Swedish Orphan Biovitrum AB (publ)

STO:SOBI

Earnings Call Transcript 2022-Q3

[Operator]

Ladies and gentlemen, welcome to the SOBI Q3 2022 Report. [Operator Instructions] I will now hand over to the company.

[Guido Oelkers, executive]

Thank you so much. Hello, everybody. This is Guido Oelkers, CEO of SOBI. So we would like to welcome you to the third quarter 2022 report and conference call for investors and analysts. The presentation was posted to sobi.com earlier. And with this, maybe we can move to the second slide.

Slide 2 has the usual safe harbor statement. We'll be making comments on our performance using constant exchange rates or CER, and numbers used in million Swedish krona and for the third quarter of 2022, unless stated otherwise. Comments will be mostly related to the third quarter performance.

Please turn to Slide #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 on to 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 question short, we will try to keep our answer short too. [Operator Instructions]

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.

So let this, please turn to Slide #4. Starting off, I'm pleased that we continue to perform well with sustained progress in support of the outlook for 2022. Revenues decreased by 6% in the quarter 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/or phasing of Doptelet sales to China, coupled with a few -- with some clawbacks in Northern Europe. In the year-to-date, revenues was up by 9%, fully underpinning the full year outlook.

We saw commercial execution across the board, launch medicines, which mean Doptelet also in China, Aspaveli and Gamifant combined advanced by 22%. And in hematology, hemophilia continued relative stability. Doptelet continued as a major contributor, having sales up 77% outside China. And Aspaveli continued a good launch. In immunology, the performance was impacted by COVID in this comparative period. Kineret is Norway based, there no COVID sales and Synagis did not have the use -- they did not have the same early start as of last year.

Gamifant more softer following a good second quarter. While we continue to invest for growth, we saw a 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. This is the first efanesoctocog alfa regulatory submission and U.S. priority review. There was a U.S.-E.U. positive regulatory opinion for loncastuximab tesirine reg -- and Kineret regulatory submission in China, and offered 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 meds 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 a lack of COVID-19 sales for Kineret. The later start this year to the RSV season for Synagis and softer quarter from Gamifant.

From a regulatory point of view, we saw higher growth in Europe from Doptelet and the launch of Aspaveli. Growth in North America was impacted by Synagis, with 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 [indiscernible].

For the topic of Rest of World, we were pleased to have concluded an exclusive distributor agreement in Japan. We've applied it in September, something we will cover a little bit later today. With this agreement, we entered 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 continued stability in all of 2022 and into next year. The Elocta decreased by 5%, while the patient growth was up mid-single digits. There was growth, as mentioned in these patients and higher factor consumption, but it was more than offset in the quarter by 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 of all and stay focused on opportunities ahead.

Please turn to Slide 7. Doptelet had another strong quarter with some impact from phasing of sales to China. Excluding the China sales grew by 77% on strong U.S. performance and strong growth in Europe. In the U.S., we saw more new patients, new prescribers, and the 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 reimbursement decisions have started to accelerate. This bodes well for 2023 performance.

In China, we started providing details last quarter, and saw the anticipated phasing with a higher comparison in the third quarter last year. The fourth quarter 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 third quarter. We have launched in the U.K., Germany and France and parts of the Middle East with earlier intermittent sales in a few countries, increased to approximately 65 patients on commercial supply by end of September step, towards the board as a 3-digit number by year-end. And this progress was quite remarkable given the situation in Europe during the later 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 continue 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 quarter. 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 lifecycle of Gamifant becomes more important. Later, Anders will discuss some new data on Gamifant for this quarter. We also expect new data at ASH and the report of -- in 2023 for the ongoing Phase III study.

Please turn to Slide #10.Last, in immunology is Synagis. We saw the RSV start a little later than in 2021, but still a good start compared to the 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.

[Henrik Stenqvist, executive]

Thank you, Guido. Hello, everybody. So if we please turn to Page 12, and I will now take you through the key financials for the third quarter of the year.

