BioArctic AB

STO:BIOA B

Earnings Call Transcript 2022-Q3

[Operator]

Good morning, and welcome to the BioArctic Q3 Report 2022. [Operator Instructions] Today, I'm pleased to present CEO, Gunilla Osswald; and CFO, Jan Mattsson, speakers. Please go ahead.

[Gunilla Osswald, executive]

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 the groundbreaking results from the Clarity AD, the Phase III study in early Alzheimer's disease patients. It was great to see some robust and consistent results in the Phase III study. And of course, I will talk more about that here today.

So 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 4 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 are 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 III and now also in regulatory phase. And 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 on 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. And as you can see, we focus on brain disorders. We have a combination of fully financed partnered projects like lecanemab, where our partner finance the clinical development part. And we have 2 programs for lecanemab, one that we'll talk more about with the results in the Clarity AD study, which focused on early Alzheimer's disease. And there is another Phase III program ongoing in earlier stages even before you get any symptom, and that is called AHEAD 3-45.

Then we have also out-licensed the backup compound, and we have 5 internal programs for Alzheimer's disease, all disease modifying. And today, we are revealing one of the mechanism of actions for one of those projects. And that is the AD-BT2803, which we now reveal that, that is related to truncated forms of amyloid beta or [indiscernible] Abeta. And that is then linked with our brain transporter technology. Now when lecanemab has shown positive Phase III results, I think that the probability of success has also increased for our other programs with a similar approach to lecanemab. And 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.

So lecanemab targets protofibrils for amyloid beta and in Parkinson's disease, we target oligomers and protofibrils for alpha-synuclein and in ALS, the protein is called TDP-43. And our ALS project, TDP-43, is progressing really well. And that's thanks to all our experience what we have done in Alzheimer and Parkinson previously. So 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. And 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. And in the future, we could also apply it to other companies' antibodies and proteins on a nonexclusive license basis.

So 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 2 license deals and several research collaborations. And 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 continues to progress well with regard to milestones. And those are linked to regulatory submissions and approvals and some is also linked to sales and marketing milestones.

And if we come all the way to the market, we can expect high single-digit royalties. And 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. So some recent highlights during the last quarter. If we start with Alzheimer's disease and lecanemab. It was fantastic when we've got the news that lecanemab showed positive results in the pivotal Phase III study that we call Clarity AD in early Alzheimer's disease. And both primary and all key secondary endpoints were met. And that's with high statistical significance. And I'll talk more about that. It was also encouraging to see the results that Eisai presented at the last Alzheimer Congress called AAIC 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. And they set the PDUFA date to 6th of January next year, which is the latest they will respond to the application. So that is less than 3 months' time from now. And 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. And during the quarter, we have executed the transition agreement with AbbVie and we are now working actively to take the projects back and to transfer all the data back to BioArctic. And 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. So now I will focus on lecanemab. And I'll start with this slide that shows the design of this pivotal Phase III study, which was designed to confirm the positive Phase IIb 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. So all the patients had to show that they had amyloid pathology in the brain like you can see on that 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. And it's seen 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. And there were also 3 clinical scales where key secondary and that was ADAS-cog14 and ADCOMS. Those 2 clinical scales were also included in the Phase IIb study with very promising results.

And in this trial, there was a new scale and activity of daily living scale called ADS, MCI, ADL. So 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. So now we come to the results of the Phase III study. And I have to say that when we've got the results, I mean, it was really, really happy. Our partner Eisai has done a tremendous work with the study. And we reported top line results in the end of September, just according to plan. The results fulfilled all our expectations and more. Lecanemab med, the primary and all key secondary endpoints in the Phase III 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 was reducing the disease progression by 27%, and with a p-value of 0.00005. And what I had hoped for was to see a p-value below 0.01, which is also required for a Phase III study if you only have one Phase III trial in your regulatory package. That was also seen an early onset of the effect, just as we saw in the Phase IIb 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. And importantly, Eisai has also communicated that this effect increases over time.

