Welcome to BioArctic Q4 report 2022. For the first part of the conference call, the participants will be in listen-only mode. During the questions and answer session, participants are able to ask questions by dialing star five on their telephone keypad. Now I will hand the conference over to CEO Gunilla Osswald and CFO Jan Mattsson. Please go ahead. Thank you. Good morning, and welcome to BioArctic presentation of the fourth quarter of 2022. I'm Gunilla Osswald. I'm the CEO of BioArctic, and I will share today's presentation with our CFO, Jan Mattsson. I will give an update on BioArctic, of course, and focus on the fantastic year we had last year, and especially the fourth quarter, with the groundbreaking results for lecanemab that was presented at the Alzheimer Congress, CTAD, in November in San Francisco with regard to the phase II results. I think it's really reassuring with some robust and consistent and positive phase III results. This year has also started in a great way with an accelerated approval of lecanemab in the U.S. It's really exciting that lecanemab, or Leqembi, as it's named in the U.S., now is available for patients in the U.S. I'll talk more about that here today. Next slide, please. BioArctic is listed at Nasdaq Stockholm Large Cap since January this year. This is our disclaimer. Next slide, please. If we have some new listeners, I will start with a short introduction to BioArctic. I think that BioArctic is a unique Swedish biopharma company. We focus on improving lives for patients with brain disorders. I think that we are unique based on four different areas together. The first one is that we focus on R&D of innovative treatments for brain diseases where there is a huge unmet medical need, like Alzheimer's disease and Parkinson's disease and other neurodegenerative disorders. Of course, this is large commercial opportunities. We have a great organization with very experienced and engaged coworkers, and important fruitful collaborations with universities and with our strategic partner, Eisai, in Alzheimer's disease. The third aspect is that we have an attractive and well-balanced project portfolio with projects spanning from very early discovery all the way to phase III, and now also in regulatory process and on the U.S. market. We have partner projects that are generating revenues by milestones and where our strategic partner carry the cost for clinical trials. We also have earlier fully own projects with substantial marketing and out-licensing potential. The fourth aspect is that we're well-financed, and we have a strong cash position with more than SEK 800 million on the bank. We have valuable collaboration agreements with companies like Eisai. During the first quarter of this year, BioArctic is now entitled to regulatory milestones of EUR 35 million. BioArctic is listed at Nasdaq Stockholm Large Cap, and we have a market cap of about SEK 27 billion. I think that BioArctic is an innovative and dynamic and very exciting company with a huge potential. Next slide, please. This slide shows our attractive and well-balanced project portfolio. Alzheimer's disease is, as you can see, our largest area. For lecanemab, which is our most advanced program, which is now on the market in the U.S. based on the accelerated approval, and it is in regulatory phase in the U.S. for a full approval, a traditional approval, and in Europe and Japan for a traditional approval. It's all driven in a great way by our partner, Eisai. They also have another large phase III program ongoing with lecanemab in earlier phases of Alzheimer's disease. Even if the first step with the first generation of disease modification treatments like lecanemab is successful, there is still a large medical need for more treatment options and for a combination of therapies. Therefore, it's important that we continue to develop more options for Alzheimer patients. We have four early disease modifying programs ongoing, including that two of them are combined with our BrainTransporter technology, which is progressing really well. During the fourth quarter, we made a data-driven decision to stop one Alzheimer project, AD1801, which was one of the early projects. Another project, AD1503, has progressed so well that we have nominated a candidate drug, and that is now called BAN1503. That has also now been combined with our BrainTransporter technology into a project called AD-BT-2803, and that is targeting truncated forms of Aβ or Pyroglu- Aβ. Based on lecanemab's positive phase III results, I think that the probability of success has increased for our other programs with a similar approach that are targeting misfolded forms of the different proteins, and those forms are called oligomers and protofibrils. That is soluble aggregated forms of the proteins that are toxic. In Parkinson's disease, the protein is alpha-synuclein, and in ALS, the protein is TDP-43. In ALS, our program with TDP-43 is progressing really well and quickly. This is thanks to all our experience in our technology platform and learnings from Alzheimer's and Parkinson's disease. We have communicated during the fourth quarter last year that we have started two new projects, both in combination with our BrainTransporter technology. That