Starting with the top line. We are showing 5 quarters of revenue here. We have already covered year-on-year changes, but sequentially, revenue in the third quarter was higher than the second quarter, also when adjusting for currency, and this is mainly driven by Synagis. 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 third quarter than earlier in the year. But it developed in line with our outlook, as communicated in connection with Q2.

Gross profit developed more favorably the 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, but the gross margin was also positively impacted by FX effect. 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. And as a result, the EBITA margin was 31%, same as in Q3 '21. There were no items affecting comparability in this quarter, 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 quarter ended at SEK 1.52, down by 5%, and operating cash flow was strong in the quarter at SEK 780 million, offsetting the investment in the loncastuximab tesirine license, so that our leverage remained at about 1.5x at the end of the quarter.

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 EBITA 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. And for clarity, revenue growth was 9% in the year-to-date period, which implies a relatively stable fourth quarter at CER compared to Q4 '21.

In terms of the margin, we continue to anticipate an adjusted EBITA margin in the low 30s percentage of revenue, including as before the cost effects of the license agreement from July for loncastuximab tesirine in hematology. And this implies an expected increase in operating expenses compared to the average of the previous quarters of this year. And this relates to various activities, such as the inclusion of spend related to the new product lonca, the timing of study costs, for example, Emapalumab Study 14, and the timing of CMC development costs for SEL-212, to name a few.

And with the '22 outlook covered, I would now hand over to Anders for the pipeline. Thank you.

[Anders Ullman, executive]

Thank you very much, Henrik. Hello, everybody. I will now take you through the pipeline highlights and update on research and development in Japan. So please turn to Slide 15.

The pipeline saw continued progress over the summer and early autumn. Efanesoctocog alfa achieved regulatory submission and priority review in the United States and the first patient used in another Phase III 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 disease. And 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 formal access for patients with rare diseases.

And with that, please turn to Slide 16. On loncastuximab, the EU CMHP is the positive opinion for the treatment of relapsed or refractory diffuse large B cell lymphoma, a debilitating disease in hematology. In addition, new data we shared on the medicine from safety run-in of the LOTIS-5 Phase III study. This study combines loncastuximab with rituximab and anti-CD20 monoclonal antibody widely used in B-cell diseases, new safety signals were observed.

Early efficacy data from safety run-in showed an encouraging 40% complete responses -- 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 the Phase II study assessing Gamifant in treatment of MAS or Macrophage Activation Syndrome associated with systemic juvenile idiopathic arthritis. 13 of these 14 patients did not experience any mass episodes and no new safety signals were observed. The data supported the ongoing Phase III EMERALD study with data due in the first half 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 & 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. And there are currently 2 machines under regulatory review, Doptelet and Aspaveli with other medicines and indications to follow. These are the first super medicines ever in Japan. To help commercialize these medicines, we have entered a distribution agreement with Asahi Kasei pharma company, previously, the distributor on C5 medicines in Japan, as I will augment the SOBI activities 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/or 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 half of 2023, we will see efanesoctocog alfa read out the second Phase III 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 III study as discussed earlier, and we will see the Phase 3 program for SEL-212. In the second half of the year, data readouts will convert to regulatory submissions, and we anticipate regulatory decisions in China for a couple of medicines.

So with that, thank you very much for your attention and for the opportunity to talk about science and pipeline in SOBI. And with this, I'm happy to hand back to Guido, who will now conclude.

[Guido Oelkers, executive]

Thanks very much. Please turn to Slide #20. So in summary, I'm pleased that SOBI continued to perform well with sustained progress in the quarter of the outlook for 2022. The pipeline continues to deliver as -- and as pointed out a lot, efanesoctocog alfa regulatory division and U.S. priority review, there was the EU positive regulatory opinion for loncastuximab tesirine and Kineret regulatory submission in China, and offered an approval in Brazil. We expect increased pipeline useful in 2023, as pointed out earlier.

We now go to Q&A. [Operator Instructions]

[Operator]

[Operator Instructions] The first question comes from the line of Christopher Uhde from SEB.

