BioArctic AB (publ)

Good morning and welcome to Bioartic's presentation for the first quarter of 2023. I'm Gunilla Osvall and I'm the CEO of Bioartic and I will share today's presentation with our CFO Jan Mattsson and our Chief Medical Officer Thomas Odegren. We will give an update on Bioartic and on Lecunema and focus on the great start of this year with the approval in the US by the accelerated pathway and the submission of applications for full market approval of lecanumab in three continents. These submissions are based on the groundbreaking results for lecanumab in the CLER-JD phase 3 study in early Alzheimer's disease. And I think it's really exciting that lecanumab, or lekemby as it's named in the US, now is available for patients in the US. And we'll talk more about that here today. Next slide, please. This is our disclaimer. Next slide, please. Bioartic's aim is through world leading innovative research, create drugs that improve the lives of patients with neurodegenerative diseases. We focus on research and development of innovative treatments for brain diseases with high unmet medical needs like Alzheimer's disease and Parkinson's disease. As you know, these diseases affect large patient groups and their relatives and comes with large costs for society. There is a high medical need for disease-modifying treatments, which is affecting the underlying disease and slowing down the disease progression. We are also building a commercial organization and preparing for commercialization of leucanumab in the Nordics, together with our partner ASI. We have an attractive and well-balanced project portfolio with projects spanning from discovery to phase three and now also in the regulatory process in three continents and on the market in the US. We have partner projects that generate revenues by milestones and royalties and where our strategic partner carry the costs for clinical trials. And we also have earlier fully owned projects with substantial marketing and licensing potential. Biotic is well financed and we have a strong cash position with about one point one billion Swedish crowns on the bank, which is approximately one hundred and ten million US dollars. We have valuable collaboration agreements with companies like a sign. And during the first quarter of this year, we got regulated milestones of thirty five million US dollars and euros. Biotic is listed at Nasdaq Stockholm large cap and our market cap is about 21 billion Swedish crowns. Biotic is an innovative and dynamic and very exciting company with a huge potential. Next slide please. Biotic has a rich and balanced project portfolio that focus on brain disorders. Alzheimer's disease is our largest area. And for leucanumab, which is our most advanced program, which now is on the market in the US based on the accelerated approval and in regulatory phase in the US, Europe, Japan and China for a full approval. All that is driven in a great way by our partner, ACI. We have one more large phase three program ongoing with leucanumab in even earlier phases of Alzheimer's disease. So even if this first step with the first disease modification treatments are successful, there is still a large medical need for more treatment options and for combination of therapies. Therefore, it's very important that we and others continue to do research for Alzheimer's disease. We have four early Alzheimer's disease disease modifying programs, including two, where we have combined the antibodies with our brain-transported technology in order to get more of the antibody into the brain and hopefully then have even better effects. Two of our projects in Alzheimer's disease are targeting truncated forms of EBITDA, such as pyroglue EBITDA, and that is including BAN1503 and ADBT2803, which is then combined with our brain transporter technology. Based on Le Canema's positive phase three results, I think that the probability of success has increased for our other programs with similar approach that are targeting misfolded aggregated forms of proteins that we call oligomers or protofibers. And that is soluble aggregated forms of the proteins, and they are toxic. In Parkinson's disease, the protein is called alphasnuclein, and in ALS, the protein is TDP43. The ALS projects that are targeting TDP43 are progressing really well and quickly, thanks to our technology platform and our vast experience from Alzheimer's disease and Parkinson's disease projects. We're also working on another rare disease, Gaucher disease, with GGVT6822, which is an enzyme replacement therapy with the aim of also being able to target the CNS effects of Gaucher disease, which is a major unmet medical need today. Our brain technology, brain transporter technology platform, which you know, I think it's a very exciting part. It's progressing really well. And we have now transferred the platform into preclinical development. And it's now included in projects in all our disease areas. And in the future, we could also foresee the brain-transported technology could be applied to other companies' antibodies or proteins on non-exclusive license basis. Leucanumab is, of course, very important for Biotic. But I want to point out that Biotic is even more than Leucanumab. And our portfolio is progressing really well. Next slide, please. We have a long-standing and successful partnership with ASI. in Alzheimer's disease all the way back since 2005. And we have two licensees and have had several research collaborations. And we have a research collaboration still ongoing with ASI. During the first quarter of this year, we got 35 million euros in regulatory milestones from ASI. And that was based on the US approval, the submissions in Europe and Japan. We have another one hundred and one million euros remaining for milestones if it continues to progress well. And they are linked to regulator approvals in Japan and Europe and some sales and marketing milestones. Biotic is entitled to royalties of high single digit percentage for the first 10 years following launch and mid single digit percentage for the following five years on a country by country basis. After the 15 year period, ASI has an option to extend the agreement period with continued royalties. I think that leucanumab is of substantial value or blockbuster potential, which means that we could, if everything continues to go well, foresee more than one billion US dollars per year in revenues without any cost for the clinical programs in Alzheimer's disease. Biotic has also retained rights to other indications outside of Alzheimer's disease, And we have the right to market in the Nordics, which we are very much looking forward to be doing together with ACI. Next slide, please. Lecambi is the name for Lecanumab when it's launched in the US. And Lecambi has the potential to become the first anti-abeta amyloid antibody to receive full approval on a global basis. Lekanumab is now in regulatory review process for a full approval in three continents. The FDA has approved Lekanumab by the accelerated pathway in the US. And we got that feedback from the FDA on the 6th of January this year. And that approval was based on the Phase 2b biomarker data showing that Lekanumab clears amyloid plaques from the brain. In the full approval applications, that are submitted. They are based on phase 3 efficacy data. ASI has submitted the application for the traditional pathway and they did that on the same day as the accelerated approval was received, which I think is very impressive. We are looking forward to an advisory committee meeting on the 9th of June and the response from the FDA by the 6th of July at the latest. Reimbursement is, of course, also important, and the Veterans Health Administration has decided to provide coverage for veterans with Alzheimer's disease. A full approval based on the phase three efficacy data will be important in order to get broader reimbursement in the US by CMS and a broader access for the patients. If Lecambi is granted a full approval on the 6th of July, then it is expected that CMS will broaden their coverage under the existing national coverage determination. ASI is also exploring less frequent dosing for maintenance dosing and subcutaneous administration, and they plan to file those submissions in the first quarter of next year. In Japan, while Lecanumab has undergone a pre-review process data during 2022, ASI has then submitted a full marketing authorization application on the 16th of January to the Japanese authorities. The application has also been granted priority review by PMTA and ASI expects a response later this year, in the second half of this year. In Europe, ASI has submitted a marketing authorization application to the European Medicines Agency on the 9th of January. And that was based on both the Phase 2b and the Phase 3 data. The application was accepted on the 26th of January and it will follow a standard review process and the response is expected on the first quarter of next year. In China, ANSI initiated the application process in December last year and priority review designation was provided in February. and response in China is expected by the first quarter of next year. I want to compliment our partner ACI for their dedication and hard work with the clinical studies and regulatory submissions in such a timely way. I think this is very important since every day matters for the patient. Next slide please. One of the three most important Alzheimer congresses every year is called ADPD. And this year, it was held in Gothenburg. The Swedish Queen, Silvia, inaugurated the meeting with a warm and crucial message of the importance of the effects for these patients. I think it was a very positive atmosphere at the Congress with a lot of hope for the patients and a lot of talking about the new era for Alzheimer's disease. It was very nice to see the great progress, both with new treatment opportunities like leucanumab and on blood-based biomarkers. Lecanumab was mentioned in numerous presentations, and Lecanumab was the focus in four different presentations on health-related outcomes, safety, and the unique binding profile of the antibody. And our CMO, Tomas Odegren, will now talk about some of these presentations at ADPD and the clinical program of Lecanumab. Next slide, please, and hand over to Tomas.

