BioArctic AB

Good morning and welcome to Biotic's presentation for the second quarter. It's very exciting times for Biotic and I have three key messages for today. The first one is that Lecambi sales are increasing. It's starting to take off in the US. It's going over expectations in Japan. It's also started really well in China. The second one is that Lecambi regulator processes continues and we are now approved in eight different geographies. which represents more than 80% of the expected market for Lecambi. The third one is that the rest of our project portfolio progressed really well, and we are preparing for Exadavnamab phase 2a study in Parkinson's disease. Next slide, please. I'm Gunilla Oswald, CEO of Biotic, and I will share today's presentation with our CFO, Anders Martin Lööf. We also have our CMO, Tomas Odegren, here for the Q&A after the presentation. Next slide, please. This is our disclaimer. Biotic is listed at Nasdaq Stockholm. Large clap. Next slide, please. A lot of things have happened during and after the second quarter. And I will start with Lekanamab, where we are in a lot of regulatory activities. Our partner ACI has had two regulatory submissions to the FDA in the USA. They have submitted supplementary BLA for intravenous maintenance dosing with less frequent dosing, which means once a month dosing. ASI has also received fast track designation for the subcutaneous administration. And then they have initiated a rolling submission for a new BLA for the subcutaneous autoinjector for maintenance dosing. We have got several regulatory approvals in South Korea, Hong Kong, Israel, United Arab Emirates, and last week also in Great Britain. We had a drawback in July when CHMP adopted a negative opinion on the market authorization for lecanumab in the EU. Our partner ASI has requested a re-examination of the opinion. Lecambi has also been launched in China and it has been initiated at the end of June in a really good way. We have long-term data, which has been requested for some time, and that was presented now, three-year data, with leucanumab at the Alzheimer Congress AIC. And this showed continued increasing benefit for the patients with maintained safety profile. If we then look at Exidavnumab, two phase one studies were published with the results. in Journal of Clinical Pharmacology. And data showed that Exidabnamab was generally well tolerated and had an excellent PK profile with an elimination half-life of about 30 days. And this supports monthly dosing. And I think this is great news in the preparation for the Phase 2a study that is starting later this year. If we look at other projects in our portfolio, it's also progressing well. And we have the first agreement signed for our brain transporter technology during the quarter, where ASI and Bioartic entered into a research evaluation agreement regarding the drug candidate BAM 2802. Next slide, please. Lecanumab is the first disease modifying Alzheimer's disease treatment, which is now approved in eight different markets around the world. And it's on its way of being establishing new standard of care for the patient. And this slide shows the situation of Lecanumab globally. If we look at the US first, I have mentioned the two submissions. with less frequent IV dosing, where the PDUFA date is set by the FDA to the 25th of January next year. For the subcutaneous autoinjector maintenance dosing, the rolling submission has been initiated and is planned to be completed later this year. Launch is ongoing in the US, Japan, and also in China. And we will talk more about that later in the presentation. And as I said, we have several approvals in the rest of the world. South Korea, Israel, Hong Kong, United Arab Emirates and recently Great Britain. The Great Britain authorization was great, and I was really happy to see that, especially since the European CJMP gave a negative opinion in July. And the ASIS has, as we said, requested re-examination and outcome is expected later this year. So next slide, please. Our partner ASI showed this slide of their quarterly report as a regulatory update for the EU. We start with CHMP standpoint with a negative opinion after considering the balance of benefit and risk. ASI's standpoint are three parts. The first one is that the protocol and the statistical analysis method for the phase three program was determined in advance And it was in consultations with regulatory authorities, including the EU regulatory authorities. The second part is with regard to the benefits. And in the phase three study, Clarity 80, Le Canemab met the primary endpoint as well as all key secondary endpoints with high statistical significance. Furthermore, long-term data up to three years have showed maintained benefit over three years. The third aspect is the risks. And the side effect of concerned is called area. And at the Alzheimer Congress AIC, when long-term data was presented, it was concluded that the risk for area is highest in the first six months and very low thereafter. And most cases are