BioArctic AB (publ)

Good morning and welcome to Biotic's presentation for the first quarter of 2024. It's very exciting times for Biotic with Lekembe which is originating from Biotic. Lekembe is the first and only disease modifying treatment for Alzheimer's disease with a full approval so far in the US, Japan and China. There will be three key messages today. I'll talk about the Lekembe sales which we see is increasing. The infrastructure has been established to a large extent in the US, and the launch goes now into the next expansion phase. The second part is that the LECANOMAB regulatory processes continues with more approvals, and China was approved early this year, and more submissions are also being filed by ASI, including a subcutaneous auto-injector file. The third aspect and key message is also around the rest of our portfolio, which is progressing really well. And we have made our first agreement on a project which is utilizing our brain-transported technology. And I'll talk more about all this here today. Next slide, please. I'm Gunilla Osvald, the CEO of Biotic, and I will share today's presentation with our CFO, Anders Martin Lööf. And Anna-Kaja Grönblad, our chief commercial officer, is also here for the Q&A after the presentation. Next slide, please. Biotic is listed at NASDAQ Stockholm large cap, and this is our disclaimer. Next slide, please. Biotic focus on disease-modifying treatments for neurodegenerative diseases. And we are now on the market in Alzheimer's disease, and we are preparing for phase two in Parkinson's disease. These are areas where there is a huge unmet medical need and very large patient populations that we aim to help. We have a great organization with highly skilled scientists and drug developers with vast experience. And we're now building a commercial organization to prepare and we are preparing for commercialization together with our partner ASI in the Nordic region. We have a broad portfolio. building on the success of Lecambi with very selective antibodies for Alzheimer's disease, Parkinson's disease and ALS. And we also have the very encouraging brain transporter technology, which helps us to get the antibodies better into the brain. I'm very encouraged by that. Our portfolio is exactly where the science now is evolving quickly. We're also well financed. We have approximately one billion Swedish crowns on the bank. And finally, the fact that our science and company leadership throughout the years have been given numerous awards validates our innovation and global leadership position within neurodegenerative diseases. We also got some new awards during this quarter. Next slide, please. So a lot of things have already happened this year. The year started with the approval of Lekembe in China, where ASI is planning for a launch in July. In Europe, it was disappointing that the scientific advisory group meeting was annulled due to process issues that was not depending on the cannabis. So the scientific advisory group meeting has to be rescheduled. At the Alzheimer's and Parkinson's Congress earlier this year, there was a very positive atmosphere with a lot of excitement in the field of Alzheimer's disease and Parkinson's disease. and with regard to the blood-brain barrier technology. Bioartic and Professor Lars Landsell presented new data on leucanoma, further supporting the unique binding profile with lower CAA binding, which is linked to lower incidence of the side effect AIA, if you compare this with competitors. ASI presented more data supporting the leucamber disease modifying properties and more data suggesting even better effects if you start early with a treatment in early Alzheimer's disease, as well as data supporting the subcutaneous as a more convenient administration alternative for Lecambi. ASI has submitted a supplementary application to the FDA for less frequent dosing intravenously with leucanumab. And earlier this week, ASI also initiated a rolling application to the FDA for Lecambi. with regard to the subcutaneous autoinjector for maintenance dosing. Bioartic and ASI have entered into a research evaluation agreement regarding BAN 2802, which is an Alzheimer's project utilizing our brain-transported technology. And this is then the first agreement done utilizing our technology, and I expect more to come. Biotic was included in NASDAQ Stockholm's new ESG Responsibility Index, which we also are happy about. Next slide, please. Lecambi is the first disease modifying treatment for Alzheimer's disease with a full approval in the US, Japan and China. And it's on its way to be established as a new standard of care for Alzheimer's patients. A lot of things is happening around the world, and if we start with the US, where it is approved and broadly reimbursed since July last year. ASI has here also submitted two files for more convenient maintenance dosing, a supplement application for less frequent IV dosing, and a new BLA for subcutaneous autoinjector administration for maintenance treatment. The launch is ongoing and now progressing into the next expansion phase. In Japan, LeCambi was approved in September and launched started late December and it's progressing really well. In Europe, as I said, we're waiting for the new scientific advisory group meeting and that will be followed by a CAG opinion meeting. And we're hoping, of course, for a positive opinion and a European Commission approval late Q3. In China, approval was granted in January and EISA is preparing for a launch in July. LECANOMAB regulator files are being reviewed in many parts of the world right now and we're hoping for several positive responses during the coming months. So I think it's a very exciting time. Next slide please. The launches are also progressing now in a very good pace. So if we start with the US, where a lot of work has been done by ASI to prepare the market and establish the pathway together with hospitals and infusion centers, etc. There is a strong momentum with 97% of the 100 integrated delivery networks, which is groups of hospitals and so forth. And ASI is now expanding their focus to the top 150 IDNs. I think it's great that prescribing facilities have been established in a broad way and can be found across the US. Many prescribing physicians have gone through a trial period and they are now in the expansion phase. We have heard that some facilities are confirming more than 200 cases of Lecambi treatment. It's also reassuring to see that the real world evidence when Lecambi is being used in clinical practice That shows that the side effect ARIA is in line with the results of clinical trials as described in the US package insert. I think that shows that Lekembe seems to be used safely and in the right way in clinical practice. So in summary, now when the pathway has been established to a large extent, ASI takes the launch to the next stage, and that is the prescription expansion phase. ASI and their partner Biogen are strengthening the go-to-market structure. with the aim of providing tailored information regarding three things. The first is, of course, regarding Lecambi. The second is regarding reimbursement and support for patients. And the third is around system efficiency in order to shorten