BioArctic AB

Good morning and welcome to Bioartic's presentation for the third quarter of 2024. I have three key messages for today. The first one is that our projects are progressing very well. And I'm really excited about our brain transporter technology, where we now have been presenting data publicly. And I will show some of those data here today. Exidabnamab, our project for Parkinson's disease, has initiated phase 2A with screening of patients. My second message is that Lekembe sales are increasing, resulting in over 60% higher royalties for us compared to previous quarter. The market in the US continues to grow, and Japan and China are above expectations. And the regulatory processes continues, and we are eagerly awaiting CHMP opinion tomorrow. The third message is that we have a solid financial situation, so we can focus on progressing our projects in a good way. And then we take the next slide, please. I'm Gunilla Oswald, I'm the CEO of Bioartic, and I will share today's presentation with our CFO, Anders Martin Lööf. We have also invited Peo Fresgård, our vice president of science and technology, and he's also the leader of our brain transporter program, and also Anna-Kaja Granblad, our chief commercial officer. And they are here for the Q&A part of the presentation. Next slide, please. Bioartic is listed at Nasdaq Stockholm large cap, and this is our disclaimer. Next slide, please. As you know, Biotic, we focus on disease-modifying treatments for neurodegenerative disorders. And we are among the leaders in the world in two different areas. The first one is for highly selective antibodies targeting aggregated forms of misfolded proteins for Alzheimer's disease, Parkinson's disease, and ALS. We also have a brain transporter technology which helps the biological treatments across the blood brain barrier to get higher concentrations in the brain where the target is for the treatment. Our business model focuses on innovation of new treatments for neurodegenerative disorders. We are also becoming a platform company with a brain transporter technology. An important part of our business model is partnering, and we see three types of partnering. The first one is for large indications like Alzheimer's disease and Parkinson's disease, where our aim is to partner before Phase 2b or at least before Phase 3. For orphan drug indications, BioRT can drive the programs longer ourselves and potentially all the way to the market. For our brain transporter technology platform, we can also partner with companies that want their biologics to have increased brain penetration. Next slide, please. So today I will start with the first message, which is about our pipeline and that how well that is progressing. And there are three things I want to start to mention first about our brain transporter technology. Some of our patents are now public and we have preclinical data validating our brain transporter technology in transgenic mice and in non-human primates. The data demonstrate a rapid, broad, and deep brain distribution of the Bt-captaled AV antibodies. Exidavnimab, which is our most advanced alphas-nuclein program, has initiated the Phase IIa study in Parkinson's disease patients, and we plan to start dosing later this year. And we're also exploring to include MSA patients. Our founder, Professor Lars Landfelt, he received the Lifetime Award at the big CTAD Congress in Madrid a couple of weeks ago. The Alzheimer's disease research community with experts, they emphasized and acknowledged his great efforts for Alzheimer's disease patients with new innovative treatments like Lecanumab, which is based on his innovative research in Alzheimer's disease. Next slide, please. The brain has a natural barrier to protect the brain, and that is called the blood brain barrier. And that is making it difficult for treatments to get into the brain, and especially biologicals, which are a little bit larger, like antibodies. At BioRTIC, we focus on brain disorders, and therefore, this kind of technology is critical for us. We are highly engaged in this area, and we invest in getting new treatments with improved brain penetration. We utilize the transferrin receptor to get active transport of our antibodies across the blood-brain barrier. Our brain transporter approach is unique in several ways. For example, with where we bind to the transferrin receptor. The binding site is the protease-like domain of the transferrin receptor. And this is positioned near the cell membrane, which makes the safety profile for hematology parameters improved, especially with regard to reticulocytes, for example. The BT technology will increase brain exposure of the antibody. It can give a broader distribution in the brain, making it possible to reach deeper brain structures. A fast blood-brain barrier transport results in rapid brain exposure and the potential for a fast effect. The increased exposure and broader distribution can potentially lead to a better effect as well. Lower doses can also result in better convenience for the patients, and we strive for subcutaneous administration. It could also lead to better safety due to lower doses and different distribution in the brain. Next slide, please. We see a stronger and broader and deeper brain distribution with a BT approach. It has now been validated in transgenic mice and in non-human primates. In the picture you see to the left, you see double transgenic mice with a human transferrin receptor and the five times FAD mice. And they are overexpressing amyloid deposits in the brain. To the left, you