Thank you, Gunilla. Dr. Sharon Cohen from the Toronto memory program in Canada presented on the CLARITY-AD quality of life results. The analysis showed statistically significant benefits of leucanumab treatment across scales assessing quality of life both for the subject affected by Alzheimer's disease as well as the care partner of the subject. As seen on the graph at the top right of the slide, The subject experienced 56% less decline in the quality of life over the 18 months treatment period compared to subjects in the placebo group on the disease specific quality of life scale. A similar result with 49% less decline in quality of life was seen on another instrument, which is used across many different disease areas, the EQ5D5L. Alzheimer's disease is a condition that profoundly affects the life of the family members. The experienced burden of caring for the subject with Alzheimer's disease by the partner or family member providing the care was assessed in CLARITY-AED with a desired burden interview. Across the 22 domains assessed, everyone detected a point estimate in favor of the Leucanumab treatment group. In aggregate, a clear increase in the burden for the care partner is seen over the 18-month study period, as seen in the black curve in the lower graph on the right-hand side. This was reduced by 38% with leucanumab treatment. The results on all instruments of quality of life were consistent across the randomization strata in ClarityAD, such as the disease stage and APOE genotype. Next slide, please. This slide goes into more details of the domains assessed with the quality of life AD instrument. A point estimate to the right of the vertical line identifies a domain detecting a numerical benefit of lecanumab treatment as perceived by the subjects. As you see in the graph, such a benefit was seen in all but two of the 13 domains. The clinical significance of lecanumab treatment is readily apparent by the observations on such domains as ability to do chores and things on the top of the graph, as well as the ability to manage money, family, friends, and life as a whole further down. Next slide, please. Three further oral presentations were given on the LECANMA program at the ADPD conference. The first was given by the co-founder of Bioarctic, Professor Lars Landfelt, who reviewed a unique binding profile of leucanumab, consequent to it being selected based on a preference for binding to soluble aggregated amyloid species. It was noted by Professor Landfelt that there may be an association between this binding profile and the relatively lower incidence of amyloid related imaging abnormalities, ARIAS, in the leucanumab phase three trial. compared to several other anti-amyloid treatment candidates. This higher risk with these other candidates is apparent despite them having been initiated with several months of a titration regimen, whereas leucanumab treatment can be initiated at the full dose from the start. The two other presentations by respectively Dr. Sabag and Dr. Hornig from the USA, detailed the leucanumab safety profile in the CLARITY-AD study focused on two aspects of the AREA data in the study. In the analysis of the possible impact on AREA of the use of antiplatelets or anticoagulants, it was seen that the incidence of AREA occurred at a similar frequency in the LECANMA-treated participants, irrespective of antiplatelet or anticoagulant use. The analysis of isolated observations of hemorrhage associated with ARIA, ARIA-H, the frequency, temporal pattern, and association with APOE genotype of isolated ARIA-H in the LECANOMAB group was similar to that in the placebo group in the CLARITY-AD study. Next slide, please. The treatment paradigm underpinning the LECANOMAB program is the need to continue treatment. to ensure that the soluble aggregated amino species that drive neurodegeneration are continuously cleared from the brain. The recent publication by Mon Farad and co-office in Neurology and Therapeutics have now applied the CLARITY-AD data to a previously published model of the impact of long-term treatment maintained for as long as the subjects remain at the stage of early AD. The data show that Lecanumab treatment applied in this manner slows the rate of disease progression and delay the progression to moderate Alzheimer's dementia with several years and thereby reduce the need for institutional care. Next slide, please. As seen in this slide, ASI is diligently continuing the important clinical development program for Lecanumab. The phase three globally conducted a head study together with the ACTC academic consortium for subjects with pre-symptomatic Alzheimer's disease is progressing well to meet the target of 1400 enrolled subjects with intermediate or elevated levels of brain amyloid. The study is supplying blood biomarkers for prescreening to enhance trial efficiency and reduce unnecessary PET scans. Lecanumab is also being assessed as background treatment in conjunction with anti-Tau therapies in the DIAN2-Tau NextGen study for subjects with dominantly inherited Alzheimer's disease. To provide a more convenient treatment option than biweekly IV infusions, ASI is exploring less frequent maintenance dosing. ASI has also developed a subcutaneous formulation of Lecanumab which is presently being assessed in subjects treated in the open labelling expansion phase of the CLARITY-AID. The subcutaneous formulation is also being progressed with the aim of providing the option for self-administration through an autoinjector. And with that, I hand it back to Gunilla for the next slide.