time for treatment. More and more patients can now benefit from the treatment of Lecambi in the US. Next slide, please. If we then look at Japan, The launch is progressing even faster than expected here, with fast establishment of the diagnosis and treatment pathway at 600 facilities within four months of launch. I think that's very impressive. I think it's further impressive that the Japanese launch is even exceeding ASI's initial targets. And it's clear that the broad spectrum of promotion activities towards healthcare professionals are efficient. But then look at China. launch is planned for july and here china is a bit different um and that is for example that that will initially be a focus on the private market furthermore asi will be leveraging on already established online health platforms and the diagnosis the streamlined diagnosis will mainly be utilizing blood-based biomarkers And that, I think, will be very important and key drivers for diagnosis and growth. Next slide, please. ASI also continues to develop Lecunma. And the first approval in the US, Japan, and China is for Lecunme intravenous administration, 10 milligrams per kg biweekly. And that is both for initiation and maintenance treatment. The file is also under regulatory review in many other regions, as I said. In order to increase the convenience for the patient, ASI has now also made two applications to the FDA for more convenient maintenance dosing. After the initiation phase, then the maintenance phase could continue with IV monthly, 10 milligrams per kid, as described in the supplementary application. The other application, was a rolling submission under FOSTRAC designation. And that was initiated by ASI earlier this week, and that is regarding a subcutaneous injection with an autoinjector with a fixed dose of 360 milligrams for maintenance dosing. The next step, which will be very important, is when the subcutaneous autoinjector can be used both for initial and maintenance treatment. And here ASI has initiated discussions with the regulatory authorities. I think that Lekembe long-term penetration will also be supported by simplified diagnosis with blood-based biomarkers. And I think it's reassuring to see how well the blood-based biomarkers are evolving over the world. Next slide, please. I think it's great to see how Lecambi brings value to patients, caregivers and society. Lecambi has been studied in a broad patient population with early Alzheimer's disease and have shown consistent and distinct efficacy and safety profile. I think it's very encouraging to note that data from the low tau group, which is then very early stage of early Alzheimer's disease, that they suggest a potential even greater treatment benefit. And that is then when you start the treatment at an early stage of mild cognitive impairment. So early start and long-term treatment bring greater benefits for patients. Reports of the side effect ARIA from the real-world clinical practice are consistent with what was observed in the clinical trial as described in the US package insert. Most reports are non-serious, asymptomatic, and occur early in the treatment. I think this indicates that safety can be appropriately monitored. The low levels of anti-drug antibodies further enables maintenance treatment effects for Lecambi. The improvement in dosage and administration is important for continued treatment. And as I just described, ASI has filed for both IV and subcutaneous maintenance treatment. in a more in a better way for the patient the subcutaneous autoinjector will be a great improvement for patients to enable easier administrations at home and this will also be less burden on health care of course the ongoing phase three study ad 345 is for preclinical ad and now we're talking about very early stages of alzheimer's disease this is before the subjects have symptoms. And this study could potentially lead to a further expansion of indication into the even earlier stages of Alzheimer's disease. And this could also potentially further expand the clinical benefit for the subjects. So I think that Lekembe brings a lot of value for many. Next slide, please. But I want to emphasize that even though Lecambia, of course, is of main interest, biotic is more than Lecambia. And I want to mention two other pipeline headlines. The first one is regarding the brain transporter technology. At the Alzheimer and Parkinson Congress, it was highlighted that active transport of antibodies into the brain is seen as the next big step for neuroscience. Our proprietary brain transporter technology continues to progress very well. And by utilizing our brain transporter technology, we get a rapid, broad and deep distribution of the antibodies into the brain. And this could potentially lead to even better efficacy and tolerability and with lower doses, of course. I want to emphasize three of our projects utilizing this technology. First, the two Alzheimer's programs, BAN 2802, where we now have signed a research evaluation agreement with ASI as the first agreement utilizing our brain-transported technology and expect more agreements to come here. The second project is BAN 2803, which is a pyroglue A-beta antibody utilizing the brain-transported technology. This looks very promising, and we have increased our investments here and we progress this project actively towards the clinical stage. In Parkinson's disease, the project called PDVT2238 is an alpha-sucline antibody with the brain-transported technology. It's developing really well, and we are progressing actively towards a candidate drug nomination. Next slide, please. The other highlight of our pipeline that I want to mention here today is regarding our alphasnuclein program. And at the Alzheimer's Pakistan Congress, again, encouraging data on alphasnuclein treatments were presented, as well as great progress on diagnosis and biology linking into alphasnuclein. This further supports our alphasnuclein programs, both Excedagnema as well as 2238. Exidabnevab, which is our selective alpha-synuclein antibody, where we are preparing for phase 2, and the phase 2A study is called EXIS. And that is for Parkinson's patients, and we plan to start dosing late this year. The aim of this study will be safety and tolerability in pharmacokinetics with exploratory biomarkers, including seeding amplification assay and digital biomarkers. The study protocol is currently being finalized through interactions with regulatory authorities. The drug project is now available, and the studies plan to be performed in Europe with the first patient's plan to be dosed, as I said, late this year. Next slide, please. So just to summarize BioAstrix portfolio in Alzheimer, Parkinson, ALS, and the brain-transported technology, our most advanced program is, of course, Lekembe. But I want to emphasize again that biotic is even more than it can be. And after the Alzheimer and Parkinson's Congress, we can again conclude that our portfolio includes exactly the targets and trends where science is breaking now. And I'm pleased to see the continued progression of our projects here and how well it's being developed. Next slide, please. And then I will hand over to Anders Martin Lööf for the Financial Summit.