see a brain where we have used a normal A-beta antibody. And you see some green of the antibody, especially in the ventricles. When we engineer the amyloid beta antibody and combine it with our brain transporter technology, then we get dramatically more antibody into the brain, as you can see in the green picture to the right. I think a picture says more than a thousand words. To the far right of this slide, you see some data from our non-human primate study. And you can see that we get substantially higher brain exposure of our amyloid beta antibody in different regions. And here we show, for example, cortex and striatum, but it's also for hippocampus and other places. And we see up to 70-fold increased levels versus the naked antibody. Importantly, when you work in this area, and as we see with several other transferrin receptor technologies, they have shown issues with hematology and reticulocyte decrease. Our safety profile so far looks very good without affecting hematology, including reticulocytes that you can see down to the right left corner. So in summary, I think we have very encouraging data and we have now combined our technology with projects in all our disease areas with antibodies for Alzheimer's disease, Parkinson's disease, ALS. And we have also started to combine it with enzyme replacement therapies, like with BTG case, where we are aiming to address CNS symptoms of Gaucher disease. This area is very much in focus. And this has been seen, for example, in recent deals in the industry. And we see an increased interest by potential partners. Next slide, please. Our alphas-nuclein portfolio is also progressing very well. And I think there are many opportunities in several neuronal synoclinopathies, such as Parkinson's disease, Parkinson's disease dementia, Lewy body dementia, and prodomal stages. And also orphan drug indications, like multiple system atrophy. I think it's reassuring that biomarkers are available now to identify the right patients with pathological alpha-synuclein. And we will also use this in our Phase IIa study with Excedavnimab. Next slide, please. The Phase IIa study with Excedavnimab will be performed in patients with mild to moderate Parkinson's disease, and we call the study EXIST. The design is a randomized double-blind placebo-controlled trial with a low and a high dose compared to placebo. The primary endpoint is safety and tolerability. The key secondary endpoints are pharmacokinetics and immunogenicity. And then we have exploratory endpoints, several of them. So several biomarkers, both biochemical biomarkers as well as digital motor and cognition markers, which are relevant for patients and an important preparation for the next proof of concept study. The study will be performed in Spain and in Poland, and the screening of patients have already started, and we plan to start treatment during this quarter. We are also exploring possibilities to add a new cohort of patients with MSA. Next slide, please. So in summary of this part of the presentation, our portfolio is progressing really well, and today I've highlighted our brain transporter projects and Excedabnema. And then next slide, please. And we come to my second part of my presentation, which is about Leukemia. The number of patients treated with Leukemia continues to grow. And I think it's very reassuring to hear that the clinical safety experience is on par or better than reported in the phase three program. On the commercial side, royalties increased with more than 60% for this third quarter compared to the second quarter this year, resulting in royalties of about 70 billion Swedish crowns to Biotic. We see continued growth in the US market and an impressive growth in Japan and China, where it exceeds expectations. ASI has lowered their outlook due to the slower uptake in the beginning now in the US, and Anders will discuss this further. On the regulatory side, LeCambius approved and also launched now also in Hong Kong, Israel, United Arab Emirates, and also now in Great Britain. Regulatory authorities are reviewing leucanumab files, and that's ongoing in 17 different markets and regions, including EU. And as we know, we're waiting for the CHMP opinion tomorrow. ASI has finalized the rolling submission of the subcutaneous autoinjector for maintenance dosing at the end of October. On the development side, ASI are continuing to do a lot of different things. For example, the AHEAD study 345, the phase three study, has completed recruitment by mid-October. The study is for preclinical Alzheimer's disease individuals, and this means individuals with elevated levels of amyloid deposits in the brain, but they do not yet have any symptoms. And they will receive the treatment with either leucanumab or placebo for four years. During the latest Alzheimer's Congress, CTAD, ASI presented new data from the Phase III Clarity-AD study, and those further support both early and maintained treatment. Next slide, please. Leucanumab is the first disease-modifying treatment for Alzheimer's disease with a full approval in the US, Japan, and China. And it's on its way to be established as a standard of care treatment for Alzheimer's patients. If we look at the US, IV administration every second week is approved and broadly reimbursed since July last year. A supplementary BLA is under review for less frequent maintenance dosing once a month with a PDUFA date in January next year. In October, ASI completed the rolling submission of the new BLA for subcutaneous administration with an autoinjector for maintenance treatment. And