BioArctic AB (publ)

Good morning and welcome to Biotic's presentation for the fourth quarter of 2024. Next slide, please. I'm Gunilla Oswald. I'm the CEO of Biotic, and I will share today's presentation with our CFO, Anders Martin Lööf. Our chief commercial officer, Anna-Kaja Grönblad, is also here for the Q&A session after the presentation. Next slide, please. Biotic is listed at Nasdaq Stockholm large cap, and this is our disclaimer. Next slide, please. Today, I would like to start with this slide, which I believe says a lot about the current status of biotic. First of all, I continue to be very excited about our brain transported technology. We had a very important event in December with the first license agreement that was signed, including the BT technology, and that was with Bristol Myers Squibb. It's now pending the HSR clearance process. I think this is very important also since it gives an external validation of our platform, as well as it opens up for further partnerships. The second part I want to mention is Exidavnamab, which started phase 2a during the fourth quarter of last year, and it's progressing really well. All patients have already been completed their screening phase for the low-dose part of the study. Thirdly, Lecambi sales continue to increase, and more and more patients are getting access to the treatment. We believe this is just the start and continued development of more convenient dosing and more convenient diagnosis will continue to drive the growth going forward. Based on these achievements, Bioartic is now entering a new era, which I call Bioartic 2.0. And that's based on that we now have continuous revenues with royalties. Quarter by quarter, are they increasing? And we're not any more dependent on the very irregular milestones. And that leads to that we get more stable finances and we expect to be profitable from this year and onwards. Our brain transporter platform has been validated and we have a strong partnering interest, which could potentially lead to several partnerships in the future. And our Alphas Nuclein portfolio with Exidavnamab and BT2238 is also receiving a lot of interest among external partners. Next slide, please. Bioartic is a global pioneer in neurodegenerative disorders. And we are among world leaders as innovators in two different areas. The first one is in generating highly selective antibodies, targeting aggregated forms of misfolded proteins, for example, Alzheimer's disease, Parkinson's disease and ALS. The second part is our brain transporter technology, which helps biological treatments come better into the brain and coming closer to the target. Our business model focus on innovation of new treatments for neurodegenerative disorders and the blood brain barrier technology, which also makes us now also be a platform company. An important part of our business model is partnering, and we see three types of partnering. The first one is for large indications like Alzheimer's disease and Parkinson's disease, where our aim is to license the project to a strategic partner before Phase 2b or at least before Phase 3. For off-and-tag indications, BioRT can drive our programs longer and potentially all the way to the market. For our brain transporter technology platform, we can also partner with companies that want their biologics to get increased brain penetration. Next slide, please. And I will continue on that path and talk about the license agreement with BMS, which is a key event for Bioartic. It's a global license for our pyroglu-A beta antibody program, which includes BAN1503 and BAN2803. BAN2803 is also utilizing the brain transporter technology. And the license was signed 19th of December. We had several interested parties and BMS were fast and committed with a very good offer. And as I have said before, we are discussing with different potential partners. And if we find the right partner with the right proposal, we will partner. And in this case, it's a very good strategic fit for both parties. It came a little bit faster than I had expected. BMS is a great partner for the PyroGyve beta program with patients in focus. We are now preparing for BMS to take over the projects, but we have to wait for the agreement to be cleared by the HSR process before the agreement can be concluded. This is our largest agreement that has been signed so far and one of the largest ones globally for such an early project. The agreement includes 100 million US dollars upfront and another 1.25 billion US dollars in milestones, plus tiered low double-digit royalties on global sales. Importantly, Biotic retains all other rights to the brain-transporter technology outside of the PyroGWay beta field. So I think that we can utilize this for several future potential partnering agreements. Next slide, please. The brain-transporter platform continues to progress well and according to plan. We had in our plan that we were going to present validation data at the last quarter last year, Q4. And those data demonstrate rapid, broad, and deep bearing distribution by utilizing the transferrin receptor. And this could then lead to increased effect, decreased side effects, lower dose, and more convenient dosing. I think that the next generation treatments for CNS will most likely include a blood brain barrier technology. We continue to evolve our BT technology with different ways of engineering, depending on which the target is, if the target is extracellularly or intracellularly, or if we want to come into the lysosome in the cell or outside the lysosome, but still in the cell. So it's different ways of engineering the brain transporter. We have a versatile platform which can be utilized across modalities. We have started with antibodies and enzymes, and we are now also looking into other modalities such as antisense, oligos, etc. We experienced great interest at JPM in San Francisco in January and continue with several discussions regarding potential future partnerships. And we are excited about the discussions, but of course, we expect these discussions, as always, to take some time. It's important for us to find the right partner with the right terms and the right commitment. Next slide, please. Another great achievement the fourth quarter last year was that Excedavnimal, our Alphas Nuclein program, started phase 2a in Parkinson's disease patients. And we are also now exploring the potential to include patients with multiple systemic atrophy, MSA. The study is progressing very well and the low dose part of the study is already