Camurus AB

STO:CAMX

Earnings Call Transcript 2021-Q4

[Operator]

Hello, everyone, and welcome to the Camurus investor call for Q4 2021. [Operator Instructions] Today, I am pleased to present CEO, Fredrik Tiberg. Please go ahead.

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Thank you so much, and hello, everyone. I hope you all have had a good start of the year. Welcome to Camurus Fourth Quarter and Full Year Results Call for 2021. Next slide, please. So as usual, before starting the presentation, please note our forward-looking statements, which are subject to a number of uncertainties, risks and assumptions. Slide 3, please. The agenda for today's call includes a summary of the full year 2021 results along with highlights from the fourth quarter. Then we will give an update on the commercial development followed by progress in the R&D pipeline. We will end the call with some takeaways, a full year 2022 outlook followed by Q&A. With me today in the call is Richard Jameson, our Chief Commercial Officer; and Jon Garay Alonso, our new CFO who joined Camurus only 2 weeks ago. It's a great pleasure to welcome Jon to the team, and I would now like to give him the opportunity to introduce himself before continuing the presentation. Jon, please, the stage is yours.

[Jon U. Garay Alonso, Chief Financial Officer]

Thanks a lot, Fredrik, and good afternoon, everyone. Wish you all are doing well. My name is Jon Garay. I am 48 years old, born in Spain. And as Fredrik has just said, I joined Camurus 2 weeks ago. Before that, I have worked 10 years at Baxter, where I initially joined as the Vice President of Finance for Europe, Middle East and Africa in the Renal Division. Through the years, my recent position has been the European Finance Director for the Medication Delivery and Pharmaceuticals Division. I have been working closely with business acceleration, operating result improvement, business model analysis and development opportunities, either organically or via M&A. And right now, I'm really thrilled to collaborate with Fredrik and Camurus management team to continue growing and developing Camurus into a global corporation. Thanks a lot, everyone. Wish you all a nice day. And Fredrik, back to you.

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Thank you, Jon. And then we will move over to Slide 5, please. So Camurus had made very significant progress in 2021, delivering strong financial and operational results in what was a difficult operating environment. As you can see in the graphs on the right-hand side, both revenue and operating results improved strongly versus previous year. Our total net revenue grew by 79% to SEK 601 million, with product sales increasing by 84% to SEK 594 million. The full year operational results was minus SEK 111 million, which is a 46% improvement compared to previous year. Our commercial teams continued to deliver strong results, which meant that we for the fourth -- tenth consecutive quarter achieved double-digit sales growth and continue to establish our position as market leader in long-acting treatment of opioid dependence across our territories. Buvidal is now available in 17 markets across Europe, Australia and the Middle East with expansion continuing. We advanced our pipeline as well through successful life cycle management and new approvals, a new program in registration phase and finished the year with 3 ongoing Phase III programs in rare diseases. So let's move in on the highlights of the fourth quarter. Slide 5, please. Highlights of the quarter included accelerated Buvidal sales in key markets, EMA acceptance of our regulatory submission for chronic pain, continued progress of our Phase III studies of CAM2029 in acromegaly and first dosing in a Phase III study of CAM2029 for treatment of neuroendocrine tumors. On the partner side, Rhythm started a new Phase III program for our weekly formulation of setmelanotide for treatment of genetic obesity disease. However, a strong quarter ended with the news in December that our U.S. licensee, Braeburn, were issued with a new CRL for Brixadi. Aside from this, it was a very positive quarter where we continued building our business towards profitability whilst progressing the pipeline. With increasing revenues, a stable cash position, Camurus has a great foundation to continue to execute on our strategy for value creation through commercialization excellence, diversification and a growing pipeline. With this, I will leave the word over to Richard for a commercial update. Slide 6, please.

