BioArctic AB (publ)

And welcome to Biotic's presentation for the third quarter of 2023. I'm Gunilla Svand, 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, with Lekembe being the first and only disease-modifying treatment with a full approval in the U.S. and now also in Japan. And both these things happened during this quarter. I think it's a beginning of a new era, and Bioartic is behind this true breakthrough in the treatment of Alzheimer's disease. I find it extremely gratifying that we now can help a large number of patients and families around the world. And I'll talk more about that here today. Next slide, please. Bioartic is listed at Nasdaq Stockholm Nordkapp, and this is our disclaimer. Next slide, please. So just a quick introduction to Biotic. Our aim is to improve the lives of patients with brain disorders. And we focus on neurodegenerative disorders. We have a world-class research and development organization, and we are happy about our great collaboration with ASI, our partner in Alzheimer's disease. We have a broad project portfolio in Alzheimer's disease, Parkinson's disease, ALS, as well as the platform of delivering biologics into the brain. We are well financed, and we have approximately one billion Swedish crowns in cash. Next slide, please. I think we have had several important highlights during and after the third quarter. I think it's amazing that we have the first and only approved disease-modifying treatment with Lecambi now in the US. And that happened early July, and we got a broad reimbursement from CMS on the same day. And it has since then initiated the launch in the US. In September, Lecambi was approved in Japan, and that made Biotic also then entitled to a milestone of 17 million euros, which is equivalent to about 200 million Bioartic and ASI have agreed on leucanumab commercialization and co-promotion structure in the Nordics. And this is, of course, something we are very much looking forward to. To the latest Alzheimer Congress, CTAD, now in October, new data, strong data on leucanumab was presented from the CLARITY AD3 study and the open label extension study. And the data supports the subcutaneous administration. It further emphasizes the importance of early treatment, and it supports maintenance dosing. I'll talk more about that here today. I was also really, really excited about the transferring receptor program that was presented with us at CTAD. And I think this makes our probability of success even higher now for our own brain transporter program, which also has really good internal data. The company has also decided to start a phase 2A with Exidapnema, which is the INN name for Bano 805 in Parkinson's disease. So we should learn now to say Exidapnema. Next slide, please. So if we start to talk a little bit about the launch in the U.S., and I think the market readiness of the Cambrian U.S. is progressing as planned. I think our partner is doing a tremendous piece of work here in preparing the market. They are building a completely new market in the U.S., and it needs a lot of infrastructure. So I think we need to have a little bit of patience to understand how important this part is. In the latter part of October, approximately 800 patients were on Lecambi treatment. And our partner, ASI, they have reiterated the expectation of 10,000 patients being on Lecambi treatment by the end of March next year. So that's the same thing they have said for quite some time now. So I think it really follows the plan. ASI is working diligently to ensure access of Lecambi to patients in the U.S. And they have estimated that approximately 2,500 neurologists and Alzheimer's specialists are ready to diagnose, treat, and monitor patients with Lecambi. And that's an impressive increase from about 1,400 in June. Another great news which came in the middle of October from CMS when they decided to remove the limitation on reimbursement of envelope pet traces. And of course, this will facilitate the possibilities to diagnose the right patients for treatment in a better way. And the third important aspect is that the CAMBI has now been approved by pharmacy and therapeutic committees as approximately 60% of the top 100 integrated delivery networks in the US. And this is compared to about 10% in June. So I think there are some tremendous important steps forward that will support further growth of Lecambi towards the 10,000 patients on treatment, which is expected by the end of March next year. And on the curves, you can see that we expect this low uptake in the beginning, and then it was expected to increase more and more further on. Next slide, please. So we're now on slide six. And I want to talk a little bit about the biomarkers. And I think this is another important area where the biomarkers are developing very well. And I think that could also be important contributions for further growth of McKembe. As I mentioned, CMS expanded the reimbursement of amyloid PET tracers in October, and this will make it easier to diagnose the right patients for Lecambia in the U.S. But today, mainly it's being done through PET or CSF. But importantly, the blood-based biomarkers are progressing really well, and I think this can make a huge difference for the future. And it will make it so much easier to identify and diagnose the relevant patients to follow the disease progression and monitor treatment effects. The blood biomarkers, they can be used for triaging. And that means that if the blood test is normal, there is no need for further CSF or PET scans. If the blood test shows intermediate level, of the proteins, then they require further confirmation by CSF or PET. And if it is high levels, that shows that it's a high likelihood that the patient would benefit from Lecambi treatment. So that is another possibility. I think that the usage of the triaging with blood biomarkers is already happening now in smaller scale, and it's expected to grow during next year. And in a couple of years, we expect the blood-based biomarkers to be used in clinical practice. And this will then clearly simplify the patient journey. And that will form the basis for further growth of Lecambi. So I think this is also a very exciting area to follow. Next slide, please. Lecambi is the first and only disease-modifying treatment with a full approval in the U.S. and now also in Japan. And it's broadening and broadening around the world. If we start to look into the U.S., more things is happening there. Our partner, Einstein, they plan to submit the supplementary BLA for intravenous maintenance therapy with once a month dosing by first quarter of next year. They also plan to submit the new BLA for the subcutaneous water injector formulation. And I think that is two important parts in making it more patient-friendly and easier for the patient. If we then turn into Japan, where the approval came on the 25th of September, now the National Health Insurance is working on the pricing and reimbursement. Normally, this takes about 60 to 90 days after approval. And we know that our partner ASI is eager to start the launch and they are planning to launch imminently after the prime listing. So that is most likely happening very late this year. Then if we look into Europe and China, it's where review is ongoing and ASI anticipate approvals in the first quarter of next year. Then ASI is working diligently with further regulatory submissions. and applications around the world, has now been submitted to 10 other countries around the world. And we have got priority review and other approaches in order to make faster reviews at a couple of countries like Israel and Great Britain. I think that I'm very excited about that. Lekanamab has the potential to become the first amyloid antibody to receive a full approval on a global level. And I think it looks really promising. Next slide, please. So some of the highlights from the Alzheimer's Congress CTAD, which was held in Boston in October, that I would like to mention is, of course, things about Leucanumab. But let me start by saying that I think it was a very positive atmosphere. And there was a sense of optimism for both the diagnosis and the treatment of Alzheimer's disease. And there was a lot of highlights and strong