BioArctic AB (publ)

Good morning and welcome to Biotic's presentation for the second quarter of 2023. I'm Gunilla Osvald and I'm the CEO of Biotic. And I will share today's presentation with our CFO, Anders Martin Lööf. I think it's very exciting times for Biotic. It can be now granted full approval by the FDA last week and with CMS announcing a broader reimbursement. It's the beginning of a new era. And Biotic is behind this true breakthrough in the treatment of Alzheimer's disease. We can now help a large number of patients and their families. And I think that is extremely gratifying. And of course, I will talk more about Lecambi here today. Next slide, please. Biotic is listed at Nasdaq Stockholm Large Clap since January this year. And this is our disclaimer. Next slide, please. Lycambi is the trade name for leucanumab and that was approved last week in the US. And that means that Lycambi is the world's first fully approved disease modifying treatment for Alzheimer's disease. On the 9th of June, the FDA advisory committee had a meeting where they at the end voted and enormously confirming the clinical benefit of Lycambi. The advisory committee reviewed the efficacy data, the biomarker data, and the quality of life data, as well as having a thorough review on the safety data. The efficacy data are consistent across scales and across items in the phase three clarity AD study. It showed a reduction of the progression of the disease and slowing of cognitive as well as functional decline by 26 to 37%. The safety data was discussed in detail, in particular with regard to the side effect area, which is a class-related side effect. Dr. Sharon Cohen, she presented health-related quality of life data from both family and patient perspective with 38 to 56% less impairment after 18 months treatment of leucanumab. This underlines the ability of leucanumab to help patients to function independently for a longer time, And that could mean, for example, that patients are being able to dress, take care of family finances, feed themselves and participate in hobbies and activities of interest. The clinically meaningful effect of the can be was emphasized in this early and broad patient population that was included in the phase three trial. On the six of July, FDA granted AFI, a traditional approval for Lecambi for the treatment of Alzheimer's disease. This means that the previous approval, which was an accelerated approval, which was based on biomarker data from the Phase IIb trial, was now converted into a full approval based on the confirmatory Phase III clarity study verifying the clinical efficacy of Lecambi. If we compare the label from the accelerated approval to the full approval label, the main difference is the inclusion of a boxed warning for monoclonal antibodies against aggregated forms of amyloid beta, including lecambi. The warning specifically relates to the side effect area and the increased risk for homozygotes of APOE4 allele to create a foundation for patient and physician to have a good dialogue regarding risk benefit. It's quite common that new kind of treatments receive box warnings. And if we think about those that received an approval last year for first in class treatments by the FDA, more than 40% of them had a box warning. And I think this is very good, and I think it supports a responsible and informed introduction of Lecambi into the U.S. market. Teresa Boraccio, who is the acting director of the Office of Neuroscience in the FDA's CDAR, she said in the press release last week, Today's action is the first verification that a drug targeting the underlying disease process of Alzheimer's disease have shown clinical benefit in this devastating disease. This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer's disease. On the same day, CMS announced that based on the full FDA approval, Medicare will now provide a broad insurance coverage of Lecambi. And that is for all patients that are eligible according to the FDA approved label. Provided that a real world evidence is collected in an available easy to use patient registry. And the items to be registered are those that normally would be entered into medical records. So I think the burden of data entry is expected to be small. And I think it's extremely gratifying that Lecambi, which is originating from biotic, with Professor Lars Lampfeldt as the inventor, now can be helping many patients and their loved ones. Next slide, please. So Lecambi has the potential to become the first disease-modifying treatment for Alzheimer's disease. and to receive a full approval on a global level in all three major continents. It has already happened in the US with the FDA providing a full approval of Lecambi last week. Reimbursement is of course also important, and the Veterans Health Administration decided earlier this year to provide coverage for veterans with Alzheimer's disease. And now Medicare, which is the major insurance part, in the US. It's also covering Lecambi on a broad level. ASI is also exploring less frequent maintenance dosing and evaluating a subcutaneous administration by an auto injector and they plan to file first quarter of next year in the US. Lakembi is now also in a regulatory review process for a full approval in many other parts of the world. The next one to think about is Japan, where Lakembi has undergone a pre-review process of data during last year. And ASI submitted a full application in the beginning of this year to the Japanese authorities. And the application has then also been granted priority review, and ASI is expecting a response in September this year. In Europe, ASI submitted the MAA 9th of January, and that was based on both Phase 2b and Phase 3 data. And the application was accepted 26th of January, and it's now following a standard review process, and the response is expected first quarter next year. In China, ASI has initiated the application process in December last year, and the priority review designation was provided in February, and we are awaiting response in China by the first quarter of next year. Regulatory process is also ongoing in other parts of the world, for example in Canada, Great Britain, and South Korea. I want to compliment our partner ACI for their dedication and hard work with the clinical studies and the regulatory processes in such a timely way. I think this is very important since every day matters for the patients. Next slide, please. And if we reflect a little bit on the population of patients with early Alzheimer's disease, it is enormous. ASI has guided and estimated that the global prevalence