asymptomatic. And I think this was reassuring to hear the presentation of the side effect profile and real-world evidence. It was also concluded that it can be well managed in accordance with the guidelines. The CHMP opinion was surprising to us and I think very disappointing. And ASI has been very clear about requesting re-examination and to work closely with the authorities to get an approval and to also make leucanumab accessible for European patients who could benefit from the treatment. And of course, we hope for a positive CHMP opinion later this year, followed by an approval in Europe early next year. We draw strength from the firm support that has been shown for Lekanamad from both researchers, the opinion leaders and patient organizations from across Europe. Many of them are now taking a stand and ensuring that their voices are being heard. Next slide please. Positive news came last week when Great Britain authorized Lakembi. I want to point out that there was a slight difference in their approval from what has been seen in other countries. They focused on lowering the risk of area, which is the main side effect of Concert. The indicated population therefore excluded what is called APOE4 homozygotes, which means that you have two alleles of APOE4. And this is a specific genetic variant, which means that you have a higher risk of getting Alzheimer's disease earlier and also higher risk of getting the side effect area. The homozygotes are about 10 to 15 percent of the Alzheimer population. So the indication that was authorized includes early Alzheimer's patients that are APOE4 homozygous, which means they have one APOE4 allele, or non-carriers, they have no APOE4 allele. And this is the vast majority of Alzheimer's patients. If we look at the indicated population in the phase III triamclarity AD, Leucanumab showed slowing of clinical decline over 18 months compared with placebo by 33% on CDR summer boxes, as you can see on the graph to the right. And it was 39% on the activity of daily living scale. It was also seen a lower frequency of area E of about 9% and symptomatic area E of about 2% in this population. In Great Britain, a consultation process involving ASI and other stakeholders will now take place before Lecambi can become available for use in the national healthcare system. The reimbursement authority called NICE, their draft recommendation was that cost effectiveness did not support routine use. The authority has requested additional information before its final decision. ASI has stated that they will work collaboratively with the NICE to make Lekembe available to eligible patients living with early Alzheimer's disease as soon as possible. Next slide, please. I want to share some key highlights from AAIC, which is one of the largest Alzheimer's conferences, which was held in Philadelphia in July this year. Long-term clinical data has been requested for leucanumab, and now ASI presented three years' data, which showed increased patient benefit with maintained safety profile. If you look at the graph to the left, we can see clear and meaningful long-term effect over 36 months, now when all patients have got leucanumab. either from the start, which means three years, or after they had had their 18-month placebo treatment in the core study, and then they had been treated for 18 months with leucanema. There are two things I want to point out to this graph. The first one is that the benefit increased over time. We can see that the benefit was 0.45 after 18 months, and it doubled to 0.95 after three years. The second thing I want to point out is that patients get more benefit if they start treatment early. So if you look at the top green curve, you see that they have more benefits. But you also see that the middle curve, which starts black, which is placebo, and then after 18 months, it's green, which means that they have got the cannabis. Then you see that they also get benefit from the treatment in comparison with the purple curve. which is control from the ADNI group, which is matched to the study. If you look at the graph to the right, I think we see very encouraging data that also was presented at the AIIC. And this is from a small sub-study in patients with no or very low tau in the brain. And this means that they are early in the disease. We can see that 60% of these patients had improvements after 18 months, which means that they were better than when they started the treatment. And more than 50% of the patients were still doing better after three years. I think we should be a little bit careful since this is only 40 patients, but I think it's encouraging and further emphasize the importance of starting treatment early. I also want to say that safety matters and it was reassuring to see that no new safety findings were reported and the very low frequency of area was reported after the first six months. And now with thousands of patients have been treated, I think this is reassuring. Key opinion leaders from both the US and Japan, they concluded that the side effect