Welcome to BioArctic Q1 Report 2024. For the first part of the conference call, the participants will be in listen-only mode. During the questions and answer session, participants are able to ask questions by dialing pound key five on their telephone keypad. Now, I will hand the conference over to CEO Gunilla Osswald and CFO Anders Martin-Löf. Please go ahead.
Thank you. Good morning, and welcome to BioArctic presentation for the first quarter of 2024. It's very exciting times for BioArctic with Leqembi, which is originating from BioArctic. Leqembi is the first and only disease-modifying treatment for Alzheimer's disease, with a full approval so far in the US, Japan, and China. There will be three key messages today. I'll talk about the Leqembi sales, which we see is increasing. The infrastructure has been established to a large extent in the US, and the Leqembi launch goes now into the next expansion phase. The second part is that the lecanemab regulatory processes continues with more approvals, and China was approved early this year, and more submissions are also being filed by Eisai, including a subcutaneous auto-injector file. The third aspect and key message is also around our...
The rest of our portfolio, which is progressing really well, and we have made our first agreement on a project which is utilizing our Brain Transporter technology. I'll talk more about all this here today. Next slide, please. I'm Gunilla Osswald, the CEO of BioArctic, and I will share today's presentation with our CFO, Anders Martin-Löf, and Anna-Kaija Grönblad, our Chief Commercial Officer, is also here for the Q&A after the presentation. Next slide, please. BioArctic is listed at Nasdaq Stockholm, Large Cap, and this is our disclaimer. Next slide, please. BioArctic focus on disease-modifying treatments for neurodegenerative diseases, and we are now on the market in Alzheimer's disease, and we are preparing for phase 2 in Parkinson's disease. These are areas where there is a huge unmet medical need and very large patient populations that we aim to help.
We have a great organization with highly skilled scientists and drug developers with vast experience, and we're now building a commercial organization to prepare... We are preparing for commercialization together with our partner, Eisai, in the Nordic region. We have a broad portfolio building on the success of Leqembi, with very selective antibodies for Alzheimer's disease, Parkinson's disease, and ALS. We also have the very encouraging BrainTransporter technology, which helps us to get the antibodies better into the brain. I'm very encouraged by that. Our portfolio is exactly where the science now is evolving quickly. We are also well-financed, and we have approximately SEK 1 billion in the bank. Finally, the fact that our science and company leadership throughout the years have been given numerous awards validates our innovation and global leadership position within neurodegenerative diseases.
We also got some new awards during this quarter. Next slide, please. A lot of things has already happened this year. The year started with the approval of Leqembi in China, where Eisai is planning for a launch in July. In Europe, it was disappointing that the Scientific Advisory Group meeting was annulled due to process issues that was not depending on lecanemab, so the Scientific Advisory Group meeting had to be rescheduled. At the Alzheimer's and Parkinson's Congress earlier this year, there was a very positive atmosphere with a lot of excitement in the fields of Alzheimer's disease and Parkinson's disease, and with regard to the blood-brain barrier technologies. BioArctic and Professor Lars Lannfelt presented new data on lecanemab, further supporting the unique binding profile with lower CAA binding, which is linked to lower incidence of the side effect ARIA-E, if you compare this with competitors.
Eisai presented more data supporting the Leqembi disease-modifying properties, and more data suggesting even better effect if you start early with the treatment in early Alzheimer's disease, as well as data supporting the subcutaneous as a more convenient administration alternative for Leqembi. Eisai has submitted a supplementary application to the FDA for less frequent dosing intravenously with lecanemab. And earlier this week, Eisai also initiated a rolling application to the FDA for Leqembi with regard to the subcutaneous auto-injector for maintenance dosing. BioArctic and Eisai have entered into a research evaluation agreement regarding BAN 2802, which is an Alzheimer project utilizing our BrainT ransporter technology. And this is then the first agreement done utilizing our technology, and I expect more to come. BioArctic was included in Nasdaq Stockholm's new ESG Responsibility Index, which we are also happy about. Next slide, please.
