Thank you so much. Good morning, and welcome to BioArctic's presentation from the third quarter. I'm Gunilla Osswald, I'm the CEO of BioArctic, and I will share today's presentation with our CFO, Jan Mattsson. I will start by giving an update on BioArctic, and I will also focus, of course, on the fantastic news that we have had with lecanemab, with a groundbreaking result from the Clarity AD, the Phase 3 study in early Alzheimer's disease patients. It was great to see so robust and consistent results in the Phase 3 study. Of course, I will talk more about that here today. Next slide, please. This is our disclaimer. Next slide, please. I'll start with a short introduction to BioArctic. I think BioArctic is a unique Swedish biopharma company focusing on improving the lives for patients with brain disorders.
I think that we are unique based on four different aspects. The first one is that we work in areas where there is a high unmet medical need with disease-modifying treatments affecting the underlying disease, in diseases like Alzheimer's disease and Parkinson's disease, areas where there is a large commercial opportunity and a huge unmet medical need. The second aspect is that we have a world-class research and development-driven organization, and we're working with leading academic sites around the world and with our great partner, Eisai, in Alzheimer's disease. The third aspect is that we have an attractive and well-balanced project portfolio with projects spanning from early discovery all the way through to Phase 3, and now also in regulatory Phase. We have a combination of both proprietary projects with substantial marketing and out-licensing potential and partnered projects that are generating income.
The fourth aspect is that we are well-financed, and we have more than SEK 850 million in the bank, and we have valuable collaboration agreements. We are listed at Nasdaq Stockholm Mid Cap, and we have a market cap of about SEK 21 billion. I think that BioArctic is an innovative and dynamic and very exciting company with a huge potential. Next slide, please. This slide shows our rich and well-balanced portfolio. As you can see, we focus on brain disorders. We have a combination of fully financed partnered projects like Lecanemab, where our partner finances the clinical development part. We have two programs for Lecanemab, one that we'll talk more about with the results in the Clarity AD study, which focuses on early Alzheimer's disease.
There is another Phase 3 program ongoing in earlier stages, even before you get any symptoms, and that is called AHEAD 3-45. We have also out-licensed the backup compound, and we have five internal programs for Alzheimer's disease, all disease-modifying. Today, we are revealing one of the mechanisms of action for one of those projects, and that is the BT-ADBT-2803, which we now reveal that is related to truncated forms of amyloid beta or pyroglu A-beta. That is then linked with our BrainTransporter technology. Now, when Lecanemab has shown positive Phase 3 results, I think that the probability of success has also increased for our other programs with a similar approach to Lecanemab. That is when we target the misfolded forms that we call oligomers or protofibrils, which are soluble aggregated forms of the protein that are toxic.
Lecanemab targets protofibrils for amyloid beta. In Parkinson's disease, we target oligomers and protofibrils for alpha-synuclein. In ALS, the protein is called TDP-43. Our ALS project, TDP-43, is progressing really well. That's thanks to all our experience, what we have done in Alzheimer's and Parkinson's previously. Now our ALS program with TDP-43 is progressing really well, and we are already humanizing the antibodies. Our BBB technology, which is meant to increase the penetration of the antibodies into the brain, is progressing really well. As you can see, we have combined that with several internal projects, and we have plans to continue to combine it with more internal projects. In the future, we could also apply it to other companies' antibodies and proteins on a non-exclusive license basis.
Of course, Lecanemab is very important for BioArctic, but I want to point out that BioArctic is even more than Lecanemab. Next slide, please. We have a long-standing and successful partnership with Eisai. We have been working with Eisai in Alzheimer's disease all the way back since 2005. We have two license deals and several research collaborations in the collaboration. Our research collaboration with Eisai are still progressing. During this quarter, we received a milestone of EUR 15 million when the FDA accepted the BLA submission of Lecanemab in the U.S. At the end of the third quarter, we have EUR 136 million remaining to be received if everything continue to progress well with regard to milestones. Those are linked to regulatory submissions and approvals, and some is also linked to sales and marketing milestones.
If we come all the way to the market, we can expect high single-digit royalties. This could be of substantial value if you consider how large this patient population is. BioArctic has also retained the right to other indications, and we have an option to market in the Nordics, which we are working on and really looking forward to do together with Eisai. Next slide, please. Some recent highlights during the last quarter. If we start with Alzheimer's disease and Lecanemab. It was fantastic when we got the news with that Lecanemab showed positive results in the pivotal Phase 3 study that we call Clarity AD in early Alzheimer's disease. Both primary and all key secondary endpoints were met, and that with high statistical significance. I'll talk more about that.
