose. I think these are challenges that other next generations just need to show that they can overcome, if at all, while the factor replacement is what you give is what you see and what you get. You can measure it.
You can definitely see that there is an improvement, and this is also what is given even when some Hemlibra patients need extra factor because of challenges to the clotting system like surgeries or trauma. What is given is factor eight replacement.
I can just add another more medical reflection, a little bit more philosophically. I mean, we can compare discussion a little bit of the diabetes area where, I mean, generally, I would say that where we have a disease that is based on lack of a protein or a factor or a mechanism that is should be there in the normal biology, if we have the possibility with modern technologies to basically replace what is missing.
That is generally the long term, the winning concept of kind of reestablishing normal biology. I think we have had a lot of, and still have a lot of Non-Insulin related therapies for diabetes, but replacing various types of short and long-acting human insulin is still the backbone of treating diabetes.
I think when we move, or at least potentially move the needle from just keeping factor levels to avoid patients to have needed to treat bleedings to from into a much more normal physiological situation with the reestablishing something close to the normal biology. I think that is a perspective that seems to resonate to many of our opinion leaders and I think raise expectations for what this may mean to patients longer term.
Yeah. I think you know we probably gave you more than you needed. I think you know we just wanted to share with you our optimism and our perspective. I think this is you know we are committed that this is gonna be one of the leading therapies in hemophilia A treatment. Thank you. Next question.
Okay. Thank you.
The next question comes from the line of Mattias Häggblom from Handelsbanken. Please go ahead.
Thank you so much. I have 2 questions, sort of related. First question on Synagis. If I look at consensus estimates for Q4, the current currency spot rate implies Q4 sales will be below $140 million, and that would be the weakest Q4 since you took over sales of the product, and I'm not sure about the logic for that.
Perhaps talk about some of the dynamics behind the current performance trends in average doses per infant, pricing per dose, and any wholesaler stocking going into the fourth 1/4 that could explain why Q4 will be so weak. Secondly, on the adjusted EBITA margin guidance of low 30s%, you're at 32% of the 9 months.
Your average EBITA margin for Q4 has been 48% the last 3 years, the period you've owned the high margin RSV franchise. I'm struggling to understand why adjusted EBITA margin would not end up at least in the mid-30s. Is it the R&D cost for Q4 that Henrik talked about before, or is it conservatism? Thanks so much.
I think we've never been known for being too excessive in our forecasting, so we are by definition conservative. You know, Henrik, you wanna bring these subjects into perspective with regard to margin development and also Synagis.
Yeah. That's right. I mentioned R&D spend. We usually generally spend more. If you look at last year, we did that as well in Q4. Another factor to be considered is, of course, also the gross margin, which was pretty high a year ago. We think that would come out slightly lower. I, you know, we don't want to get into guiding by product and 1/4. It's difficult to be much more specific than that.
Maybe a quick Follow-Up on the Synagis number for Q3, although Q4 is of course the implied remainder of the year, so to say. Q3 then, was there any stocking effect that you then can quantify to help us understand the numbers as opposed to-
No. No material stocking effects moving into Q4.
Thank you.
Yeah. I mean. Yeah. So, I mean, to be honest, we guided on a normal Synagis season or a normal Synagis year, and we will see this. It's tough to be honest predict this because, you know, there are many factors influencing, let's say this sale. I think at this stage, we are not yet comfortable, let's say, by increasing any guidance.
We basically guided on this and then, and you know, as Henrik said, we are not providing guidance per product per season per 1/4. Good. Does it give you a feel? I mean, you know, it is not always. I mean, it is we are on a good track, yeah. Yes.
Thank you so much.
You know, yeah, we are not at this moment here to raise to increase guidance or anything. You know, because there are still, there is still even though it's only 2 months to go, but still 2 months to go in a volatile environment. Next up. Next, maybe next question.
The next question comes from the line of Peter Östling from Pareto Securities. Please go ahead.
Yes. Thank you. Two quick ones. One, you can call it Follow-Up on Synagis. You're talking about that you expect a more normalized season and refer to the last season as not normal. Yet that season provided the highest sales for at least the last 5, 6 years. I was just wondering what kind of reference you are using when you talk about the normalized Synagis season. That's my first question.
Yeah. I mean, basically, when we look at this, you know, we look at a Q4 performance, which probably would be more in line prior to COVID. Yeah. That basically is what we had in mind for normalized. Yeah.
Okay. Yet last year we didn't see a normal RSV season in Q4 and Q1.
No. I mean, last year.
But-
It was-
Still you had-
Basically. Yeah.
Yeah. Still you had very high sales.
Yes. That's correct. We had very good sales. I mean, we have still the same team and you know, it could be more, but you know, when you compare it. Because this season is a little bit of, again, of an anomaly. Partially it started earlier, then the question is how many doses for the season will a patient get?
Let's say when you compare it with a 2021, 2022 season, we had also patients that got the one or the other dose more based and it was fully supported by the respective governmental bodies. Let's say whilst here, let's say, you know, people would.
You know, and then there's a question on how the phasing of the season is given that, you know, you had a bit less sales than last year in Q3. You know, therefore we basically believe, you know, let's not get ahead of ourselves. Let's guide towards a normal, more normal season as opposed to, you know, a very skewed season that we had in the 2021-2022 season. You know-
Okay.
It could be more.
Okay.
We see that we can execute, and we have a good influx of patient and let's say. You know, at this stage we want to hold our horses.
Okay. Finally on Gamifant. If I heard you correctly, it seems like you have more or less reached the end of the line when it comes to the current indications. You talked about product life management in order to grow this franchise further. I was just wondering, if we look at the current indication, is it around SEK 200-250 million that is the run rate that we should expect for these indications before you eventually or maybe get some other indications in 2024?