Thank you, Gunilla. If we turn to slide 15, As Gunilla has already mentioned, the launch is progressing really well, and now we're starting to see that in our financials. The global Acambi sales were 2.82 billion yen in the quarter. That's roughly 200 million Swedish, or $18 million. That represented a 170% increase over Q4 2023. On that, we get a royalty rate of 9% on global net sales. In addition, we get 1% more on U.S. sales and 1.5% on ex-U.S. sales that we then pass through to our apartment lifehack. So the 21.3 million in revenues that we recorded during the first quarter, that includes the pass-through warranties that we pass on. But you see a very, very steep increase, so quarter over quarter. And this growth is likely to continue during the year. The U.S. launch is now in the expansion phase, as Camilla mentioned. ASI and Vardian are increasing their sales force to drive sales, not only in the larger hospitals, but now in their satellite clinics. We have seen a strong start in Japan. The pathway has been established at 600 sites, but more and more sites are coming online. So we'll see very steep growth there as well. And a launch is planned for China in July, and that will further support the growth during the year. If you turn to the next slide, you can see that ASI has, for the very first time, issued a forecast for near-term sales. And they are predicting more than a 10-fold increase in sales of the Cambie from 2023 to 2024, going from 4.3 billion yen, roughly 300 million Swedish in 2023, to 56.5 billion yen, i.e. 3.9 billion Swedish in 2024. The lion's share of the market will come from the U.S. So 77% is expected to come from the U.S., but already 18% is expected to come from Japan. For us, this would then correspond to royalty of roughly 400 million in recorded revenue or roughly 360 million net after the royalties paid out to LIFAR. And in the coming year, this is likely to continue. We have briefly mentioned that the subcutaneous maintenance formulation is likely to be approved in 2025. We will also see subcutaneous formulation for initial treatment, and ASI indicated that that could be approved in 2026. We're also seeing the implementation of lab-based biomarkers starting already this year in China. It's happening in Sweden, and we expect that to continue all over the globe. And all of this lowers the barriers to treatment. So when ASA has predicted what's going to happen mid-term, they are expecting roughly a five-fold increase in sales from 2024 to 2026. And in their revenue simulation that they presented in March, they said that they would have revenues of 290 billion yen, so roughly 20 billion Swedish or $1.9 billion in 2026. So we are really just in the beginning of the growth phase for Likambi. If you then turn to the next slide, I'll go through our numbers for the quarter. On the left-hand side, you see that our first quarter net revenues were 30 million. That's quite a big drop from a year ago when we had 393 million in revenues. But that's explained by the fact that we had three milestones totaling 35 million euros in the first quarter of 2023, and there were no milestones paid during this quarter. We are still entitled to more milestones. We are expecting a milestone when we get approval in the EU this year. And in the following years, we are entitled to sales milestones in 25, 26 and 27. So that will continue. But over time, the two new revenue streams will take over more and more. Right now, the royalty revenue was 21 million, co-promotion was 3 million. But over time, those two revenue streams will, of course, make up the lion's share of revenues and that will increase the lumpiness of our revenues. And they're obviously very lumpy right now. But over time, it will be much, much smoother. If you turn to the middle graph, you see our operating expenses. And first, this is the first time you see them by function. So the total operating expenses increased to 101 million from 79 in the first quarter. 75% of that increase comes from R&D and in total 63% of our operating expenses come from R&D. And that's an increase from last year when 59% of our R&D expenses came from R&D. On top of that, we have 12% of our expenses come from sales and marketing. Those two ratios will continue to increase. Our costs will increase during 2024. Due to the fact that we are investing heavily into the programs, especially the ones that Gunilla mentioned, we're starting our phase two trial for hexadalaminol later this year. We're also investing in our all-summit programs where we selected our candidate drugs last year and are now performing IND-enabling studies. We're also building up our commercial organization that will accelerate towards the latter part of the year. So we are expecting a continued increase. But more and more, the larger and larger share of our costs would be from R&D and sales and marketing rather than G&A. On the left hand side, you see our operating profit, which was a negative. So it was an operating loss of 73 million for the first quarter, which is roughly in line with what we saw the fourth quarter last year. If we look at our financial position on the next slide, Starting from the right hand side, you see that our net loss was 58 million, which is roughly 50 million better than the operating loss. That is explained by a fairly strong financial net of plus 15.7 million during the quarter. On the middle graph, you see on the other hand that the operating cash flow was weaker than our operating result. And that is due to the fact that the royalty payments are lagging the royalty revenues by roughly two quarters. this quarter we saw a 45 million increase in working capital and this will continue to increase when our royalties increase so this lag will continue but it has a very limited impact on our financial position you see on the right hand side that we we have a cash position including short-term investment of 991 million so we can continue to work long-term to focus on advancing our portfolio in the fastest possible way without thinking too much about financials. Looking for the remainder of the year, I think it's unlikely that we will be profitable in 2024. But as royalties grow, I think there's a very high likelihood that we will be profitable again in 2025 and onwards. That was all from my end and I hand the word back to Gunilla for some closing remarks.