data being presented for Lecambi. If we start with the subcutaneous treatment, which I think looks very promising, and both the pharmacokinetic and the pharmacodynamic six-month results show that it met the bioequivalence criteria, which is a very important step. And also data that was presented showed that amyloid test data showed 14% more reduction of amyloid plaques after subcutaneous administration compared to intravenous administration. So even stronger effects and with similar levels of the adverse events regarding area. And it showed that it's probably more the AUC and the average concentration, which is linked to this rather than Cmax. The other next really important part, which I think was very encouraging, was that they showed that if you start treatment with the Camby very early in the disease, then you can potentially have even better results of effect. So the data presented from a subset with patients in early stages that had low levels of the protein tau. And here they showed, and you can see that on the two graphs here to the right, that 76% of leucanumab-treated patients did not decline over the 18-month period compared to 55% of the placebo-treated patients. And 60% of the leucanumab-treated patients were even improved. And if you compare that with 28% for placebo. We should be aware that it's only small groups of patients, but it's very encouraging for patients in very early phases of the disease. So I'm really encouraged by this. And then data from the open label extension study showed that the treatment really can be continued to have an effect even after 18 months treatment. And that's pointing to the importance of continued treatment for the benefit of the patient. Professor Lars Landfelt also presented data on leucanema binding profile showing that relatively low binding to CAA are linking to the relatively low frequency of side effects compared to other anti-amyloid antibodies. Another highlight from the Congress was the external validation of the transferring the transporter concept for better brain penetration of antibodies. And I think this increased the probability of success for our brain transporter platform even further. And as I mentioned earlier, the blood-based biomarkers continue to develop well for diagnostics, disease progression, as well as treatment monitoring for Alzheimer's disease. And it's already being included in clinical practice by some leading key opinion leaders, for example, here in Sweden and elsewhere. And I think it has great opportunities for the future. Next slide, please. Now we are on slide nine. So building on the success of Alzheimer's disease, we see a lot of similarities and opportunities for our ALPHAs Nuclein Program. which is intended for neuronal synuclein neopathy. And as we can see, both leucanumab and exudabnumab are very selective antibodies towards the toxic aggregated forms of the protein. And these forms are called oligomers or protofibers. In Alzheimer's disease, the protein is called amloibica, and in Parkinson's disease, the protein is called alpha-synuclein. And in Alzheimer's disease, we have the first disease-modifying treatments that come through, with the Chembin being the first and only fully approved disease-modifying treatment in the U.S. and Japan so far. The development for Parkinson's disease and other synucleinopathies are lagging behind Alzheimer's disease, but can really benefit from some of the important learnings that we have from the Alzheimer's disease. And I think there is a lot of potential indication that it gives further opportunities for the future in both areas. In Alzheimer's disease, for example, going even earlier, Down syndrome with dementia and so forth, and for synucleinopathies, we have Parkinson's disease, and we have Lewy body dementia, Parkinson's disease dementia, and multiple systemic atrophy, for example. Next slide, please. I also want to talk a little bit now today about Exidabnema, which previously was called Balno 805, which is a potential disease-modifying antibody for Parkinson's disease and other synoclinopathies. And here we now are progressing towards starting phase two next year. And as you know, for example, Parkinson's disease is the second most common neurodegenerative disorder. And I think that when we look at our antibody and compare that with competitors, we have a unique antibody. It's the most selective antibody that I've seen. It's very selective for the pathological forms of alpha-sucline, the oligomers and protofibers. More than 100,000-fold selectivity versus the physiological forms, monomers, in the body. So I think that is one of the unique parts. Another part which I want to mention is that how we think of biotic is that If you have a clear link to genetics, that makes it a higher probability of success and a lower risk. And we have the same thing here with Alzheimer's disease as we have for amyloid beta in Alzheimer's disease. We have very strong preclinical data, as you can see up to the right, where our antibody really makes motor symptoms come much later. and makes the lifespan of this very aggressive Parkinson's disease model. They had a doubling in lifespan. Down to the right, there you see some of the phase one results. And Exedabnamab was well tolerated in all doses up to the highest dose, which was six grams, so a very high dose. we saw excellent PK profile with an elimination half-life of about 30 days, which supports once a month dosing. We also just recently had our patent granted in, well, previously US and now also Japan, where we have a patent life up to 2046, including extensions. I think that is also a really good benefit for this program. taking it forward. So if we go to the next slide, slide 11, there we see some of the opportunities for Exidabnimab in the future. The company has taken the decision to drive Exidabnimab forward by ourselves a bit longer, and we see a lot of opportunities here. But of course we would like to have a new partner before we go into phase three, but we can definitely drive it forward a bit longer ourselves. And we have now worked hard to bring back data and material back from AbbVie. We have written clinical study reports, and we are now preparing for the Phase IIa study in Parkinson's disease to start next autumn. And after Phase IIa, we have several different opportunities for this program. For example, Parkinson's disease, but also the areas where we have a lot of expertise in the dementia area, such as, for example, Parkinson's disease dementia and Lewy body dementia. So I think that's really important opportunities as well for this program. And as well as we can drive it also in multiple system atrophy. An area which is progressing really well here as well, it's like a red thread, both in Alzheimer's and Parkinson's disease, is the biomarker. And that has been one of the limitations in Parkinson's disease. But it's great to see that there is positive progress also for the biomarkers in this area as well. So there are now biomarkers coming forward, which makes it, for example, possible to identify the right patients with pathological alpha-nuclein, for example, with seeding amplification assets. And I'm really excited to see the program and the progress of Exidapnema now going forward and going into patients. Next slide, please. So, in summary, we have an innovative and balanced project portfolio with focus on neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, ALS, and also our brain-transported technology. So, I've been talking a lot about both Lecameron and Exidavnema here today, but I also want to mention that our TDP43 project for ALS is progressing really well. And for those who are really data-oriented, you can see that the program has moved one step forward in this for us, just to show the progress of that portfolio program as well. And the Brain Transporter platform continues to progress very well, and we have now increased our focus even more on our two different Alzheimer's disease Brain Transporter projects. And we are further encouraged by the data presented at CTAD together with our own data. Next slide, please. So by that, we come to the financial summary, and I will hand over to our CFO Anders Martin. Next slide, please.