Leqembi is the first disease-modifying treatment for Alzheimer's disease, with a full approval in the U.S., Japan, and China, and it's on its way to be established as a new standard of care for Alzheimer's patients.... A lot of things is happening around the world, and if we start with the U.S., where it is approved and broadly reimbursed since July last year. Eisai has here also submitted two files for more convenient maintenance dosing. A supplement application for less frequent IV dosing, and a new BLA for subcutaneous auto-injector administration for maintenance treatment. The launch is ongoing and now progressing into the next expansion phase. In Japan, Leqembi was approved in September, and launch started late December, and it's progressing really well.
In Europe, as I said, we are waiting for the new Scientific Advisory Group meeting, and that will be followed by a CHMP opinion meeting, and we're hoping, of course, for a positive opinion and a European Commission approval late Q3. In China, approval was granted in January, and Eisai is preparing for a launch in July. Lecanemab regulatory files are being reviewed in many parts of the world right now, and we're hoping for several positive responses during the coming months. So I think it's a very exciting time. Next slide, please. The launches are also progressing now in a very good pace. So if we start with the U.S., where a lot of work has been done by Eisai to prepare the market and establish the pathway together with hospitals and infusion centers, et cetera.
There is a strong momentum with 97% of the 100 integrated delivery networks, which is, groups of hospitals and so forth. Eisai is now expanding their focus to the top 150 IDN. I think it's great that the prescribing facilities have been established, in a broad way and can be found across the U.S. Many prescribing physicians have gone through a trial period, and they are now in the expansion phase. We have heard that some facilities are confirming more than 200 cases of Leqembi treatment. It's also reassuring to see that the real-world evidence when Leqembi is being used in clinical practice, that shows that the side effects area is in line with the results of clinical trials as described in the U.S. packaging insert.
I think that shows that Leqembi seems to be used safely and in the right way in clinical practice. So in summary, now when the pathway has been established to a large extent, Eisai takes the launch to the next stage, and that is the prescription expansion phase. Eisai and their partner, Biogen, are strengthening the go-to-market structure with the aim of providing tailored information regarding three things. The first is, of course, regarding Leqembi, the second is regarding reimbursement and support for patients, and the third is re- around system efficiency in order to shortening time for treatment. More and more patients can now benefit from the treatment of Leqembi in the US. Next slide, please. If we then look at Japan, the launch is progressing even faster than expected here, with fast establishment of the diagnosis and treatment pathway at 600 facilities within four months of launch.
I think that's very impressive. I think it's further impressive that the Japanese launch is even exceeding Eisai's initial targets. And it's clear that the broad spectrum of promotion activities towards healthcare professionals are efficient. If we then look at China, the launch is planned for July, and here, China is a bit different, and that is, for example, that there will initially be a focus on the private market. Furthermore, Eisai will be leveraging on already established online health platforms, and the diagnosis, the streamlined diagnosis will mainly be utilizing blood-based biomarkers. And, that, I think, will be very important and key drivers for diagnosis and growth. Next slide, please.
Eisai also continues to develop lecanemab, and the first approval in the US, Japan, and China is for Leqembi intravenous administration, 10 milligrams per kg biweekly, and that is both for initiation and maintenance treatment. The file is also under regulatory review in many other regions, as I said. In order to increase the convenience for the patients, Eisai has now also made two applications to the FDA for more convenient maintenance dosing. After the initiation phase, then the maintenance phase could continue with IV monthly, 10 milligrams per kg, as described in the supplementary application. The other application was a rolling submission under Fast Track designation, and that was initiated by Eisai earlier this week, and that is regarding a subcutaneous injection with an auto-injector, with a fixed dose of 360 milligrams for maintenance dosing.
The next step, which will be very important, is when the subcutaneous auto-injector can be used both for initial and maintenance treatment. Here, Eisai has initiated discussions with the regulatory authorities. I think that Leqembi long-term penetration will also be supported by simplified diagnosis with blood-based biomarkers, and I think it's reassuring to see how well the blood-based biomarkers are evolving over the world. Next slide, please. I think it's great to see how Leqembi brings value to patients, caregivers, and society. Leqembi has been studied in a broad patient population with early Alzheimer's disease, and have shown consistent and distinct efficacy and safety profile. I think it's very encouraging to note that data from the low tau group, which is then very early stage of early Alzheimer's disease, that they suggest a potential even greater treatment benefit.