Thank you so much, Anders. So we're coming to the final part of the presentation with some closing remarks and upcoming news flow. Next slide, please. So the upcoming news flow, if we look at this quarter, the initiation of the US submission of licanumab for the subcutaneous autoinjector maintenance dosing under the fast track designation was just achieved this week. And we are hoping for an approval of licanumab in Great Britain. If we look at the next quarter, we're looking forward to the next big congress for Alzheimer's disease called AAIC, which is in Philadelphia during the summer. And there we will see more presentations on leucanumab and more interesting data. In July, ASI plans to launch Leukemia in China. And in Europe, we of course hope for a positive CHMP opinion after a new scientific advisory group meeting. And if so, then we could expect approval in EU during late Q3. And then during the fourth quarter of this year, we plan to start the phase two A study in Parkinson's disease with Excedavnima. And we're looking forward to being able to present some more data on our brain transporter programs. Other potential approvals of Lekembe could also come during the rest of the year. So I think it's a lot of exciting times ahead for biotic. Next slide please. So to summarize today's presentation, Lekembe is approved in the US, Japan and China with huge patient populations with early Alzheimer's disease. And even if a small part of the population will have treatment with Lekembe, that would be huge. And I think it's gratifying that we can help many patients. The launch is showing strong momentum now, and it will be exciting to see more and more patients being able to get access to Lecambi treatment. We're hoping for more approvals, and ASI continues with more regulatory applications and further development of Lecambi. Our pipeline is progressing very well, and the first brain transporter agreement has been signed. Our finances remain solid. We have almost one billion Swedish crowns in cash, which I think is great, so we can focus on driving the project forward towards the patients. Next slide, please. So Biotics' aim is to improve the lives of patients with neurodegenerative disorders, and I think that we are very well on our way. And I think it's extremely gratifying that we now can help more and more patients and their families. And by that, I say thank you so much for your attention, and we are happy to take questions.