[Christopher Uhde, analyst]

I guess the first one is quick, just about geographic expansion that you mentioned. So in terms of Orfadin, are you selling directly or via a partner?

And then 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 to the extent that there is one is in R&D where -- and so 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, and then just basically because of -- you got some delays for some products in the pipeline in terms of the program?.

And then finally, just related to that on costs. So with these delays, does it affect the previous guidance on R&D to sales? Should we expect some shifting of costs to 2024? And also, the midpoint of your guidance of 13% to 15% implies almost SEK 900 million in R&D for Q4. Yes, that's it for me.

[Guido Oelkers, executive]

Maybe I'll start with the easy bit on Orfadin. So we have a partner and that allows us to let's say, to book most of the sales in the investment. So that is maybe the easier bid. The -- 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. Let's say, the slide -- I think we can follow this for Anders, maybe he talk about some of the changes we are doing in the R&D.

[Anders Ullman, executive]

I mean, first of all, I will probably respectfully disagree that R&D is a weak spot. I believe for 10 months now -- and I must say I'm quite impressed by the caliber of scientists and operational people we have. I think we -- 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 these 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.

So 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 core asset team, cross-functional, commercial, TechOps and R&D represented with senior leaders in charge of these programs.

We are improving our planning process. We are user integrating with between our global and U.S. medical organization, and we have scaled up our R&D investments in Japan to enter into that market. So I feel very - clearly, we have had a couple of important studies that have not delivered exactly to the aggressive timelines we have. 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 indicated in areas with very rare diseases. We study 14 has -- our EMERALD study had 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, and we can see that we now have very good traction with that study, and I'm pretty confident that we will deliver to the current time line and to the timelines that Guido indicated in his presentation. I hope that answers your question, but I'm happy to take any follow-up questions.

[Guido Oelkers, executive]

Maybe [indiscernible]. Henrik, do you want to comment?

[Henrik Stenqvist, executive]

Yes. No -- Christopher, you're right that we do expect more R&D coming in Q4 related to various activities, as I mentioned before, and we don't plan for pushing a lot of these costs into next year. And there is no change to what we've said when it comes to the relation between R&D spend and revenues.

[Guido Oelkers, executive]

Very good.

[Henrik Stenqvist, executive]

And this is a kind of typical that you have a bit of a different periodic distribution of our R&D costs, and this is nothing unusual, I would say.

[Guido Oelkers, executive]

Very good. Maybe we can go for the next question because it was more alluded.

[Operator]

The next question comes from the line of Adam Karlsson from ABG.

[Adam Karlsson, analyst]

I have one on the 2022 outlook and one on Elocta. First on the unchanged 2022 outlook and what that implies for Q4. I think you gave some flavor there, but just to clarify that perhaps we've only got 2 months left of 2022. So I guess my question is what the biggest uncertainties are that holds you back from talking about 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 are you just using up to formally change guidance at this point?

And then also on the outlook. You added that it excludes any potential share of losses and profits on nirsevimab after Sanofi seemed to have submitted their BLA. Do you anticipate that there could be any share losses already in 2022? That's my third question.

[Guido Oelkers, executive]

No. I mean, basically, when you look at the outlook. Yes. So with regard to the 2022 outlook, what are the main uncertainties? There is always -- when you have synergies, when you have a lot of the sales skewed to the last quarter, as it always happens, there's always a bit of uncertainty. I mean the world is also reasonably volatile. Hence, 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. So that's basically -- but we are prudent and hence, we don't want to get ahead of ourselves in today's environment, which I think may be understood. And with regard to nirsevimab 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 we -- let's say, it's a milestone view. But apart from that -- that's it, yes. And maybe we can open the floor for other questions. So it's approved…

[Adam Karlsson, analyst]

Understood. I had another one on Elocta but perhaps I jump back in the queue for keeping it to one.

[Operator]

The next question comes from the line of Eun Yang from Jefferies.