Thank you, Gunilla. We should then be on slide 14. First of all, I want to comment a little bit on the sales that have been achieved so far with Lecambi in the market. We have received some questions whether we think this is according to expectations or if we think the revenues are low. But we clearly think that this is as expected, and we are according to plan or actually exceeding plans in some ways. And I will try to explain why we think so. So first of all, when the drug was launched, it takes time to make sure that the hospitals start using the drug code and get all the necessary approvals in it to make that happen. And at Gunilla, that is progressing according to plan. The number of IDNs... that are using it has increased from 10% to 60% already. But that's not enough. The patient also has to get the drug. So even if the hospital is using the drug, it takes up to two months before the patient actually can get this treatment and the sales are starting to be generated. So what should be expected is that in the first two months or so after the launch, there should be very, very low levels, very cheap patients. can get their treatment. Then in the third month, you should start to see that some patients are actually starting to get treatment, but those are basically coming from the hospitals that were using the drug from the very beginning. And then in the following months, you should start to see patients coming on from new hospitals that are starting to use the drug after the launch. So basically, what you should see are very low numbers for July, August. You should start seeing increases in September, and then you should start to see sort of a catch-up effect from October and onwards. And that is exactly what we are seeing so far. If you look at the graph on the left-hand side, you see the weekly average revenues in the U.S. And the October figure, that's the first week of October. I think the sales in the U.S. were in the neighborhood of... $0.5 million, and that's roughly 100% up from four weeks before. So we are really starting to see this catch-up effect, and we think that this will continue. Gunilla has already mentioned that all the hospitals are now coming online. We will also see the PEP reimbursement in the US being implemented in the last few months of this year. And this will also be then helped by the Japanese launch that we expect will start around year end. So we really think that we are in a positive trend. This is according to plan. And if we turn to the left-hand side of the picture, you see that ASI has set an aim to reach 10 billion yen in sales for their fiscal year 2023. That would mean roughly that they have to sell some 65 million U.S. dollars in in Q4 of this year and the first quarter of next year. And we clearly think that this is feasible. And for us, that would mean we get single digit royalties, high single digit royalties on those numbers. So I think this is all in the right ballpark range. However, it's really, really hard to extrapolate from just a few weeks to see exactly where we end up. So this should be seen sort of as a ballpark estimate rather than any guidance or a forecast. But I do think that the numbers that are set up to ASI are really feasible. And I hope you now understand what that would mean for us in the next few quarters. If we then turn to slide 15, on the left-hand side, you see our net revenues. And for the quarter, we had revenues of $209 million. And for the nine-month period, we had revenues of $605 million. more or less explained only by the milestone payments we have received, totaling 52 million euros in the nine-month period, and we received the Japanese milestone of 17 million in the third quarter. But we should also start to look at the new revenue streams that are included in our revenues now. We recorded 2.5 million Swedish of royalty in the third quarter, and we also got co-promotion revenues of 3.6 million. So royalty is, of course, the royalty on the global sales for Lecambi. The co-promotion revenues is what we are getting out of the collaboration with ASI in the Nordic for the commercialization of Lecambi here. And we are, of course, we have not launched the product yet already, but we are working together. So we are receiving some reimbursement from Marcos as we split the profit from that collaboration 50-50. Over time, these two revenue streams will, of course, be the most important revenue streams for bioarchitecture. But I would say next year, you should probably expect that they would be half of the revenues that we have in that war park range. The rest will probably be milestones. And then from 2025 and onwards, you should expect that the royalties and co-promotion revenues will make up the majority of the revenues for bioarchitecture. Turning down to the expenditures in the middle graph, you can see that our operating expenses decreased to $78 million in the third quarter from the second quarter, increased year over year. But the decrease from the second to the third quarter is mainly explained by personnel costs that went down from the second to the third quarter due to non-recurring wind effects in the second quarter due to our stock option programs. We have then reiterated our operating expense guidance, but we have narrowed down the range a little bit. So we now expect to have full year costs of 350 to 370 million Swedish kronor for 2023. It is an increase from 2022 by 246 million. And we will continue to see increases in our costs over the coming years. Next year, we will increase our R&D costs as our project portfolio is progressing really, really well. Gunilla mentioned the Parkinson project that is now entering clinical trials. For example, we're also building up our commercial organization a little bit more. I think we're at roughly 50% now, so it will continue to increase during next year as well.