Then all 4 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 III study with low rates of area. And this is despite that lecanemab is not being titrated, we're giving the full dose directly. And also, Eisai has broadened the patient population in this trial to include more comorbidities and more concomitant medications, including anticoagulants. And furthermore, Eisai has really put an effort into getting an increased number of minorities in the U.S. population included in this trial. And we got 25% of the U.S. population was minorities. And all this is with the aim to measure the Medicare population for the U.S. in order to support future discussions with CMS regarding reimbursement.

We have also shown that lecanemab modifies the underlying disease pathology in the Phase IIb 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.

So this slide shows how Eisai has modeled long-term effects of lecanemab. And this is based on the Phase IIb results, and this was published earlier this year. It shows that lecanemab could delay the progression of Alzheimer's dementia by several years. And 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 a longer period, and then we can see more benefits. So the results from the modeling that shows the potential clinical value of lecanemab. And I think it's an easy way to understand and try to explain the clinical meaningfulness of the results.

So lecanemab can slow the rate of disease progression, and it can delay progression of Alzheimer's dementia with several years. And 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. And of course, this is important for patients and families and for society. This model will be updated with the Clarity AD results at the later stage -- or as soon as possible, I would say.

So next slide, please. So this slide summarizes the broad late-stage clinical program for lecanemab. And 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 this early AD stages, which means mild Alzheimer's disease and the stage before called mild cognitive impairment due to Alzheimer's disease. And this is where we have the positive Phase III 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 I study with have volunteers, an auto injector for subcutaneous administration to make it even more convenient for the patient. There is also another open-label extension study ongoing for the patients from the Phase IIb study. And 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.

And then as I mentioned in the beginning of my presentation that there is another Phase III study also ongoing in even earlier stages of Alzheimer's disease. And here, we are talking about subjects without any symptoms, but they have increased levels of amyloid in the brain 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. So I think this AHEAD 3-45 study is also very exciting to follow.

Furthermore, 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. So this is a combination trial. So I think it's a really impressive broad clinical program that Eisai are progressing for lecanemab.

Next slide, please. So I will now summarize lecanemab, which has the potential to lead the paradigm 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 III study that confirmed the Phase IIb results with high statistical significance. We have the opportunity to be first with a full approval in the U.S., and 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. So we can expect the FDA decision within 3 months, so by 6th of January at the latest. And then the most important is, of course, to get full approval. And here, Eisai are aiming to submit applications for full approval in the U.S., Europe and in Japan by the end of the first quarter next year. So there is then a potential for a full approval in the U.S. already next year and in Europe and Japan even next year or the year after.

Lecanemab really seems to be the best anti-amyloid antibody, in my opinion. And I think that we have a great opportunity to differentiate versus other late-stage competitors, and that's based on 5 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. So the last aspect is that we are the only one who can give the treatment like a full dose from day 1 of the other late -- compared to the other late-stage antibody.

Then since it's going so well, it's really important to think about future as well. And 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 projects, and this is in parallel with the therapeutics. And 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 frequency -- dosing frequency during maintenance phase when the amyloid deposit has been cleared from the brain.

And also, of course, when we now have seen so good effect, it's important to think about who other patients -- what other indication patients could benefit from treatment with lecanemab in the future. So I think it looks really, really great for lecanemab, and we have very exciting times ahead of us.

Next slide, please. So by that, we come to the financial summary, and I hand over to our CFO, Jan Mattsson.

[Jan Mattsson, executive]

Thank you, Gunilla. I'd like to start with again reminding you that presently 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 218 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, Eisai, and also from the final settlement with AbbVie of the Parkinson 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. And the main reason for the cost increase is related to onetime effect, 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 to SEK 260 million for the financial year '22 compared to SEK 166 million in last year. And 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 million compared to minus SEK 35 million in Q3 of last year. Net results for the quarter was SEK 137 million compared to minus SEK 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.

And in summary, BioArctic continues to have a strong financial position. And with that, next slide, and please back to Gunilla.