[Eun Yang, analyst]

I have a question on nirsevimab. So in the past, you guided as BLA filing in the fourth quarter, but today is an acceptance. So question number 1 is, has it been filed already. And second question is to Henrik. So you paid $175 million to opting completely for nirsevimab, how is it going to be treated in P&L for the guidance for this year?

[Guido Oelkers, executive]

I mean, I'm not sure that we -- that the nirsevimab market is tried. I mean not that I'm aware of. And maybe -- Henrik, you want to comment on the treatment.

[Henrik Stenqvist, executive]

Yes. The milestone will be capitalized. So no material P&L effect this year.

[Guido Oelkers, executive]

Next one, please.

[Operator]

The next question comes from the line of Viktor Sundberg from Nordea.

[Viktor Sundberg, analyst]

So my first question is on Elocta. So you're talking about this clawback in Greece and Italy. Is it possible to quantify that effect? And how much that impacted sales in Q3 given that this may be should be viewed as a one-off perhaps?

[Guido Oelkers, executive]

Yes. I mean, basically, it's a mix of clawback and price. This would have been a very stable business based on the patient growth -- the price and patient growth or the impact of patient growth and volumes due to consumption would have offset each other. And basically, the clawback is a difference. And -- but I don't think we are commenting any further on this.

[Viktor Sundberg, analyst]

And 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 new 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 half of 2023 for Synagis, but if we assume that you can keep some of that business, it might be business as usual. I'm just a bit curious how you were thinking about guidance for next year, taking into account nirsevimab and it's anticipated…

[Guido Oelkers, executive]

Yes, we will provide guidance as usual. And for next year, we will provide guidance on the 8th of February 2023. But basically, there will be an effect, obviously, of nirsevimab, but as you can see, it's a broader indication, and whether the 1% of patients, a little bit more than 1% of babies is now going to be the foremost target of Sanofi will have to be seen and whether -- it's clearly not enough to satisfy the growth needs.

So -- but I think there will be an effect. To what extent, I think we will probably be -- provide some more profound thinking on the 8th of February, but we don't think that this is going to be a Cassandra scenario that we are expecting. And it is -- as you said, if it affects us in a material way, it will be for the second half of next year.

[Viktor Sundberg, analyst]

And just a very quick question, final here on inflation also. I see that you believe that you're insulated from inflation this year in your report here. But 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 want to get a feel for how to model this going forward.

[Guido Oelkers, executive]

I mean, we are insulated in -- 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 under this then makes its way into the COGS. Henrik, you want to comment on inflation in a broader way?

[Henrik Stenqvist, executive]

Yes. No -- but we don't see any material effects yet. As Guido said, we -- our supply agreements are regulated through indexes. And it takes some time, obviously, before it will hit the P&L and remember that we are relatively profitable. So it takes really material increases to really have a material impact on the margin. When it comes to the rest, yes, I mean, there will be inflationary pressures, but we work quite hard on procurement activities. So we expect to be able to mitigate that to a large extent.

[Guido Oelkers, executive]

Yes. And we -- I mean, as we reported also earlier, we asked -- we will have forward-looking some significant relief on the change of supply in the case of Doptelet which should help us as well.

Maybe we open up for the next question.

[Operator]

The next question comes from the line of Sarita Kapila from Morgan Stanley.

[Sarita Kapila, analyst]

And the first is just on how we should be thinking about the sales trajectory for Aspaveli, particularly given the increase in competition in PNH from iptacopan and then as iptacopan moved into new indications like C3G. And then secondly, on haemophilia. Sanofi has kind of previously highlighted that the haemophilia market could reach SEK 13 billion by 2030 and 40% to 50% of patients could stay on factor.

But to what extent do you think that new innovation in the nonfactor space, for example, Mim8, our next-generation HEMLIBRA from Roche and Chugai could impact the number of patients that stay on factor longer term?

[Guido Oelkers, executive]

Thank you. We start with Aspaveli . And there, obviously, a lot will have to be shown. But when you look at the landscape right now, I mean, we feel very good in our clause with Aspaveli .