[Richard Jameson, Chief Commercial Officer]

Thank you, Fredrik. Good afternoon, everybody. It's a good -- we had a good fourth quarter, and I'll update on this, as we saw continued progress with Buvidal in our markets. So if we can move to Slide 7, please. In Q4, we accelerated sales, gaining further traction in several markets and grew market share, notably in the U.K., Australia, Sweden and Finland. As access opened, we have increased our engagement with all stakeholders in these markets, though in others, such as Germany and Norway, restrictions remained. However, we're now seeing the markets beginning to open this year. Sales increased 19% versus the previous quarter. And at the end of the year, approximately 25,000 patients were in treatment in the month with Buvidal. Our geographical expansion also progressed with regulatory approval in Israel, and reimbursement approval in Belgium allowed us to launch in the community setting. Pricing and reimbursement processes in other countries are ongoing with outcomes expected in the coming months. As the real-world experience with Buvidal grows and treatment centers publish our outcomes and demonstrate the impact Buvidal is having for patients, we are seeing increasing government recognition of the value the product brings. This has resulted in the allocation of additional funding for opioid dependence and specifically, long-acting buprenorphine. Increased funding has been seen in England, Scotland, Wales, France and Denmark. And as an example, I will share a very significant investment by the U.K. government on the next slide. Overall, we remain on track to achieve our market leadership across our countries and deliver further launches in Europe and MENA and -- to achieve our goal to have more than 100,000 patients in treatment on Buvidal by 2026. So if we can move to Slide 8, please. As I mentioned, in the U.K., in quarter 4, we saw the government publish a new drug strategy that has the aim to deliver a world-class treatment and recovery system. This was backed by a substantial investment of GBP 900 million, of which GBP 780 million was directed to rebuild drug treatment and recovery services. And as a result of the growing awareness of the benefits that Buvidal brings to patients in wider society, the drug strategy has included guidance on the role long-acting buprenorphine will play, and I'd qualify some statements from the strategy that states that they will first explore the rollout of the potentially revolutionary buprenorphine to drive down drug deaths, ensure that additional funding means a full range of evidence-based interventions are available in every area and that the system is responding to new and promising innovations such as forms of long-acting buprenorphine. They also explore the benefit of making long-acting buprenorphine available to prisoners to assess the impact on the engagement with treatment and protection from overdose and relapse after release. Our teams are already engaging wide groups of stakeholders to support this ambition through provision of medical education, ensuring staff are trained with Buvidal, supporting the expansion of infrastructure and ensuring patient pathways are in place to accelerate access and capturing and publishing the real-world improvements in outcomes so they can be shared across geographies. So on that note, moving to Slide 9, please. We aim to ensure we take every opportunity to share the growing scientific, evidence-based and real-world experience with Buvidal. You can see on the slide the scientific congresses in 2022, and we will have presentations and workshops at the key meetings during the year. So on that brief update, I'll hand back to Fredrik for a pipeline update. So can we please move to Slide 10.