[Gunilla Osswald, executive]

Upcoming news and closing remarks. So next slide, please. So 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, 29th of November in San Francisco. And we'll see more data then from the Phase III study. And there is so much data in this clinical study. So we can expect to see more data also coming in future Alzheimer Congresses, like ADPD in March next year.

Then the rolling submission under the accelerated approval pathway, as I said, has been accepted by the FDA and we have a priority review. And we will expect a response within the coming 3 months. And we also look forward to provide more information on our other projects when that is relevant.

Next slide, please. So 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. And everything we do is with patients in mind and our aim is to help patients with brain disorders. And I really think that we are on our way to help the Alzheimer's patients soon. And I think that we have very exciting times ahead.

So next slide, please. So by that, I say thank you so much for your attention. We're happy to take questions.

[Operator]

[Operator Instructions] The first question comes from the line of Fredrik Thor with Redeye.

[Fredrik Thor, analyst]

Congratulations on the results again. My first question was about BioArctic beyond lecanemab, as I said, what type of -- can you accelerate your internal programs given the increased financial positions and increasing strong position in the Nordic market or -- Yes, what type of -- Yes. Can you accelerate your other programs on the way given a success for lecanemab?

[Gunilla Osswald, executive]

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. So 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 subcutaneous and then other patient populations. So I think lecanemab is a huge opportunity even further than what we just have seen in results to. So that's my first comment.

And then as you can see, we have step-by-step expanded our portfolio. And I think that we -- to some parts, it takes the time it takes no matter how much money you have. It's like the pregnancy, it takes 9 months, even if you have 3 women. It's kind of the same thing in some steps when you do drug development. But 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. And I'm really impressed, as I said, with TDP-43, the ALS project, how quickly that program is progressing based on utilizing all our experience from both Alzheimer and Parkinson.

But also, we will see how we can drive the whole portfolio in the most optimal way. So we will come back more with that. So thank you. Great question.

[Fredrik Thor, analyst]

And also in relation to that, in-licensing assets from other companies, is that something that's -- yes, is that [indiscernible] or is that a potential?

[Gunilla Osswald, executive]

Thank you for that question. So we get -- just like we have an open door policy and we get questions about our old portfolio all the time, we are also looking at other alternatives and getting proposals. But I must say that what is unique with BioArctic is that it's really an innovative company with a lot of ideas. So for us, it's rather prioritizing among so many great ideas rather than -- so 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.

[Fredrik Thor, analyst]

Perfect. And maybe as a final question for me, when it comes to the accelerated approval in the U.S., I mean, given that it was so clear with the Clarity AD, do you hope to see some initial sales even before the full approval or should we expect that full approval maybe for reimbursement processes and so on also beyond Medicare, for example?

[Gunilla Osswald, executive]

Yes. No, I think the accelerated approval, I think there is a couple of things, which is great with doing this process. And one is that when you have got that approval, you can start to build up the infrastructure and the prepare sites and so forth. And you can start to do some sales and marketing. But I think it will be limited until the full approval and a broader reimbursement. But also, I think that now when we have the robust Clarity AD result, that gives a high likelihood that we can have a full approval as well. And then I expect good discussions to be happening with CMS. So I see very positively on this, but it has to take step by step. But I think now we can see some sales already next year.

[Fredrik Thor, analyst]

Okay. And maybe a very short final question about the Japanese application process. Can you maybe very shortly remind us of the timeframe from -- the potential timeframe for an approval given that your [indiscernible] application as you mentioned.

[Gunilla Osswald, executive]

Yes. Thank you so much. So in Japan, there is also a very specific process. Each regulatory pathway is different for the different regions. So 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. So they have been reviewing the preclinical and the CMC data and so forth and the Phase IIb data. So 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 2 authorities to focus on the Phase III results. And they have already reviewed the preclinical, the majority of CMC and the Phase IIb results.

So I think both for the U.S. and for Japan, they have a much easier way with our review for a full approval. In Europe, it's different because there, the processes are different. That would be a full application with everything at the same time. So I think we will expect a little longer time for Europe than we do for U.S. and Japan for the approval process.