is manageable and that their real-world evidence data showed lower frequency than has been reported in clinical trials. It was also emphasized that continuation of treatment is important even after the plaques have been removed from the brain. And that was demonstrated by data on biomarkers who start to deteriorate if treatment stops, whereas continued benefit was shown for when treatment was continued. Next slide, please. There has been a lot of discussion about if the effect by leucanumab and this kind of treatment are clinically meaningful. And I just want to explain a bit about the scale that is being used in this kind of clinical trials. It's called CDR sum of boxes. And that is measuring cognition and function with three items each. The cognitive items are memory, orientation and judgment or problem solving. The functional items are community affairs, home and hobbies and personal care. Sometimes I hear that 0.5 difference on an 18 point scale is not clinically important. And to me, that is just completely wrong. I think that for a patient, 0.5 could mean a difference from having a slight impairment to being unable to function independently on one of the items on this gate. And no one can convince me that that's not meaningful for a patient with this devastating and deadly disease. What we hear that patients want is longer time to enjoy life with their loved ones, especially in the less severe stages. And leucanumab has showed An average saving of about 5.3 months already after an 18-month treatment. And this is longer if treatment continues. So I think the effect is clearly meaningful benefit for the patient. Next slide, please. The cannabinoid development continues both with the IV maintenance dose, which is less frequent than once a month. but also subcutaneous with an auto-injector to make it more convenient for patients and to be able to make it easy administration at home. I think it is also great to see how the blood-based biomarkers for diagnosis will simplify the patient journey and help to identify patients in a much easier way in contrast to PET and CSF, which sometimes can be challenging. And this development with the blood-based biomarkers goes even faster and better than I had expected. Professor Oskar Hansson from Sweden, he presented data at AIIC on blood-based biomarkers with 90% accuracy in diagnosing Alzheimer's disease. This is remarkable. It's better than both primary care physicians and even specialists. And I think this is important for the opportunity to diagnose patients earlier and on a broader scale. This is already being used, for example, in China, and it's being piloted in Sweden and in many other countries at the moment. Treatment earlier has, as I said, shown more benefit, which is encouraging for the phase three study called AHEAD 345. And this is ongoing in subjects without symptoms, but with elevated amyloid deposits in the brain. And this study already used blood-based biomarkers to identify the right patients. And the recruitment for this phase three trial expects to be completed this year. Next slide please. So I've been talking a lot about leucanumab and lecambi, but I want to say that biotic is of course more than that as well. We have a broad project portfolio for treatment of neurodegenerative diseases. And our programs progress well, and we're very pleased with the first agreement in place for our brain transporter technology, the BAN 2802 collaboration with ASI to evaluate this asset. I also want to point out that BAN 2803, which is another Alzheimer's program with the brain transporter technology, that looks great. And we plan to show data from this program later this year. Our Parkinson's disease program, Exidavna, is actively preparing for starting phase two next quarter. Next slide, please. We think that our alphacinuclein portfolio has many opportunities in several neuronal synucleinopathies, such as Parkinson's disease, Parkinson's disease dementia, Lewy body dementia, and prodomal stages. as well as the orphan indication multiple system atrophy. I think it's reassuring that biomarkers are available to identify the right patient with pathological alpha-synuclein, and we will also use this in our Phase IIa study. Next slide, please. The Phase IIa study with Exedavnimab is called Exist, and it will be performed on patients with mild to moderate Parkinson's disease. The design is a randomized double-blind placebo-controlled trial with a low dose and a high dose compared to placebo. The primary endpoint will be safety and tolerability, and the secondary key endpoints will be pharmacokinetics and immunogenicity. Several biomarkers will be explored, both biochemical biomarkers as well as digital and cognition markers, which are relevant for patients and will be also an important preparation for the next proof of concept studies. So it's a lot of activities happening at Biotic at the moment in order to start this study later this year. Next slide, please. So by that, I will hand over to Anders Martin Lööf for the financial summary.