is a Parkinson program with a selective antibody targeting soluble alpha-synuclein aggregates together with the BrainTransporter technology. A new indication, a new disease, which is an orphan drug indication, which is called Gaucher disease. Here we are targeting also the CNS effects of Gaucher disease, where there is no available treatment today. This is GD-BT6822, and this is an enzyme replacement therapy, which is really important to get better into the brain, and that's why we're utilizing our BrainTransporter technology. As you can see, you have heard me before say that I'm very excited about our blood-brain barrier technology. It's progressing really well, and it's now combined with several of our internal projects and in all disease areas we are working. In the future, I think that the BrainTransporter technology could also be applied to other companies, antibodies or proteins which they would like to have coming better into the brain on a non-exclusive license basis. I think this is a really important area for BioArctic in the long-term perspective. To summarize the portfolio, I think lecanemab is very important for BioArctic, but I also want to point out that BioArctic is even more than lecanemab. I think that we have had a very good progress in our portfolio as a whole during 2022. Next slide, please. We have a great long-standing and successful partnership with Eisai in Alzheimer's disease. We have been working with them all the way back since 2005. We have two licensees. We have had several research collaborations. A research collaboration is still ongoing with Eisai. At the end of last year, we had up to EUR 136.6 million remaining for milestones for lecanemab. During the first quarter of this year, now we're entitled to another EUR 35 million in regulatory submissions from Eisai. After that, we will have EUR 101 million remaining to be received if lecanemab continues to progress well. These milestones are linked to regulatory approvals and some safe and marketing milestones. If we come all the way to the market, we can also expect high single-digit royalties. That could of course be of substantial value because if you think about how large this patient population is, this could mean a lot for patients and for BioArctic, of course. We have retained rights to other indications, and we also have an option to market in the Nordics, which we are looking forward to, and we are discussing at the moment with Eisai. Next slide, please. Some recent highlights during the fourth quarter. We start with Alzheimer's disease and lecanemab. As I said, detailed and positive results were presented from lecanemab phase III study called CLARITY-AD. It was Eisai and investigators who presented the data at the Alzheimer's Congress called CTAD in San Francisco in November. It was really impressive that the results were simultaneously published in The New England Journal of Medicine. At the end of the quarter, Eisai also initiated submission of lecanemab data to the Chinese regulatory authorities via rolling submission. If we then look at the early portfolio, as I said, we made a data-driven decision to stop one Alzheimer project called AD-1803. This was a science-driven decision. On the other hand, we had a really good progress with another project, AD-1503, where we nominated a candidate drug. This is now one substance, one antibody that we now call BAN1503. That has now also been combined with our BrainTransporter technology in a project that we call AD-BT-2803. During the last quarter, we also communicated that we have started two new projects combined with our BrainTransporter technology. It is the BT, PD-BT2238, which is a selective antibody against soluble alpha-synuclein aggregates and combined with the BT technology. As I said, the new disease, Gaucher disease, where we have an enzyme replacement therapy combined with our BrainTransporter to get the enzyme into the brain in a more sufficient way. That is called GD-BT6822. I think that we had a very good progress in our early portfolio during 2022. Next slide, please. If you then think about what has happened this year so far, I think this year has started in a great way as well. In the U.S., lecanemab which has the brand name Leqembi, was granted accelerated approval as a treatment for Alzheimer's disease by the FDA on the 6th of January, which was the PDUFA date. The accelerated approval is based on the phase II-B biomarker data showing that lecanemab clears amyloid deposits from the brain in a clear way. This is great, but the most important is, as I've said before, to get a full traditional approval. Eisai submitted a supplementary BLA to the FDA for a full traditional approval on the same day as they got the accelerated approval. I think this is very impressive. The application for a traditional approval is then of course, based on the phase III efficacy data from Clarity AD. That is an important step in order to get a broader reimbursement in the U.S. and a broader access for the patients. Looking at what's happening in Europe, Eisai has also submitted a marketing authorization application to the European authority, EMA, and that happened on the 9th of January. This is of course, based on both the phase II-B and