We see some early signals. I mean this is a vertical launch yet, no, simply because it is a product that needs to go through a certain cycle, and Ullman will then talk about also the competitiveness. And let's say -- but 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. And we are confident based on the medical profile to take a significant share in this market now. Will more competition make it easier? Answer is clearly not. But this is a very differentiated product that we feel we have in our hands, and maybe Ullman, you can talk to this, how you see it from a medical perspective.

[Anders Ullman, executive]

Very happy to do. Hello, everyone. I do believe that the data that we have published so far in the print and Pegasus studies show clearly that there is quite a dramatic improvement that you can achieve in prior treated patients with 5 inhibited patients as well as in naive patients. And 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.

But if you look at least at the little information that has been published so far, it is a more relaxed approach. So for example, just to pick one, the sort of leaving the hemoglobin level unchanged, the margin that is given for iptacopan is 2 grams per deciliter, while in the print study, it was less than 1. So 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. And if you look into those 2 studies, it is somewhere between 3 to almost 4 grams per deciliter hemoglobin improvement and also LDH. So I think we have fairly good hard facts that make us believe that we are definitely competitive.

[Guido Oelkers, executive]

And we are quite reassured by the feedback that we get from patients and for physicians when they have switched to pegcetacoplan.

[Anders Ullman, executive]

Maybe just one more. It is not the clinical data but more on a mode of action. So 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 line block at the C3 level and not if you block either Factor B or D, just of note.

[Guido Oelkers, executive]

So 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 identifying the patients and getting through vaccination and then ultimately bring the product -- bringing the patient on the product. And don't forget, in summer, it's very difficult in Europe to switch patients.

[Anders Ullman, executive]

So second question on…

[Guido Oelkers, executive]

Yes. The second question now is on haemophilia, and there basically, what do we expect there? I mean, we think that the factor treatment is still there to stay, particularly also because we look with efanesoctocog alfa, the product has a very favorable profile and obviously blessed by very strong clinical data, and 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, no forward-looking with new therapies ahead. And 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. Ullman, maybe you want to give a perspective from a scientific level.

[Anders Ullman, executive]

Yes. 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 the Factor 9. And I just saw an abstract yesterday they tried to increase HEMLIBRA novel next generation -- but try to increase the HEMLIBRA dose -- And there is 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 generation just need to show that they can overcome if at all, while the factory placement 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 crossing system like surgeries or trauma , what is given is Factor 8 replacement.

[Henrik Stenqvist, executive]

I can add another more medical reflection a little bit more philosophical. We can compare this as a little bit of the diabetes area where 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 novel biology.

I think we have had a lot of -- still has a lot of non-insulin related tapes for diabetes, but replacing various types of short and long-acting human insulin is still the backbone of treating their rates. And I think when we know fully potentially move the needle from just keeping factor levels to avoid patients to have needed to treat bleedings to come into a much more normal physiological situation with the reestablishing but includes to the normal biology.

I think that is a perspective that seems to resonate to many of our opinion leaders, and I think raised expectations for what this may mean to patients longer term.

[Guido Oelkers, executive]

Yes. I think it will be -- we probably gave you more than you needed. But they -- I think just , we wanted to share with you our optimism and our perspective. And I think this is -- we are committed that this is coney one of the leading therapies in Haemophilia A treatment.

[Operator]

The next question comes from the line of Mattias Häggblom from Handelsbanken.

[Mattias Häggblom, analyst]

I have 2 questions sort of related. So first question on Synagis. If I look at consensus estimates for Q4, you use the currency stock rate implies Q4 sales will be below $140 million. And that will be the week of Q4 since you have to grow the sales of the product. And I'm not sure about the logic for that. So perhaps talk about some of the dynamics behind the current performance trends in average doses printed pricing for those and any wholesale destocking going into the fourth quarter that could explain why Q4 would be so weak.