fully recruited. And then there is three months dosing and then follow up. We are now preparing for a safety interim review on the third quarter this year before progressing into the high dose part. And we expect full study results first half of next year. I think that our alphas-nuclein program is very exciting, especially based on two different things. One is that we have a highly selective antibody and to our knowledge is the most selective antibody, which is binding strongly to the pathological forms of alphas-nuclein while sparing the physiological monomeric forms. And the second aspect is that we see several opportunities for indications going forward. For example, in Parkinson's disease, Parkinson's disease dementia, Lewy body dementia, predominantly Parkinson's disease and multiple systemic atrophy. And all data that we have generated so far really support further progress. So really exciting about this program. Next slide, please. Then let's turn to Lekembe. The number of patients treated with Lekembe continues to grow, and it's more than 20,000 patients treated by now. And I think it's reassuring to hear that the clinical safety experience is on par with what was reported in the phase three program. If we start on the regulatory side, Lekembe is now approved in 10 different geographies, with Mexico and Macau added now in January. Regulator review was ongoing in 17 additional markets and regions, including the European Union. In EU, CHMP gave a positive opinion the 14th of November last year, and we were waiting for the European Commission decision in January. But the European Commission has asked the CHMP to consider two questions regarding information on the safety of leucanumab that became available after the adoption of the CHMP opinion in November, and whether this may require an update of the opinion, and to consider whether the wording of the risk minimization measures in the opinion is clear enough to ensure correct implementation. Our partner, ASI, who are driving the regulatory process, they believe the existing information is clear and sufficient to address the questions. And we now expect the CHMP meeting the last week of February to address these questions. And we are looking forward to the response from the European Union. And I really hope that European patients can get access to Lecambi soon. In January... Of this year, the FDA approved less frequent maintenance dosing intravenously every fourth week. This means that after 18 months treatment, patients could reduce their dosing to once a month for the maintenance phase. I think this is a great step since it is important to continue dosing to get the most benefit for the patients. Also after that, the plaques have been cleared. In January, the FDA also accepted the new application, the new BLA, for the subcutaneous autoinjector with maintenance dosing. And the PDUFA date has been set to the 31st of August. If we then look at the development side, the AHEAD 345, the phase 3 study, completed recruitment mid-October. And this study is for pre-symptomatic Alzheimer's disease, which means individuals with elevated levels of amyloid deposits in the brain, but they do not yet have any symptoms. They will receive treatment with leucanumab or placebo for four years. During the latest Alzheimer's Congress called CTAD, ASI presented new data from the Phase 3 Clarity-AD study, further supporting early and maintained treatment. Data presented at CTAD suggests that initiation of Lekembe in early stages of the disease can support clinical stability and even improvement in many patients if you start very early. I think this is positive news for the AHEAD 345 study, which will evaluate the possibility to prevent or delay onset of Alzheimer's disease. Long-term data over 36 months from the open label extension study were also presented at CETAN, suggesting continued benefit over time and the importance of continued treatment even after plaques have been cleared and to maintain the suppression of the Alzheimer pathology. This makes the less frequent maintenance dosing a benefit for the patient. I think it was also reassuring to hear that the clinical safety experience in clinical practice is on par with what has been reported in the phase three program. And if we look at the commercial side, as I said, we have more than 20,000 patients on Lekembe treatment globally. And the number of patients that are getting access is constantly increasing. And Anders will talk more about this. Next slide, please. I want to point out three major things that could broaden the use of Lecambi and accelerate the uptake of Lecambi. The first one is subcutaneous autoinjector, which I think will make it much more convenient for the patient. And the first BLA has been submitted for maintenance dosing with a PDUFA date, as I said, late August. Thereafter, ASI plan to submit a supplementary BLA for subcutaneous water injector administration for the induction phase as well. The subcutaneous administration will make the treatment much more convenient for patients and caregivers with at-home administrations and with less requirements and lower costs for administration compared to intravenous administration. The second aspect is simplified diagnosis based on blood-based biomarkers. Today, blood-based biomarkers are being used for screening, and then they should be confirmed by PET or CSF. Within the next year, we believe that blood-based biomarkers will also be accepted as confirmational, and this will be making the diagnosis considerably simplified and increasing the opportunities for primary care diagnosis. The third aspect is to broaden the indication to even earlier stages of Alzheimer's disease. As I alluded to with the AHEAD 345 study in pre-symptomatic individuals. even before the symptoms appear. But the individuals have elevated levels of amyloid beta in the brain. So I think Lekembe has huge opportunities to help many patients. And we expect the uptake to be more rapid, especially from 2026 and onwards. Next slide, please. So in summary, our portfolio is progressing really well, all the way from very early innovative discovery and all the way to helping patients on the market with these devastating diseases. And today I have highlighted Lekembe, Exidavnema, our Pyroglu-A beta programs and our BT platform. And I'm really pleased to know that Bioartic's innovations and research with high quality is being recognized externally. Next slide, please. And then I will hand over to Anders Martin Lööf for the financial summary.

