Camurus Ab

Thank you so much, and hello, everyone. I hope you all have had a good start of the year. Welcome to Canary's 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 three, 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 John Garay Alonso, our new CFO, who joined Cameras only two weeks ago. It's a great pleasure to welcome John to the team, and I would now like to give him the opportunity to introduce himself before continuing the presentation. John, please, the stage is yours.

Thanks a lot, Frederic, and good afternoon, everyone. Wish you all are doing well. My name is John Garay. I'm 48 years old, born in Spain. And as Fredrik has just said, I joined Camurus two 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. And through the years, my recent position has been the European finance director for the medication delivery and pharmaceuticals divisions. 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 Frederic 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 Frederic, back to you.

Thank you, John. And then we'll move over to slide five, please. So Cameros 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 601 million SEK. with product sales increasing by 84% to 594 million SECs. The full year operational results was minus 111 million SECs, 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. Hugadong is now available in 17 markets across Europe, Australia and the Middle East, with expansion continuing. We advanced our pipeline as well through successful lifecycle management and new approvals, a new program in registration phase and finished the year with three ongoing Phase III programs in rare diseases. So let's move in on the highlights of the fourth quarter. Slide five, please. Highlights of the quarter included accelerated duvidal sales in key markets, EMA acceptance of our regulatory submission for chronic pain, continued progress of our Phase III studies of CAMP 2029 and acromegaly, and first dosing in a phase three study of CAM-2029 for treatment of neuroendocrine tumors. On the partner side, Rhythm started a new phase three program for our weekly formulation of CET melanotype for treatment of genetic obesity disease. However, a strong quarter ended with the news in December that our U.S. scientists at Braeburn were issued with a new CRL public study. Aside from this, it was a very positive quarter where we continued building our business towards profitability while 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 six, please.

Thank you, Frederik. Good afternoon, everybody. We had a good fourth quarter, and I'll update on this as we saw continued progress with Bovdal in our markets. So we can move to slide seven, please. In Q4, we accelerated sales, getting further traction in several markets and grew market share, notably in the UK, 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 Boverdahl. Our geographical expansion also progressed with regulatory approval in Israel, and reimbursement approval in Belgium allow us to launch in the community setting. Pricing and reimbursement processes in other countries are ongoing without outcomes expected in the coming months. As the real-world experience with Buberdal grows and treatment centers publish their outcomes and demonstrate the impact Buberdal 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 UK 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 Buvedal by 2026. So if we can move to slide eight, please. As I mentioned, in the UK, in quarter four, 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 900 million, of which 780 million was directed to rebuild drug treatment and recovery services. And as a result of the growing awareness of the benefits that bubidol brings to patients and wider society, the drug strategy has included guidance on the role long-acting buprenorphine will play I quote with 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 benefits 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 Buvedal, supporting the expansion of infrastructure and ensuring patient pathways are in place to accelerate access, and capturing and publishing the real-world improvements and outcomes so they can be shared across geographies. So on that note, moving to slide nine, please. We aim to ensure we take every opportunity to share the growing scientific and evidence-based and real-world experience with Bruvadel. 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 Frederick for a pipeline update. So can we please move to slide 10?