Thank you very much, Gunilla. Starting with the royalties, we are very happy to see that the Lecambi royalties are continuing to grow actually at an exponential pace. The global sales were 6.3 billion yen, that is roughly 40 million dollars. That's roughly 120 percent higher than the quarter before. And if you then look at our royalties, they increased to 42.6 million Swedish krona. That's a doubling from the quarter before. Or if you look on annual figures, it's a 70-fold increase year over year. That's 7,000%, if we're talking percent. So we really see really, really high growth numbers. That's mainly driven by the U.S. market. And we're really happy to see that the U.S. expansion started picking up speed during this quarter. As you may recall, the first two quarters after the launch in the second half of last year, it was fairly slow for the US clinics. They were struggling a little bit to get the infrastructure together and start treating patients. That started to happen towards the end of the year. And in the first quarter, they were starting to treat patients more on a pilot scale. What we saw now in the second quarter is that they are really scaling up. Now they're starting to treat a lot of patients. And that is then further supported by a larger commercial infrastructure by AHA and Biogen. They had an increase of roughly 30% and now have 450 positions in place. And that helps to increase the number of sites that are starting to treat. So it was very reassuring to see that the number of hospitals that started ordering that can be increased by 40% in the second quarter over the first quarter. All in all, this means that we saw a big increase in sales during the quarter. So the April sales were 0.9 billion yen, growing to 2.1 billion in June. That means we went from 6 million per month in April to 13 million dollars per month in June. So in total, 30 million dollars. So now I would say that we're now on a really good trajectory in the US. It took a little bit longer than was initially expected when the product was launched. But now things start to look really, really good in the US. We also saw a very strong start in Japan with roughly $10 million in sales already in the second quarter after the launch. Here we did not see the slowish implementation that we saw in the first two quarters in the US. Already now, 500 facilities have started prescribing after the 650 that had implemented the pathway at the end of the first quarter. And then you should bear in mind that of the 800 doctors that have started prescribing, only 70 have started prescribing to large numbers of patients. And that will, of course, increase in the coming quarters. So we know that growth will continue to be very, very strong in Japan. The launch in China was also mentioned by Gunilla. That's also a really interesting market. That happened a little bit ahead of time. And here, ASI is adopting a really interesting model with using an online platform and blood-based biomarkers. So potentially, this could be a model for how to handle this in the future in the rest of the world. And China really has a large potential. Initially, ASI is targeting the private market, but that is relatively large in China. And in the long term, ASI is expecting China to be an even larger market than Japan and in the order of China. So it will be interesting to see how this takes off in the coming quarters. If we then turn to the next slide, this high growth is expected to continue by ASI. They issued a forecast at the end of their fiscal year where they expect that they can be to grow from roughly $30 million in 2023 to $360 million in 2024. So that's more than a tenfold increase. And in their last quarterly earnings call, they said that they were doing according to plan or even better than planning in certain markets. So they still expect to see these numbers. To us, this was correspondent to royalties of roughly 400 million Swedish kronas from the second quarter of 24 to the first quarter of 25. And those are really big numbers for us. But you should still remember, this is still only the beginning. ESA is expecting a five-fold increase from 2024 to 2026. So if that comes through, then LeCambria will be selling for roughly $2 billion in 2026. So, of course, it's hard to tell exactly what will happen. But Gunilla has mentioned that there are a lot of developments that will happen underpin this you will see a much easier administration with subcutaneous version coming out in the coming years and I also believe that we'll see the blood-based biomarker diagnosis being implemented in that time period so we firmly believe that this market is set to grow immensely over the next few years. If we then turn to our finances looking first at the net revenues on the left hand side they have been very very lumpy in the past due to the milestone payments that have occurred from time to time. For this quarter, we had 50 million of net revenue, 50 million Swedish. There were no milestone payments in this quarter. And I think it is unlikely that we'll see any milestone payments during this year. The one milestone that could happen is if we get approval in the EU. But if we get CHMP opinion in the May timeframe, it will take probably a month or two for the European Commission to to give their full approval. So it's unlikely that we will see that milestone this year, even if Le Cambry is approved in Europe. But over time, the new revenue streams will shift the revenue mix over time. They will not see this lumpiness in the future. You saw royalty now of 43 million in the second quarter and co-promotion revenues of 3 million. If we get approval in Europe, the co-promotion revenues will continue to increase over time. And we have already talked about