Thank you so much, Thomas. So reflecting on the population of patients with early Alzheimer's disease, I think this is enormous. ASI has estimated the global prevalence for future early Alzheimer's disease subjects to include about 240 million people by 2032, of which about 75 million people are in the Americas, EMEA and Japan. Of course, will not all patients be treated with disease modifying therapies. The patients need to come to health care. And to be diagnosed with mild cognitive impairment or mild Alzheimer's disease with confirmed amyloid beta pathology. And they have to fulfill other requirements such as, for example, not having pacemaker and so forth in order to be eligible for disease modifying treatment. So even if a proportion of all patients with early Alzheimer's disease will be treated, it's still a huge opportunity. More and more patients could potentially be treated if we work and handle some of the challenges. ASI has estimated that approximately 3 million patients will be treated with disease modifying treatments by 2032. And I think that's a lot of patients that we hopefully will be able to help. There are several opportunities that could be worked on to increase access, and some of them are listed here to the right. It's important to increase patient awareness, especially on mild cognitive impairment. and earlier signs of the disease, since there are no such treatments available today, and working on less stigma for Alzheimer's disease patients. Education on primary care, on diagnosis and biomarkers and treatment options is of course also important. Access to specialist care is a very important area to try to facilitate. I think for example memory clinics and so forth has an important role in order to making sure that the right patients get the right treatment. In the beginning the confirmation of pathology has to be done by lumbar puncture CSF or PET scan. In the future hopefully more and more blood-based biomarkers can be used. Following treatment with MRI is important for safety aspects and access to infusions and so forth. So it's a lot of things to work on to facilitate access. When we get more improved diagnostics with blood based biomarkers, that will definitely help. And it's great that the blood based biomarkers are progressing so well in parallel with the treatment options like leucanumab. Another really important opportunity to increase access is the subcutaneous formulation. And that will make the administration more convenient in getting the treatment earlier or easier and at home. We and our partners are working on all these aspects for the benefit of the patients. And we, of course, would like as many relevant patients as possible that could benefit from leucanumab to be able to get access It's wanted by the patients. Next slide, please. And by that, we come to the financial summary and hand over to our CFO, Jan Mattsson.