That is then when you start the treatment at an early stage of mild cognitive impairment. Early start and long-term treatment bring greater benefit for patients. Reports of the side effect ARIA from the real-world clinical practice are consistent with what was observed in the clinical trial, as described in the U.S. packaging insert. Most reports are non-serious, asymptomatic, and occur early in the treatment. I think this indicates that safety can be appropriately monitored. The low levels of anti-drug antibodies further enables maintenance treatment effect for Leqembi. The improvement in dosage and administration is important for continued treatment, and as I just described, Eisai has filed for both IV and subcutaneous maintenance treatment in a more in a better way for the patient.
The subcutaneous auto-injector will be a great improvement for patients to enable easier administrations at home, and this will also be less burden on healthcare, of course. The ongoing phase III study, AHEAD 3-45, is for preclinical AD, and now we're talking about very early stages of Alzheimer's disease. This is before the subjects have symptoms. This study could potentially lead to a further expansion of indication into the even earlier stages of Alzheimer's disease. This could also potentially further expand the clinical benefit for the subjects. So I think that Leqembi brings a lot of value for many. Next slide, please. But I want to emphasize that even though Leqembi, of course, is of main interest, BioArctic is more than Leqembi, and I want to mention two other pipeline highlights. The first one is regarding the BrainTransporter technology.
At the Alzheimer's Parkinson Congress, it was highlighted that active transport of antibodies into the brain is seen as the next big step for neuroscience. Our proprietary BrainTransporter technology continues to progress very well. By utilizing our BrainTransporter technology, we get a rapid, broad, and deep distribution of the antibodies into the brain. This could potentially lead to even better efficacy and tolerability, and with lower doses, of course. I want to emphasize three of our projects utilizing this technology. First, the two Alzheimer's programs, BAN2802, where we now have signed a research evaluation agreement with Eisai, as the first agreement utilizing our BrainTransporter technology, and expect more agreements to come here. The second project is BAN2803, which is a pyroglu-Abeta antibody utilizing the BrainTransporter technology.
This looks very promising, and we have increased our investments here, and we progress this project actively towards the clinical stage. In Parkinson's disease, the project called B, PD-BT2238, is an alpha-synuclein antibody with a brain transporter technology. It's developing really well, and we are progressing actively towards a candidate drug nomination. Next slide, please. The other highlight of our pipeline that I want to mention here today is regarding our alpha-synuclein program. And at the Alzheimer Parkinson Co-Congress, again, encouraging data on alpha-synuclein treatments were presented, as well as great progress on diagnosis and biology linking into alpha-synuclein. This further supports our alpha-synuclein programs, both exidavnemab as well as 2238.
Exidavnemab, which is our selective alpha-synuclein antibody, where we are preparing for phase II, and the phase II-A study is called EXIST, and that is in for Parkinson patients, and we plan to start dosing late this year. The aim of this study will be safety and tolerability and pharmacokinetics with exploratory biomarkers, including seeding amplification assays, and digital biomarkers. The study protocol is currently being finalized through interactions with regulatory authorities. The drug project is now available, and the study is planned to be performed in Europe, with the first patients planned to be dosed, as I said, late this year. Next slide, please. So just to summarize, BioArctic's portfolio in Alzheimer's, Parkinson's, ALS, and the BrainTransporter technology, our most advanced program is, of course, Leqembi. But I want to emphasize again that BioArctic is even more than Leqembi.
After the Alzheimer's and Parkinson's Congress, we can again conclude that our portfolio includes exactly the targets and trends where science is breaking now. I'm pleased to see the continued progression of our projects here and how well it's being developed. Next slide, please. Then I will hand over to Anders Martin-Löf for the financial side.
Thank you, Gunilla. If we turn to slide 15, as Gunilla has already mentioned, the launch is progressing really well, and now we're starting to see that in our financials. The global Leqembi sales were JPY 2.82 billion in the quarter. That's roughly SEK 200 million or $80 million. That represented a 170% increase over Q4 2023. On that, we get a royalty rate of 9% on global net sales. In addition, we get one percent more on US sales and 1.5% on ex-US sales that we then pass through to our partner, Ligand. So, so the 21.3 million in revenues that we recorded during the first quarter, that includes some the pass-through royalties that we pass on.