It was also encouraging to see the results that Eisai presented at the last Alzheimer's Congress, called AAIC, during at the end of the summer, where the data continued to support and strengthen lecanemab, and also Eisai presented data on a subcutaneous formulation. The FDA accepted the Biologics License Application or BLA for short, which Eisai submitted, and they granted priority review for lecanemab under this accelerated approval pathway. They set the PDUFA date to 6th of January next year, which is the latest date they will respond to the application. That is less than three months time from now. This also resulted in the milestone of EUR 15 million that we got from Eisai during this quarter. In Parkinson's disease, as you know, our partner took a strategic decision in April to terminate the collaboration on our alpha-synuclein portfolio.
During the quarter, we have executed a transition agreement with AbbVie, and we are now working actively to take the projects back and to transfer all the data back to BioArctic. We are currently reviewing different options, how to progress the project best forward, with the aim of finding a new partner at the right point in time. Next slide, please. Now I will focus on lecanemab, and I'll start with this slide that shows the design of this pivotal Phase 3 study, which was designed to confirm the positive Phase 2b results. This is a large study with 1,795 patients around the world with early Alzheimer's disease. U.S., Europe, and Asia was involved, and Sweden had 4 sites also involved.
The patients included were early Alzheimer's disease patients, which means that they had either mild Alzheimer's disease or the stage before, called mild cognitive impairment due to Alzheimer's disease. All the patients had to show that they had amyloid pathology in the brain, like you can see on that little PET scan on this slide. Where you see the red and the yellow, that means that the patients have amyloid deposits in the brain. In this study, patients were randomized to either get lecanemab or placebo for 18 months. The primary objective in this study was a clinical scale called CDR Sum of Boxes, and that is a scale that has both cognition and functional aspects in it. It seemed like a very clinically meaningful scale that the regulatory authorities prefer.
The key secondary endpoints were to show that we clear amyloid deposits from the brain via amyloid PET scan. There were also three clinical scales that were key secondary, and that was ADAS-Cog-14 and ADCOMS. Those two clinical scales were also included in the Phase 2b study with very promising results. In this trial, there was a new scale, an activity of daily living scale called ADCS-MCI-ADL. I'm really looking forward to seeing those results because that's the first time that we have used that scale, and that's very meaningful for patients and relatives. Now there is an open label extension study ongoing for the patients in this who have participated in this trial, and Eisai is exploring a subcutaneous formulation in the open label extension study. Next slide. Now we come to the results of the Phase 3 study.
I have to say that when we got the results, I mean, we were really, really happy. Our partner, Eisai, has done a tremendous work with this study. We reported top-line results at the end of September, just according to plan. The results fulfilled all our expectations and more. Lecanemab met the primary and all key secondary endpoints in the Phase 3 Clarity AD study, and this with high statistical significance and with a relatively low frequency of the side effect called ARIA. What really impressed me was that the results are so robust and consistent. The primary endpoint, CDR Sum of Boxes, reduced the disease progression by 27% and with a P value of 0.00005.
What I had hoped for was to see a p-value below 0.01, which is often required for a Phase 3 study if you only have one Phase 3 trial in your regulatory package. There was also seen an early onset of the effect, just as we saw in the Phase 2b study. Now we also saw an early onset of effect, which showed a statistically significant effect on CDR Sum of Boxes already after 6 months and at all time points thereafter. Importantly, Eisai has also communicated that this effect increases over time. All four secondary endpoints were met with high statistical significance and with p-values below 0.01. The safety profile of lecanemab has previously shown to be very good, and now it was confirmed in the Phase 3 study with low rates of ARIA.
This is despite that lecanemab is not being titrated. We're giving the full dose directly. Eisai has broadened the patient population in this trial to include more comorbidities and more concomitant medications, including anticoagulants. Eisai has really put an effort into getting an increased number of minorities in the US population included in this trial, and we got 25% of the US population was minorities. All this is with the aim to mirror the Medicare population for the US in order to support future discussions with CMS regarding reimbursement. We have also shown that lecanemab modifies the underlying disease pathology in the Phase 2b study. The slowing down disease progression is clinically meaningful, and it means more time in less severe stages of Alzheimer's disease, and I'll show you more about that on the next slide, please.