On the left-hand side is your operating profit.

It was 131 million for the third quarter, and for the nine-month period, 331 million. And given that we have also then given you some guidance for cost, you can deduct that the profit for the year will be in the range of 250 million and upwards on the operating profit level. Turning then to slide 16, talking a little bit about the cash position. As you see on the left side, we have cash and cash equivalents, including short-term investments that were over 998 million Swedish at the end of September. But if you look on the middle graph, it seems like we had a cash flow that was negative 53 million, i.e. roughly 184 million below our operating profits. And this is explained by the milestone that was received from Japan. It was recorded as revenue in September, but it wasn't paid in September. So we had roughly 200 million in accounts receivable from Asia that would be received in October. So all in all, we think that the cash position at the end of the year should be roughly in the 1.1 billion Swedish range. So you understand that we will go up from the end of September position. And the net profit was 125 million Swedish for the third quarter, and 316 for the January to September period. I think it would be negative in the fourth quarter, so it will go down a little bit from that level. I think that concludes the financial part, and I will leave the work back to Gunilla for some concluding remarks.

Thank you so much, Anders. So then come to upcoming news. So next slide, please. And now we are on slide 18. So if we think about what's ahead of us, we are now looking forward to what's happening in Japan with the price and reimbursement decision that we expect in December and the imminent launch of Lecambi in Japan via If we then look at next year, then in March, we look forward to the next big Alzheimer and Parkinson's Congress called ADPD in Lisbon in March, where we expect several presentations of Lekanema. If we then look at the regulatory part, we also have some really important things coming first quarter next year, and that is the response in Europe and China. from regulatory authorities. And if we get an approval in Europe, which we hope, then we can, in the second quarter, see the first sales of the cannabinoid in Europe as well. And then for the first quarter, the filing of the maintenance dosing in the US as an S-BLA and the new BLA for subcutaneous autoinjector formulation, also planned for the first quarter of next year. But I think it's really exciting times for us, and we can conclude that we have had a fantastic year so far. And this last quarter has really been a highlight with the approval in the US and in Japan. And we have a very exciting year ahead of us. So then if you take the next slide, please, and we can then conclude. that Lecendi, which is originating from Biotic, is now the world's first and only fully approved disease-modifying treatment for Alzheimer's disease. And this is leading to a paradigm shift in the treatment of Alzheimer's disease. And I think that Biotic is an innovative and dynamic and very exciting company with a huge potential. So thank you so much for your attention and happy to take some questions. And the next slide, please.