If you wish to ask a question, please dial pound key 5 on your telephone keypad to enter the queue. If you wish to withdraw your question, please dial pound key 6 on your telephone keypad. The next question comes from Alastair Campbell from Royal Bank of Canada. Please go ahead.

Hi there, thanks very much for taking my questions, and it's great to see LeCambie gaining momentum in the US. Two questions, please. First of all, on AHEAD 345, just looking at the status on clinicaltrials.gov, it looks like that's now primary completion around 2029. So I guess if you give me an update on how recruitment's going and sort of what the timeframe looks like for that, and frankly, you know, if it reads out in 2029, gets on on April 2030, What sort of timeframe do you have left to sort of get a commercial benefit from that given the contract in place? And then the second question is just simply on cash position. Given your potential milestones later this year, what do you feel about where the cash may end at the end of the year? Thank you.

Thank you so much for your questions. If we look at the AHEAD 345 study in the very early Alzheimer's disease, even before the subjects have any treatment, the aim of this study is to have 1400 subjects. The study is ongoing around the world, the majority in the US, but also in other parts of the world. I think the inclusion is going really well. and hope asa is hoping to conclude the enrollment into this trial during this year and then it's a four-year treatment in this trial um and then we will wait and see for the for the results but i'm really encouraged by the data that we have seen with very early um patients of mild cognitive impairment that they seem to maybe have even more benefits And then thinking about when this can be ready, I will not speculate exactly on when that can be. And our patent expiry, including extension, is around 2032. So I think that there is still time for that. And then you also asked about more milestones, and I hand that question to Anders.

Yeah, you asked about the cash position towards the end of the year, and assuming that we get approval in Europe, which we believe will happen during the second half, we're assuming that we will have a cash position between 800 and 900 million towards the end of the year in Swedish. Thank you.

Thank you.

The next question comes from Joseph Hedden from RX Securities. Please go ahead.