This slide shows how Eisai has modeled long-term effects of lecanemab, and this is based on the Phase 2b results, and this was published earlier this year. It shows that lecanemab could delay the progression of Alzheimer dementia by several years. I think this is an important way to describe the long-term effects of lecanemab since the clinical trials that we just spoke about is 18-month treatment, and lecanemab is meant to be treated for longer period, and then we can see more benefits. The results from the modeling that shows the potential clinical value of lecanemab, and I think it's an easier way to understand and try to explain the clinically meaningfulness of the results. Lecanemab can slow the rate of disease progression, and it can delay progression of Alzheimer dementia with several years.
That means that the patients are getting more healthy years in earlier stages. It also means that we could reduce the need for institutionalization care. Of course, this is important for patients and families and for society. This model will be updated with the Clarity AD results, at a later stage or as soon as possible, I would say. Next slide, please. This slide summarizes the broad late-stage clinical program for lecanemab. I think that our partner, Eisai, are doing a tremendous piece of work here, and they are very committed to lecanemab. The focus has now been on these early AD stages, which means mild Alzheimer's disease and the stage before called mild cognitive impairment due to Alzheimer's disease.
This is where we have the positive Phase 3 results and where the open label extension study is now ongoing with the subcutaneous formulation. The study is also still ongoing in China. Eisai are also exploring, in another study, a Phase 1 study with healthy volunteers, an auto-injector for subcutaneous administration to make it even more convenient for the patients. There is also another open label extension study ongoing for the patients from the Phase 2B study. Here, Eisai are exploring if maintenance dosing after the 18-month treatment, if the maintenance dosing then could be given less frequently, and they are exploring to give Lecanemab either once a month or every third month. As I mentioned in the beginning of my presentation, there is another Phase 3 study also ongoing in even earlier stages of Alzheimer's disease.
Here we are talking about subjects without any symptoms, but they have increased levels of amyloid in the brain or and are at risk of getting symptoms. If we start treatment even earlier, so maybe we can have an even larger effect and delay the symptoms even further. I think this AHEAD 3-45 study is also very exciting to follow. The first combination trial is also ongoing, and in this study, all patients get Lecanemab, and half of the patients are randomized to either get placebo or to get a tau treatment as well. This is a combination trial. I think it's a really impressive broad clinical program that Eisai are progressing for Lecanemab. Next slide, please. I will now summarize Lecanemab, which has the potential to lead the paradigmatic shift in the treatment of Alzheimer's disease.
I think that we have a very high likelihood of success based on the robust and consistent results that we saw in the Phase 3 study that confirmed the Phase 2B results with high statistical significance. We have the opportunity to be first with a full approval in the U.S. We have the opportunity to be the first disease-modifying treatment for Alzheimer's disease in Europe and in Japan. The rolling BLA submission to the FDA under the accelerated approval pathway has been completed by Eisai, and the FDA has accepted the submission and granted a priority review. We can expect the FDA decision within three months. By 6th of January at the latest. Then the most important is of course to get full approvals.
Here Eisai are aiming to submit applications for full approvals in the U.S., Europe, and in Japan by the end of the first quarter next year. There is then a potential for a full approval in the U.S. already next year, and in Europe and Japan either next year or the year after. Lecanemab really seems to be the best anti-amyloid antibody, in my opinion. I think that we have a great opportunity to differentiate versus other late-stage competitors. That's based on five different aspects. The first one is that we have a unique binding profile that is selectively targeting the toxic protofibrils of amyloid beta. The second one is that we have a rapid and profound brain amyloid clearance effect with lecanemab.
The third one is that we have shown an early onset of clinical effect in slowing of cognitive decline, and importantly, increasing over time. The fourth aspect is that we have a good tolerability profile with a relatively low frequency of ARIA-E, even though we do not titrate. The last aspect is that we are the only one who can give the treatment like a full dose from day one compared to the other late-stage antibodies. Since it's going so well, it's really important to think about future as well. Here we see that we are developing the subcutaneous injection as an important alternative, and even more with an auto-injector that can do it even more convenient administrations at home for the patients.
The blood biomarkers, as you have heard me say before, is making great progress, and this in parallel with the therapeutics. Eisai are already utilizing the blood biomarkers in order to screen patients for AHEAD 3-45 and to explore less frequent dosing in the open label extension study when they are exploring the dosing frequency during maintenance Phase when the amyloid deposit has been cleared from the brain. Also, of course, when we now have seen some good effect, it's important to think about what other patients, what other indications patients could benefit from treatment with lecanemab in the future. I think it looks really, really great for lecanemab, and we have very exciting times ahead of us. Next slide, please. By that, we come to the financial summary, and I hand over to our CFO, Jan Mattsson.