for future early Alzheimer's disease could include about 240 million people by 2032. Of which then about 75 million of those people are in Americas, EMEA and Japan. But of course all the patients will not be treated by disease modifying therapies. The patients first of course need to come to healthcare and they need to be diagnosed with mild cognitive impairment or mild Alzheimer's disease with confirmed amyloid beta pathology in order to be eligible for a disease modifying treatment. Even if only a proportion of all patients with early Alzheimer's disease will be treated it's still a huge opportunity. And more and more patients could potentially be treated if we work on some of the challenges. ASI has estimated that approximately 3 million patients will be treated with disease modifying therapies by 2032, which is a lot of patients. There are several opportunities that could increase access, and some of them are listed to the right. We could, for example, work on increasing patient awareness, especially on the mild cognitive impairment part, which is not diagnosed so well yet. But now when there is a treatment, it's more focused on that as well. Also earlier signs of the disease and working on less stigma for Alzheimer's disease patients. Education or primary care on both diagnosis and biomarkers and treatment options. So they can refer the patients to specialists. Access to specialist care is, of course, also important to try to facilitate. And it's important role for the memory clinics to make sure that the right patients get the right treatment. Parts that are linked to that is, of course, confirming pathology with CSF or amyloid PET, following treatment with MRI. and ensuring access to infusions and so forth. Improved diagnostics is an important part and it's really reassuring to see how well the blood-based biomarkers are progressing in parallel with the treatment options. And the subcutaneous formulation is another important opportunity to increase access and make the administration more convenient by getting the treatment and also make it possible to get the treatment easier and at home. And we are working with our partners on all these aspects for the benefit of the patients. Of course, we would like as many patients as possible that could benefit from Lecambam to be able to get access to the treatment. ASI has forecasted that 10,000 patients will be treated by Lecambi at the end of first quarter next year. If we think about what that means with regard to the US Alzheimer population of approximately 6.7 million, that's about 0.15% of the Alzheimer population in the US. So I think that we can conclude that there is substantial room for growth and that Lecambi can be a treatment of major importance. Next slide, please. We are very happy about our long standing and successful partnership with ASI all the way back since 2005. And we have two license deals and several research collaborations with ASI. So far, we have received 35 million euros in regulator milestones from ASI this year. And we have another 101 million euros still remaining in milestones. if Lekanma continues to progress well. And that is mainly linked to regulatory approvals and to sales and marketing milestones. The next potential milestone would be related to regulatory approvals in Japan and in Europe. Biotic is also entitled to royalties of high single digit percentage for the first 10 years following launch and mid single digit percentage for the following five years on a country by country basis. I think this is of substantial value for Biotic, and it could be a blockbuster potential of leucanumab, which means that we could see revenues of more than one billion US dollars per year without having any cost for the clinical program in Alzheimer's disease and very limited costs for commercialization. Biotic has also retained rights to other indications and to market in the Nordics. And we are now preparing for that and very much looking forward to doing that together with ASI. Next slide, please. Leucanumab is, of course, a key project for Biotic. But I would like to emphasize that Biotic is more than Leucanumab. Alzheimer's disease is our largest area. And for Leucanumab, we have one more additional large phase three trial, which is ongoing in even earlier phases of Alzheimer's disease. So even before the symptoms appear. And even if it's the first step with the disease modifying treatments, which will be successful, there is still a large medical need for more treatment options and for combination of therapies. So therefore, it's important that Bioartic and many others continue research in this area. And we have four early disease modifying programs, including two of those that are combined with our brain transporter technology. We have also two of the four projects that are targeting truncated forms such as pyroglue A-beta. And that one of them is combined with our brain transporter technology. Based on Biotics positive phase three results, I think that the probability of success has increased in our other programs with similar approach when we are targeting the toxic soluble aggregated forms of proteins that we call oligomers or protofibers. In Alzheimer's disease, the proteins is amyloid beta, and in Parkinson's disease, the protein is alpha-synuclein, and in ALS, the protein is TDP43. I also want to mention that I think that our ALS program targeting TDP43 is progressing very well and quickly, and that is thanks to our technology platform and our vast experience from Alzheimer's disease and Parkinson's disease projects. We're also working on another rare disease, Gaucher disease, with an enzyme replacement therapy with the aim of also being able to target the CNS symptoms of Gaucher disease. And this is an unmet medical need today. And this is a rare disease indication. And then finally, our brain transporter technology, which I think is a very exciting part, is progressing really well. And it's now in preclinical development phase. And the brain transporter technology has now been included in projects in all our disease areas. And in the future, if it continues to progress well, our brain transporter technology could also be applied to other companies' antibodies or proteins on non-exclusive license basis. As I said, I think leucanumab is, of course, very important for biotic. But I want you to remember that biotic is more than leucanumab. And our portfolio is progressing really well. Next slide, please. And by that, we come to the financial summary and I will hand over to our CFO, Anders Martin Lööf. Next slide, please.