ASI is also preparing a submission for induction treatment with subcutaneous autoinjector to be submitted after the approval of the subcutaneous maintenance treatment. As I said, in Japan and China, the launch is exceeding expectations. And in Europe, we're waiting for the CHMP opinion following the re-examination. And we expect the information tomorrow. And of course, we hope it will be positive. So we also can give Alzheimer patients in Europe access to Lecambi. Lecambi is also approved now in eight, in total in eight countries and regions and under review in another 17 countries and regions. Next slide, please. I would like to share with you some of the key highlights from the CTAD Congress for Alzheimer's Disease, which is one of the largest Alzheimer's Congresses, and it was held in Madrid at the end of October. ASI presented three years long-term data with leucanumab, which showed increased patient benefit with maintained safety profile. we can see clear and meaningful long-term treatment effect. And that was shown over 36 months when all patients now have got leucanumab. Either from the start, which means three years treatment, or if they had placebo in the core study, then they have been treated for 18 months. So if we look at the graph to the left, we see the benefit increased over time. The benefit was 0.45 on the CDR summer boxes scale after 18 months, and it doubled to 0.95 after three years. Patients get benefit if they start treatment early, then they get more benefit. And that's what you see in the green top curve. But we also see the patient can benefit by starting later, as we see with the middle curve, where the black is when they had placebo and the green is when they have started to get leucanumab. And we can compare that with the purple curve, which is a matched historical control group from ADNI. And also, I think it's very reassuring to hear the experience from key opinion leaders from clinical practice from both the US and from Japan. They reported at CTAD a wide patient acceptance and compliance. Very few patients want to stop treatment. They also concluded that the treatment is safe and no new safety findings reported and that the side effects are manageable. The side effects in focus are especially area E and H, and they are similar to the clinical studies, even though it's now being used in clinical practice. They are mainly asymptomatic and transient and comes during the first six months. Very few areas are reported after six months. The patient journey is improving in several ways. For example, with blood-based biomarkers. Safety matters, of course, and approximately 18,000 patients have now been treated with Lekemvi. And I think it's reassuring that no new safety findings have been reported and that there is a low frequency of area after the first six months. And that the key opinion leaders concluded that this side effect are manageable with a lower or similar frequency than was seen in the clinical trials. Next slide, please. More data that were presented at CTAD supporting starting treatment earlier, and that could benefit patients more, and also to continue dosing. After the Alzheimer Congress called AAIC in July, then ASI presented the graph to the left, which I think is very encouraging data from a small sub-study in patients with no or very low tau, which means that they are early in their disease. 60% of these patients had improved after 18 months and more than 50% were still doing better after 36 months. We should, of course, be a bit careful since only 40 patients are part of this study. But I think it's encouraging and further emphasize the importance of starting treatment early. Now at CTAD, at this Congress, ASI presented the graph to the right. And now there are more patients that are in early stages. And they are then measured by amyloid PET and had baseline levels below 60 centiloids. What we see here is that after 18 months of leucanumab treatment, there were 51% less decline versus placebo. And this is in contrast to the fourth population of the study, which was 27% less decline versus placebo. We see similar results also when we look at other scales measuring cognition and activities of daily living. I think also it's very exciting and we hear more and more patient stories with patients benefiting from Lecambi treatment. Next slide, please. Lecandimab development continues with subcutaneous autoinjector, which could make administration much more convenient and possible to give at home in an easier way. And I think this is of great support for the patients and for society. The blood-based biomarkers for diagnosis will also simplify the patient journey and help to identify patients in a much easier way than to do it with PET scans and CSF samplings, which sometimes could be challenging. And this development is going really well. Professor Susanne Schindler from WashU, she presented data at CTAD on blood-based biomarkers and stating that prime time is now. And it's already used now for screening. And I think the usage for confirmation is not far away, could be expected next year and onwards. And then again, treatment earlier has shown more benefit, which is encouraging for the phase three study ahead 3.4.5. in subjects who do not yet have symptoms, but they have elevated amyloid deposits in the brain. This study is already using blood-based biomarkers to identify the right patients, and recruitment has now been completed. Next slide, please. So by that, I hand over to the third key message about our solid finances, and I will hand over to Anders Martin.