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Thank you, Richard. And so over to a short R&D update, moving over to Slide 11, please. So during the period, we continued to advance our pipeline of innovative programs focused on treatment of CNS and rare diseases, in particular our Phase III and registration processes where we continue to deliver several important milestones. Slide 12, please. So in Q4, we continued to make progress on the regulatory side with Buvidal receiving market approval in Israel, adding to the earlier approvals in the EU, U.K., Switzerland, Australia and New Zealand and progressing regulatory approvals in a number of countries in the Middle East as well, where we are expecting 4 new approvals in 2022. Now over to Brixadi in the U.S. Unfortunately, the year ended with the news from our licensee, Braeburn, that they have been issued with a new complete response letter by the FDA on the 15th of December 2021. Again, this was due to quality-related aspects at their third-party U.S. manufacturer. This was, of course, disappointing to us all, especially in the light of the growing medical need in the U.S. and that the only remaining hurdle for approval of Brixadi was these quality issues at the manufacturer. We are awaiting information from Braeburn on how they will resolve the CRL. Of course, it involves discussions with the authorities and we can expect to -- on when we can expect the resubmission of the NDA in the U.S. We'll keep you updated on any substantial developments when they come and can be communicated. Over to Slide 13, please. On our end, as mentioned, in the fourth quarter, we have done significant advancement on the regulatory side, submitting an application to extend the indication for Buvidal to chronic pain, for instance. This is a type 2 variation application which was accepted by EMA in November and is currently under review, with the CHMP opinion expected in the second half of 2022. In parallel, our teams have completed a second submission of the application to TGA in Australia. There is a high unmet need in chronic pain, especially in patients standing on high doses of opioids or those patients who are dependent on opioids. If approved, Buvidal will be the first long-acting injectable product approved for treatment of chronic pain in Europe or Australia. Initial market estimates for this patient subgroup targeted by the expanded indication for Buvidal or potential expanded indication, I should say, indicates an additional opportunity of more than EUR 150 million in the current market that we foresee. Over to the next slide and an update on 2029. Slide 14, please. So CAM2029 is our subcutaneous depot of octreotide in development for treatment of 3 rare diseases: acromegaly, neuroendocrine tumors and polycystic liver disease. The product is designed and being evaluated for enhanced efficacy and improved treatment compliance. Slide 15, please. We have a large clinical program ongoing with CAM2029 with 4 successfully completed clinical Phase I/II studies to date; 2 ongoing Phase III studies in acromegaly; and the recently started Phase III study, SORENTO, in patients with neuroendocrine tumors. In addition to that, we have completed preparations for a Phase II/III study, POSITANO, in polycystic liver disease. During the quarter, we have also completed a bridging pharmacokinetic study of CAM2029, administered with our newly developed injection pen versus the current prefilled syringe format. The top line results of this study achieved the objectives, demonstrating comparable pharmacokinetics for the 2 devices. Moreover, the injection pen met our criteria for ease of use and injection time. The pen is now being introduced in all Phase III programs for CAM2029 and further strengthens its differentiated product profile. Moving to Slide 16. So updating then on the individual indications for CAM2029, starting with acromegaly. This is a rare orphan disease caused by excess growth hormone production secretion, resulting in severe symptoms and morbidity for patients. Current medical treatments have limited efficacy and can be burdensome for patients and the health care system as they require administration by trained health care professionals. At the moment, we have 2 ongoing Phase III studies assessing the efficacy and safety of CAM2029 as a potentially more convenient and effective treatment alternative for patients -- for this patient group. The studies included 6 months randomized placebo-controlled study and a 12-month long-term safety extension study. At the end of the quarter, we had over 100 patients included in the 2 studies out of a total target of 147 patients. COVID-19 has been a significant challenge for the recruitment as well as the study conduct. However, we have a great clinical team who have done an excellent job together with our CRO and investigators, and we are still expecting to complete the study and deliver top line efficacy results as