Thank you, Gunilla. If you start looking at the left hand side on the revenues graph, you see that our net revenues for the quarter were 3 million. But for the first half of the year, our revenues were 397 million. And that is explained by the three milestones that we received in the first quarter, totaling 35 million euros. And as Gunilla pointed out, we are entitled to one further milestone that could occur later this year if we do see approval in Japan that is forecasted for September by ASI. Over time, our revenues will become less lumpy as we now are receiving royalties after the launch of Lecambi. However, it will take some time before those revenues actually will become larger than the milestone payments. And just as an example, Gunilla mentioned that ASI are forecasting to have 10,000 patients only can be at the end of the first quarter of 2024. And if we would have 10,000 patients on average during full quarter, that would generate in the ballpark of 50 million Swedish kronors for that quarter. You should not see that as a forecast for the first few quarters of next year, but that gives a hunch for when do we expect to see significant royalties that are at par with the milestone payments. If we then turn to the midsection, you see that their operating expenses increased from 50 to 104 million in the second quarter, and they also doubled for the full six-month period, going from 98 to 200 million. That is mostly driven by increasing personnel costs that increased from 23 to 72 million in the second quarter. However, that is primarily driven by non-recurring costs for stock options and related social security contributions, and also by a repurchase that was made from Gunilla. So if you take away that, the increase of 48 million in personnel costs during the quarter, of the 48, roughly eight were driven by increasing staff. The rest were these non-recurring costs. However, over the longer term, our costs will continue to increase due to the build up of our commercial organization and certainly when we progress our project portfolio further. But they will not increase in the second half of the year. We still reiterate our full year guidance of 330 to 380 million of operating expenses. So you see that the costs are expected to decrease during the second half of the year compared with the first half. If you then look at the right hand side, you see that operating loss was 101 million for the second quarter, but we made a profit of 200 million for the first half of the year. And if you then combine that with our full year guidance, you understand that we should have a possibility to be profitable for 2023, even without an expected approval in Japan. If we then turn to slide 10, starting with the mid-graph, you see our cash flow. That was a negative 64 million in the second quarter. But all in all, for the full six-month period, it was a positive 235 million. And that's roughly 35 million better than the operating profit. And that is mostly due to the fact that the costs that are recorded in the operating profits are, to some extent, non-cash costs, especially the stock option costs. If we then look at the left-hand side, you see that we started the year with 805 million in cash, and we're currently at 1 billion 42 million. And we'll see when we end up towards the end of the year, if we get an approval in Japan, I believe that we will be above 1 billion Swedish at the end of the year. And on the right-hand side, you see the net result. We made a loss of 102 million for the second quarter and a profit of 192 for the combined period, January to June. And the decrease from the operating profits is mainly explained by a tax recorded of 20 million in the first quarter of this year. That concludes the financial section and I hand back to Gunilla.