But you see a very, very steep increase over quarter-over-quarter, and this growth is likely to continue during the year. The U.S. launch is now in the expansion phase, as Gunilla mentioned. Eisai and Biogen are increasing their sales force to drive sales, not only in the larger hospitals, but now in their satellite clinics. We have seen a strong start in Japan, the pathway has been established at 600 sites, but more and more sites are coming online, so we'll see very steep growth there as well. And the launch is sometime for China in July, and that will further support the growth during the year.
If you turn to the next slide, we can see that Eisai has, for the very first time, issued a forecast for near-term sales, and they are predicting more than a tenfold increase in sales of Leqembi from 2023- 2024, going from JPY 4.3 billion, roughly SEK 300 million in 2023, to JPY 56.5 billion, i.e., SEK 3.9 billion in 2024. The lion's share of the market will come from the U.S., so 77% is expected to come from the U.S., but already 18% is expected to come from Japan. For us, this would then correspond to royalty of roughly SEK 400 million in recorded revenue or roughly SEK 360 million net after the royalties paid out to Ligand.
In the coming year, this is likely to continue. We have briefly mentioned that the subcutaneous maintenance formulation is likely to be approved in 2025. We will also see subcutaneous formulation for initial treatment, and Eisai indicated that that will be approved in 2026. We're also seeing the implementation of lab-based biomarkers starting already this year in China. It's happening in Sweden, and we expect that to continue all over the globe. And all of this lowers the barriers to treatment. So when Eisai has predicted what's going to happen midterm, they are expecting roughly a 5-fold increase in sales from 2024- 2026.
They, in their revenue simulation that they presented in market, they said that they would have revenues of JPY 290 billion, so roughly SEK 20 billion or $1.9 billion in 2026. So we are really just in the beginning of the growth phase for Leqembi. If you then turn to the next slide, I'll go through our numbers for the quarter. On the left-hand side, you see that our first quarter net revenues were SEK 30 million. That's quite a big drop from a year ago, when we had SEK 393 million in revenues. But that's explained by the fact that we had three milestones totaling EUR 35 million in the first quarter of 2023, and there were no milestones paid during this quarter. We are still entitled to more milestones.
We are expecting a milestone when we get approval in the EU this year, and in the following years, we are entitled to sales milestones in 2025, 2026 and 2027. So that will continue, but over time, the two new revenue streams will take over more and more. Right now, the royalty revenue was SEK 21 million, co-promotion was SEK 3 million, but over time, those two revenue streams will, of course, make up the lion's share of our revenues, and that will, of course, increase the lumpiness of our revenues. They're obviously very lumpy right now, but over time, it will be much, much smoother. If you turn to the middle graph, you see our operating expenses. First, this is the first time you've seen them by function.
So the total operating expenses increased to SEK 101 million from SEK 79 million in the first quarter. 75% of that increase comes from R&D. And in total, 63% of our operating expenses come from R&D, and that's an increase from last year, when 59% of our R&D expenses came from R&D. On top of that, we have twelve percent of our expenses come from sales and marketing. Those two ratios will continue to increase. Our costs will increase during 2024 due to the fact that we are investing heavily into the programs, especially the ones that Gunilla mentioned. We're starting our phase II trial for exidavnemab later this year. We're also investing in our ALS programs, where we selected our candidate drugs last year and are now performing IND-enabling studies.
We're also building up our commercial organization that will accelerate towards the latter part of the year, so we are expecting a continued increase. But more and more, larger and larger share with over, of course, will be from R&D and sales and marketing rather than G&A. On the left-hand side, you see our operating profit, which was negative, so it was an operating loss of SEK 73 million for the first quarter, which is roughly in line with what we saw the fourth quarter last year. If we look at our financial position on the next slide, starting from the right-hand side, you see that our net loss was SEK 58 million, which is roughly SEK 50 million better than the operating loss. That is explained by a fairly strong financial net of +SEK 15.7 million during the quarter.
On the middle graph, you see on the other hand, that our operating cash flow was weaker than our operating results, and that is due to the fact that the royalty payments are lagging the royalty revenues by roughly two quarters. So in this quarter, we saw a SEK 45 million increase in working capital, and this will continue to increase when our royalties increase. So this lag will continue, but it has a very limited impact on our financial position. You see on the right-hand side that we have a cash position, including short-term investments of SEK 991 million. So we can continue to work long-term to focus on advancing our portfolio in the fastest possible way without thinking too much about financials.