If you wish to ask a question, please dial star 5 on your telephone keypad to enter the queue. If you wish to withdraw your question, please dial star 5 again on your telephone keypad. The next question comes from Eric Hultgaard from Carnegie. Please go ahead.

Hi there. First, congrats on the progress with the US launch of Lecambi. A couple of questions from my part, mainly related to Xtazimab. First, when and if, or do you plan to publish or present additional data from the phase one study that would sort of increase confidence in a positive outcome of the phase IIa study, including like how much of the drug is entering the brain, target engagement, and other factors that are important. Then secondly, is it fair to assume a similar design and endpoints as used in Cortina's Pasadena study, or are you considering any changes in the design including endpoints, biomarker enrichment, or sort of selecting sort of more early stage patients in the study. And then finally, could you guide a bit on what the costs will be for conducting the phase 2A study, sort of ballpark number or cost per patient estimate, et cetera? Thanks a lot.

Thank you so much, Erik. A lot of great questions. And I have to say that it's quite early days yet about the exudabnema. We should be aware the phase one program we have so far, as you know, is very good data, but for single doses. And also including some Asian patients and also including subcutaneous formulation. So all that work, we've just written a clinical report. We're working on the manuscript and working on to see when we can present more data at external congresses. But just to manage expectations, I mean, you should be aware it's a single-dose study. So the next study that we plan to do is really to do multiple-dose study in practice on patients. And we are working now hard on the design and thinking about the endpoints and biomarkers and so forth. But I think you need to understand it's a phase 2A study with multiple dosing and a shorter dosing period before we go into a phase 2B study, just to manage expectations. And we will come back to more about the design and the cost of that, I think, when we have that more nail-bound in detail.

Right. But maybe you should mention, Gunilla, that we are really looking at biomarker enrichment to find the right stations to enter the trial. And that's a big piece of news. I think that there could be a possibility for us that could improve the probability of success of a trial like this compared to all the other trials that have been conducted in parks and disease previously.

So I think it's hard to say that we're still working on exactly the design of the study. Right.

Just to follow up there, Gunilla, on that topic, I think biomarkers obviously would be a huge advance for the field. So are you planning to, how validated are the biomarkers in PDM? Are you considering only enrolling sort of biomarker positive patients, or will this try to sort of evaluate biomarkers?

So I think it's fair to say that, I mean, this is an area which is really evolving right now. And we are really, I mean, among the lead here. So we are evaluating now, especially this, which looks really promising with the seed amplification assay. As Anders said, that's a possibility to identify the right patients. And we will, of course, also see, maybe you can use it also for seeing some pharmacodynamic effects and so forth. So I think the first study, I mean, it will be more for pharmacokinetics and safety. And then we will see how much we can do with biomarkers. The next study after that, which I showed, we are discussing several different opportunities, several different indications. And here we will be guided by some of the journal readouts that will happen, but we have some really cool ideas about what we would like to do ourselves. Also, where we will be utilizing all our expertise in cognition and so forth, and really utilizing the best of the biomarkers, like Anders talked about, and other things. So I think that the next study is more for safety, PK, and a little bit of biomarkers. And then the step after that will be the really important.

And as for the cost, Eric, this is not a huge trial. It's not super, super expensive. And we haven't finalized the protocol, of course, so we don't have a fixed cost. But it will be in the ballpark range of 100 million Swedish over a two-year period, something like that.

So then you understand it's more of a safety PK study with some biomarkers. And then the study after that will be more of an efficacy study. And that would be more costly.

Okay, got it. Thanks a lot.

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

Yes, hi. Thank you for taking my question. So, yeah, also a question maybe on the alpha-synuclein phase 2 study with BAN 0805. I guess that, in theory, the idea of targeting aggregated forms where you have these 10,000-fold selectivities that you don't target monomers in systemic circulation, which I guess could cause side effects. So I just wonder, After you have reviewed the package from AbbVie, do you see that in the data as well, that it looks better than, let's say, presinacumab or synpanumab in terms of systemic side effects? And have you seen anything in terms of higher brain concentration due to the higher selectivity for aggregates? That's my first question. Thanks.