Thank you, Gunilla. I'll start to talk a little bit about the Lecambi revenues on this slide. It's been known for a while that the global sales of Lecambi in the third quarter were roughly 10 billion yen or 67 million dollars. That means that our royalties that you see on the left hand side increased to 69.8 million Swedish kronas. That's a 64% increase over the second quarter of 2024, or if you like, 3,200% over the third quarter of 2023. So we're seeing very, very rapid growth in our royalty revenues. If you look a little bit on the different geographies, the sales in the US were 5.9 billion yen in the third quarter or $39 million. And that's roughly 30% higher than in the second quarter. And it seems that there is a very good demand for Initially, it was thought that diagnosis with PET and CSF would be a bottleneck. That's what the market expected. That does not seem to be the case. And that has actually been facilitated by the start of... of the implementation of using blood-based biomarkers for pre-screening patients in the US. So even though PET capacity is fairly scarce, when you use blood-based biomarkers, you can pre-qualify the patients, and you have a lot more patients that are actually positive when they do their PET scans. So that has helped the diagnosis process, and the inflow of patients is now fairly big, and it is feasible to get reimbursement. However, what ASI has seen now lately is that there has been a bottleneck in infusion capacity. So they stated that they have roughly 6000 patients lined up that could not be treated due to the lack of infusion capacity. They're working really hard on that problem and have contracted more facilities. And the capacity is expected to to increase by 90 percent in the following two quarters. So they're expecting to treat the 6000 patients that are lined up for treatment. But that has held back the sales in the US during the last few quarters. I think this also underlines the importance of the subcutaneous administration. If Lecambi is going to grow to hundreds of thousands of patients, infusion capacity could become a really big problem in the world, but We are in a fortunate position that the subcutaneous version is evolving really, really well. ASA is expecting approval for maintenance therapy using the subcutaneous version by mid next year and with induction therapy towards the beginning of 2026. So I think these problems will be alleviated over time. If we then turn to Japan, we saw very rapid growth, 80% from the second quarter, up to 2.7 billion yen or $18 million. They're now treating some 5,000 patients over 800 facilities. And that's almost half of what they're treating in the U.S., where they've been going for a much longer time. So I think the Japanese market is doing really well. Here, I think it's interesting to note that they're now starting a direct-to-consumer campaign to raise awareness about mild cognitive impairment and to promote early diagnosis. And as Gunilla showed, early diagnosis is going to be really, really important. And I think the largest growth area in the coming years will be mild cognitive impairment. Especially since that's probably the period of the disease when we can have the largest impact. So I think what you see in Japan will be followed in other regions that you start to focus on these earlier patients. Turning then to China, where the product was launched in late June. They sold for about 1.2 billion yen in the first quarter, where it was actually on the market, so $8 million. So already up to 3,000 patients in China in the first quarter of sales, which is really, really strong. Here, ASA is using a self-pay model. There is no reimbursement from the larger... healthcare system. And there's relying solely on blood-based biomarkers and using a digital platform. And this is also a model that I think could be copied and used in different parts of the world over time. We will not see that short term, but in the longer term, I think blood-based biomarkers and focusing on MCI and using subcutaneous version is where we are heading in the years to come. All in all, due to the slightly slower development in the US, ASA reduced their fiscal year forecast. It was 56.5 billion yen, or $370 million, and they reduced it down to 45 billion yen, or $280 million. That means that they're expecting sales of roughly $170 million in the two quarters to come. However, the mid- and long-term forecasts have not been changed, and we still have the same belief in the potential of the product. It is a number of things that we have to sort out. It is a complicated product to administer in the beginning, and that is now being sorted out. But longer term, those problems will diminish since we have a number of developments that will help the implementation of the Cambria treatment going forward. If we then turn to the next slide, I will comment on our financials. On the left-hand side, you see our net revenues that decreased from the third quarter of 2023 from 209 to 77 million Swedish kronor. Of course, in 2023, we received a big milestone for the Japanese approval, so it's not really comparable. I should also mention that we're not expecting any milestone payments in the coming quarter. We didn't get anything in Q3 this year, and we will not get any milestones in the fourth quarter, even if we see a positive CHMP opinion. That will then happen during next year if we get the positive opinion and approval. But I think you can also see the