Thank you, Richard. And so over to a short R&D update, moving over to slide 11, please. So during the period, we continue to advance our pipeline of innovative programs focused on treatment of CNS and rare diseases. In particular, our phase three and registration processes, where we continue to deliver several important milestones. Slide 12, please. So in Q4, we continue to make progress on the regulatory side with Bugrav, receiving market approval in Israel, adding to the earlier approvals in the EU, UK, Switzerland, Australia, and New Zealand, and progressing regulatory approvals in a number of countries in the Middle East as well, where we are expecting four new approvals in 2022. Now over to Bricsadi in the US. Unfortunately, the year ended with the news from our licensee, Braeburn, that they had 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 Bricsadi was these quality issues at their manufacturer. We are awaiting information from Breybarn on how they will resolve the CRL, Of course, this involves discussions with the authorities, and when we can expect the resubmission of the NDA in the US. 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 bubital 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 a 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 could 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 Bergdahl or potential expanded indication, I should say, indicate an additional opportunity of more than 150 million euros in the current market that we perceive. Over to the next slide and an update on 2029. Slide four in, please. So, CAM-2029 is our subcutaneous depot of actritide in development for treatment of three 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 CAM-2029. With four successfully completed clinical phase 1-2 studies to date, two ongoing phase 3 studies in acromegaly, and the recently started phase 3 study in patients with neuroendocrine tumors. In addition to that, we have completed preparations for a phase 2-3 study, Positano, in polycystic liver disease. During the quarter, we have also completed a bridging pharmacokinetics study of CAM-2029 administered with our newly developed injection pen versus the current pre-filled syringe format. The top-line results of this study achieved the objectives demonstrating comparable pharmacokinetics for the two devices. Moreover, the injection pen met our criteria for ease of use and injection time. The PEM is now being introduced in all phase three programs for CAM 2029, and further strengthens its differentiated product profile. Moving to slide 16. So, updating then on the individual indications for CAM 2029, 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 healthcare system as they require administration by trained healthcare professionals. At the moment, we have two ongoing phase three studies assessing the efficacy and safety of CAM-2029 as a potentially more convenient and effective treatment alternative for patients, for these patient groups. The studies include a six-month 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 two 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're 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 US and Europe. Based on a third-party assessment, peak sales of CAM-2029 in Acromegaly in the US and Europe are estimated to the range of $120 to $180 million. So, with that said, moving over to the next indication, the randocrine tumor, slide 17. Here, in the quarter, we dosed the first patient in the Sorrento Phase III study. This is a randomized active control study with the primary objective to demonstrate superior efficacy with CAM2029 versus standard of care. in patients with gastroenteropancreatic neuroendocrine tumors. The study will engage more than 90 clinical centers around the world, and we already had 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 Gethnet is very significant, in the range of 720, estimated in the range of 720 to $1 billion. To put this in perspective, current sales of first-generation smothersatin analog products are about $3 billion, with the majority of these sales being for treatment of Gethnet. So over to slide 18, please, and the last indication that we are currently pursuing, that being the registration program for CAM-2029 in polycystic liver disease, where there is currently no approved medical treatment available to patients. The study we are conducting is a randomized placebo-controlled phase 2-3 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 is a high unmet need for an effective treatment in PLD and a significant estimated market potential again of, in this case, $270 to $420 million. In conclusion, We have a wide-ranging program for CAM-2029 across three 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 diseases. During the fourth quarter, RISM initiated the first out of two planned phase three studies with CAM4072. Just after the year, we announced that the first dosing in this phase three study had occurred in a patient switched from daily injections. The second phase three study in de novo patients with Bardet-Biedl syndrome is also under preparation. RISM has come far since the start of our partnership It will be really exciting to follow the further progress of this promising programme. Slide 20, please. To summarise 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 ten quarters in a row as a new commercial organisation. We saw an accelerated patient uptake in the quarter, which is very promising, and 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 bubidol indication to chronic pain was successfully submitted and accepted by the authorities. Multiple phase III milestones with CAM 2029 and weekly set Milanotide were achieved. And on the corporate side, corporate development side, we delivered strong financial performance and are on track to execute on our strategy. Then moving on over to this year, 2022. Next slide, please. Slide 21. So after a strong finished last year, we look forward to a very productive 2022, with continued commercialization progress through market expansion, new approvals, and preparations for launching chronic pain. We will also advance our pipeline, with completed recruitment in phase three studies anticipated, and top-line phase three results in acromegaly. On the corporate side, we are expecting to reach profitability during the year while continuing to invest heavily in R&D. So finishing off with the 2022 financial outlook, we are guiding at total revenues of 900 to 950 million SEC, excluding any Bricsady-related milestones in the U.S. Product sales are guided at 875 to 925 million SEC and are operating results between minus 60 to 10 million SEC. I think it's worth a note that this includes R&D investments of over half a billion SEC in our promising pipeline. So our operational result from the commercial activity is very strong. Slide 24, please. So in conclusion, cameras 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... Thank you.

Ladies and gentlemen, if you do wish to ask a question, please press 01 on your telephone keypad. If you wish to withdraw your question, you may do so by pressing 02 to cancel. There will be a brief pause while questions are being registered. Our first question comes from Susanna Quickburner from Handelsbanken. Please go ahead.

Hello. Hi, guys. Susanna Krexbrenner, Handelsblanken here. Thank you for taking my question. I have three, please. So perhaps starting with Buvidal sales, perhaps you can explain the 4K additional patients in Q4, where they came from, in other words, a breakdown of the 25K patients on drug, e.g. high-pricing countries versus low-pricing countries. And then question number two, what form of communication have you had with Braeburn since the CRL in December 2021? Email exchange, in-person meetings, calls. I'd be grateful for an update. And then question number three, 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?

Thank you, Susanna. I think we can start with the first question, which I believe was the question about where the patient 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. UK has been coming and doing a very nice job good progress in the UK, but also the rest of the market. 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?

The second question.

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. You could probably assume that that is also the case in this case. So I think that's the two things. In terms of their intentions, we're hoping to get it, and we're 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 in time is the timeframe that was required for the last resubmission, which was approximately six months. And at that time point, we had assumed that it would probably take four months. 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, a product that is dearly needed. It is subject to priority review, so the review time is expected to be the same, that is, maximum six months after a submission. But unfortunately, without the details, I cannot communicate this in any more detail. substance.

Thank you.

Is that fine for you, Susanna, or do you have any other questions?

But in terms of the type of communication you have, can you expand in terms of have there been any in-person meetings? Is this email exchange?

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

Okay, thank you. I'll wait to hear if anyone else has questions.

Our next question comes from Erik Hultgaard with Carnegie. Please go ahead.