Thank you so much, Victor. Great question. And I think it's fair to say again that the first study was single adult administration. So you should not expect so much long-term effects on biomarkers and so forth. But we will be presenting more of the results. You saw the PK data looks really good, supporting further progression. The safety solubility profile was really good. And we also are looking now also into, we saw some effects on the blood biomarkers that would help us also in setting the dose for the next study. So we will come back with more presentation of data from this. But I just want to manage expectations both from Eric and from you that, I mean, it's an early study and the next study will be like repeated dosing, maybe three months dosing and so forth. before we go into the really important efficacy studies later on. But it looks very good on the safety tolerability perspective. We can go up high in dose, higher if we want to, than what we see from the competitors. And then I also want just to mention on one of the compounds you talked about, which is SOPS, had a completely different binding profile than both prasinusumab and our compound 0805 or exidabnumab. So I think it's important to realize that every antibody needs to be think about as a unique antibody. And there are some important differences you need to understand for why some antibodies work and some don't. The same thing in Alzheimer's disease as we see in Parkinson's disease.

Okay, thank you. And I follow up also on the Parkinson's programs. I just wonder what kind of feedback you have received from partnership discussions. What are people, say, hesitant about and why? They want to see more data in your program. I assume that partnership is still part of the strategy, but you have to take it a bit further on your own first. And, you know, have setbacks in vaccines and other trials, people are cautious on alpha-synuclein or is it something else? Thank you.

Yeah, no, I think, I mean, we have had quite some interest and so forth. And I think we had a really good discussion with several partners. But we see that we have a great opportunity to drive this program further, and we have the financial muscles to do that. So what we want to do, and we have some really cool ideas for the future, so we would like now to drive it forward and then by that be able to increase the value and increase interest before we get into a further partnering discussion. And we need a new partner before phase three, but there's quite some time to that. So I really think that we will have some really exciting time driving exosamab further ourselves and finding a new approach to help patients in the future.

Okay, thanks. And just a quick final one. You talked about your binding study on aggregates versus monomers, but I also wonder, have you done any preclinical work or binding studies versus the other antibodies that have been

in trials before or is that or do you plan to do any of those kind of studies which you have done in Alzheimer's different yes we of course we have done that and we have shown some of those data previously and we will definitely show some of that also going forward and we see that we I don't know any other antibody which is so selective as the 805 or Exudabnumab versus the monomers. And we believe that that is very important, maybe even more important than in Alzheimer's disease because you have more abundant monomers. So you really want to have a high selectivity, which we do. So we will come back with that. But I am so happy to hear about the excitement about Exudabnumab, which I am excited about. Maybe we'll give more room for this in the future.

Okay, thank you very much.

The next question comes from Louisa Morgado from Van Lanshot Kempen. Please go ahead.

Hi, Tima. Thank you for taking my questions. Maybe going back a bit on the Lekanoma program. I was wondering, given this positive data for the subcutaneous formulation. And since it's weekly versus the biweekly IV formulation, what proportion do you estimate? So what proportion of patients do you estimate that will go for one formulation and vice versa? And also another question, when do you expect maybe to initiate commercialization in the Nordics? So for Lecambia, of course. Yes.

Thank you so much, Louise. Two great questions. So I think the first thing is that I was really happy at CETA when I presented the sub-Q data, six-month data, that it really looks like subcutaneous will be a good alternative for the patients. I think it's also very good to be able to do it weekly. Patients and families can support at home. You can give the injection through an auto-injector at home, in contrast to the IV infusion, which mainly will be done at infusion centers. It could also be done ambulatory, of course. I think it's really hard to say exactly how many will be on one or the other. But I really see subcutaneous as a really good alternative for the patients that will help to facilitate the administration. And I think this is also an important differentiating factors versus some competitors, which is not having subcu. So I think subcu will be a very important part. I think some patients will still think IV is good. I think we will see both. But definitely I'm excited about the sub-Q part. So we will follow that and see. And then the Nordics, we hope, of course, then for an approval first quarter of next year. And then after that, you know, Europe is very different from country to country. Some countries in Europe, like Germany, ASIC can start to launch quickly. Whereas in the Nordics, it's also different in the different Nordic countries. You do the pricing and reimbursement discussion. And that ASI will be driving those parts. And normally that takes about a year. So I think that helps to guide a bit when we plan the launch in the Nordics. So we are very excited about this. And we are, of course, preparing and starting to think about and also see how can we prepare the infrastructure and so forth, which is really important to make society ready for this kind of new treatment paradigm.

Yes, thank you so much. That was very helpful.

Thank you, Lisa.

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

Hello, and thank you. I was wondering a bit about the collaborative launch in the Nordics. Could you say anything about how big of an internal commercial organization you expect to have at Biotic?

Sure. Right now, we have people in the range of 11, 12 people or something like that. That will increase a little bit when we recruit account managers. So for us, I would say our part of the commercialization will be roughly, say, 18 to 20 people or something like that. And then ASI will have a smaller sales force, and then we will share the cost for that. So they will reimburse us for part of our costs. So we have a 50-50 split on the profit level.