Thank you so much Anders. And now we come to the upcoming news flow and closing remarks. Next slide and slide 12. So more data on Lekanumab will be presented at coming Alzheimer's disease congresses. And the next one is next week in Amsterdam. And there will be several presentations of Lekanumab. And you saw more details of that in the press release that was issued this morning. And then the next congress after that is CTAD in Boston in October, where there also will be several presentations on Lekanumab. The regulatory process continues and ASI expects response from the regulatory authorities in Japan in September and in Europe and China responses during first quarter of 2024. We will of course provide more information on other parts of the world when that is relevant. So I think that we can conclude that we had a fantastic first half of this year and that we have a very exciting time ahead of us. Next slide please. But I would like to conclude by saying that Biotic's aim is through world leading innovative research to create drugs that improve the lives of patients with neurodegenerative diseases. And we can conclude that Lekembe, which is originating from Biotic, is now the world's first and only fully approved disease modifying treatment for Alzheimer's disease. And it's leading a padding shift in the treatment of Alzheimer's disease. I think that Biotic is an innovative and dynamic and very exciting company with a huge potential. So by that, I say thank you for your attention, and we're happy to take some questions.

Operator, are there any questions?

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 Frederick Thor from Red Eye. Please go ahead.

Hello and thank you. My question was a bit, you mentioned this a bit maybe, but Do you have an update on how royalty revenues will be recognized? Will it be the same quarter as the sales or will it be with a delay?

So I should answer that. Yes, we will record the royalties based on the actual sales of each quarter going forward. And ASI will report the sales and then we will issue our reports after ASI. So you would see that. the sales figures for Lycambi first in ASA reports, and then you can basically deduct our royalties from that.

Perfect. And my next question was a bit about how Lycambi is purchased. You mentioned a bit here that basically the 10,000 patients you mentioned, yeah, a deduction for that would be that it would be recognized, the purchase would be on a monthly or a quarterly basis, but I was just wondering if you can elaborate a bit on how kind of the the pharmacies or how they are purchasing the Camby. Is it in bulk or continuously?

Well, they probably buy some stock, but not much. So they're basically buying continuously. So for your modeling, I would just assume that they're buying continuously. Thank you.

And maybe a final question was a bit on BAN0805. Is there any progress on On the partnering discussions, for example, is it reasonable to see any progress this year?

I think with regard to our Parkinson's program, we are preparing for phase two. We're doing a lot of work and we are reviewing to see which is the best way forward, if that is to drive it ourselves. into phase two or if it is with a partner. So we will come back with more information later this year if we have more information then.

Okay, thank you. That's all for me.

Thank you Fredrik.

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

Hi, good morning. Just a few questions for me, please. First, I mean, we saw some changes in ASI when it comes to the head of Alzheimer's disease. Maybe you can give us some clarity with that, if that have any implication for the further development of Lekembe, or do you have any more color on why that happened now, one week after the approval?