phase III data, so all the data. This application was accepted by the European authorities on the 26th of January. It has now started the regulatory process also in Europe, and this will follow a standard review process. Turning to Japan, where lecanemab has undergone a pre-review process of data during last year. On the 16th of January, Eisai submitted a marketing authorization application to the Japanese authorities called PMDA. This was also based on all the data, phase II and phase III, so all the data now. The application has also been granted priority review after that. I really want to complement our partner, Eisai, for their dedication and hard work with the clinical studies and the regulatory submission in such a timely way. I think that this is very important since every day matters for the patient. Next slide, please. If we just reflect back to the results from the phase III study with lecanemab called Clarity AD, which I think demonstrated a clinically meaningful effect. lecanemab met the primary and all key secondary endpoints in the phase III Clarity AD study. The study encompassed almost 1,800 subjects with early Alzheimer's disease. It was highly statistical significant results, showing a reduction of disease progression by 27% as measured by the primary endpoint, which is called CDR Sum of Boxes, and with a side effect profile that was within expectations. Clarity AD has shown consistent, highly statistical significant effects and confirmed the phase II-B results. The graph that you see there to the left shows the primary endpoint, CDR Sum of Boxes, which is a combination of functional endpoints and cognitive endpoints. We can note that the statistical significant effect is shown already after six months, and that it continues to increase over time. Slowing down of the disease progression, that means also more time in less severe stages of the disease. The safety profile was confirmed in phase III with low rates of ARIA. Despite that, lecanemab is given with a full dose from day one, and no titration is required. Full days dose from day one, that means also that we can have an earlier onset effect, still we have a fairly low rate of ARIA. lecanemab has also shown an effect on several biomarkers reflecting both amyloid and tau and different aspects of neurodegeneration. I think this is also pointing towards that lecanemab modifies the underlying disease pathology. Next slide, please. Eisai has modeled the long-term effects of lecanemab based on the phase II-B results that was published earlier last year. That shows that lecanemab could delay the progression of Alzheimer's disease by several years. I think this is an important way to describe what could the long-term effects be of lecanemab. Since the clinical studies are only 18-month treatment, the expected treatment for patients is of course much longer. Therefore, it's important to do some disease modeling to see what this could mean for the patient. The results from the modeling, they show the potential clinical value in a way that I think might be easier to understand the clinical meaningfulness of the results. What lecanemab has shown in this modeling is that it can slow the rate of disease progression, it can delay the progression of Alzheimer dementia for several years, and especially thinking about that you can have more healthier years in the earlier stages and delay going into, for example, the moderate stage of Alzheimer's disease. You also reduce the need for institutionalization care. I think all this is important for patients, their families, and for society. This model will be updated with Clarity AD results, and we will look forward to those results. Next slide, please. Our partner, Eisai, are very committed to lecanemab and are driving a broad clinical program in different stages of Alzheimer's disease. The focus on what I've just been talking about is on the early phases of Alzheimer's disease, which is mild Alzheimer's disease and the stage before you get that diagnosis, which is called mild cognitive impairment due to Alzheimer's disease. This is the population that is called Early AD, and that's why we have the positive phase III results and where there is an open label extension study ongoing, which is now also exploring a subcutaneous formulation. That is important to make it even more convenient for patients. There is another open label extension study ongoing, which is for the patients who are part of the phase II-B study. In this open label extension study, Eisai is exploring if a maintenance dosing could be given less frequently, maybe once a month or maybe every 3rd month. That is also a study which is ongoing. Furthermore, another phase III study is ongoing, and now we're talking about much earlier stages of Alzheimer's disease. We're talking about subjects who are without symptoms but have increased levels of amyloid in the brain. The thinking here is that if we start treatment even earlier, maybe we can have an even larger effect and delay the symptoms even further. There is also a combination trial ongoing for dominantly inherited Alzheimer's disease subjects. In this trial, lecanemab is given in combination with tau treatment to explore a combination if that could be helpful