Thank you, Gunilla. I will then start to focus on the Lecambi sales. As you can see here on the slide, the global sales for the fourth quarter of 2024 were 13.3 billion yen. That corresponds to $87 million, i.e. a 33% increase from the third quarter of 2024. So we now really see a solid development. And of course, if you compare year over year, it's more of a tenfold increase. So we are in a rapid growth phase. For us, this means that the royalties increased by 38% from the third quarter to 96.7 million Swedish. For the full year, we recorded roughly 230 million Swedish in royalties. This is primarily then driven by the U.S. expansion. It's now in line with the updated forecast that ASA issued in their last quarterly report. The U.S. sales were 7.7 billion yen, corresponding to $50 billion, which means that the sales grew by 31% over the Q3 numbers. And we're now up to 13,500 patients. As you may recall, ASI described the problem with an infusion capacity bottleneck in the last quarterly report. And now that problem is being resolved. The capacity has been increasing rapidly. So the 6,000 patients that ASI hinted were waiting for treatment due to capacity issues are now being included at a very rapid pace. So now they're up to 3,500 patients. So they are really working hard to resolve that problem. Over time, the infusion capacity will also become less of a problem. Already now, maintenance therapy, as Gunilla mentioned, is approved in the U.S. using infusions, so that reduces the number of infusions for patients that have been on treatment for a long time by 50%. But also, even more importantly, the subcutaneous version removes the need for infusions entirely. And we expect that to be approved for maintenance therapy in the third quarter of this year. expect induction therapy with the subcutaneous version to become approved in the first half of next year. So all in all, we believe that the growth will continue in the US in 2025. And in 2026, there will be a much stronger focus on the primary care sector. And ASA has started preparation for that already now in 2025. So we will see a shift moving over more to general practitioners in the primary care sector going from specialist only. In Japan, we saw a really strong development. Japan has been a really strong market from the very beginning. The sales were 4.1 billion yen in the fourth quarter, corresponding to $27 million. Strong 49% growth over the third quarter. And as you can see, the number of patients is more than half of the numbers in the U.S., even though Japan is a much smaller market and the drug has been on sale for two quarters less in Japan. So really, really strong development there. And there you can see that ASA has already started promoting directly to consumers to raise awareness about mild cognitive impairment and to promote early diagnosis. And I think that is the way to go also in the U.S., and that's the development that we expect to start in the U.S. as well. China is also very strong. It may seem that it's not growing, since the sales on the fourth quarter were roughly the same as in the third quarter, coming in at 1.3 billion yen or $8 million. However, the sales in the first quarter of... of sales in China, which was the third quarter, were probably a little bit stronger than the underlying demand as there was some inventory buildup. So all in all, I would say China is moving really well. The underlying demand is increasing, and we will continue to see solid growth there, even though ASA is only selling towards the private market, but that's still a significant market. To conclude, we believe that EISA is on track to reach their financial year forecast of 45.5 billion yen. That is for the period that started in the second quarter of 2024 and that will end of March 2025. That then will correspond to $280 million. And as you can see from the accumulated sales in the first three quarters of that period, that were 29.6 billion yen or $194 million, they need to generate roughly as much sales in the coming quarter as they did in the last quarter to reach the forecast. And we believe that they will continue to grow. So we believe there is a very high likelihood that we will actually beat their forecast. Going forward, as Yanila mentioned, we believe that we will see continued growth in 2025, but really it will be incredibly exciting to follow what will happen in 2026 when the blood-based biomarkers really make a dent in the diagnosis process and the subcutaneous version becomes available so that the patients can take the drug at home or in a much easier way with the healthcare practitioner. than they do today with infusions. So we believe that 2026 will be a very exciting year to follow. We then turn to the next slide, looking a little bit more on our figures. Starting on the left-hand side, you see that our net revenues were 101 million for the quarter. Historically, as you can see, they have been fairly lumpy and it has been smoothing out a little bit now when the royalties are growing. I'm happy to say that it will be lumpy again since we will start to generate quite significant milestones in 2025. We have already said that we expect a $100 million upfront payment from from BMS that will be recorded in its entirety when the agreement is closed. We're also expecting some milestones from ASI, so we could probably expect some 30% more than we expect from BMS by milestones from ASI. So all in all, I would say in a sort of $130 million range for 2025. Over time, the recurring revenues will increase, but not only in 2024. You see, the royalties were 97 million in Q4 of this year. They will continue to grow, but they will be smaller than the milestones in 2025. The co-promotion revenues will also start growing over time, but probably not to a significant level in 2025, as the launch in the Nordics will most likely take place in the beginning of 2026 rather than 2025. If we then turn to the costs in the middle graph, you see that the operating expenses increased to 143 million in the fourth quarter. R&D was roughly 67% of that. And the total cost for 2024 were 459 million. That's actually a little bit lower than we guided for the year. And that is due to the fact that there were some CNC costs that did not occur towards the end of the year since we entered the deal with BMS. So I guess that's beneficial that we were lower than our forecasted costs. For 2025, we do expect the cost to increase. Our project portfolio is progressing well. We spend more on our clinical trials and CNC programmes, so we expect the costs to increase by roughly 50-80% in 2025. It's really hard to make good estimates, so we will have to come back to that. But if I were yesterday, I would say we are in the 50-80% increase range. Looking then at the operating profit, our operating loss was 53 million for the fourth quarter. But as Gunilla mentioned, we are expecting to be very profitable in 2025. And if you put the numbers together, the pre-tax profit for 2025 should be in the neighborhood of roughly a billion Swedish, which is a really, really strong result for a company like ours. If you then turn to the next slide, some more details, you see the net result for the fourth quarter was 31 million. That's roughly 20 million better than our operating loss. So that's primarily due to the financial net of roughly 10 million and the negative tax effect of 12 million. If you look at the cash flow in the middle graph, it was roughly in line with the result. Typically, it's usually a little bit worse than our results since we have accounts payable that continue to grow with the growing royalties since there's a lag between the payments and the recording of the revenues. But this time around, we did not see that effect. But going forward, we still expect to see the cash flow trailing the net result. And on the right hand side, you see a cash balance. We ended the year with roughly 780 million Swedish in cash. We, of course, expect that position to grow significantly in 2025. So we will end 2025 with an even more solid position so we can really focus on doing what is right long term for the company. and sort of focus on the right projects and focus on entering the right deals. As Gunilla mentioned, we will partner our programs if we find the right deals, but we don't have to. And that's a significant strength that I'm really happy to have as CFO of this company. So with that, I will hand the word back to Gunilla for some closing remarks.