[Operator]

The next question comes from the line of Zoe Karamanoli from RBC Capital Markets.

[Zoe Karamanoli, analyst]

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? And if yes, what exactly are the elements that give you confidence for this? That's the first question.

[Gunilla Osswald, executive]

That's a great question. Thank you so much, Zoe. So I think, I mean, now when we have shown both in the Phase IIb and now in the Phase III 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, that can be a read-through in other biomarkers. What -- and 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.

So in the very early stages, for the A45 study for those who have increased levels of amyloid in the brain, the scale is called PACC5, and that's the way to measure those early symptom signal. And that study is 4-year trial in comparison to the Clarity AD, which was 18-month treatment. And depending on how much amyloid deposits you have in the brain, you are getting different levels of dosing. So 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. And maybe we can show an even better effect if we start even earlier. So I'm really excited to see the progress of this study in the future.

[Zoe Karamanoli, analyst]

Okay. That's great. And then can I go back to the timelines for the U.S. approval and the European one. So 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 6th of January, is it possible that we could see the PDUFA date pushed out to -- for the FDA to also review the Phase III data? That's the first part. And 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?

[Gunilla Osswald, executive]

Yes, great questions. So 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 by the end of first quarter. And 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. And then your question was also about -- I mean, the PDUFA date is set to 6th of January, and it might come earlier, and it might come on the 6th of January. I cannot really comment on that.

And I think it's important to understand that there is 2 different processes. There is one process for the accelerated approval pathway, which is really based on the Phase IIb 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. So that is the accelerated approval pathway. So 6th of January or maybe earlier, we will say that depends on the FDA review time.

Then for full approval, that is then based on the efficacy data. And that is what we have in the Clarity AD study. And that is then a full approval application that Eisai is working on for -- I mean, more or less the whole world, but they are starting with 3 regions, U.S., Europe to EMA and Japan. And 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 timeline, they have 60 days to accept the application and then there is up to 6 months if we get a priority review process. So 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. It's a very different process in Europe. So I think that the expectation is more that we could see an approval in the first half of 2024, maybe earlier, but I think realistically, something there. And then the reimbursement discussion. So I think that we could see sales in Europe during 2024. That's my expectation. And Japan, with this pre-review process and the submission. So maybe approval in 2023 or 2024. So was that answering your question?

[Zoe Karamanoli, analyst]

Yes. Just one clarification for the reimbursement then in the Nordics, if you get approval in the first half?

[Gunilla Osswald, executive]

In the Nordics, what I'm saying is I think that we could look forward to, if everything continues to progress well, to see it in the Nordic market on the second half of 2024.

[Operator]

The next question comes from Patrik Ling from DNB Markets.

[Patrik Ling, analyst]

Great. I also actually have a few questions regarding your pipeline. I mean you talked about the pregnancy over doing research here, Gunilla. So 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 pregnancy you are? So when could we expect these projects to actually shift from discovery to preclinical or from preclinical into Phase I?

[Gunilla Osswald, executive]

Excellent question. So I think that the discovery phase is the phase where it's harder is to say how long time you really need because this is really innovative research. But when you come into preclinical, then it's easier because then it's often between -- normally 2 to 3 years, in that phase. And in the discovery phase, I think, I hope that we can see some progress during next year.

[Patrik Ling, analyst]

Okay. And given that, for example. Sorry, go ahead, Gunilla.

[Gunilla Osswald, executive]

I'm not telling you exactly which project, but I really hope to see progress of something into preclinical next year.

[Patrik Ling, analyst]

Okay. And 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.

[Gunilla Osswald, executive]

Yes. And what we have said is that we were waiting for these results to see what we learned from the Phase III result. And 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. And we have also a patent on traumatic brain injury. But now we are actually thinking about even further indications. So we're doing more work in other indications as well. So we will really explore different options before we decide which one to progress first. So since we have some other great ideas, it will probably take a bit longer time also for Down syndrome.