Thank you, Gunilla. I'd like to start with again reminding you that at present our revenue consists of milestone payments and compensation from collaboration agreements, and that means that we don't have any steady revenues yet. Net revenues in the quarter amounted to SEK 280 million compared to SEK 4 million in the previous quarter of 2021. The main reason for this big increase is explained by the EUR 50 million milestone payment from our strategic partner at Eisai, and also from the final settlement with AbbVie of the Parkinson's project, and that amounted to SEK 48 million. Total costs in the quarter were higher than in last year and amounted to SEK 87 million compared to SEK 42 million in previous year.
The main reason for the cost increase is related to one-time effects, but also to the fact that we continue to build a commercial organization and to further progressing our expanded portfolio. Operating profit was SEK 133 million in the quarter compared to a loss of SEK 37 million, and the reason for this has to do with higher revenues in the quarter. Operating expenses are expected to be in the range of SEK 220 million-SEK 260 million for the financial year 2022, compared to SEK 166 million in last year. The reasons for the increase is the buildup of the commercial organization, but also, costs for the expanded in-house project portfolio. Next slide, please. The cash balance amounted to SEK 863 million at the end of September.
Operating cash flow amounted to SEK 112 compared to -35 in Q3 of last year. Net results for the quarter was SEK 137 million compared to -38 million in Q3 of previous year. The main reason for the increase for this and also for the positive cash flow effect is related to higher revenues. In summary, BioArctic continues to have a strong financial position. With that, next slide, and please back to Gunilla.
Upcoming news and closing remarks. Next slide, please. Our upcoming news flow is that we are really looking forward now to when Eisai will present the Clarity AD results at the Alzheimer's Congress called CTAD, November 29 in San Francisco. We'll see more data then from the Phase 3 study. There is so much data in these clinical studies, so we can expect to see more data also coming in future Alzheimer congresses, like AD/PD in March next year. The rolling submission under the accelerated approval pathway, as I said, has been accepted by the FDA, and it has a priority review. We will expect a response within the coming three months. We also look forward to provide more information on our other projects when that is relevant. Next slide, please.
I'll just close by saying that BioArctic is built on great science. We have great projects, we have great partners, and great people working at BioArctic. Everything we do is with patients in mind, and our aim is to help patients with brain disorders. I really think that we are on our way to help the Alzheimer patients soon. I think that we have very exciting times ahead. Next slide, please. With that, I say thank you so much for your attention, and we're happy to take questions.
Thank you, Gunilla. If you do wish to ask a question, please press zero-one on your telephone keypad. If you wish to withdraw your question, you may do so by pressing zero-two to cancel. The first question comes from the line of Fredrik Thor from Redeye. Go ahead, Fredrik. Your line is open.
Hello. Thanks for taking my questions, and congratulations on the results again. My first question was about BioArctic beyond lecanemab, as you said. Can you accelerate your internal programs given the increased financial position and increasingly strong position in the Nordic market? Or, can you accelerate your other programs in any way given the success with lecanemab?
Thank you so much, Fredrik, for that question. Great question. I think the first thing I would like to say is that lecanemab is more than Clarity AD. That's the first thing to say. I mean, we really look forward to the hope for an accelerated approval in short and a full approval for the early AD and then a subcutaneous and then other patient populations. I think lecanemab is a huge opportunity even further than what we just have seen the results to. That's my first comment. As you can see, we have step by step expanded our portfolio. I think that we to some part, it takes the time it takes no matter how much money you have. It's like, you know, the pregnancy takes nine months, even if you have three women.
It's kind of the same thing in some steps when you do drug development. Of course, we are looking into how for the whole portfolio now when we know the results, we are really looking into to see what can we do to progress potentially something even more quickly. I'm really impressed, as I said, with the TDP-43, the ALS project, how quickly that program is progressing based on utilizing all our experience from both Alzheimer's and Parkinson's. Also we will see how we can drive the whole portfolio in the most optimal way. We will come back more with that. Thank you. Great question.
Yeah. Also in relation to that, in-licensing assets from other companies, is that something that, yeah, is that true now?
Yeah.
Is that a potential?