Looking for the remainder of the year, I think it's unlikely that we will be profitable in 2024, but as royalties grow, I think there's a very, very high likelihood that we will be profitable again in 2025 and onwards. That was all from my end, and I hand over back to Gunilla for some closing remarks.
Thank you so much, Anders. So we are coming to the final part of the presentation with some closing remarks and upcoming news flow. Next slide, please. So the upcoming news flow, if we look at this quarter, the initiation of the U.S. submission of lecanemab for the subcutaneous auto-injector maintenance dosing under the Fast Track designation was just achieved this week, and we are hoping for an approval of lecanemab in Great Britain. If we look at the next quarter, we are looking forward to the next big congress for Alzheimer's in Alzheimer's disease, called AAIC, which is in Philadelphia during the summer. And there, we will see more presentations on lecanemab and more interesting data. In July, Eisai plans to launch Leqembi in China. And in Europe, we of course hope for a positive CHMP opinion after a new Scientific Advisory Group meeting.
If so, then we could expect an approval in the EU during late Q3. Then, during the fourth quarter of this year, we plan to start the phase 2a study in Parkinson's disease with exidavnemab, and we're looking forward to being able to present some more data on our BrainTransporter programs. Other potential approvals of Leqembi could also come during the rest of the year. I think it's a lot of exciting times ahead for BioArctic. Next slide, please. To summarize today's presentation, Leqembi is approved in the U.S., Japan and China, with huge patient populations with early Alzheimer's disease. Even if a small part of the population will have treatment with Leqembi, that will be huge, and I think it's gratifying that we can help many patients.
The launch is showing strong momentum now, and it will be exciting to see more and more patients being able to get access to Leqembi treatment. We are hoping for more approvals, and Eisai continues with more regulatory applications and further development of lecanemab. Our pipeline is progressing very well, and the first brain transporter agreement has been signed. Our finances remain solid. We have almost SEK 1 billion in cash, which I think is great, so we can focus on driving the project forward towards the patient. Next slide, please. So BioArctic's aim is to improve the lives of patients with neurodegenerative disorders, and I think that we are very well on our way. And I think it's extremely gratifying that we now can help more and more patients and their families.
By that, I say thank you so much for your attention, and we are happy to take questions.
If you wish to ask a question, please dial pound key five on your telephone keypad to enter the queue. If you wish to withdraw your question, please dial pound key six on your telephone keypad. The next question comes from Alistair Campbell from Royal Bank of Canada. Please go ahead.
Hi there. Thanks very much for taking my questions, and it's great to see Leqembi gaining momentum in the US. Two questions, please. First of all, on AHEAD 345, just looking at the status on clinicaltrials.gov, it looks like that's now primary completion around 2029. So I guess if you could give me an update on how recruitment's going and sort of what the timeframe looks like for that. And frankly, you know, if it reads out in 2029, gets on label 2030, what sort of time frames you have left to sort of get a commercial benefit from that, given the contract in place? And then the second question is just simply on cash position.
Given, you know, potential milestones later this year, what do you feel about where the cash may end at the end of the year? Thank you.
Thank you so much for your questions. So, if we look at the AHEAD 345 study in the very early Alzheimer's disease, even before the subjects have any treatment, the aim of this study is to have 1,400 subjects. I think that, and the study is ongoing around the world, the majority in the US, but also in other parts of the world. I think the inclusion is going really well, and Eisai is hoping to conclude the enrollment into this trial during this year. Then it's a four-year treatment in this trial. Then we will wait and see for the results. But I'm really encouraged by the data that we have seen with very early patients of mild cognitive impairment, that they seem to maybe have even more benefit.
And then, thinking about when this can be ready, it's, I will not speculate exactly on when that can be. But our patent expiry, including extension, is around 2032. So I think that there is still time for that. And then, you also asked about more milestones, and I hand that question to Anders.
Yeah, you asked about the cash position towards the end of the year. And assuming that we get the approval in Europe, which we believe will happen during the second half, we're assuming that we will have a cash position between SEK 800 million and SEK 900 million towards the end of the year in Swedish. Thank you.
Thank you very much. Thank you.
The next question comes from Joseph Heddon from Rx Securities. Please go ahead.