So I think first of all, I would like to say that we have a great collaboration with ASI and with many different people at ASI. And Ivan Chang was the head of Alzheimer's disease in the US. It was just announced that he will retire and be replaced by the son of the CEO. And this is a family owned company. I think by putting in the son, it shows how important they think this is with the Alzheimer's disease. So, of course, I personally will miss Ivan, but there are many other very important people in ASI doing a tremendous piece of work. So I'm very confident that ASI will drive this program forward in the best possible way. So I'm sad, but I'm not worried if I put it like that.

OK, great. Could I also ask when it comes to The other potential indications for Leukemia are the ones that ASI do not have any rights to. Maybe you can update us a little bit what is happening there on your side first and whether you're having any discussions with ASI if they are interested in actually taking the full rights to Leukemia in one way or the other.

Excellent question. Thank you, Patrik. So just as you said, bioartic still owns other indications, and we have been looking into several different indications. What we have communicated so far is, for example, Down syndrome and dementia. Now we're looking into a couple of other indications that might be even more interesting and important. And we are doing some ex vivo work to see that leucanumab is the right treatment for that. And then, of course, we will be discussing this with ASI. But I think the first very important part was to see that Alzheimer's disease, which is a huge indication that that's not disturbed in any way. So that was the first step. But of course, we are working on the other indications and we'll start to discuss that, of course, with ASI first. But otherwise, there are other opportunities with other partners in the future. potentially. So we have to be patient and see, but now we are really happy about the Alzheimer's disease to start with.

Great, great. Then my last question, when it comes to your own sales and marketing in the Nordic regions, I mean, you always say that you will sell and market the product in collaboration with the ASIC, so maybe you can give us some some clarity on exactly how that collaboration will work in the Nordic, what you will be responsible for, what ASI will be responsible for etc.

So we have a great collaboration with ASI both in Japan and in the US and now we're also building a great collaboration with a European organization where and of course we will benefit a lot from all the great work on the global level that commercialization aspects for Lekhanomab and Dikembe is being done. Then if we come more, so a lot of interactions on global level, a lot of interaction on European level. And now we are working also very close with the Nordic organization. And discussions are ongoing exactly on who will be doing what and how. And we will come back to that when we can. And what I can say is that we are building our organization stepwise. We have started with the strategic positions and the more field based key account managers and so forth, they will be later on closer to a hopeful registration. But so now it's really, I mean, a building of the strategic positions and we have built positions for the Swedish market. We have also a couple of people now in Denmark. We have a couple of people in Finland, and we have just recruited a first person in Norway. And we have also built biotic as a subsidiary in the Nordic countries. So we're taking this stepwise in order, but there is a lot to do in order to help healthcare and society to be ready. because this is a new kind of treatment, a disease modifying treatment that does not exist yet on the market. And it's for a new kind of population. We go earlier than normal, ordinary diagnosis today. So we also go into the mild cognitive impairment, which is a new kind of diagnosis and then it also requires some infrastructure so there's a lot of work to prepare that we have started to work together with ASI and work with the society in order to make a really successful launch in Europe which is our aim of course.

Great. Then just to follow up, could you say anything about how the financials in the Nordic region will work?

The only thing I can say is that it's not royalty-based. I mean, it's based on that we will be doing the commercialization together. And exact details, we have to come back to later.

Okay, great. Thank you.

Thank you. The next question comes from Victor Sundberg from Nordea. Please go ahead.