planned before the end of this year, 2022. This will be followed by regulatory submission in the U.S. and Europe. Based on a third-party assessment, peak sales of CAM2029 in acromegaly in the U.S. and Europe are estimated to the range of $120 million to $180 million. So with that said, moving over to the next indication, neuroendocrine tumors, Slide 17. Here, in the quarter, we dosed the first patient in the SORENTO Phase III study. This is a randomized active-controlled study with the primary objective to demonstrate superior efficacy with CAM2029 versus standard of care in patients with gastroenteropancreatic neuroendocrine tumors. We started to engage more than 90 clinical centers around the world, and we already have a handful of patients enrolled and dosed. There is high interest to participate in the study, and we estimate that recruitment could be completed in 2022, with top line results being expected in the second half of 2024. As you can see on the right-hand side, the estimated market potential for 2029 in GEP-NET is very significant, in the range of 720 -- estimated in the range of $720 million to $1 billion. To put this in perspective, current sales of first-generation somatostatin analog products are about $3 billion, with the majority of these sales being for treatment of GEP-NET. So over to Slide 18, please, and the last indication that we are currently pursuing, that being the registration program for CAM2029 in polycystic liver disease, where there's currently no approved medical treatment available to patients. The study we are conducting is a randomized -- or starting to conduct is a randomized placebo-controlled Phase II/III study assessing the efficacy and safety in patients with symptomatic polycystic liver disease. The study is expected to be initiated within the next few months. There's a high unmet need for an effective treatment in PLD and a significant estimated market potential again of, in this case, $270 million to $420 million. In conclusion, we have a wide-ranging product -- program for CAM2029 across 3 rare disease indications and with blockbuster potential. Slide 19, please. So before concluding this short R&D update, I would just like to mention our partner Rhythm's recent progress with a weekly formulation of setmelanotide for treatment of genetic obesity disease. During the fourth quarter, Rhythm initiated the first out of 2 planned Phase III studies with CAM4072. Just after the year, we announced that the first dosing in this Phase III study had occurred in a patient who switched from daily injections. The second Phase III study in de novo patients with Bardet-Biedl syndrome is also under preparation. Rhythm has come far since the start of our partnership, and it will be really exciting to follow the further progress of this promising program. Slide 20, please. To summarize the year and in this case, the quarter, we have done good progress, as you can see from these key takeaways. On the commercial side, we have delivered double-digit sales growth 10 quarters in a row as a new commercial organization. We saw an accelerated patient uptake in the quarter, which is very promising, and the allocation of significant new funding streams for innovative treatment of opioid dependence in key large markets around Europe. On the pipeline side, an EMA application for extending the Buvidal indication to chronic pain was successfully submitted and accepted by the authorities. Multiple Phase III milestones with CAM2029 and weekly setmelanotide were achieved. And on the corporate side -- corporate development side, we delivered strong financial performance and are on track to execute on our strategy. Now moving on -- over to this year, 2022. Next slide, please, Slide 21. So after a strong finish last year, we look forward to a very productive 2022 with continued commercialization progress through market expansion, new approvals and preparation for launch in chronic pain. We will also advance our pipeline with completed recruitment in 3 Phase III studies anticipated and top line Phase III results in acromegaly. On the corporate side, we are expecting to reach profitability during the year whilst continuing to invest heavily in R&D. So finishing off with the 2022 financial outlook, we are guiding at total revenues of SEK 900 million to SEK 950 million excluding any big study-related milestones in the U.S. Product sales are guided at SEK 875 million to SEK 925 million and our operating results between minus SEK 60 million to SEK 10 million. I think it's worth to note that this includes R&D investments of over SEK 0.5 billion in our promising pipeline. So our operational results in -- from the commercial activity is very strong. Slide 24, please. So in conclusion, Camurus had a strong finish to 2021, which we believe sets the tone for 2022. And with that said, thank you for listening. And now over to the Q&A. We're all happy to take your questions. Please, over to the...