Good morning, and thanks for taking my questions. Just referring to your news flow slide, in particular, the potential EU approval. I know some of the language used in terms of the Scientific Advisory Group. Could you just fill us in, has this happened to your knowledge yet? And if it hasn't, do you have any idea when this could happen? Just trying to get a sense of what the risk to that timeline still is. And then secondly, it's clear that blood-based biomarkers are quite important to Eisai's projections. And it's something that you and Eisai talk about a lot. I just wanted to get an idea, does Eisai have any deals with providers of these tests in the space currently, or has it got any proprietary technology?
Are there any data on the real-world use of any of the available tests so far in the Leqembi launch? Thank you.
Thank you so much, Joseph. Great questions. So first of all, with regard to Europe and the Scientific Advisory Group, it has not happened yet. We are looking forward to seeing how it evolves, and I think that these timelines that we have laid out, I think is realistic. We don't know exactly when the different things will happen, but I really hope for a positive opinion here, so an approval, so European patients also can get access to Leqembi. Your second question, with regard to the blood-based biomarkers, I think it's evolving really well. Our partner, Eisai, has said that they have different collaborations, for example, with C2N and with Sysmex and so forth, and I think, yeah, you should ask them more about this, but this is what we know so far.
I think that at the Alzheimer's congresses, there is presentations every time about more and more solid data coming out of the blood-based biomarkers. It's both about Aβ42 over 40 ratio, but especially on the phospho-tau biomarkers, which is evolving really, really well. This is being utilized already here in Sweden in clinical practice, which is being tested, as we heard, China. It's also being used for triaging in other parts of the world, including the U.S., starting there. I think it will be more used in a broader clinical setting in a couple of years, it looks really good.
It's already used also, for example, in the screening phase of the AHEAD study, where the first part is linked to a blood test, and in that screening phase, in order to see, and then it's followed up by other biomarkers. So I really strongly believe in the blood-based biomarkers, that that will really help also to make a broader finding of the right patients that can benefit from Leqembi.
Okay. Thanks, Gunilla. That's great. Thank you.
Thank you.
The next question comes from Patrik Ling from DNB Markets. Please go ahead.
Yes, good morning, everyone.
Hi.
Maybe to start with a follow-up question to Joseph's question about the SAG meeting. You said that it hasn't happened yet, but has it been scheduled yet, so we know when it's going to be?
No, it has not happened yet, and we don't have all the details about how it and when it will happen, so we need to come back to that when we know more.
Okay.
But I think that the timeline I laid out, I believe in those.
Okay.
We have to wait until we know more.
Okay, great. Great. Then I actually had a follow-up on this research evaluation collaboration that you have with Eisai on BAN2802. Maybe if you could give us a little bit more color on what that actually includes, what will happen, what are the timelines, when what type of evaluations are you doing together, and so on?
Yeah. So I think this is regarding the project called BAN2802, and that's one of the two Alzheimer's projects that we are investing heavily in now, and driving forward strongly, which is based on really selective antibodies combined with the BrainTransporter technology. And here we have laid out for BAN2802 a very clear development program that we will share the costs with Eisai. And that's a program which is about two years that we will be doing and then preparing this project for towards clinical stage. So I'm really enthusiastic about this project, and I'm also really enthusiastic. I've got the question, so what about BAN2803? Does that mean that you're not driving that forward? And I just must say that BAN2803 also looks really encouraging.
I think it's a very strong position for BioArctic to have two very good programs, as it looks like, utilizing the BrainTransporter technology for Alzheimer's patients, as well as that we also have it for Parkinson's disease, and then also in the future for ALS and other parts.
Great. First step now is a two-year evaluation where you split the cost 50/50, I suppose?
So I'll not comment exactly on how the split is, but we will share the costs with ASI, and then after that, about two-year period, then there will be an option for ASI to go into a license deal.
Okay.
That's, of course, what the aim is from those companies to start this project and do the collaboration together.
Great, great, great. Then, then I also had a question about the EXIST trial. Maybe I missed that, or maybe you can just remind me. Have you said anything about potential size of that trial? How many patients you're gonna include?
No, we have not. And I think that the next Q report, we will reveal more information. It should just be, I mean, managing expectations. This is a small study, and it's really safety tolerability where we will be looking at two different doses and compare with placebo. But it's mainly safety tolerability in PK and with some exploratory biomarkers. So it's really a study which is preparing us for the next important step, and that is to select the indication or indications for phase IIb, which will be the most important parts where we'll really be exploring full efficacy.