Thank you for that question. We get just like we have an open door policy and we get questions about our portfolio all the time, we are also looking at other alternatives and getting proposals. I must say that what is unique with BioArctic is that it's really an innovative company with a lot of ideas. For us, it's rather prioritizing among so many great ideas rather than. The bar is very high if we should in-license something. I'm not saying that we will never do it. We are looking at the options that we can see, but it's a very high bar since we have so many interesting things internally.
Perfect. Maybe as a final question from me, when it comes to the accelerated approval in the U.S., I mean, given that the data was so clear from Clarity AD, do you hope to see some initial sales even before the full approval, or should we expect that a full approval is needed for reimbursement processes, so also beyond the Medicare, for example?
Yeah. No, I think in the accelerated approval, I think there is a couple of things which is great with doing this process. One is that when you have got that approval, you can start to build up the infrastructure and prepare sites and so forth. You can start to do some sales and marketing. I think it will be limited until the full approval and a broader reimbursement. I think that now when we have the robust Clarity AD results and that gives a high likelihood that we can have a full approval as well, and then I expect good discussions to be happening with the CMS. I see very positively on this, but it has to take step by step. I think that we can see some sales already next year.
Okay. Maybe a very short final question about the Japanese application process. Can you maybe just very shortly remind us of the timeframe from the potential timeframe for an approval given that you sending an application as you mentioned?
Yeah. Thank you so much. In Japan, there is also a very specific process. Each regulatory pathway is different for the different regions. In Japan, there is a possibility to submit data in a pre-review process pathway, and that is what Eisai has been doing during this year. They have been reviewing the preclinical and the CMC data and so forth and the Phase 2B data. What will be new for them to review in a similar way to in the U.S. when the full submission will be submitted is really for those two authorities to focus on the Phase 3 results. They have already reviewed the preclinical, the majority of CMC and the Phase 2B results.
I think both for the US and for Japan, they have a much easier way with a review for a full approval. In Europe, it's different because there the processes are different. There will be a full application with everything, at the same time. I think we will expect a little longer time for Europe than we do for US and Japan, for the approval process period.
Perfect. Yeah, that's all for me. Thank you.
Thank you so much, Fredrik.
The next question comes from the line of Zoe Knapska from RBC Capital Markets. Your line is now open. Go ahead.
Yeah. Hi, thank you for taking my question, and congratulations again on the great news on Lecanemab. The first question is, it will be good to understand how you see the results from Clarity AD in relation to the prevention study in the AHEAD 3-45, and in particular, whether you think there is some read across, from the positive data from Clarity AD. If yes, what exactly are the elements that give you confidence for this? That's the first question.
That's a great question. Thank you so much, Zoe. I think, I mean, now when we have shown both in the Phase 2b and now in the Phase 3 in the early stages of Alzheimer's disease that we have, we really can clear the amyloid from the brain, and we have an early effect delaying the time to dementia. I think that I expect quite substantial read-through into the AHEAD 3-45 with regard to that I expect that we will also show that we clear amyloid deposits from the brain. And I also expect that there can be a read-through in other biomarkers. I think that the AHEAD 3-45 study, we should be aware that there is another clinical scale because it's so early, so you can't use the clinical scales that we have in the Clarity AD study.
In the very early stages for the A45 study, for those who have increased levels of amyloid in the brain, there the scale is called PACC5, and that's a way to measure those early symptom signals. That study is 4-year trial in comparison to the Clarity AD, which was 18-month treatment. Depending on how much amyloid deposits you have in the brain, you are getting different levels of dosing. Higher dose if you have more amyloid deposits in the brain and slightly lower if you have intermediate levels of amyloid deposits in your brain in the AHEAD 3-45 study. Maybe we can show an even better effect if we start even earlier. I'm really excited to see the progress of this study in the future.
Okay. That's great. Thank you. Can I go back to the timelines for the U.S. approval and the European one? Eisai announced that it plans filing data from Clarity AD to the U.S., EU, and Japan for full approval by end of this year. In your view, given the PDUFA date is set for the sixth of January, is it possible that we could see the PDUFA date pushed out to for the FDA to also review the Phase 3 data? That's the first part. Then second part is, what is your current assumption about EU approval, and how long do you anticipate it will take to receive reimbursement in the Nordics following an approval?