for the patient. We go to the next slide, please. By that, I will hand over to our CFO, Jan Mattsson, for the financial summary. Thank you, Gunilla. I would like to repeat saying that at present our revenue consists of milestone payments and compensation from collaboration agreements, and that means that we don't have any steady revenues yet. Net revenues amounted to SEK 2 million in the quarter, compared to SEK 5 million in Q4 of previous year. The main reason for this deviation is related to the fact that we in 2021 still recognize income from the AbbVie cooperation. Total costs in the quarter were higher than in last year and amounted to SEK 62 million compared to SEK 45 million in previous year. The main reason for the cost increase was related to the fact that we build a commercial organization but also to some one-time effects. Operating results was negative SEK 61 million in the quarter compared to negative SEK 39 million same quarter of last year. Operating expenses are expected to be in the range of SEK 330 million-SEK 380 million for the financial year 2023 compared to SEK 247 million in 2022. The reason for the increase is the build-up of the commercial organization prior to the launch of lecanemab and to cost for the expanded in-house portfolio. Next slide, please. Cash balance amounted to SEK 805 million at the end of December. However, milestone revenues of EUR 35 million in Q1 of 2023 will substantially strengthen our cash balance. Operating cash flow amounted to minus SEK 58 million during Q4 compared to SEK 39 million in Q4 2021. Net result for the quarter was minus SEK 68 million compared to minus SEK 19 million in Q4 previous year. The main reason for the lower net result this quarter has to do with the positive tax effect in Q4 2021, but also the build-up of the commercial organization. In summary, BioArctic have a very strong financial position. With that, please next slide, please, back to Gunilla. Thank you, Jan. I will now come to some upcoming news and closing remarks. Thank you for that slide. Perfect. We start with Alzheimer's disease, and here both Eisai and BioArctic will present more data on lecanemab at the next coming Alzheimer Congress, which is AD/PD, which will happen in Gothenburg at the end of March. With regard to regulatory progress, we are awaiting FDA's response on the acceptance of the supplementary BLA for a traditional approval. At that time point, we will also get information of the new PDUFA date linked to that response. We will also hear later on about more submissions in other countries, et cetera. We are also looking forward to providing more information about our other projects when that is relevant. Next slide, please. I'll just close by saying that BioArctic is built on great science. I think that we have great projects, great partners, and there is great coworkers working for BioArctic. Everything we do is with patients in mind, and our aim is to help patients with brain disorders. We are now clearly on the way to help Alzheimer patients. I think that we have very exciting times ahead of us. Next slide, please. By that, I say thank you for your attention. I'm happy to take some questions together with Jan. If you wish to ask a question, please dial star five on your telephone keypad to enter the queue. If you wish to withdraw your question, please dial star five again on your telephone keypad. The next question comes from Viktor Sundberg from Nordea. Please go ahead. Yes. Good morning. Viktor Sundberg from Nordea. I have two questions, if I may. Just a question on the Down Syndrome program. I guess the confidence here to pursue that program has increased given the outcome of Clarity. However, I struggle a bit with how you will design this in this indication. I mean, Eisai needed a pretty large study to find a treatment effect in Alzheimer's, but you don't have that luxury here to recruit as many patients. I just wondered if you could elaborate a bit on how you're thinking here in terms of potential study design, endpoints, et cetera, to find a treatment effect in Down Syndrome. Thank you. Thank you so much, Viktor. I think it's a great question. As I said, I mean BioArctic we have the rights to other indications outside of Alzheimer's disease, and we have done some preclinical work shown that our target exists in Down syndrome patients, was really expected. We also have can see that we can have an effect in, for example, a traumatic brain injury if you have dementia linked to that. We're also now seeing other potential indications. What we are doing right now is really exploring which indications would be the best ones to progress with the gotulecanumab. If you just saying that there might be others as well that are interesting. We then turn back to Down Syndrome in your question, they need some other there are some other things you need to think about when you think about Down Syndrome patients with dementia. There are some differences in scales, and there are some other differences. It's really important to be very careful with the design. We are in close contact with the experts in this area. I cannot reveal details about the design at the moment, but you are absolutely right that there are some differences that