No, because the reason I ask is, I mean, if you plan to include, you know, patients with basically five different indications, my impressions before has been that you will, based on the results here, decide on where to continue with phase II. And my thinking was that maybe you needed, you know-
Yeah, um-
A reasonably large amount of patients in these different indications to be able to actually decide where to go next.
Thank you for your question. I will help to clarify. The next study that we are now preparing will be done in Parkinson's patients, and that is, as I said, safety tolerability. That is not the study as such, will not include the different kind of patient populations, different indications. That will be decided based on several other things, and not based on the data as such in this study. I mean, it will, for example, we'll be looking at competitors, which is also progressing in some of those indications. We will also look at where do we think we have the largest possibility to be successful with regard to biomarkers and clinically fixed endpoints and so forth.
So I think it should be clearly expected that this phase I package that has been done was a large phase I package with, for single doses, with different doses and also IV and subcu, and also different ethnicities and the Japanese patients and so forth. So but there has not been a multiple ascending dose study done yet. So that's part of the phase II-A study. So it's really safety, tolerability, and a small study should be expected. And meanwhile, that study is ongoing, we will do a lot of strategic work, looking at the different indications that potentially could come after and select the best indication for phase IIb. So it will only be Parkinson's disease patients in the phase II-A study, the safety, tolerability study.
But that doesn't mean that it has to be Parkinson's disease patients only in the next step. It could be different indications. Did that help?
Great, great. Definitely, definitely, I got it now. Great. Thank you very much, guys.
Thank you so much, Patrick.
The next question comes from Fredrik Thor from Redeye. Please go ahead.
Hello, and thank you. My question, you maybe touched upon this a bit, but about the cost development for 2024. Could you elaborate on this, and is it the same as before, roughly 30%-50% increase from the previous year?
Yes, we don't have an update yet. So, we stand by our previous guidance.
Okay. And my second question was about, the subcutaneous dose and first off, the, the maintenance dose, and then also the potential to have the, the initial dose also be subcutaneous. Could you explain kind of the difference between these two? How much increase, would you say, for example, if the initial dose also going to be subcutaneous compared to only for the maintenance?
I think, of course, it's a very good first step with the subcutaneous administration with an auto-injector, like a pen. So I think that would be a really good step for the longer term maintenance phase, and that is what the submission that was just initiated was about. But of course, it's good to have the alternative to start also with a subcutaneous auto-injector. And as you might recall that I said in a previous call, that when ASI presented the data from the ongoing study with the subcutaneous auto-injector, that was even better exposure and even better reduction of plaques with the subcutaneous formulation.
So that's why there is, of course, a discussion ongoing about which dose should we use for the initiation phase, and potentially also adjust the dose for the maintenance phase. That's the discussions which are ongoing. In order to sort that out, that will then help to see when the initiation dose can be. But of course, that will really help the patients and be a very attractive alternative. But I can't say exactly how much of the sales in the future, which is expected to be dependent on the other, one or the other. I think it's really good to have different options and different alternatives for the patients.
Mm. Perfect. Yeah, that's all for me. Thank you.
Thank you so much, Fredrik.
As a reminder, if you wish to ask a question, please dial pound key five on your telephone keypad.
So, it doesn't seem like there are any telephone questions, but we have some written questions come in. So, the first one was about approval in the EU, but I think you've already answered that, Gunilla, with the expected timeline of late Q3. Could be the timeline we see right now. But maybe for you, Anders, to clarify a bit about the milestones. You mentioned something about that, but maybe you could clarify how much we still have in expected milestones and when that could happen.
Yes. Thank you, Oskar. Yes, so, so in total, we have EUR 84 million of outstanding milestones. And we are expecting, as I said, the milestone when we get approval in EU. We cannot communicate the exact size of that, but when we got approval in the US, we got EUR 25 million. Europe is slightly smaller, so that will be slightly smaller than 25. The rest of the milestones are mainly sales related, so you can basically assume that they will happen during 2025, 2026, and 2027, spread out over those years. Hope that clarifies the milestone development that we're expecting.