Thank you so much, Anders. And then we're coming to the final part of the presentation with upcoming news flow and some closing remarks. Next slide, please. So if we look at our upcoming news flow during this quarter, we are eagerly awaiting the HSR clearance process for the BMS agreement. And of course, we hope for a positive outcome to be followed by an upfront payment of 100 million US dollars. We are also eagerly awaiting a CHMP response at the end of February, and we are looking forward to more regulatory responses. Next important Congress is ADPD in Vienna in beginning of April, and there we look forward to presentations on both Lekanamab and also on Exedabnamab. We are also preparing for our first Capital Market Day, 2nd of June. And then during the third quarter, we are waiting for more regulatory responses and the Exidevnamab safety review and progression into the high dose part of the phase 2A study to follow that. So then we go to the next slide and I would like to summarize today's presentation by saying that our pipeline is progressing really well and we have very encouraging brain transporter data that has been presented and generating a lot of interest. Lecambi is now approved in 10 different geographies and the sales of Lecambi continue to increase. Royalty revenues continue to grow and it's gratifying to see that we're helping more and more patients. And thirdly, our financial position remains strong. We have almost 800 million Swedish crowns in cash and we expect to be profitable this year and onwards. Next slide, please. So by that, I thank you for your attention, and we're happy to take some questions.