[Operator]

[Operator Instructions] Our first question comes from Suzanna Queckbörner from Handelsbanken.

[Suzanna Queckbörner, Research Analyst]

Suzanna Queckbörner, Handelsbanken here. I have 3, please. So perhaps starting with Buvidal sales. Perhaps you can explain the 4,000 additional patients in Q4, where they came from; in other words, a breakdown of the 25,000 patients on drug, e.g. high-pricing countries versus low-pricing countries. And then question #2, what form of communication have you had with Braeburn since the CRL in December 2021, e-mail exchange, in-person meetings, calls? I'd be grateful for an update. And then question #3, has Braeburn had any post-CRL meetings with the FDA up until now? Based on the previous CRL FDA turnaround of 2021, is a shorter or longer time to resubmission expected this time?

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Thank you, Suzanna. I think we can start with the first question, which I believe was the question about where the patients came from. I mean we have strong sales development in all markets, especially in the established markets where we have the largest patient base, and that's also where we're continuing to have the largest growth. So this includes Australia, the Nordics, U.K. has been coming -- and doing a very nice, good progress in the U.K. but also the rest of the markets. So really, patients are spread across our markets. And I think there is not much more we can say about that. It's really reflecting the sales in the different markets. When it comes to the second question, which I believe I need to get repeated, can you please...

[Suzanna Queckbörner, Research Analyst]

The second question...

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Yes. With regards to Braeburn communication, I can say that we do have communication with Braeburn. Unfortunately, that is subject to confidentiality agreements, of course, with them, and we cannot give you any detailed insight into those communications. But we do have communications up and lining. And I would also say that in this situation, most companies search advice and communications with the regulatory authorities to get assistance and help, and you could probably assume that, that is also the case in this case. So I think that's the 2 things. In terms of their intentions, we're hoping to get and we are waiting for a detailed plan for the resubmission and resolving the current issues. And as I have said, as soon as we have that plan, we will also inform the market. The only reference I can give meantime is the time frame that was required for the last resubmission, which was approximately 6 months. And at that time point, we had assumed that it would probably take 4 months. So obviously, this is not exactly the same scenario as last year, but I think as a reference -- this product is, of course, as you know, I mean, a product that is clearly needed. It is subject to priority review, so the review time is expected to be the same, that is maximum 6 months after submission. But I cannot -- unfortunately, without the details, I cannot communicate this any -- in any more substance. Is that fine for you, Suzanna? Or do you have any other questions?

[Suzanna Queckbörner, Research Analyst]

In terms of the types of communication you have, can you expand in terms of have there been any in-person meetings? Is this e-mail exchange?

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Well, I think what I can say is that there has been definitely communication on the various different levels. And I think that's probably what I can say at this point.

[Operator]

Our next question comes from Erik Hultgård with Carnegie.

[Erik Hultgård, Research Analyst]

I have a couple, if I may. First, on your guidance for '22. You assume growth of around 50% for Buvidal. So I was just wondering if you could break down a little bit where -- what markets -- what's the top 3 markets that is expected to contribute most to growth. Is it the established markets? Or is it actually some new geographies as well? And secondly, also in terms of guidance, what's the sort of upside potential that you see in guidance? For example, does the guidance assume an inflection point in Germany during the second half? Or is this true upside to guidance? And then finally, on chronic pain, could you elaborate a little bit on what you expect -- how a potential label could look like? Would it -- is it more -- is it reflective of the design and the inclusion criteria in the Phase III study? Or would it be more narrow and more focused on specific type of addiction patients and whether this -- and how this is connected to your sales target of EUR 150 million? So a lot of questions there but appreciate it.

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Yes. We can start with the first one. I think it's important just to recognize that we're continuing to grow in our established markets. Even in the markets like Finland, we're still adding -- with over 60% market share, we're still continuing to grow. So it's -- so obviously, from a patient number perspective, the established markets will continue to be those that provide the majority of the growth. But from a growth rate perspective, we will see new markets becoming more and more important and especially then newer, larger markets. Maybe, Richard, you want to go into that in more detail.

[Richard Jameson, Chief Commercial Officer]

Yes. I mean we just started releasing it in Spain and France. They're big markets. So of course, we can start looking at treatment penetration there. Obviously, from what I presented in the U.K. with the government investment, that will be a large opportunity for us. And Australia still continues to grow very well as well as we move forward. So I think all the established markets and some growth from the newer markets coming in.

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Yes. I think, I mean it's important to see the size of the opportunity. Only in the U.K., there are about 160,000 patients in treatment. So if we're coming up in similar market penetration as we have in our other markets, of course, that's a very significant growth opportunity. And similarly, in Germany, I think you asked that question, is -- how much this, what should I say, remuneration process to doctors will play and if there is any changes coming into that system in Germany. I can say that, that has not been part of our principal assumptions behind our outlook and would probably represent an upside on that. Anything else you would like to hear about the outlook? Otherwise I'd go over to chronic pain.