And then secondly, on the adjusted EBITA margin guidance of low 30s, you're at 33% of the 9 months. Your average EBITDA margin 1for Q2 has been 48% the last 3 years, the period you owned the high-margin RFP franchise. I'm struggling to understand why adjusted EBIT margin would not stand up at least in the mid-30s. So is it the R&D cost for Q4 that Henrik talked about before, or is it conservativism?

[Guido Oelkers, executive]

Yes. I think we never be known for being too excesses in our forecasting. So we are, by definition, conservative as you know. Henrik would you want to bring this subject into perspective with regard to margin development and also Synagis.

[Henrik Stenqvist, executive]

Yes. 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. But I -- the way -- we don't want to get into guiding by product and quarter. So it's difficult to be much more specific than that.

[Mattias Häggblom, analyst]

So maybe a quick follow-up then on the Synagis number for Q3, although Q4 is, of course, implied the remainder of the year, I should say. But Q3 then was there any stocking effect that you then can quantify to help us understand the number.

[Henrik Stenqvist, executive]

No material stocking effects moving into Q4.

[Guido Oelkers, executive]

So I mean, the -- to be honest this -- we will have -- we guided on a normal Synagis season or normal Synagis here, and we will see this. And it's tough, to be honest, predict this because there are many factors influencing let's say, this sale. And I think at this stage, we are not yet comfortable, let's say, by increasing in the guidance. So we basically guided on this. And as Henrik said, we are not providing guidance per product per quarter.

Good. That would give you a feel. I mean, you know, it is not always -- I mean, it is -- we are in a good track. But we are not yet at this moment year-to-date to increase guidance or anything. But because there's still -- even though it's only 2 months to go, but still 2 months to go in a volatile. Let's move to next question.

[Operator]

The next question comes from the line of Peter Östling from Pareto Securities.

[Peter Östling, analyst]

Yes. Two quick ones. One, you can call it a follow-up on Synagis. You're talking about that you expect a more normalized season and referred to the loss season, that's not normal. But yet that season provided the highest sales for at least the last 5, 6 years. So I was just wondering what kind of reference you are using when you talk about the normalized Synagis season? That's my first question.

[Guido Oelkers, executive]

Yes. I mean, basically, when we look at this, we look at Q4 performance, which probably would be more in line prior to COVID, yes. So that basically is what we have in mind for normalized.

[Peter Östling, analyst]

Okay. But yes, last year, we didn't see a normal RSV season in Q4 and Q1?

[Guido Oelkers, executive]

No, last year it was.

[Peter Östling, analyst]

Yes. But still, you had very high sales.

[Guido Oelkers, executive]

Yes. That's correct. We had very good sales. I mean we have still the same team and it could be more. But when you compare it -- because this seen is a little bit of -- again, as an anomaly, partially it started earlier. Then the question is how many doses for the season will the patient get. Let's say, when you compare it with the '21, '22 season, we had also patients that got the one or the other to was more based and it was fully supported by the respective governmental bodies. Let's say, wise here, let's say, people would -- that there's a question on how the phasing of the season is given that you had a bit of a spell less than last year in Q3.

And therefore, we basically believe let's not get ahead of ourselves. Let's dive towards a normal -- more normal season as opposed to a very, very skewed season that we had in the '21, '22. But it could be more. And we see that we can execute, and we have a good influx of patients. And let's say -- but at this stage, we want to make -- we want to hold our horses.

[Peter Östling, analyst]

And then finally on Gamifant, if I heard you correctly, it seems like you have more or less reached at the end of the line when it comes to the current indications and you talked about product life management in order to grow this franchise further. And I was just wondering if that -- if we look at the current indication, is it around SEK 200 million, SEK 250 million that is the run rate that we should expect for these indications before you eventually-- or maybe get some other indications in '24?

[Guido Oelkers, executive]

Yes. I mean, basically, yes, there is a certain ceiling when -- because the product basically -- on the one hand, we don't see the heavier patients that we used to see. Let's say, that impact had historically. We have a decent influx of new patients. But there is also, let's say, on the fact that people think they know that the place of the product. If you want to ship -- if you want to borne the space of the product, we 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 U.S. as we speak. We think that there are some opportunities for productivity improvements, but to break out in a more significant way out of this economic frame. I think we can grow the product. This is -- there's no question, even within this frame still. But if you want to go beyond that, you would need to -- you need to also move into newer indication. We have a couple of ideas in this regard. And 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.