really need to be considered when you make this kind of go into other kind of indications like this. We have to come back with that. Okay. Thanks. Just a follow-up question here on the BrainTransporter technology as well. I mean, it looks very impressive if you can continue to show about the 10 x higher brain uptake versus naked antibody at therapeutic doses. That is the real challenge, I guess. Just wondering here if there are any more key experiments left to really replicate that you can keep that 10 x higher uptake versus naked antibody. I guess I'm looking for the next steps here in the BrainTransporter technology, especially for mAb158 or lecanemab potentially here going forward. I know it's early days, but just wondering w hat the path forward here is for that program in Alzheimer's. Thank you so much for that question. As you know, I mean, I'm very excited about the brain technology, the BrainTransporter technology. Because, I mean, as we have seen, lecanemab goes into the brain to some extent and we get an effect and so forth. The thinking is if we can get in more antibody into the brain, what we also have seen is we have shown this with mAb158 and with a couple of other programs, that we get more antibody into the brain, we get a broader distribution. That says to me that we could potentially also get an even better effect and maybe give a lower dose and also potentially have a better side effect. I think this is a very exciting approach, I can say that you've seen that getting this further, we have expanded it now into several different projects and in all disease areas. I can say that the that we have shown now with several of our programs that we can increase the level of antibody into the brain. It's not just shown with one antibody. With regard to your question on timing and so forth, I will not be able to give today more information about the exact timing for which program. What we have revealed is that one of the programs in Alzheimer's disease is linked to truncated forms of amyloid beta, that we also have a new program in the alpha-synuclein program. We also have a program linked to TDP-43, and we have the Gaucher disease enzyme replacement therapy. We have another Alzheimer program that I can't talk so much more about yet. I think it all looks very positive, and we will come back with more information when we can. Okay. Thank you. Just the key differentiating factor here versus other transmembrane receptor technologies, is that the two hits technology on the receptor, is that how I should think about that versus, say, Roche, Denali, and the other companies... Yeah. with the technology here, for Brains huttle? Yeah. Thanks. Of course, this is. I mean, everyone would like to have more antibody into the brain. Of course, it's a very hot area. Those who are most of advanced with regard to how far they have come in this in the clinical area is Roche and Denali. We have recruited people, and we are investing in this area quite heavily at BioArctic. We have recruited one of the best brains from Roche Basel and also a guy who has been working at both Genentech and Denali. The way that we are driving our approach is differentiated from both Roche and Denali, but I cannot disclose exact details. We can just say that we are very excited about, and we think that we have a differentiated approach that we are progressing. We are a bit, after them, but we think that we have something that we will show is very, very, good for the patient. Okay. Thank you very much. Thank you. The next question comes from Zoe Karamanoli from RBC Capital Markets. Please go ahead. Hi. Thank you for taking my questions. My first question has two parts. The first part is, can you give us an update on the progress on the pre-launch preparations in the Nordics? The second part, any color from interactions with neurologists since the full data was presented at CTAD. In particular, what are they most excited about, or also equally, what they're most concerned? From your side, what do you see as the biggest hurdle for launch? Thank you. Thank you so much, Zoe. There was a lot of questions in there. We start with the first one with regard to pre-launch activities. Of course, it is very, very important to-- If you think what we're doing, we're coming with a new kind of treatment, a disease-modifying treatment, which is not yet available on the market in the Nordics. It's a new kind of treatment. It's also coming to a slightly new kind of patient population because we are going earlier than you get the normal diagnosis of Myasthenia Gravis. It's also the stage before. It's a lot of work that needs to be prepared, and we also need to give this by infusions. There are also some other technologies like MRI and so forth, which is needed. There's a lot of work to help to understand the patient journey, to really see how can we help to facilitate and get the awareness in the different countries about what needs to be done in order to be able to take on these new medications for the benefit of the patient. There is a lot of work in understanding exactly where the hurdles are and to get discussions going with different parts in the different regions to see how can the community also help to be ready to