Yeah. Great questions. I think what I'm aware of is Eisai has said that we will, and as we had in our press release, that they will submit regulatory submissions for regulatory approvals by at least the end of first quarter. If it comes earlier, I think it's fantastic, but I think it should be expected at least by the end of the first quarter. Your question was also about, I mean, the PDUFA date is set to sixth of January, and it might come earlier, and it might come on the sixth of January. I cannot really comment on that. I think it's important to understand that there is two different processes.
There is one process for the accelerated approval pathway, which is really based on the Phase 2B results, showing that we have a strong effect on clearing amyloid deposits from the brain with a high likelihood of also being linked to a clinical effect. That is the accelerated approval pathway. Sixth of January or maybe earlier, we will see. That depends on the FDA review time. For a full approval, that is based on the efficacy data, and that is what we have in the Clarity AD study. That is a full approval application that Eisai is working on, I mean, more or less the whole world, but they are starting with the three regions, U.S., Europe to EMA, and Japan.
That's what they have said and we said in the press release is at least by the end of first quarter of next year. Then I think, I mean, the timing for an approval in the U.S. for a full approval, when that submission is sent in, then if we then get a priority review, which we could expect since we got that previously as well, then according to the normal timelines, they have 60 days to accept the application. Then there is up to 6 months if we get priority review process. I think there is a high likelihood that we can see a full approval next year in the U.S. In Europe, it's different. You know, it's a very different process in Europe.
I think that the expectations is more that we could see an approval in the first half of 2024, maybe earlier, but I think realistically something there. Then the reimbursement discussion. I think that we could see sales in Europe during 2024. That's my expectation. Japan, with this pre-review process and the submission, maybe approval 2023 or 2024.
Okay.
Was I answering your question?
Yes. I just want a clarification for the reimbursement then in the Nordics if you get approval in the first half of-
Yeah. In the Nordics, what I'm saying is I think that we could look forward to, if everything continued to progress well, to see it in the Nordic market in the second half of 2024.
Okay, thank you.
Yeah.
The next question comes from Patrik Ling from DNB Markets. Patrik, please go ahead. Your line is now open.
Great. Thank you. I also actually have a few questions regarding your pipeline. I mean, you talked about the progress of doing research here, Gunilla. Maybe, I mean, despite the fact that you do have some quite substantial financial resources, could you tell us a little bit more about where exactly in the progress you are? When could we you know, expect these projects to actually shift from discovery to preclinical or from preclinical into Phase one?
Excellent question. I think that the discovery Phase is the Phase where it's hardest to say how long time you really need, because this is really innovative research. When you come into preclinical, then it's easier because then it's often between normally two to three years, that Phase. In the discovery Phase, I think that I hope that we can see some progress during next year.
Okay.
Uh.
Given that.
I'm not telling you.
Sorry, go ahead, Gunilla.
I'm not telling you exactly which project, but I really hope to see progress of something into preclinical next year.
When should we expect something to move into the clinical Phase? I mean, if we think about lecanemab and the indications that you still have, not out-licensed, Down syndrome and traumatic brain injury, I mean, it's been in preclinical for quite some time.
Yes. What we have said is that we were waiting for these results to see what we learn from the Phase 3 results. Now, as you know, we have been doing work on Down syndrome, where we have shown that Lecanemab could have a benefit by looking into postmortem brains and so forth. We have also a patent on traumatic brain injury. Now we are actually thinking about even further indications, so we're doing more work in other indications as well. We will really explore different options before we decide which one to progress first.
Okay. Great.
Since we have some other great ideas, it will probably take a bit longer time also for Down syndrome.
Okay. Great. Could I also ask, when it comes to your project in ALS with TDP-43, that that is a protein that seem to be implicated in quite a few different neurodegenerative diseases. Are you considering expanding that project into other potential indications as well?
That's a great question, and absolutely yes. You need to start somewhere. For us, what we think is that ALS is an area where there's a huge unmet medical need. It's an orphan drug indication that makes it possible for us to drive longer. Also, just as you said, frontotemporal dementia and also Alzheimer's disease. I mean, half of the Alzheimer's disease patients roughly have also TDP-43 aggregates.
Mm-hmm.
I think the whole Alzheimer's field talk more and more also about comorbidity, also alpha-synuclein and TDP-43. I think that we have a portfolio that is great for many different indications, but actually also for Alzheimer's disease, both alpha-synuclein and TDP-43 in the long run. I think it's important, just like you see how I try to lay it out for lecanemab that you do life cycle management with more and more things happening after the first like. I see the same opportunity both for the alpha-synuclein and for the TDP-43 that you have to start somewhere, and then I can see several other indications. For alpha-synuclein we could also see MSA, multiple system atrophy, and Lewy body dementia. I think all of these have opportunities for several different indications in the future.