Good morning, and thanks for taking my questions. Just referring to your news flow slide, in particular the potential EU approval, I know some of the language used in terms of the scientific advisory group. Could you just fill us in? Has this happened to your knowledge yet? And if it hasn't, do you have any idea when this could happen? Just trying to get the sense of what the risk to that timeline still is. And then secondly, it's clear that blood-based biomarkers are quite important to ISAI's projections. And it's something that you and ISAI talk about a lot. I just wanted to get an idea, does ISAI have any deals with providers of these tests in the space currently? Or has it got any proprietary technology? And also, Are there any data on the real world use of any of the available tests so far in the LeCambion? Thank you.

Thank you so much, Josef. Great questions. So first of all, with regard to Europe and the Scientific Advisory Group, it has not happened yet. We are looking forward to seeing how it evolves. And I think that these timelines that we have laid out i think is realistic we don't know exactly when the different things will happen but and i really hope for for a positive opinion here so and an approval so european patients also can get access to to lecambi your second question with regard to the blood-based biomarkers i think it's evolving really well our partner asi has said that they have different collaborations, for example, with C2N and with CISMEX and so forth. And I think you should ask them more about this, but this is what we know so far. And I think that at the Alzheimer's Congresses, there is presentations every time about more and more solid data coming out of the blood-based biomarkers. And it's both about a beta 42 over 40 ratio, but especially on the phospho tau biomarkers, which is evolving really, really well. So this is being utilized already here in Sweden in clinical practice, which is being tested, as we heard, China. It's also being used for triaging in other parts of the world, including the US, to starting that. I think it will be more used in a broader clinical setting in a couple of years. So it looks really good. It's already used also, for example, in the screening phase of the head study where the first part is linked to a blood test and in that screening phase in order to see and then it's followed up by other biomarkers. So I really strongly believe in the blood-based biomarkers that that will really help also to make a broader finding of the right patients that can benefit from the chem.

Okay, that's great. Thank you.

Thank you. The next question comes from Patrick Ling from DNB Markets. Please go ahead.

Good morning, everyone. Just maybe to start with a follow-up question to Joseph's question about the SAG meeting. You said that it hasn't happened yet, but has it been scheduled yet? Do we know when it's going to be?

It has not happened yet, and we don't have all the details about how and when it will happen. So we need to come back to that when we know more. But I think that the time I laid out, I believe in those. But we have to wait until we know more.

Okay, great, great. Then I actually had a follow-up on this research evaluation collaboration that you have with ASI on BAN 28.02. Maybe if you could give us a little bit more color on what that actually includes, what will happen What are the timelines? What type of evaluations are you doing together and so on?

Yeah, so I think this is regarding the project called BAN 2802. And that's one of the two Alzheimer projects that we are investing heavily in now and driving forward strongly, which is based on really selective antibodies combined with the brain transporter technology. And here we have laid out for BAN 2802 a very clear development program that we will share the costs with ASI. And that's a program which is about two years that we will be doing and then preparing this project for towards clinical stage. So I'm really enthusiastic about this project and I'm also really enthusiastic I've got the question, so what about BAN 2803? Does that mean that you're not driving that forward? And I just must say that BAN 2803 also looks really encouraging. So I think it's a very strong position for Biotics to have two very good programs as it looks like utilizing the brain-transported technology for Alzheimer's patients, as well as that we also have it for Parkinson's disease and also in the future for ALS and other parts.

Great. So first step now is a two-year evaluation where you split the cost 50-50, I suppose?

I'll not comment exactly on how the split is, but we will share the costs with ASI. And then after that, about two-year period, then there will be an option for ASI to go into a license deal. And that's, of course, what the aim is for most companies to start with. that project and do the collaboration together.

Great, great, great. Then I also had a question about the EXIST trial. Maybe I missed that, or maybe you can just remind me. Have you said anything about the potential size of that trial? How many patients you're going to include?

No, we have not. And I think that the next Q report, we will give you more information. It should just be, I mean, managing expectations. This is a small study. And it's really safety-tolerability where we will be looking at two different doses and compare with placebo. But it's mainly safety-tolerability in PK and with some exploratory biomarkers. So it's really a study which is preparing us for the next important step, and that is to select the indication or indications for Phase IIb, which will be the most important parts where we'll really be exploring full efficacy.