If you wish to ask a question, please dial pound key 5 on your telephone keypad to enter the queue. If you wish to withdraw your question, please dial pound key 6 on your telephone keypad. The next question comes from Joseph Hedden from RX Securities. Please go ahead.

Good morning, thanks for taking my questions. Firstly, to Anders, just on the milestones, just hoping to clarify there, was that you're saying you expect in the ballpark of 130 million US is available overall, and so that includes the BMS upfront payment and then presumably the EU approval milestone, but also possibly a sales milestone in there?

Yeah, that's correct. I messed it up a little bit. So yes, we are expecting $100 million from BMS and then roughly, well, a third of that in addition from ASIC. So you're correct. We're expecting a sales milestone and a regulatory milestone from ASIC.

Okay, brilliant. That's great. Thanks. And then possibly, just now that we've had a couple of weeks since finding out there were additional questions after the positive CHMB, have you been able to find out what additional kind of safety information that came out that has been referred to by the European Commission? What was the new emerging data after the

So I don't think we should comment anything about an ongoing process. So we just have to wait now and stay tuned and wait for the review. But I think, I mean, what we have been reassured by ASI is that there is no new safety signals that the current information and the data which is available should be able to address the questions.

Okay, thanks. And then just lastly from me, when you're talking about the BMS deal, and congratulations, it's a fantastic deal. You said that several parties were interested. So where are you seeing the interest there? Is that specifically in the pyroglutamate antibody portfolio, or is it for programs involving the brain transporter technology specifically?

I would say both. And what we see now is continued interest both on our brain transporter technology to utilize that together with other companies' assets. And for example, also for our alpha-synuclein portfolio, where we have exodavnumab and we have also an antibody combined with our brain transporter technology that we call 2238. So I would say both.

Okay, that's great. Thanks, Gunilla. Thanks, Anders.

Thank you, Josef.

Hi, team. Thank you for taking my questions.

Maybe a first one. The next question comes from Louisa Morgado from Van Lanshot Kempen. Please go ahead.

Hi, team. Thank you for taking my questions. Maybe to start out, you mentioned the costs over 2025. Could you elaborate a bit in terms of where do you expect to, of course, redirect the stream that you will have from the royalties and the BMS deal? What are your priorities within your pipeline?

So, yeah, if I start a little bit, I mean, we focus, of course, on the most... sort of the most fully developed program that we have in our pipeline. And when we get closer to the clinic, then we will start to generate significant CNC costs. And then, of course, we are running one clinical program for Prexidabnamab, and the cost for that will continue to increase. As for what other program we can engage in in the future, we will probably come back a little bit more on our capital market stage to see what we do in the future. Maybe Gunilla wants to comment on more than that.

Yeah, no, but I think definitely, I mean, exudabnema when you are in clinical stage, that costs a bit more than being in the early discovery stage. And then also, I mean, we have another really interesting program we haven't talked about today. which is also Alzheimer's, the next generation Alzheimer's program that we are evaluating together with ASI, BAN 2802. That's also a very exciting program that we, of course, will continue to invest in. And then also the brain transporter. I mean, that's an area where we invest and will continue to invest. Because as I tried to explain, I mean, there is a lot of opportunities for this technology. And there is so much more we can do also with our programs, but also to prepare this technology for other modalities and so forth. And then we haven't talked today about our TDP43 program, but that's also a very important program, both with naked antibodies, but also combined with our brain transporter technology. And then, I mean, the G-case program for Gaucher disease, where we are opening up the avenue also with enzyme replacement therapies. So I think that we have some really, really interesting programs at different stages in our portfolio. And then we will, of course, look at expanding when we have more money.