[Erik Hultgård, Research Analyst]

Probably, I guess, what's the downside to guidance?

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Yes, I think -- I mean the continued risk, we don't really know what is happening on the kind of macro level and if we will get a new epidemic coming in. But I think we have tried to -- this is the guidance -- the best guidance we can give based on our current understanding. But of course, there are, as always, risks that -- but none that I would like to particularly stress at this moment.

[Erik Hultgård, Research Analyst]

It sounds like you have pretty good growth, and a large part of your expected growth for '22 is actually from already established markets, which suggested limited downside risk to that one. Is that correct?

[Fredrik Tiberg, CEO, President, Head of Research & Director]

I think that's a fair assumption. What do you say, Richard?

[Richard Jameson, Chief Commercial Officer]

Yes, I agree.

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Yes. And over to the chronic pain. Of course, we are -- our application is for a subset of patients. That subset will be subject to a discussion with the regulatory authorities, but it is more of a high risk in even opioid-dependent population. And that is the basis also for our market estimates, providing then the EUR 150 million that we were referring to in the presentation earlier. So I think we will see more of that once we have completed the negotiations and discussions with the EMA and the CHMP.

[Erik Hultgård, Research Analyst]

Great. And just a follow-up on that. What is the risk -- the principal regulatory risk for chronic pain? Are regulators actually willing -- is it -- what type of label you will be able to receive, I'm guessing another sort of opioid-based treatment for chronic pain, I guess, is not in the interest of the public, so I guess it's more about how you sort of frame the...

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Yes. I mean we are directing this to patients with a high medical need. And I think that there is very little in terms of at least the discussions we have had so far -- we had a pre-meeting prior to submission with the authorities. And so far, we have had a good understanding for the importance of this medication in this subgroup. We're not anticipating to develop this product for a general chronic pain label.

[Operator]

Next, we have a follow-up question from Suzanna Queckbörner with Handelsbanken.

[Suzanna Queckbörner, Research Analyst]

Again, I just wanted one final question. On CAM2029 in acromegaly, I was wondering. Now as the Phase III is progressing, have you established any possible licensing partners? Is there anyone in discussions on the horizon? And how are you considering the future commercial requirements?

[Fredrik Tiberg, CEO, President, Head of Research & Director]

That's a very good question. So yes, I mean, our anticipation right now is we have retained all rights to all significant markets. We do have discussions, I would say, outside the U.S. and Europe, and they are progressing. We have interest from several different geographies, but our focus, of course, for our own sake is the commercialization in the key markets, and this may include the U.S. We're doing a lot of work on that right now, both in terms of market analysis, and we are also preparing -- already started the preparations of the NDA, so applications -- and MAA applications in Europe. So there is a lot of things going on in parallel. But we have absolutely not excluded commercializing the product ourselves. And we see that this is a very attractive product because it's a small target group of physicians, both in the U.S. and Europe, and that gives us quite a lot of leeway. And we already have a very strong commercial infrastructure in Europe and Australia, which we could leverage in this case.

[Operator]

Next, we have a follow-up question from Erik Hultgård with Carnegie.

[Erik Hultgård, Research Analyst]

Just a follow-up on CAM2029. And I guess the acromegaly appears to be quite a low-risk type of design against placebo, but the NET study with active control and superiority design appears to be a somewhat more challenging hurdle to cross. So I was just wondering if I could sort of get your level of confidence that this will actually be a positive Phase III study. What is the sort of assumed delta versus active control that we have assumed and sort of the power of the study? And what type of sort of margins that you have assumed in order to reach superiority? And maybe if you could comment on whether there's a way forward in case the study would be a non-inferior outcome.