No, because the reason I ask is, I mean, if you plan to include, you know, patients with basically five different indications, my impressions before has been that you will have, you will, based on the results here, decide on where to continue with phase two. And my thinking was that maybe you needed, you know, a reasonably... large amount of patients in these different indications to be able to actually decide where to go next.

Thank you for your question. Then I will help to clarify. The next study that we are now preparing will be done in Parkinson's patients. And that is, as I said, safety tolerability. And that is not, the study as such will not include the different kind of patient populations and different indications. That will be decided based on several other things and not based on the data as such in this study. I mean, for example, we'll be looking at competitors, which is also progressing in some of those indications. We will also look at where do we think we have the largest possibility to be successful with regard to biomarkers and clinically fixed endpoints and so forth. So I think it should be clearly expected that The phase one package that has been done was a large phase one package for single doses with both different doses and also IV and sub-Q and also different ethnicities and Japanese patients and so forth. But there has not been a multiple ascending dose study done yet. So that's part of the phase 2A study. So it's really safety, tolerability, and a small study should be expected. And meanwhile, that study is ongoing. We will do a lot of strategic work looking at the different indications that potentially could come after and select the best indication for phase 2B. So it will only be Parkinson's disease patients in the phase 2A study, the safety, tolerability study. But that doesn't mean that it has to be Parkinson's disease patients only in the next step. it could be a different indication. Did that help?

Great. Great. Definitely. Definitely. I got it now. Great. Thank you very much, guys.

Thank you so much, Patrick.

The next question comes from Frederick Thor from Red Eye. Please go ahead.

Hello, and thank you. My question, you may have touched upon this a bit, but about cost development for 24. Could you elaborate on this? And is it the same as before, roughly 30 to 50% increase from the previous year?

Yes, we don't have an update yet. So we stand by our previous guidance.

Okay. And my second question was about the subcutaneous dose and first off the maintenance dose and then also the potential to have the initial dose also be subcutaneous. Could you explain kind of the difference between these two? How much increase would you say, for example, if the initial dose also could be subcutaneous compared to only for the maintenance?

I think of course it's a very good first step with the subcutaneous administration with an auto-injector like a pen. So I think that would be a really good step for the longer-term maintenance phase. And that is what the submission that was just initiated was about. But of course it's good to have the alternative to start also with a subcutaneous auto-injector. And as you might recall that I said in a previous call, that when ASI presented the data from the ongoing study with the subcutaneous autoinjector, that was even better exposure and even better reduction of plaques with the subcutaneous formulation. So that's why there is, of course, a discussion ongoing about which dose should we use for the initiation phase and potentially also adjust the dose for the maintenance phase. That's the discussions which are ongoing. And in order to sort that out, that will then help to see when the initiation dose can be. But of course, that will really help the patient and be a very attractive alternative. But I can't say exactly how much of the sales in the future, which is expected to be dependent on the other one or the other. I think it's really good to have different options and different alternatives for the patient.

Perfect. Yeah, that's all for me. Thank you.

Thank you so much, Fredrik.

As a reminder, if you wish to ask a question, please dial pound key five on your telephone keypad.

So it doesn't seem like there are any telephone questions, but we have some questions, written questions come in. So the first one was about approval in the EU, but I think you've already answered that, Gunilla, with the expected timeline of late Q3. Could be a timeline we see right now. But maybe for you Anders, to clarify a bit about the milestones. You mentioned something about that, but maybe you can clarify how much we still have in expected milestones and when that could happen.

Yes, thank you Oskar. Yes, so in total we have 84 million euros of outstanding milestones. And we are expecting, as I said, a milestone when we get approval in EU. We cannot communicate the exact size of that, but when we got approval in the US, we got 25 million euros. Europe is slightly smaller, so that will be slightly smaller than 2025. The rest of the milestones are mainly sales-related, so you can basically assume that they will happen during 2025, 2026, and 2027, and spread out over those years. I hope that clarifies the milestone development that we're expecting.