Okay, perfect. That's very clear. And maybe a final question in terms of, so you mentioned the blood-based biomarkers that should be approved as very soon or somewhat soon and could be conformational as well. Could you expand a bit here in terms of what do you expect of how this will be combined, of course, with all the other methods of diagnostics and conformational, of course?

Yes, I think right now, I mean, they are already used for screening and in different kind of triaging systems. So, I mean, if you have a clearly strong result, then you know that you have amyloid pathology. And if you don't have it, then you know it's something else. It's not Alzheimer's disease. So it's especially in those in the middle where you need to have the conformational part through PET and CSF. Or CSF, I mean. But I think now also more and more data is coming in and they're working on both the regulator processes and user guidance and so forth that will also then help with the confirmatory part directly. And I think that would be very important because that opens up so then you're not dependent on PET scans and PET centers and so forth. You are not dependent on doing CSF sampling and lumbar puncture. So I think that will open up the possibilities for a much, much more broad spread. So I think this is a really important part. And I'm so pleased to see that it's going faster than I thought some years ago. And it's really progressing so well. And there are several companies who are developing blood-based biomarkers. And of course, we are agnostic to which one it is, but I mean, there are several coming that can help to simplify the patient journey.

Okay, Claire, thank you for taking my questions. That's all.

Thank you so much, Louisa.

The next question comes from Rajan Sharma from Goldman Sachs. Please go ahead.

Hi, thanks for taking my question. So, firstly, just on Exidab Venomab, sorry, in MSA, could you maybe just kind of talk to your rationale for exploring the drug in that setting? And then also, could you just kind of help us understand specifically what it is you're exploring? Is it still dosing? Or is it just trying to gain additional confidence in the mechanism? And then secondly, when would you expect an update on a go-forward decision? And then I have a follow-up for Anders as well.

Yes, if I start then with Excedavnimab, I mean, we are really pleased to see how the progression of the phase 2A study in Parkinson's disease, how that is evolving. And we started with the low dose first, and then we will do an evaluation of the safety in Q3. After that, we will then go to a higher dose in Parkinson's disease. And we are also thinking about then going into another panel with MSA patients in order to prepare for different, to open up more possibilities for phase 2b. And as I said, I mean, I see several possibilities for phase 2b. It could be Parkinson's disease. It could be Parkinson's disease dementia. It could be Lewy body dementia. It could be preclinical Parkinson's disease. And it could be MSA. So what we are doing is, is really preparing ourselves for different opportunities for Phase 2b and onwards.

Okay, thank you. And then maybe just to clarify on that then, so if you decide to progress in MSA, for example, does that mean you won't progress in some of the other indications or could you potentially do multiple indications with the drug?

So I think, I mean, there are multiple opportunities. And I think that we will follow, of course, the whole field of alpha-synuclein. But there are many possibilities. And we have also then, of course, I mean, we have Exidavnimab, and we have also the next generation, 2238, with brain transporter. So we see different opportunities for, or different possibilities to drive in several indications. And we are at the moment reviewing different opportunities and different pros and cons with different indications. So we will come back to that. And also it depends on, of course, if we are doing this ourselves or if we have a partner at that stage.

Okay, perfect. Thanks, Canela. And then I just had a follow-up for Anders on expenses in 2025. Anders, I think you said 50% to 80% growth. in 2025 on expenses. So could you just kind of help us understand what gets you to the bookends of that range? And then maybe if you could just discuss expectations for tax in 2025 as well. Thank you.

Right. So, well, most of the increase will, of course, then come in R&D. And it's very, very hard to give a proper forecast for R&D costs because it really depends on how fast our programs evolve. So we may have a guess in the beginning of the year and then things start to go faster in some projects and slower in other projects and that's a big problem. big effect on the costs. So I don't really want to go into too much detail because then I will just be wrong because things will really evolve during the year. But expect most of it to come in R&D, most of the increase. And for the tax, yes, if we, for example, would make a pre-tax profit of 1 billion, we will pay roughly 200 million in tax for 2025. So we will be paying taxes. And it will probably be in that range that I mentioned.