get these kind of treatments accessible to patients when it is registered and available for patients. There's a lot of work ongoing, but it will take some time until it is approved in the Nordics because, I mean, the submission was just submitted now in January. I think that a lot of awareness and working on the different parts to see how we can go through the hurdles and so forth. I think your second question was with regard to the CTAD presentation and the phase III data, what we are most excited about and maybe concerned about. I would say the most exciting, I think, is the consistency in data, the robustness of data that we have seen for all clinical scales. The new scale that we have not spoken so much about previously, which is the activities of daily living scale, which is even more slowing down of the disease, which really is something that patients and relatives also report. I think that's also in quality of life and these kind of things. I think that excites me a lot, that to see that we can make a difference for the patients. What we are most concerned about, of course, we always have to be concerned about if there are side effects. Any treatment you take is always you need to think risk-benefit. We need to continue to follow the different side effect profiles for this treatment just as you have to do for all other treatments. Overall, I think, I mean, it's clearly shown that we have a very good risk-benefit profile. For each and every patient, the doctor and the patient and relative needs to think about what's the best thing for each and every patient. You had one more question which I forgot. Could you help me? No, I think that that's fine. I think it was around the hurdle, but I think you covered that basically in you. Okay. Okay. Thanks. Thank you. One more thing, then I'll stop. Are there any circumstances under which you will not be able to commercialize in the Nordics? What you expect will happen then? I think, I mean, we have very good discussions with Eisai, and we are really looking forward to. We have recruited great people, and we are recruiting more. We are building an organization. I think you saw that we have started now also BioArctic in Denmark. We have a couple of people employed already in Denmark. We are also going to other Nordic countries, and we have fantastic people in our commercial organization, and we are expanding and expanding. We are in great discussions with Eisai, and we'll tell you more when we have come further in those discussions. Okay. there isn't a... 'Cause I think in the release, there was under circumstances you will be able to commercialize. It's basically if you have recruited all the people, you will commercialize. Is that right? That's definitely our plan. Yeah. Okay. Definitely. Okay. Thank you. Please state your name and company. Please go ahead. This is Samir Devani, Rx Securities. Can you hear me? Yes. Hi. Hi, Gunilla. Hi, Jan. Congrats on a great quarter. I've just got a few additional questions. Does your guidance assume that you undertake any clinical trials this year? I'm just particularly thinking about BAN0805. I guess that's the first question. Second question is on BAN1503. It's great to see that now identified product candidate identified. Is it fair to assume that the earliest you'll probably see a clinical trial there would be 2024? Then my final question is just on the Gaucher disease BT product. Is that using the full enzyme or is it a truncated enzyme that you're using there? Thanks very much. Thank you so much, Samir. That was three great questions. The first one with BAN0805, our alpha-synuclein program in Parkinson's disease. We are just now discussing what is the best way forward, and we also are in discussions with potential partners. We will see which approach will be the most wanted way going ourselves or going with a partner. That's a little bit too early to say. I think, I mean, I really would like this program to go forward because I think it can help Parkinson patients. Of course, it can be Parkinson, it can be also other indications. Then I think your next question was regard to BAN1503, where I think it's very reassuring to see that our Pyroglu program has progressed so well. We think it's clearly differentiated from donanemab, and we have now selected one compound as a candidate drug. We have also seen that we would like to combine this with our BrainTransporter technology and drive that program forward as quickly as we can. I think that your progression on 2024, I think is you will have to wait a bit longer because it will take longer time before that goes into clinical trials. I will come back more with more guidance at a later stage. Your last question was about Gaucher disease, and I'm not prepared to discuss details about exactly. What I can say is that we are going for an enzyme replacement therapy where we are combining that with our BrainTransporter. Okay, that's great. Just maybe one follow-up. I can say back again, if I'm just thinking about one more thing about BAN0805, I mean, what we are doing, we're not just sitting and waiting. We're doing a lot of things to prepare for progression towards phase II with a different kind of biomarker work and so forth. We are soon we have got everything back from AbbVie. That is a lot of work, and we are writing the report of the first clinical studies and so forth. A lot of work is ongoing. If I just reflected, maybe I sounded like 0805 is just sitting on the shelf. Definitely not. We are working a lot on this, and we are preparing, getting everything back from AbbVie, also preparing for progressing it towards phase II. I hope that responded your three questions. Yes, that's fully understood. Just maybe one follow-up on 1503. Just to be clear, Eisai doesn't have an option on that drug, does it? It'll have to do a different, separate deal with you to get access to that. Yeah. Yeah. Yeah. Absolutely. 