Yes, hi, and thank you for taking my questions. I have three if I may. So I had one on the brain transporter technology. I noted here in the quarter that Biogen exercise is option to develop and commercialize Denali's antibody transport vehicle program based on the previous collaboration that was formed in 2020. And based on the fact that your technology, as far as I can see, is also based on latching onto the transferring receptor, I wondered if you could perhaps map your program on top of Denali's progress. If you think that you're also on the same development stage as a Denali program or what is left before we can see a similar collaboration, perhaps with you and ASI or other players that are developing amyloid beta antibodies. or if you need to show some more proof of concept data before that could be materialized. I'm just trying to understand where in the timeline you are with your brain transport technology. And another question I had was also on the timeline for CMS covering more than one PET scan in conjunction with amyloid beta antibodies. Still, to me, at least, this remains a bit unclear. I don't know if you have got any more indication when a more generous reimbursement policy for PET scans could be implemented in And a final question I had was also if you plan to provide financial guidance on net revenues perhaps next year as you probably record more substantial royalty income going forward as you mentioned today here. Thank you.

Thank you so much for great questions Victor. I'll start with the first two and then hand over to Anders for the third. So the first one was with regard to brain transporter and in that area It's a very, very hot area, of course, to get antibodies and proteins coming better into the brain. And there are two companies who are in the lead here when you think about transferring receptor facilitation. And that is Denali, as you mentioned. It's also Roche. And we have recruited people both from Roche in Basel and from Denali in San Francisco. they are working on on they and many others we are investing in this area and we think that we have something which is really competitive versus those who are in the league right now um and but of course denali and roche are ahead but we think that we um the same way as in the amlog beta field we have something which is coming a bit later but that we think is is hopefully better And the timeline here is that we are in preclinical phase. And we have now combined it with the programs in all our different disease areas. I think it's fair to say that it's our Alzheimer's programs who are the most advanced among those. And we will come back with more information when we have that as possibilities. But of course, I mean, this has huge opportunities to be combined with many different programs. And I'm very excited about the future here. But sorry, I can't give you any more exact details here. And with CMS and the PET scan reimbursement, I wish I knew more. But what I can say is I know that there is a lot of pressure on CMS and requests. that they should start to reimburse the amyloid PET scans on a broader base since they are one of the important ways to diagnose the patients and show that they have an amyloid pathology. There are other ways for example with the CSF sampling and so forth but so far we can just hope that they soon will do the reimbursement on a broader way and there as well. And then for the financial guidance I hand over to Anders.

Right now so of course it will be very hard for us to guide on the revenues for the royalties without proper guidance from ASI and we don't know when they will start guiding on only can be revenues So for us right now, we can't really tell when we will be able to guide on our royalty revenues.

Okay, thank you very much. Thanks.

Thank you, Victor.

The next question comes from Eric Hultgaard from Carnegie. Please go ahead.

Hi there. Congratulations to the full approval and the broader coverage from CMS. I have one question more to add, and it's related to the market access in Europe. So what do you expect in the Nordics in terms of reimbursement, pricing and reimbursement, and also in the top five markets? What timelines should we think about as we approach the European approval. Thank you.

Excellent question Erik. Thank you so much. So I think that as you know market access in Europe is really country by country and it's very different among different countries. So without any specifics to Lekanema, what normally happens is that countries like Germany and Austria are very early on with regard to the launch, whereas other countries take different long time. And even though we hope the Nordics should be as quickly as possible, it will be a bit later, of course, than Germany. So I think we will just have to take it step by step. And it's really important to have the dialogues with regard to the reimbursement parts. So I think it will be stepwise, different country by country in Europe as normal. So we'll see. We'll come back with more information when we have it.

So it's sort of like the standard six, 12 months in sort of the major market? Yeah, I don't think we have any.

Yeah, I don't think we have any information about that. We should be anything else than the standard times. So we'll see. And then I think what no one knows is UK. and Great Britain with their new process and how that will work with regard to regulatory. But then we know NICE takes time if you think that UK is also one of your five big countries.

And then maybe I can sneak in one for Anders as well on the marketing infrastructure in in the Nordics and how you think about facing costs. So when do you anticipate to sort of add sales reps and the bulk of cost? Is it post-European approval, post-reimbursement or at what time point?