trend that during the year our revenues are growing and that is what we expect to continue. Those are the royalty revenues that are growing over time and that trend will of course continue. We also have some co-promotion revenues in the area of 3 million that will grow if we get the approval in Europe. We don't know that yet, but hopefully that will happen shortly if we get this positive CHMP opinion. Looking at the costs on the mid-graph, you see that their operating expenses increased to 95 million from 78 million one year ago. R&D is now 72% of our total operating expenses. It was 68 million in the third quarter of this year. That's roughly 100% higher from a year ago when it was 33 million. However, it's down from the second quarter when our R&D expenses were 84 million. And this is fairly lumpy. It goes up and down a little bit when we have larger payments for clinical trials and CNC work. But the long-term trend is that the cost will continue to increase on the R&D side as we are progressing our project portfolio. We're now, as Gunilla mentioned, starting our phase two trial with Exedavnamab. We're also investing heavily in our other programs that are falling behind that are making really good progress. And then we will invest significantly in CMC, etc. So you should expect growing R&D costs in the coming year. We were planning to increase our spending in marketing and sales, but we have held back some recruitments until we get the final CHMP opinion. If that's positive, you'll see an increase in the next year. If not, probably not. We have previously guided that the full year cost would be roughly 30 to 50 percent higher in 2024 over 2023. We're still in that range and now I expect that the cost will be roughly 35 to 40 percent higher in 2024 versus 2023. If you then turn to the right hand side, you see that the operating loss was 26 million Swedish. And that's when we made the profit in the third quarter of 2023. Of course, that was driven by a milestone received in 2020. 2023 that we need not get now but you also see I think again it's interesting to see the trend that without any milestones we're also decreasing our loss so it's really starting to see the impact of growing royalties that are starting to finance more and more of our R&D spending. If we turn to the next slide, you see that the net result was 20 million, so that's roughly 6 million better than the operating result, and that's explained by financial net. On the middle graph, you see that the cash flow from operating activities was negative 80 million. That's roughly 60 million lower than the net loss. And this is basically due to the delay of royalties that we get paid for the royalties roughly two quarters after the sales have occurred. so we have a growing accounts receivable so our current assets containing these numbers are roughly 110 million related to royalties. On the right hand side you see our cash balance still very strong we have over 800 million including short-term investments at the end of the third quarter. We think that we will end the year with more than 700 million in cash and short-term investments And going forward, we have mentioned this before, we will become profitable based on the Canby royalties. So we will maintain a very, very strong financial situation going forward in the coming years. However, we will not talk today about exactly when we will become profitable. There are a number of moving parts, but long term, this will lead to profitability. With that, I hand the word back to Gunilla for some closing remarks.

Thank you so much, Anders. So we are coming towards upcoming news flow and some closing remarks. So next slide, please. The upcoming news flow. So this fourth quarter, we plan to start the Exidabnimab phase 2a study in Parkinson's patients with a dosing. So we hope to be able to communicate that. And then we're also awaiting, of course, the CHMP opinion of licanumab in EU tomorrow. We do not yet know the outcome. I think it's not decided yet. But of course, we're hoping for a positive outcome and then a potential approval in the European Commission within 67 days. In January next year, we also expect response from the FDA regarding less frequent monthly IV maintenance dosing of Lekembe in the US. And regarding the subcutaneous autoinjector, we expect responses next year regarding maintenance dosing and 2026 also for the induction treatment. And of course, we're also hoping for further regulatory approvals and launches in several other countries and regions. Next slide, please. So to summarize today's presentation, our pipeline is progressing very well and we are very encouraged by the brain transporter data that has been presented and generating a lot of interest. We're looking forward to the Exidabnimab phase 2A start, and Lekembe is approved in eight geographies and now launched in seven of them, including Japan and China, where there are very large patient populations with early Alzheimer's disease. And even a small part of the population will be huge, and it's gratifying that we can help many patients. Lekembe royalties revenues continue to grow as the sales continue to increase. And we heard Anders explain that our finances remain solid and we have about 800 million Swedish crowns in cash, which I think is great. So we can focus on driving the project forward towards patients. Next slide, please. So by that, I say thank you so much for your attention and we're happy to take some questions.