Hi there. Thanks a lot for taking my questions. I have a couple, if I may. First, on your guidance for 2022, you assume growth of around 50% for Duvidal. So I was just wondering if you could break down a little bit what markets, what the top three markets that is expected to contribute most to growth? Is it the established market or is it actually some new yogurts 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 affliction point in Germany during the second half or is this pure 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? Is it reflective of the design and the inclusion criteria in the Phase III study, or will it be more narrow and more focused on specific type of addiction patients? and how this is connected to your sales target of 150 million euros. So a lot of questions there.

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 obviously from a patient number perspective the established markets will continue to be those that provide the majority of the growth in but from a growth rate perspective we will see new markets becoming more and more important and especially then you know, newer, larger markets. Maybe, Richard, you want to go into that in more detail? Yes. I mean, we just started releasing in Spain and France.

They're big markets. Of course, we can start looking at accelerate penetration there. Obviously, from what I presented in the UK 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 established markets have some growth from the newer markets coming in.

Yeah, I think it's important to see the size of the opportunity. Only in the UK 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, how much this, what should I say, remuneration process to doctors will play in if there is any changes coming into that system in Germany. I can say that that is not being part of our principle assumptions behind our outlook and I would probably represent an upside on that. Anything else you would like to hear about the outlook? Otherwise, I'll go over to chronic pain.

I think it's probably, I guess, what's the downside to guidance?

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've tried to This is the best guidance we can give based on our current understanding. But of course there are, as always, risks, but none that I would like to particularly stress at this moment.

It sounds like you have pretty good growth and a large part of your expected growth for 2022 is actually from already established markets, which suggest pretty limited downside risk to guidance. Is that correct?

I think that's a fair assumption. What do you say, Richard? Yeah, exactly. Yeah. And over to the chronic pain, of course, we are, you know, our application is for a subset of patients. That subset will be, you know, subject to a discussion with the regulatory authorities. but it is more of a high-risk and even opioid-dependent population. And that is the basis also for our market estimates, providing them the 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.

Right, thank you. And just to follow up on that, what do you see as the risk, the principle regulatory risk for chronic pain? Are regulators actually willing, is it what type of level you will be able to achieve, I guess, getting 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 situation.

Yeah, 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 you know, a general chronic pain label.

Great. Thank you so much.

Next, we have a follow-up question from Susanna Quick-Burner with Handelsbanken. Please go ahead.

Hello. Again, I just wanted one final question on CAMS 2029 in acromegaly. I was wondering now, as the phase three 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?

That's a very good question. So, yeah, I mean, our anticipation right now is we have retained all rights to all significant markets. We do have discussions outside the US 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 US. We're doing a lot of work on that right now, both in terms of market analysis and we're 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 the commercializing the product ourselves. And we see this as a very attractive product because it's a small target group of physicians, both in the US 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.

Next, we have a follow-up question from Erik Hultgaard with Carnegie. Please go ahead.

Yes, I can just follow up on CAM 2029. I guess the Acromegaly pre-study appears to be quite a low-risk type of design against placebo, but the The next study with an active control and superiority design appears to be somewhat more challenging hurdle to pass. So I was just wondering if I could sort of get your level of confidence that this will actually be a positive phase three 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 is a way forward in case the study would be a non-inferior outcome.

Yeah, I think that I'm happy to go into the kind of biostatistical background at a different location, but I can say that, you know, the study is powered, it's 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 drug 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 US, 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. But I'm happy to go into the details in the next call or in a different location.

Sounds good. Thank you.

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

Wait a second. We do have a few email questions here that have come in. So one from John Findring has a question that you may address. Can you split the revenues between Epicil and Bovidal? I would like to just say that Epicil, it's a small percentage, or maybe 1% of our overall revenues from product sales, so for that comment. And we were also asked about the potential market for CAM 2038 relative to Bovidal. 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 the increased R&D in the fourth quarter. Can we say something about the increased R&D costs?

So basically, thanks a lot, Frederic. The increase we are facing and we are showing in our financial statements in Q4 is mainly driven by the acceleration of our phase three studies. Probably what I'm going to tell you, it will resonate and link with the comments done by Frederic about our CAM 2029 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 Frederick 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 addresses your question.

And finally then from Patrick Ling, we have a question regarding the pricing developments. And what was the average price per patient and month 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 pair, 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 jeffrey's healthcare and that is about what are the reasons for the second brixadi crl i think we have um stated that in our press release and it's a 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? And we do not have any comment to that at this stage, unfortunately. And we also got the question about if any of our assumptions for revenues are correlated to a European label expansion for Buberal 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 the 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 two questions here from Peter Östling. What are the assumptions behind the low-end and high-end for the 2022 EBITDIA? 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 Buberal and Sublocade in Australia? We got also from Peter. I'll leave that over to Richard to answer. Yes, please.

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

So, Fredrik, was there any other questions? Okay, so with that said, I just want to thank you, everybody, for listening in to 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.