[Anders Ullman, executive]

No -- Yes, we say that we have already data presented at one meeting is an abstract. And so far on -- and a strong reason to believe that our ongoing program for secondary HLA would be positive. So 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. And we have, of course, significantly improved our safety database. So I think we have here a very clear target clearly targeting antibody for a very important mechanism in many important disease system, and we are now based on the early experiences, having very concrete dialogues about further indications. And these are things that, of course, is not necessarily a thing from 1 month to another. But I believe that we have a lot of potential, probably in U.S. and potential in other markets and Japan is one, et cetera, going forward.

But I think it's a very, very exciting drug. It has -- for everything we can judge a very benign safety profile, and there are more indications where it's definitely worth to test exactly how, when and how we do this in terms of feasibility costs et cetera is currently under consideration.

[Guido Oelkers, executive]

Very good. Yes, maybe we open up for the next question.

[Operator]

The next question comes from the line of Alistair Campbell from RBC.

[Alistair Campbell, analyst]

Just one last one on Elocta. I just wanted 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? And then does that have any read across implications for your ambitions to get a proven price for efanesoctocog when it comes to market?

[Guido Oelkers, executive]

Yes. Absolutely. I mean basically, what we see right now is not this - for -- at least for Elocta it is very significant, sharp price decreases. What we see is that the mix is changing so that we see countries growing faster where we have lower prices in higher-priced countries. And this also by the launches and the uptake in, for instance, in Central Eastern Europe that basically by definition is changing the average price mix.

We haven't seen the, let's say, the larger group of significant price decreases as such. It's more, let's say, prices in some tender situation where you need to be competitive, but these are more like single-digit events employee. With regard to efanesoctocog alfa and we have not obviously switched patients yet, but we -- what we will do is, let's say that we will try now to broaden this, let's say, 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. That will be the one or the other opportunity for price increase. But 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. So I think -- and given the fact that this is a once-a-week treatment and the COGS expectations we have from what we -- from the contracts that we have signed, we think that we at least can look forward to a broadly stable gross margin mix and -- but expand the product by its share.

Maybe the next question.

[Operator]

Our last question comes from the line of Adam Karlsson from ABG.

[Adam Karlsson, analyst]

Just a quick follow-up, if I could, on -- after daily. As was mentioned previously, obviously, we have readouts in danikopan 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-month head start in Europe that you've had with Aspaveli will prove. And I guess how confident do you feel that SOBI's is fully capitalizing on this given the pace of the launch?

[Guido Oelkers, executive]

Yes -- No, I think we have a head start. I think it's very important because when you think about it, let's say, what we know on the product is once the product is prescribed patients as well as physicians have a positive experience. And it's because this is in a market where the vast majority of patients are still anemic despite C5 treatment. Hence, 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? Obviously, I mentioned that at least it is earlier launch phase, it takes a while to bring patients into the funnel through the funnel. And we see administrative burden, in particular of the vaccine. Now this takes a while. We think that we have pathways of further accelerating this, but we think it's important, and but we believe in the competitiveness of the product, as Ullman pointed out earlier, I mean, -- and so we think we have a very competitive product that can stand up also when other treatments have been launched. And this is not "is not just the hypertensive agents where you may improve blood pressure by a marginal account."

This is a very serious disease. And when patients are reporting that the dynamic, they are talking more of brain fork and very serious impairments of the daily activities. So hence, improving 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. Is there another question?

[Operator]

There are currently no other questions at this time.

[Guido Oelkers, executive]

Yes, we're also in time. I mean everybody is super disciplined. Thank you so much, and that we don't want to be extravagant. This was -- thank you for your interest. We recognize that there's 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.

[Operator]

Thank you. This now concludes our presentation. Thank you all for attending. You may now disconnect.