Yeah. I mean, basically, you know, there is a certain ceiling. Because the product basically, you know, on the one hand we don't see the heavier patients that we used to see. Let's say that impacted historically. We have a decent influx of new patients. You know, there's also, let's say, you know, an effect that people think they know the place of the product.
If you want to broaden the space of the product, you need new data. We will present real world data, real world evidence at ASH, and that I think this will be quite impressive. If you wanted to change the economic frame, what we are doing, obviously we are adjusting our commercial/medical marketing mix in the US as we speak.
We think that there are some opportunities for productivity improvements. To break out in a more significant way out of this economic frame, I think we can grow the product. There's just no question, even within this frame still. If you want to go beyond that, you need to also move into newer indication. We have a couple of ideas in this regard. We have obviously, this study 14 which is ongoing and where we make now some progress and maybe Anders you want to comment on this.
Again, there we can say that we have already data presented at one meeting as an abstract and so we're on the and I have strong reason to believe that our ongoing program for secondary HLH will be positive. That is of course the nearest Time-Wise expansion we can do. In the meantime, we have also expanding our Post-Marketing database with On-Label and with some Off-Label use and indications. We have of course significantly improved our safety database. I think we have here a very clear target, clearly targeting antibody for a very important mechanism in many important diseases.
We are now based on the early experiences having very concrete dialogues about further indications. These are things that of course is not materializing from one month to another. I believe that we have a lot of potential probably in U.S. and potential also in other markets and Japan is one, et cetera, going forward. I think it's a very exciting drug. It has a from everything we can judge a very benign safety profile. There are more indications where it's definitely worth to test exactly how, when, and how we do this in terms of feasibility costs and et cetera is currently under consideration.
Very good. Yeah. Maybe we open up for the next question. Thank you.
The next question comes from the line of Alistair Campbell from RBC. Please go ahead.
Oh, thanks very much for squeezing in the question. It's just that one last one on the Elocta. Just want to understand in terms of the price pressure you're seeing there, would you describe that price pressure kind of in line with expectations or perhaps a bit worse than you might have been expecting? Does that have any read-across implications for your ambitions to get a premium price for efanesoctocog when it comes to market? Thank you.
Yeah. Absolutely. I mean, basically what we see right now is not these very significant sharp price decreases for at least Elocta. What we see is, you know, that the mix is changing so that we see countries growing fast where we have lower prices than in higher priced countries.
You know, this also by the launches and the uptake in, for instance, Central Eastern Europe, that basically by definition is changing the average price mix. We haven't seen, you know, a larger group of significant price decreases as such. It's more, let's say, you know, prices in sometimes tender situation where you need to be competitive, but these are more like single digit events.
With regard to efanesoctocog alfa, you know, we have not obviously switched patients yet. You know, what we will do is, let's say that we will try now to broaden the market share with efanesoctocog alfa, and that's the main driver of growth.
I mean, we don't expect prices for, let's say, on a cost per therapy to be different in most markets. There will be the one or the other opportunity for a price increase. I don't think that this is the main driver. The main driver is really bringing more patients and switching patients from factor treatments as well as new therapies onto this product. Yeah.
I think, you know, given the fact that this is a once-a-week treatment and the COGS expectations we have from the contracts that we have signed, we think that we at least, you know, can look forward to a broadly stable gross margin mix and expand the product by its share.
Thanks, Guido. Very clear. Thank you.
Thank you. Maybe the next question.
Our last question comes from the line of Adam Karlsson from ABG. Please go ahead.
Hi. Thanks for taking. Just a quick Follow-Up, if I could on Aspaveli. As was mentioned previously, obviously we've had readouts on danicopan and iptacopan. But putting sort of questions of the precise data that they report and the sequencing of those drugs aside, I wondered if you could comment how important do you think this 18 months head start in Europe that you've had with Aspaveli will prove? I guess how confident do you feel that Sobi is fully capitalizing on this, given the pace of the launch? Thank you.
Yeah. No, I think we have a head start. I think it's very important because when you think about it, let's say, you know, we, what we know from the product is once the product is prescribed, patients as well as physicians have a positive experience. It's because, you know, this is in a market where the vast majority of patients are still anemic despite C5 treatment. Hence, you know, they will have a positive experience and we will be able to take significant share.
Now, how quickly can we do this in this environment? You know, obviously I mentioned, you know, that at least at this earlier launch phase, it takes a while to bring patients into the funnel, through the funnel. With the administrative burden, particularly of the vaccine.
Now this takes a while. We think that we have pathways of further accelerating this, but you know, we think it's important, but we believe in the competitiveness of the product, as Armin pointed out earlier. I mean, you know, we think we have a very competitive product that can stand up also when other treatments have been launched.
You know, this is not just, inverted commas here, is not just a antihypertensive agent where you may improve blood pressure by a marginal account. This is a very serious disease. You know, when patients are reporting that they're anemic, they are talking more of brain fog and very serious impairment of their daily activities.
Hence, improving a life here, at a significant margin is maybe not something people will give up quite easily. At least this is our assumption at this stage.
Great. Thank you.
You're welcome. Thank you. Is there another question?
There are currently no further questions at this time.
We are also on time. I mean, everybody is super disciplined. Thank you so much. You know, and then we don't want to be extravagant. Thank you for your interest. We recognize that there is a lot of other stuff ongoing today. I wish everybody a great day and as you can see, we are upbeat for our future and trying to carry the positive momentum of today into tomorrow. Thank you.
Thank you. This now concludes our presentation. Thank you all for attending. You may now disconnect.