Perfect, thank you. And also about, as you mentioned, the increased PET coverage in the U.S. I was wondering, can you elaborate a bit on how much of an obstacle was it before that and how quick of an impact do you expect to see with this increased coverage?

I think that's a great question. And I think if you compare different parts of the world, different regions, use PET different much, if you put it like that. So the alternative to PET has been CSF sampling with lumbar puncture. And a country like Sweden, we are very good at doing lumbar puncture. That's kind of normal routine practice. In a country like the U.S., they are not at all as used to doing lumbar puncture. So there has been a clear drawback, not having had a PET tracer with broader reimbursement. So I think for the US, this will be an important part. And for some other countries, it will be very important to have that, at least until we have the blood biomarkers coming further ahead. So I think that will make a difference in the US. But then I think, I mean, you wish it would be coming through directly, and it will not. It will take a little bit of time here again. before it really goes through all the infrastructure at the different hospitals and so forth and coming into the list of each hospital and being used in the broader sense. But I think it's definitely a very positive part to see this happening.

Perfect. And a final question from my end about the subcutaneous formulation in terms of different geographical market, let's say Europe versus U.S. I know you have discussed a bit before me, but do you expect that to be higher for the subcutaneous in Europe, for example, compared to the U.S., or roughly the same split between the two? Ivy?

I mean, I don't think anyone can respond to that. I mean, I think it's fair to say that the first focus now would be the U.S. for the subcutaneous and the autoinjector. So that's the first part where ASI now is preparing for the filing in the first quarter of next year. And then we'll take region by region, but it will start in the US.

Okay. Thank you.

The next question comes from Alistair Campbell from Royal Bank of Canada. Please go ahead.

Great. Thanks for taking my questions. I've got a couple. First of all, if I just sort of come back on that last question a little bit. Are you aware of time frame or any plans currently from ICI to bring other subcutaneous or the maintenance IV formulations to the market in Europe? So is there any planning in place for that right now? And then the other question really is sort of asking you to get the crystal ball out and think about brain transporter technology. We're clearly very impressive in terms of speed of removing amyloid and also a very impressive side effect profile. So I guess, first of all, just to understand how far behind Roche you believe you are with your program. And then secondly, given that Roche has shown very strong data in terms of removing amyloid for the membrane very quickly, do you think that still leaves room for a differentiated binding profile to still mean you can drive a meaningful efficacy difference as well? Thank you.

A lot of excellent questions, Alistair, as always. So I think we start with the subcutaneous, and I think the subcutaneous, I mean, what ASI showed was that it could be used both as a starting on subcutaneous, which they had by the de novo patients who had got placebo or come new into the open-label extension part of the as subcutaneous substudies, so it showed that you can start that. It also showed that you can go from IV to subcutaneous, and you could think about that as a maintenance treatment. So I think all options are open based on the data we have seen so far. So I think it's a little bit too early to say exactly how it will be used, but I think to me, I mean, the most important part was to see that it really seemed to work as was expected, and I think it even showed a little bit higher exposure, a little bit stronger efficacy on clearing the amyloid deposits from the brain. So I think it looks really, really promising. But it's a little bit early to say exactly how it will be used. And then with regard to the brain transporter, I think it was very impressive to see the results as these had. And I think it's hard to say that we are a little bit more than two years until we are in the clinical setting. But after that, we see that we could drive this very quickly forward because we have the possibilities to benefit from the pyroglue antibodies on animals where we think that we have some clear benefits with our brain transporter molecule, pyroglue molecule. And also we have the other brain transporter Alzheimer's program, which also, I think, has a lot of great opportunities. So I think what I've said many times before, what really interests me with the brain transporter technology, when you get more antibody into the brain, what we see is that you get much, much broader distribution into the brain. You get it fast, broad, and deeper. as compared to a naked antibody. And this, I said all the time, this opens up the opportunity for maybe having even better efficacy. And maybe also even better on the scientific profile. So I think we're eager to see how we can drive our program forward in a speedy way to see how we can really help patients with this alternative as well. So I'm really, really eager to see how that will be progressing forward. Did I answer your question?

Yes, that's great. Thank you.

Okay. Thank you very much. The next question comes from Joseph Hedden from RX Securities. Please go ahead.

Good morning. Thanks for taking my question. ISI has given a lot of metrics about the launch of LeCambie in the US so far, and it's clear that there are multiple challenges in building a new market like the company's trying to do at the moment. One of those seems to be scanning. So ISI talked about the importance of Medicare's broadening of coverage of PET scans. I was wondering your thoughts on the importance of that versus MRI, being as Lekembe needs some MRI monitoring on infusion, and where does CMS's current coverage sit on that, and is this a significant barrier to prescribing that ISI is experiencing? Thanks.