If I'm to guess today, we would like to add our key account managers ahead of the launch. But not by much. So we will know better during next year when we start to see what's happening on the reimbursement side, when we can actually launch the product. So right now it's hard to tell. I don't think that we will add more sales reps in the first half of next year. So some time point after that, but hard to tell exactly when.

Definitely post approval for the key account managers. Definitely, yes. But then more strategic positions before that.

All right. Thank you so much.

As a reminder, if you wish to ask a question, please dial star 5 on your telephone keypad.

There doesn't seem to be any more questions in queue by telephone, Gunilla and Anders, but we have a few questions online that are posted. Maybe I can just sneak one of those in because then I saw Joseph is coming on. So there are two questions regarding the subcutaneous development by ASI, wondering a bit about what kind of level of data is required for such a submission. Gunilla, is that anything you can comment on?

Yeah, I think that's a great question. And of course, patients for patients, we really would like also to be able to provide a subcutaneous administration. And they say it's also working on this together with an auto injector to make it very convenient for the patients. And what has been done is a couple of phase one studies to show the bioavailability level. And now it's being evaluated in the open label extension part. of the CLARITY-AD study. And in that extension, ASI has also informed that there are both patients that have been coming from the CLARITY-AD study who have been on IV infusion previously with leucanumab and those who also have been on placebo. So they are kind of newcomers. But there is also some de novo patients in that part. which will be included in the evaluation of the subcutaneous formulation. So that is expected to be what is needed for sub-Q filing for the U.S., which ASI has guided that that is expected to happen the first quarter of next year. So that was the answer to the sub-Q.

Thank you. I'm not sure if we're going to go to the question Q now with Joseph Hedden, maybe, operator.

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

Hi there. Thank you for taking my questions and congratulations on the full approval. I just wanted to ask a few, perhaps the first one, around the online portal that ICI have been talking about for the Medicare coverage with evidence development. I've said that it's a relatively easy to use portal and that it's relatively standard patient information, takes five minutes. I just wondered whether you'd seen it and what your thoughts are on that.

Thank you so much, Josef. Of course, everyone is eager to understand more details about this online portal that Medicare is providing. It's free to use and it said that it should be easy to use and with the same kind of information that you normally assemble anyway. And that it should take between five and ten minutes to do the recording. I, as the curious person, tried to log in, but I was not allowed in since I'm not a physician in the U.S. So I don't know the details really more than what I just said.

Okay, okay. And then perhaps, ISO's got a target of 10,000 U.S. patients, it seems, by the end of their financial year, so March 24th. I was curious as to how did that fit with your internal forecasts? What's that relative to your thinking?

It's really hard for us to make internal forecasts without thinking about ASIS forecasts. They are very much in line with ASIS forecasts. I think it's important to note that 10,000 patients, as Gunilla pointed out, that's some 0.15% of the Alzheimer population. There is plenty of room to grow from there. There are question marks. How fast will it be to introduce this new product since you do need the infrastructure for PET and MR and infusion centers? We think that will be sorted out. Longer term, the market will be huge. But for the first six months or so, it's really hard to estimate how quick the uptake would be. So it seems ASA has made a fair assumption, and it's hard for us to make any better assumptions because they are the ones who are on the ground and have estimated this. They have mentioned that they have educated already 1,200 physicians that are ready to prescribe the drug, that they've educated 700 infusion centers. So that would probably mean that they can start prescribing right away. But on the other hand, getting all these infusions going, performing all these MRIs and PET scans is only going to take some time. So we'll see what happens, but our expectations are in line with ASA's expectations, basically.

Okay, okay, that makes sense, thanks. And then perhaps just one on subcutaneous licanumab and the AAIC presentation. I noticed that one of those presentations is on some subcutaneous data. Could you tell us if that's from the previous phase one study or is this the first data emerging from the phase three open label extension?

To manage expectations, I think it's fair to say we should expect mainly simulations and what this could mean with regard to efficacy and safety and so forth. I think that true data from the phase three trials open label extension part is expected later. So it's more from the first studies, the phase one studies, and then some modeling that should be expected.