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Yes. I think that I'm happy to go into the kind of biostatistical background at a different occasion, but I can say that the study is powered -- it is a high-powered study. That's where the 302 patients come from, and it's based on previous clinical work with these active ingredients or with these active substances from a number of previous published studies. So in terms of treatment difference, we have set our treatment difference based on those data points. And we believe -- and I think also we have a very enthusiastic steering group in this case with people from all leading establishments in the U.S., north in Canada and Europe and who are all kind of very well acquainted with the data that exists in the literature and with the statistical assumptions that we have put for powering the study. So -- but I'm happy to go into the details in the next call or in a different occasion.

[Operator]

There are no further questions. I will now hand back to Fredrik.

[Fredrik Tiberg, CEO, President, Head of Research & Director]

Wait a second. We do have a few e-mail questions here that have come in. So one from [ John Feindring ] has a question that you may address. Can you split the revenues between episil and Buvidal? I think that I would like to just say that episil is -- we have -- it's a small percentage or maybe 1% of our overall revenues from product sales, so that comment. We were also asked about the potential market for CAM2038 relative to Buvidal. I think this is a difficult -- I mean it's the same compound so I think that's difficult to answer. And finally, "Fredrik, say something about increased R&D in the fourth quarter." Can we say something about the increased R&D costs?

[Jon U. Garay Alonso, Chief Financial Officer]

So regarding the -- thanks a lot, Fredrik. The increase we are facing in -- we are showing in our financial statements in Q4 is mainly driven by the acceleration of our Phase III studies. Probably what I'm going to tell you will resonate and link with the comments done by Fredrik about our CAM2029 and chronic pain indication going on. So we are doing our best to accelerate those studies. You see the increase in Q4. And also, you remember Fredrik, at the end of his statement 20 minutes ago, he has also mentioned that we expect this increase to continue in 2022 in a way to accelerate the conclusion of our studies and bring the product to the market as soon as possible. So I hope this addressed your question.

[Fredrik Tiberg, CEO, President, Head of Research & Director]

And finally then from Patrik Ling. We have a question regarding the pricing development. And what was the average price per patient amount in Q4 now as you have launched Buvidal in new markets and have gotten more reimbursement approvals? I do think that what we can say about that is that we do not have any difference in Q4 compared to Q3 in average price. They are on par, and we have been very similar across the entire year of 2021. So I think that's our best answer in this case. We also have a comment or a question from Grace Lee from Jefferies Healthcare, and that is about what are the reasons for the second Brixadi CRL. I think we have stated that in our press release, and it's quality-related issues at Braeburn's third-party manufacturer. And we have also got a question about does it make sense to repatriate the U.S. rights and find another partner. We do not have any comment to that at this stage, unfortunately. And we also got a question about if any of our assumptions for revenues for our -- are correlated to European label expansion for Buvidal in chronic pain. And we can say that our outlook is not dependent or related to the expansion into chronic pain. And then we got a question about can you remind us of any clinical milestones expected this year for the products in development. I think we can refer to our presentation there. And finally, there is also a question -- or 2 questions here from [ Pietro Asling ]. What are the assumptions behind the low end and high end for the 2022 EBITDA? And is it only sales or anything else? And I would like to say that it's a combination -- we have looked at this. It's a combination of sales and development costs. And can you say something about the estimated market share split between Buvidal and Sublocade in Australia? We got -- also from [ Pietro ]. I'll leave that over to Richard to answer. Yes, please.

[Richard Jameson, Chief Commercial Officer]

Yes. So currently, the data is demonstrating that of the long-acting segment in Australia, Buvidal has about 80% share of that segment, 8-0.

[Fredrik Tiberg, CEO, President, Head of Research & Director]

So was there any other questions? Okay. So with that said, I just want to thank you, everybody, for listening into this call. And we look forward to meeting you at the investment events coming here in the spring. And also, of course, we look forward to your attendance at our next -- first call of 2022, our Q1 call in May. Thank you very much for listening, and it's always a great pleasure to be able to update you. Thank you.