Thank you very much.

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

Okay, thank you so much. So we've gotten a few written questions. I'll start with one from Frederic Thor at Red Eye. And he wants to know if we're planning any study with the kind of patients with Down syndrome. That's something we've been talking about in the past. Gunilla, maybe you can clarify.

Thank you for the question, Fredrik. As you know, we have data showing that leucanumab binds to post-mortem brains of Down syndrome, which is exactly what you would expect. We are reviewing this opportunity and having discussions. This is a patient population where you should be a bit careful because they have a higher risk of side effects, but also they have an opportunity to get an effect. So, yes, we have plans, but it's not imminent. But we are definitely looking into this for the future.

Good, thank you. Then Nils-Oke Thulin has written a bunch of questions. Some of them came early in the call, so I think we've answered most of them. He wants to know a bit about if we can say anything on the competition with Eli Lilly. I think that might be something that we haven't commented on. In the subcutaneous, we've talked about the different adverse events, if we can say anything about that. But I think you mentioned, Gunilla, that they are in line with the phase three studies as far as what we've seen so far. But maybe if you want to say anything on what we see in competition or what we've heard about competition yet by either Biogen or ACI, what they've mentioned. We have anything we can say? No, not really. Right.

We say commented a little bit in the US. They are, of course, seeing competition from Kizunla. They are not sort of overwhelmed by the competition. So it doesn't have had a really large impact on their sales, that was their comment. As for the the traits of the products, how they are compared with each other, we won't comment on that. There haven't been performed any comparative trials, so we refrain from commenting on that.

I think one clear benefit for Lecambi will be in the future the subcutaneous administration, for example.

Yeah. Payments from BMS to expect in 2025. Anders, I think you've mentioned the expectation there.

Yes. So we expect to get the upfront payment once HSR clearance has been achieved and the deal has been closed. So that could be recorded in the first quarter if everything goes to plan. So then we'll record the full $100 million. Other than that, we're not expecting to record any other revenue in 2025 from BMS.

Thank you. And then, Gunilla, you did mention there was a question here about the why not collaborate with ASI regarding BT, but you mentioned.

Maybe I should clarify that. Yes, we are collaborating with ASI also on the brain transporter technology. I mean, this technology can be utilized for many different programs. And we have then the pyroglue program has now been partnered with BMS. But we also have the band 28 or two, which also is it's an undisclosed target for Alzheimer's disease. This is modifying properties that we have combined with our brain transporter technology and that is in a research evaluation agreement and a collaboration with ASI where we are reviewing that program so definitely.

And additional potential BT agreements I think you also highlighted as a great potential for the future So I think we mentioned that. Then we have a question here from Joel Blod, and he wants to know if we can elaborate a bit further on this CHMP meeting in February, and then how long after that meeting that we can expect the decision from the EU Commission, and also when the sales could start in Europe following a positive decision from the EU Commission.

So I will start and then I'll hand over to Anna-Kaja. So I'll just say, I mean, the CHMP meeting, as I said, we now will be eagerly awaiting the outcome of that discussion at the end of February. And then after CHMP, the normal process is then that it goes to European Commission and we expect their response within 67 days. And we just have to have patience and wait and see. So that's the process. And then when do we expect to start selling in Europe, Anna-Kaja?

Well, I think maybe something to add here is also that, of course, after the formal EC decision is the clarification of the risk minimization measures with the cap and the pass. So it depends also a little bit on that when those are approved and rolled out. So and usually, I mean, the first countries to launch in Europe, as you probably know, is in Germany and Austria. But I think there's a lot of question marks around those still steps that you mentioned. So it's difficult to set a date, I would say. And it's up to ASA, of course, to comment on that.

And then in the Nordics, when can Nordic patients have access?

So, and as you know, we have then the market access process with the, we are HTA countries, so we will have to start with the health economic evaluations. And when it comes to the Those timelines for hospital products, there is no exact timeline. But based on ACE-INR's experience, it's usually around a year at least. And especially since this is a new treatment modality which is coming for the authorities. We expect that there will be, of course, a need to educate on the therapeutic area, and they will probably have questions on how to evaluate the effect, et cetera, et cetera. So I think we shouldn't underestimate that need to educate also the authorities and payers on this specific area and Lakembi. So it will take some time, but we are prepared for the questions for days. Thank you.