1503, that's BioArctic. Yeah. Okay. That's great. Thanks very much. Thank you. The next question comes from Patrik Ling from DNB. Please go ahead. Hi, guys. thanks for taking my questions. Most of them have been answered, but, the first question is really if you have any early feedback from Eisai, what is happening on the U.S. market now since they started the launch, 23rd of January? Thank you so much, Patrik. I think what we can say is that we are really happy to see how well Eisai has prepared everything with regard to the market and made it available. It's already available. We know patients are being treated, from the launch part, and we are looking forward to their webcast on Monday, where they will most likely reveal more information about it. I will not reveal anything more than we are happy that it's already on the market and we know patients are being treated. Could I ask, I mean, if a patient elect to pay for the drug themselves, will they also have to pay for the MRI scans that you need to do? I think that is, what Eisai has done, I mean, they put together teams who are helping the patients to understand exactly, how things, what has to be paid for and things like that to see how could this be afforded. I think it is an issue before it's broader, reimbursement in the U.S. We are eagerly waiting for further discussions between CMS and so forth and Eisai when we have got a traditional approval. Until then, I think it's quite costly for patients, who would like to have access to their treatment. We should be aware that we should expect a slow uptake until we have a full traditional approval and a better reimbursement in the U.S. You're right, they have to pay for a lot of extra things. Things that normally, if you're living in Sweden, I mean, you get diagnostic parts and so forth through our caring situation, and it's different in the U.S. Great. Lastly, could maybe you can remind me what the mechanism of action was for the AD-1803 that you terminated during the quarter. The AD1801 that was the project that was linked to ApoE. Was it the truncated ApoE? No. Oh, yeah. I mean, It was fragments towards ApoE. Okay. Yeah. the truncated Aβ, the Pyroglu program- Oh, sorry. Yeah. that did well. That is now CD nominated and has a brand, 1503, and now combined also with the BrainTransporter, which I'm very excited about. It's a lot of numbers to learn now. I know. So, just so I got it right, the ApoE fragment project, that's the one that you've terminated, right? Yes. Yes. Okay, great. Good. Thank you. Thank you very much, Gunilla and Jan. That's all for me. Thank you, Patrik. The next question comes from Fredrik Thor from Redeye. Please go ahead. Hello, thank you. My first question was about the milestone payments. Can we expect the payment for the approval in the EU and Japan? What we have said, I mean, is that our milestones that are remaining are linked to regulatory approvals. I think that, yeah, you are absolutely right there. Okay, good. You also mentioned that the operating expenses will increase, of course, given the pre-launch activities in the Nordics. Can you guide us a bit on, will it be a gradual increase, or should it take the expenses to increase mainly in, for example, H2 or Q4? Sorry, could you repeat that question? I couldn't hear it. yes. You mentioned in the report that expenses will increase in 2023 due to... Yeah. the pre-launch activities in the Nordics. Can you guide us a bit on will it be like a gradual increase over the year or mainly like in Q4 or H2, for example? It will be, it will increase over the year, likely. Okay. I mean, since we will be expanding the commercial organization step by step into other Nordic countries and so forth, I think you could expect this year some gradual increase. Yeah. Yeah. Okay. Maybe a final question. I think you maybe touched a little bit, but the timeline in the U.S. for the full approval, when is the earliest you believe that you could get fully approved lecanemab in the U.S.? Yeah, I mean, that's difficult to say. If I just explain the normal kind of process, and then everything can go faster. The process is like when you have submitted an application to the FDA, they have up to 60 days to say if that application is acceptable, if you have everything in there. If they confirm then that it's complete, then they also will respond if we get priority review or standard review. If we get priority review, which we had last time, then it is up to six months from that they will then re-respond if we get an approval or not. Then they will set the PDUFA