Thank you, Anders. Then I see that we have a written question also on the face-to-face study, but I think you've clarified that at length, Gunilla, in your response to Patrick. So maybe then a question, two questions from Komachi. First one is if we could say anything about the patient number or number of patients currently on Lekembe, and secondly, maybe a bit more explanation on the brain transporter technology and if that uses the transfer and receptors similar to what Roche Brain Shuttle or Denali's program does.

Yeah, I think the brain transporter technology is definitely using the transfer and receptor in the approaches that we're utilizing right now. And they have a lot of similarities with both Roche and Denali. But they also have some important differences that we will be able to communicate more later on. And we are really encouraged by the Roche data that was presented at the previous Alzheimer Congresses, where they showed really impressive data. It's still early days, but it's the first clinical data that has been shown. And I think that really has made us focus and invest even more strongly in our brain transporters. Because it really looks like the next generation of approach to get the antibodies better into the brain. So I strongly, as you have heard before, believe in this. And there is a possibility for better side effect profile and lower doses. So it has some clear similarities, but also some important differences.

And do you want to say anything about it? patient numbers Camilla?

No.

And we don't know I think is the correct answer. We don't know exactly.

I think you have to reveal on what we said with regard to you saw the number of miles on the slides and we saw more also about what we understood about the sales. I think we have to stay there for now.

Right. And ASI commented on this and said that they will not communicate patient numbers going forward because it's really really hard to estimate actual patient numbers is much battery information to look at the numbers and connection sales. So there will be no communication regarding that.

Thank you. Maybe just a follow on from Goldman Sachs and Ryan about the brain transporter technology. He's wondering, Gunilla, if you can say anything about when this might enter the clinic and also if the collaboration with ACI regarding this band 2802 program changes anything in the development plans that we have for that program or the other programs?

You know that we C-denominated those two projects at the end of last year. Normally, when we do a C-denomination, that means about two years to come into the clinical phase. Roughly, that's the timeline. And then does the collaboration change any of the development plans? I mean, what it does is that it makes us want to invest even more in all our brain transporter programs. And that we're also opening up the brain transporter thinking in a broader way also potentially for other areas and other companies' projects for the future as well. So I think it really strengthens the position. So it does not mean that we are lowering the ambition in any of our projects. Just the contrary, that we are increasing our efforts in all our brain transporter linked programs and in that technology platform as well.

Maybe we should clarify a little bit on the timelines for the research evaluation agreement. Gunilla mentioned that it would take roughly two years, but maybe we should clarify that you're thinking more towards the end of 2025 that we'll get the results, not mid-2026, because we're right now in mid-2024, so two years from now will be mid-2026. And I think you were thinking from the beginning of 2024 to the end of 2025, so roughly the same time frame as when we expect to become ready for protein trials.

Thank you, Anders.

Thank you. Then one question from Peter, and that refers to AI and utilizing AI in pharma development. Can we say anything on our efforts in this area, Gunilla?

Absolutely. I think it's really important to be part of the AI explosion. And definitely we have some pilot projects ongoing at Bioartic. And it's definitely used typically in different areas of, I think, areas like imaging areas with regard to side effect profiles in the future and so forth. And also there are initiatives ongoing also in clinical trials, even though we are not utilizing it for right now for our own studies, for example, where you can utilize AI patients. but i think this is an area that we are clearly watching and there is ai is built in so many different areas already today so and i think it's important for us and all others to to be in this i think it will be a part but it's really important how you do it and that you do it in um in a safe way and so forth and then you realize um the opportunities but also mitigate some of the risks that are linked to ai so i'll not go into any details more right now but maybe we can do that in the future and tell you about some of the examples but we are using it and we'll be using it more in the future thank you um i don't see any more written questions online operator are there any more questions

waiting in on the phone it doesn't seem that way so i guess then that concludes our call today and thank you everybody for listening in and thank you nilan andersen and i care for being here for the presentation and then q a thank you see you next time