Thank you so much for that question. According to my understanding, it is covered in the US with the MRI scan. And I think an important aspect here is that you have a certain number of MRI scans that you should be doing when you start treatment with this kind of new treatment. And it's especially during the first six months. And since Lekembe has shown a lower frequency of area, my expectation is that you will have fewer uh needs of mri scans compared to some of the competitors or all the other competitors that have shown more area and if you have area and then you need to do more mri scan so i think that that looks like another benefit for for the camera but as i'm and i've understood it the mri scans are reimbursed in the us

Okay, that's clear. Thanks. And then if I could ask just on Nordic timeline, so if we expect a European approval in the first quarter, when realistically do you expect to make your first Nordic sales? And, you know, when and where? I know that you're going to have to go through pricing and reimbursement negotiations. At what point can we expect that to happen?

So just as I said, I think, I mean, if we get an approval then first quarter next year, which we hope for, then it's about the year. So I think it's fair to expect the first launch in the beginning of 2025. And of course, I would like to see Sweden coming first. We'll see. But all the Nordic countries are important, of course. I think Sweden is sometimes a bit faster than some of the other Nordic countries.

Okay, great. And just on the revenues you've recorded due to co-promotion, can we expect similar levels in the coming quarters preceding the Nordic launch? Is that the kind of run rate we can expect?

It's going to be a little bit lower than that for the next few quarters. And then when we ramp up our sales force a little bit, it will start to increase and then As soon as we start selling, it will increase quite a bit.

Okay, that's great. Thanks very much. Thanks for taking my question.

Thank you, Joseph.

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

Hi again, a couple of follow-ups, if I may. First on the sub-Q formulation, given that it's one sort of fixed dose regimen, are you considering or are ETI considering developing a lower dose option given the higher exposure observed? I assume that dosing a 50-kilogram dose person versus 100 kilogram person gets very different exposures. So that's my first follow up. And then secondly, on the blood brain shuttle technology, when can we expect you to share some more data on the potential differentiation versus denial of technologies? Thank you.

So excellent questions again, Erik. Thank you so much. The first question was with regard to the sub-Q. I mean, I think that it was clearly seen that the fixed dose of 720 milligrams showed some benefits over the 10 milligrams per kg dosing IV. So there is an opportunity of lowering the dose. And that is, of course, under discussion that you need to think through the data. further. I don't think anything is finally decided yet, but of course, it's obvious thought that that's one of the things you can think about. And then with regard to the fixed dose, I think it's a trade-off between being easy to use for patients and so forth. And that is exactly what Asa will be looking at also, to see what this means when you have different body weights and so forth. So that's all in the evaluation, and that must be done in order to submit the file. But I think it's fantastic that you can have the alternative for patients to give it IV with an auto-injector, that it's much more user-friendly for the patient. And it looks very promising, so I'm really happy about that, and we'll see exactly what dose and how. when we come further. And then with regard to the brain and transporter technology, as you know, this is a very, very competitive area. And we think that we have something which is clearly differentiated and has some clear benefits. So I would say I would guide you to fourth quarter of next year. Then I think we can talk more about how we differentiate and why. from competitors. But you have to stay tuned a bit longer. I wish I could tell you. I'm so excited about this. But it's too competitive to reveal things so early. But we are confident with the data we saw and our own data that it looks very promising.

All right. Thank you so much.

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

We have another brain transporter question in the queue here online. I'll read it to you and maybe you can answer. It's from Victor and he says, regarding the brain transporter technology, what is the commercial prospects for this technology? Is it most likely a scenario out licensing deal or how are you thinking about this going forward?

Excellent question. Thank you so much, Victor. I think that the first thing we would like to do is exactly what we're doing now, is to link it to our own antibodies and proteins. Like you have seen that we now have it in two Alzheimer's programs. We have it also in an alpha-synuclein program. We're also working on it together with a CBC43 antibody. And we also have it in another program for an enzyme replacement therapy to address CNS symptoms of Gaucher's disease. So the first thing we're thinking is to utilize this as a differentiated benefit for our internal program. But of course, this is a huge opportunity with the platform technology that you also could add to other companies' biological therapeutics. So we are thinking about a bit later on to also see if we can help Other companies, for example, think about brain tumors and other things where you also would like to have more of your biologic therapeutic in the brain. So I think, and then we're thinking several non-exclusive licensees, but then we talk long-term future. For now, we're using it to make the benefit for our own program. But I think it has a lot of opportunity for the future. I'm very excited about the brain transported technology.

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

So I hope you heard the last question about the brain transport and my response. And if you did that, then I think there were no more questions. So then I say thank you so much for your attention and all the great questions. And I wish you a great rest of the day. Thank you so much.