Thank you, Anders. Then I see that we have a written question also on the phase II-A study, but I think you've clarified that at length, Gunilla, in your response to Patrik. So maybe then a question - two questions from Komachi. First one is, if we could say anything about the patient number or number of patients currently on Leqembi, and secondly, maybe a bit more explanation on the BrainTransporter technology, and if that uses the transferrin receptor, such, like similar to what Roche Brain Shuttle or Denali's program does.
Yeah, I think the brain transporter technology is definitely using the transferrin receptor in the approaches that we're utilizing right now. And they have a lot of similarities with both Roche and Denali, but they also have some important differences that we will be able to communicate more later on. And we are really encouraged by the Roche data that was presented at the previous Alzheimer congresses, where they showed really impressive data. It's still early days, but it's the first clinical data that has been shown, and I think that really has made us focus and invest even more strongly in our brain transporter, because it really looks like the next generation of approach to get the antibodies better into the brain.
So I strongly, as you have heard before, believe in this, and there is a possibility for better effect, better side effect profile and, and lower doses. So, it has some, some clear similarities, but also some important differences.
And, do you want to say anything about the patient numbers, Gunilla?
No.
No? Okay. And we don't know, I think, is the correct answer.
Yeah, we don't know exactly. So I think you have to reveal on what we said with regard to... You saw the number of vials on the slide, and you saw more also about what we understood about the sales.
Yeah.
I think we have to stay there for now.
Right. And ASI commented on this and said that they will not communicate patient numbers going forward, because it's really, really hard to estimate the actual patient numbers. It's much better information to look at vial numbers and actual sales. So there will be no communication regarding that going forward.
Thank you. Maybe just a follow-on from Goldman Sachs and Ryan about the BrainTransporter technology. He's wondering, Gunilla, if you can say anything about when this might enter the clinic, and also if the collaboration with Eisai regarding this BAN2802 program changes anything in the development plans that we have for that program or the other programs?
And so, I think it's, you know, that we CD-nominated those two projects at the end of last year. And normally, when we do a CD nomination, that means about two years to coming into the clinical phase. So roughly, that's the timeline. And then does the collaboration change any of the development plans? I mean, that, what it does is that it makes us want to invest even more in all our brain transporter programs. And that we're also opening up the brain transporter thinking in a broader way, also potentially for other areas, and other companies', projects for the future as well. So I think it really strengthens the position.
So it does not mean that we are lowering the ambition in any of our projects, just the contrary, that we are increasing our efforts in all our Brain Transporter-linked programs and in that technology platform as well.
Maybe we should clarify a little bit on the timelines for the research evaluation agreement. Gunilla mentioned that it would take roughly two years, but maybe we should clarify that you're thinking more towards the end of 2025, that we'll get the results, not mid-2026. 'Cause we're right now in mid-2024, so two years from now-
Uh-huh. Uh-huh
... will be mid-2026.
Okay. Sorry.
And I think you were thinking from the beginning of 2024-
Yeah.
to the end of 2025.
Yeah. Thank you.
So roughly the same time frame as when we expect to become ready for protein trials.
Hmm. Thank you, Anders.
Thank you. Then one question from Peter, and that refers to AI and utilizing AI in pharma development. Can we say anything on our efforts in this area, Gunilla?
Absolutely. I think, it's really important to be part of the AI explosion. And, definitely, we have some pilot projects ongoing at, BioArctic. And it's definitely used typically in different areas of... I think areas like imaging, areas, with regard to, side effect profiles in the future and so forth. And also there are initiatives ongoing also in clinical trials, even though we are not utilizing it for, right now for our own studies, for example, with, where you can utilize AI patients. But, I think this is an area that we are clearly watching, and there is AI built in so many different areas, already today. So and I think it's important for us and, all others to, be in this. I think it will be a part.
But it's really important how you do it, and that you do it in a safe way and so forth, and that you realize the opportunities, but also mitigate some of the risks that are linked to AI. So I'll not go into any details more right now, but maybe we can do that in the future, tell you about some of the examples. But we are using it, and we'll be using it more in the future.
Thank you. I don't see any more written questions online. Operator, are there any more questions waiting on the phone? Doesn't seem that way. So, I guess then that concludes our call today, and thank you everybody for listening in. And thank you, Gunilla, Anders, and Laura Kerr, for being here for the presentation and then Q&A. Thank you. See you next time.