Okay, okay, great. Thank you very much and congrats to you all again.

Thank you so much, Joseph.

There are no more questions at this time. So I hand the conference back to the speakers for any closing comments.

Thank you, speaker. I know there's another question, though, on online, which I think we should also mention. And that's a that's a question. If I've understood this correctly, there's a talking about the expiration date of patents and patent life, but also the time it takes to develop a new drug. And maybe you can say something then about. future plans for BioArctic when it comes to developing new drugs? How long will that take and when will we have other BioArctic drugs on the market to sort of take the next step as a company?

Of course, I mean it's important to realize that the development of Lekembe has taken some time. But the most important was that it's successful. And of course, for the first projects, it takes a bit of time. We still have a good time for until patent expiry with the extension, which is up to 2032. I think it's also important to know that there is the regulatory data extension time that you also can think about and the market exclusivity time, which is 12 years in the US and 10 years in Europe. So that's one part of the question as I understand it and the second part of the question is in the future what would we expect from different kind of treatments and I think it really depends on the kind of treatment. For some treatments I can think of ways of doing it faster. For other treatments I could think about being a combination therapist and so forth. So it really needs to be taken project by project. But of course, with regard to our projects, we will ensure that we do the most efficient and timely drug development programs possible for those programs. So it has to be taken project by project.

Thank you. And we have another question that just popped up here too. Let me just read it. There are important differences between subcutaneous and IV administration. It may affect the distribution in the body and so forth also in CSAF. Is there any indication that the subcutaneous will be better?

I think that's an excellent question. If we think about what has been presented previously, and we'll look forward to more presentation next week, but what has been presented previously is that the hypothesis is that it is the average concentration which really steers the efficacy. But it is the Cmax, the maximum concentration, that potentially is more linked to the side effect. And if that holds true in the clinical setting, that would mean that we would expect a similar efficacy, but a lower frequency of side effects with regard to area, for example, from the sub-Q treatment. So I think it would be very, very interesting when we have the data and we'll see if those hypotheses hold true in the clinical setting. So there are indications definitely on that. it could be better and definitely it's more convenient and it will be more of a fixed dose to everyone instead of for IV infusion it is depending on the body weight. Also with the auto-injector I think that makes it very much more convenient for the patients or caregiver to provide this. What is being studied now is once a week the dosing that is easily done for example at home. So we have to stay tuned until we have the data but definitely the hypothesis says that it could be better with regard to safety.

Thank you Gunilla. Just another question came in. Can you comment something on the AHEAD 345 study?

Yeah, the H345 study is another very exciting phase three program, which is ongoing around the world. It started in the US, but it's also in other parts of the world. And we are also hoping that it will come to Sweden soon. And it's not fully recruited. It is being recruited more and more. And this is, as you know, more of a prophylactic study where you will start to get the treatment before you have any symptoms. What you do in the screening phase is you find out that you have increased levels of amyloid in the brain. And then depending on how much increased levels you have of amyloid in the brain, you get either then randomized or coming into the A3 part of the study with a slightly lower dose. Or if you have more amyloid in the brain, you come into the A4-5 study and then you get a slightly higher dose. And this is a four-year treatment period. And it will be based on, for the A45, a clinical outcome called the PAK5 and then biomarkers. So we will come back with more information on this study also when we have more information to give. But that's definitely a very exciting study to follow as well.

Thank you, Gunilla. No further questions in the question queue. Do you want to end with a few summarizing comments?

Yeah, thank you so much for many great questions and comments. And I think that, as I said, we have had a fantastic start of this year where we are now are really changing the treatment for Alzheimer's disease based on leucanum abdicambi, which is originating from biotic. And I think it's also transforming Bioartic to a new kind of company where we will be looking forward to more stable income and with regard to royalties. And I really look forward to when the royalties are higher than the milestone. So you have to follow us and stay tuned. And thank you so much for today. And I wish you all a great summer.