date. If we get a standard review, then it is 10 months instead of 6 months. Of course, if it could be a potential for a faster process since it has been a rolling submission and they have already made an accelerated approval. What they have to review is mainly the phase III data. Of course, phase III is a lot of data, so they need that time of course to go through that. I think I laid out what you could see as the normal process, so to say. Yeah. That's all for me. Thank you very much. Thank you. There are no more questions at this time, so I hand the conference back to the speakers. Thank you, computerized voice. This is. We have a few questions online, Gunilla. I'll read them to you and let you answer. First one comes from Stefan Quiberg. Was early AD diagnosed? I'm assuming this is for the study. Was early AD diagnosed either by PET or CSF? If so, was the outcome different for either or is CSF more sensitive than PET? Fantastic question. Thank you so much, Stefan. In the Clarity-AD trial, the patients could do either amyloid PET or CSF sample in order to be identified to be suitable for the trial. I think both of those tests are very good in identifying the right patient because what we would like to know if the patients have amyloid pathology. Both of those tests are very good. They are coming with some pros and cons, both of them. CSF are a little bit more sensitive, so you can pick up changes at an earlier stage, and the PET scan can show different regions in the brain. I think both of them are very good. In this stage, the most of the patients were diagnosed by amyloid PET and some by CSF. It doesn't matter for the inclusion because, I mean, both of them are very good ways to identify the right patient. I think that was the response. Thank you, Gunilla. We'll go on to the next question that's by Peter Herrmann. Can you elaborate on the further development of BAN0805 against Parkinson's disease, please? I think you mentioned some of it. Is there anything you would like to add there? No, I think that I already responded to that question, that we're working a lot at the moment in making sure that we get everything back from AbbVie and writing the clinical report, preparing with biomarkers and so forth, to progress into the next stage. Meanwhile, we're also discussing with some potential partners. We will see which way is the best for BAN0805 and BioArctic. Thank you. Next question comes from Teodor Fagerlund. What can we expect from BioArctic in terms of milestones going forward into 2023, 2024? When will lecanemab become available in the market or to the public? Maybe you can just add some flavor there on the different regions. Thank you so much, Teodor. Great questions. We, as I said, we have just got EUR 35 million in milestones that we are eligible to, and we'll get them during the first quarter of this year. We have remaining milestones linked to regulatory submissions in the larger regions. That could potentially happen later this year. You mean regulatory approvals? Approvals. Thank you. Then, we also have some milestones linked to sales and marketing, which could happen this year or more likely next year. When does lecanemab become available to the public? This is different in different regions. lecanemab is already available in the U.S., but on a very limited basis because of limited reimbursement. It is available, and we hope that it will be broad, more broadly available, if we get a full approval and better reimbursement from CMS. That we have to wait until later this year to see how that progress. When it can be available in Japan, Eisai has said that they expect a potential approval later this year. In Europe, if you think about how that process looks like, I think it's realistic to expect that could be an a potential approval during the spring next year. Then you also need to negotiate the price and so forth. In Sweden, for example, I think next year could be likely, if everything progress well. I hope that responded that question. Thank you, Gunilla. We have a fourth question as well, and that's the last one we have in the line queue right now. It's from Bertrand Delsuc. "Hello, can you say when we would have more data from the SC subcutaneous formulation of lecanemab? Thank you so much. Our partner, Eisai, is working diligently on the sub-Q formulation in order to help patients with good alternatives for feasibility. They've already shown some data on this at previous onsite congresses, they have it now being evaluated in the open-label extension study to the Clarity AD trial. What they also have said is that they are working hard on a regulatory application about a year or so later after the first full application. I think we will have to stay tuned and see, but I think they are doing everything they can to help this in the best possible way. Of course, they need to have interactions with regulatory authorities and so forth before we can comment anything further. Thank you. I think that was the last question online. Computer voice, do we have any additional questions in the queue, telephone queue? There are no more questions from the telco. I think, we, thank everybody for dialing in, and that concludes this Q4 call. See you back in Q1. Thank you.