Thank you. We have another question from Frederick from Red Eye, and he's wondering about the timeline of the BMS program, if we can say anything about that, when do we believe that could reach the clinic, and then potentially the market, and anything we can say on market potential or addressing patient population, and if there's anything that difference it from LeCambie in that sense when it comes to potential patient population.

I can just say that now it's of course up to BMS to drive this forward. We had in our plans to go into phase one next year, 2026, but of course it's now up to BMS how they will drive this. They are very committed and have great plans for this programme, but I will refer to them to comment on that. But I see, I mean, there is a huge market potential both for, for example, 2803 and for 2802 and for many others. I mean, this is a huge patient population where there is a clear unmet medical need. I think Lecambi is coming and really being the first one to help out. But I think there will be more and there is room for many different alternatives in the future. So I think that's my answer right now.

Yeah, good. Then we have a couple of questions here from RBC. And the first one is, do we believe that the maintenance approval, and I assume that that refers to the IV approval that came just now, will move the needle in any way for Lecambi when it comes to the launch? Or do you think it's more of wait and see for the induction dose of sub-Q before... we really can see a difference in the market.

I think it is an important approval because the patients who have been on treatment for 18 months, of course, it's good for them to be able to have less frequent dosing. So they want to continue dosing and getting the most benefit out of the treatment. So I think it is important. And then when they also then later on get the subcutaneous alternative instead, even more convenient. But of course, the most important one is when we have the subcutaneous autoinjector also for induction. And that's 2026. But I think all of every approval is important. But the sub-Q will definitely, I expect, to move the needle.

Yeah, thank you. And then beyond infusion capacity, which we know has been somewhat of a hurdle in the US, which now, as Anders alluded to, seems to be easing off. Are there any other hurdles on getting patients started that we can comment on?

I mean, of course, there have been other challenges, for example, with the diagnosis side. If you are depending on a PET scan and the reimbursement of PET tracers, which has also been solved to some extent. And also people have gotten more and more used to doing CSF sampling and lumbar puncture. But of course, the blood-based biomarkers will really help here. So I think that is an important part as an example. And I think what the blood-based biomarkers already have helped to make sure that those patients who are coming for confirmational through CSF or PET scan are the right patients and have not been diluted into patients who are not the right patients as a capacity issue. So I think that, I mean, step by step, there are several things happening. And Anna-Kaja, I want to add.

Yes, I think also what we hear, both from the US market but also here in the Nordics, is that I think the quality of the patients being referred to the memory clinics also needs to be improved, I would say, because if you look at some studies that have been done both in the US and in Sweden, it's that And there's only a fraction of the patients today at the clinics who are kind of eligible for a potential treatment. So I think that this will be an important thing to work on for the clinics and for us in the future.

Thank you. And then a question from Peter Herma. How important do you consider the AHEAD 345 study to be for the extended use of Lecambi in the long run? And it seems to him to be a very important study. And is there any, he also talks about competitors. Maybe we can just comment on if there are any similar studies ongoing as well.

So I'm really excited about the AHEAD 345 study, especially when you look at the data that ASI have presented from the CLARITY 80 study, when they look at the very early patients who have lower levels of amyloid in the brain, or if you look at those with low tau, for example. If you look at those patients who are at a very early stage, they seem to have a quite high proportion of being stable or even improve. So I think in this I had 3, 4, 5 study by starting early individuals who have the pathology, but not yet symptoms. So think about if we can really push forward the time for when symptoms appear or potentially maybe even stop. I think this is a very important study to follow. And I think ASI is doing a tremendous piece of work here together with the Alzheimer Clinical Trial Consortium who are driving the program. And they are really pioneering. There are other studies also in this area since the whole field realized that it might be even better to go as early as possible. So I think this is really good for patients that we will be following. And then again, blood-based biomarkers would be very important. And they're already utilized in the AHEAD study in the screening phase.

Thank you, Gunilla. Thank you, Anders. Thank you, Anna-Kaja. I think that was the last question that we have here. And there doesn't seem to be any more people on the phone lines either calling in. So I think that concludes today's call. Thank you, everybody, for listening in and see you next time.

Thank you.