Okay, great. My last question really. I mean, when it comes to the presentation that Eisai will host on the CTAD meeting, what should we expect them to present? Will we see? You know, I suppose that we will see more granular data on all the different endpoints, but do you think that they will also show different subgroups? I mean, MCI patients versus mild Alzheimer's and stuff like that.
Yeah. I wish I knew. I'm as excited as you, Patrick. What I just have to say, I'm quite humble when I realize with all my experience in drug, clinical drug development that this is a huge amount of data. It's enormous amount of data. I am really impressed that Eisai could present the top line results just according to plan in the same month as they had the last patient out. What I expect is definitely to see some curves and granular data of the primary endpoint and the key secondary endpoint. I hope that we can see some subgroups. What they showed previously, the subgroup analysis they showed previously was that, you know, the MCI versus mild and also symptomatic treatment with as concomitant or not, and APOE4 carriers or not.
I hope so, but I don't know. I don't really know what the expectation is there. We should be aware that there is also a lot of biomarkers in this trial, both, apart from the amyloid PET, there's also tau PET, and there is CSF with, phospho-tau and, Aβ and many other things, and the blood biomarkers. There is a lot of data that I think we can look forward to at future congresses. I don't think those will be ready, now. I think those, detailed biomarkers, data will be later next year. I hope that, I mean, I don't know, but that's what, how I'm thinking.
Okay, great. Thank you very much. Looking forward to the data presentation on the twenty-ninth. Thank you.
Definitely so. Thank you.
The next question comes from the line of Joseph Hedden from Rx Securities. Please go ahead. Your line is open.
Good morning, and thank you for taking my questions, and congratulations again on the Clarity AD data. I wanted to ask a question on the lecanemab milestones. I realize that this is a sensitive area, but is there anything you can say about what the next one is linked to? I mean, I realize we're in the U.S., we're now gonna be going through two processes, the accelerated approval pathway and the full approval. Are there separate milestones linked to those pathways? Maybe anything you could say on the relative split between the 136 remaining, what's regulatory and what's commercial? That's the first question.
Thank you so much, Joseph. As you know, I'm very careful not revealing more than we have agreed with Eisai. What we have remaining, just as you know, is EUR 136 million. They are linked to regulatory submissions and approvals, and we will see which one comes first. Then some sales and marketing milestones. But unfortunately, I cannot reveal more details right now.
Okay. Thanks, Gunilla. I just wanted to ask one on the TDP-43 program. I realize that's protein misfolding. Again, is the premise similar to with lecanemab and BAN0805 in that you're targeting the protofibrils and oligomers so that they're really thought to be the most neurotoxic. Is it the same premise, or is there another kind of element that differentiates perhaps the approach that you're looking at to what some of the other competitors are?
Yeah. There is a lot of similarities that we target the aggregated forms. I think that for the alpha-synuclein and for the TDP-43, it's both the soluble and the insoluble. It's the aggregated forms, but it's definitely oligomers, protofibrils and also the inclusion. No, I think, I mean, there is a lot of similarities. I think that I have increased my thinking around probability of success for both the alpha-synuclein and the TDP programs that we have. If you think about alpha-synuclein, we have a very huge selectivity for the pathological forms, the protofibrils and oligomers versus the physiological forms, the monomers. Here we have more than 100,000-fold selectivity with BAN0805, which is, we haven't seen anything like that from any of the competitors.
I think that is a differentiating factor, which I'm really excited to see what that could mean in the clinic.
Okay. Is it on that front, it seems BAN0805 is, you know, well-differentiated with its binding specificity. Is it too early to say whether TDP-43 the program there is significantly different from some of the others that we see?
Yeah, that's too early. Too early.
Okay.
I mean, we are humanizing the antibody right now. When we have it, then we will characterize it, and then we can talk more about those details. We have the same thinking, and we're utilizing the same approach when we are generating the antibodies.
Great. Understood. Thank you.
Thank you so much, Joseph.
There are no more questions at this time, so I hand the word back to you, Gunilla and Jan for any closing remarks.
No, I just want to say thank you so much for your attention and for all great questions. Please stay with us, and I'm really excited about the future. Thank you very much for today.