[Patrik Ling, analyst]

Okay. Great. Could I also ask, when it comes to your project in ALS with TDP-43, that is protein that seems to be implicated in quite a few different neurodegenerative diseases. Are you considering expanding that project into other potential indications as well?

[Gunilla Osswald, executive]

That's a great question. And absolutely, yes, but you need to start somewhere. And 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. But also, just as you said, front and temporal dementia and also Alzheimer's disease. I mean, half of the Alzheimer's disease patients roughly have also TDP-43 aggregates. And I think the whole Alzheimer field talk more and more also about comorbidity, also alpha-synuclein and TDP-43. So 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.

So 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 [indiscernible] I see the same opportunity, both for the alpha-synuclein and for the TDP-43. But you have to start somewhere, and then I can see several other indications. For alpha-synuclein, we could also see MSA, multiple systemic atrophy, and Lewy body dementia. So I think all of these have opportunities for several different indications in the future.

[Patrik Ling, analyst]

Okay. Great. Then 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 -- 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 and stuff like that?

[Gunilla Osswald, executive]

Yes. I wish I knew. I'm as excited as you, Patrik. And I -- well, I just had to say I'm quite humbled when I realized with all my experience in clinical drug development that this is a huge amount of data. It's enormous amount of data. And 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. So 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 the MCI versus mild and also symptomatic treatment as concomitant or not, and [indiscernible] carriers or not. So I hope so, but I don't know. So I don't really know what the expectation is like.

But then also, 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 [indiscernible] and many other things and the blood biomarkers. So there is a lot of data that I think we can look forward to at future congresses. So and I don't think those will be ready now. So I think those detailed biomarker data will be later next year. So I hope that -- I mean, I don't know, but that was how I'm thinking.

[Operator]

The next question comes from the line of Joseph Hedden from Rx Securities.

[Joseph Hedden, analyst]

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 going through -- going to be going through 2 processes, the accelerated approval pathway and the full approval, is that set for milestones linked to those pathways. And maybe anything you could say on the split between -- the relative split between the EUR 136 million remaining, what's regulatory and what's commercial?

[Gunilla Osswald, executive]

Thank you so much, Joseph. As you know, I'm very careful not revealing more than what we have agreed with Eisai. So what we have remaining, just as you know, is EUR 136 million. And they are linked to regulatory submissions and approvals, and we will see which one comes first and then some sales marking milestones. But unfortunately, I cannot reveal more details right now.

[Joseph Hedden, analyst]

Okay. And then just wanted to last 1 on the TDP-43 program. Is the -- that protein solving -- again, it's the premise similar to with lecanemab and BAN0805 in that you're targeting the specific wounds and elements -- all elements. So that's -- so 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?

[Gunilla Osswald, executive]

Yes. So 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. So it's the aggregated forms, but it's definitely oligomers, protofibrils and also the inclusion. And no, I think, I mean, there is a lot of similarities.

So I think that I have increased my thinking around probability of success for both the alpha-synuclein and the TDP programs that we have. And if you think about alpha-synuclein, we have a very huge selectivity from -- for the pathological forms the protofibrils and oligomers versus the physiological forms, the monomers. And 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. So I think that is a differentiating factor, which I'm really excited to see what that could mean in the clinic.

[Joseph Hedden, analyst]

And then so is it -- on that front, it seems BAN0805 is very well differentiated with its binding specificity. Is it too early to say whether TDP-43, whether the program there is significantly different from some of the others that we see?

[Gunilla Osswald, executive]

Yes, that's too early. Too early. I mean we're humanizing the antibody right now. So when we have it, then we will characterize it, and then we can talk more about those details. But we have the same thinking and we're utilizing the same approach when we are generating the antibody.

[Operator]

There are no more questions at this time. So I hand the word back to you, Gunilla and Jan, for any closing remarks.

[Gunilla Osswald, executive]

I just want to say thank you so much for your attention and for all great questions. And please stay with us, and I'm really excited about the future. So thank you very much for today.

[Operator]

Thank you. That concludes today's call. You may now disconnect your lines.