the royalties. They will increase over time. And this will be fast if the ASI forecast for 2024 is correct. We are to expect roughly 360 million Swedish in royalties over the coming three quarters, i.e. roughly an average of 120 million royalties per quarter. Probably less than in the next quarter, but higher than that in the first quarter of 2025. So I think you will see a big shift of these curves in the coming three quarters. If you then look at the operating expenses on the middle graph, you see that they grew to 121 million Swedish up from 104 in the second quarter. The majority of this is made up of R&D expenses. They grew to 84 million Swedish up from 41 a year ago. So a big increase there. And this is what we really want to do. We are focusing a lot of resources into our portfolio and are trying to accelerate our programs that Gunilla mentioned as much as possible. We also saw an increase in marketing and sales costs going to 60 million from 10 million a year ago. And this cost increase that goes on quarter over quarter will continue during the remainder of the year, mainly in the R&D department, where we are registering our project portfolio successfully, starting on phase two clinical trials, and we're preparing other programs for R&D as well. We will also see some increased activity in the commercial organizations, but here we are really careful. We are not expanding our organization until we have a final CHMP opinion. And we have previously stated that we expected the total cost for 2024 to increase by roughly 30 to 50% compared to 2023. That's still correct. We will probably be somewhere towards the middle of that range in 2024. And on the right hand side, you see that our operating loss was 76 million for the quarter, roughly in line with previous quarters. If we turn to the next slide and look on the left hand graph, you see that the net result of 68 million, the loss of 68 million is slightly better than the operating loss of 76 million. That's mainly driven by a strong financial net. The cash flow that you see on the middle graph is then however slightly worse than the operating loss. It's 18 million lower at 94 million compared to the 76 million in operating loss. And that's mainly driven by our growing accounts receivable due to that the royalties that we receive from ASI are paid 120 days after the end of the quarter. So you will continue to see this lag between cash flow and revenues as long as the royalties keep growing significantly. Then on the left hand side, you see our cash balance. We had roughly 890 million Swedish in cash and short term investments at the end of the second quarter. It's still a very, very solid position that is roughly or over, I would say, six times our quarterly costs. So we're very well funded. However, this is towards the end of the year. We have previously said that we expect to have cash between 800 and 900 million. That will then probably not be the case since we will probably not have the payment of the EU milestones. So I think we will be roughly in the range of 600 to 700 million instead. However, this is really not dramatic. We still think there is a very good chance that Lecambi will be approved in Europe and that we will receive that milestone. And even more importantly, we expect to be profitable from next year since we see that the Lecambi sales are really on a good trajectory. We still stand by that guidance, I would say. So all in all, we're doing really, really well. We're really happy to see that Lecambi is now on a really good trajectory. And with that, I leave the floor back to Gunilla for some closing remarks.

Thank you so much, Anders. And then some closing remarks and upcoming news flow. So next slide, please. So if we look into the fourth quarter of this year, we plan to start the phase 2a study in Parkinson's disease with Exedavnamab. And we're looking forward to also present some data on our brain transporter program. That's something I'm really looking forward to as well. ASI plans to complete the rolling submission of leucanumab with a subcutaneous autoinjector to the FDA. And the next important Alzheimer's Congress is called CTAD, which will be in Madrid at the end of October, when leucanumab will be presented. by, for example, Professor Lars Landfelt, who will also get the Lifetime Achievement Award. We look forward to the re-examination in Europe and hope for a positive opinion from the CHMP during the fourth quarter of this year. We also hope for more potential approvers of leucanumab that could also come later this year and next year. So I think there is a lot of exciting times ahead for biopsy. Next slide, please. To summarize today's presentation, Lekembe is approved in eight geographies and now launched in the US, Japan and China. And if you think about this, it's very large patient populations with early Alzheimer's disease that can now benefit from the treatment. And even a small part of those populations will be huge. And I think it's very gratifying that we can help many patients. The launch is starting to take off, as we heard Anders say, and it will be exciting to see more and more patients being able to get access to Lecambi treatment. We're hoping for more approvals and ASI continues with more regulatory applications and further development of Lecandema. Our pipeline is progressing really well, and the first brain transporter agreement has been signed and we are looking forward to the phase 2A start of Exidabnema. Our finances remain solid, and we have almost 0.9 billion Swedish crowns on the bank. I think it's great that we can focus on driving the project forward towards patients. Next slide, please. So by that, we say thank you for your attention, and we're happy to take some questions.