Thank you, Nic Gunilla. Net revenues in the quarter amounted to 393 million compared to 4 million in Q1 of previous year. And the reason for this increase is related to the three regulatory milestone payments totaling 35 million euro. that we received from ASI and that we recognized in the first quarter. Total costs in the quarter were higher than in last year and amounted to 96 million compared to 48 in previous year. The main reason for the cost increase is related to one time effects that are linked to our milestones from ASI. This led to a milestone payment to LifeArk and to variable remuneration to the bioarctic employees. Operating result was 301 million in the quarter compared to minus 44 same quarter of last year. And our operating expenses are expected to be in the range of 330 to 380 million for the full financial year 2023. compared to 246 in 2022. The reason for the cost increase is the build-up of the commercial organization prior to the launch of the Canemab in the Nordics and to costs for the expanded in-house project portfolio. Next slide, please. Cash balance amounted to 1.1 billion SEK at the end of March. The reason for this increase has to do with the received milestones. Operating cash flow amounted to 299 million during Q1 compared to minus 40 in Q1 2022. Net results for the quarter was 294 million compared to minus 44 in Q1 of previous year and in summary Bioarctic continues to have a strong financial position which is even stronger than a quarter ago. And with that next slide please and back to Gunilla.

Thank you so much, Jan. And now come to the upcoming news flow and some closing remarks. So next slide please. The upcoming news flow, if we look at this, we can also note that we had a very intensive and great first quarter. Looking forward in the coming period that we are in now, the second quarter of this year, We will look forward to the U.S. Advisory Committee meeting on the 9th of June and then we have the regulatory processes and reimbursement in the U.S. in the coming months. The regulatory process in Japan for the second half of this year with a response and China and Europe within the coming year. And of course, we'll come back with more information when that is relevant. We also look forward to further Alzheimer congresses. And the next one to look forward to is AAC in July in Amsterdam. And we will also provide more information from our other projects when that is relevant. And early next year, first quarter of next year, our partner AAC is also preparing to file maintenance dosing with less frequent dosing and subcutaneous formulation if all those results is positive. So that's also something to look forward to. So I think that we can conclude that we have had a great start this year and that we have a very exciting year ahead of us. Next slide, please. So I would like to end today's presentation by thanking our CFO, Jan Maxson, for his valuable time as a CFO. And he will now move into a new role as VP Finance at Bioartic. And I would also like to welcome Anders Martin Lööf with our new CFO from 1st of May. Next slide, please. So by that, I say thank you so much for your attention and we're happy to take some questions.

Operator, we're happy to take some questions.

If you wish to ask a question, please dial star five on your telephone keypad to enter the queue. If you wish to withdraw your question, please dial star five again on your telephone keypad. The next question comes from Joseph Hedden from RX Securities. Please go ahead.

Good morning, and thanks for taking my questions. Congratulations again on all of the events achieved over the quarter. A couple of questions. Firstly, Lacanema, having been approved earlier in the year, was launched pretty quickly by ISAI in the US, although we know that largely it would only be available to private payers for the majority of the quarter until the VHA decision. Can you confirm if ISO has made any sales and are you due any royalties for sales made in Q1? Or if not, when do you expect to record first royalties? That's the first question. Second question, I noticed that the VHA's criteria for prescribing Lekembe to people under coverage excludes the use of the drug in APOE for homozygotes and that's not in line with the accelerated approval label. What are your thoughts on that and is that a potential risk for other insurers to follow suit in your view? Thanks very much.

So I think the first question will be for Johan.

Yeah. We have not yet done information about the lecanebub sales in the US and we have consequently not received any royalty for the Kanemab. We are in discussions with ASI about royalty and sales reporting and we will get back to that next quarter for more information.

Okay and for the second question if I start and then we can see if Thomas wants to build. So I think with regard to the accelerated approval we should recognize that there were very few homozygotes in the top dose of the Phase 2b trial. So I think that might be one of the reasons for why they were a bit reluctant for the first approval, that they would like to see more data from the Veterans Health Administration. But we don't really know exactly why they have limited it. But I think that the most important, as we have said all the time, would be a full traditional approval, which is based on all the efficacy data from the large phase three trial. And you're right, it's not excluded in the label, but they did this as a first step. And they pioneered by taking this decision and grant coverage in the US before CMS. So maybe they wanted to be a little bit more careful when they started. I don't know, Tomas, if you want to build any further.

No, I mean, I would just want to add that in the appropriate use guidelines that have been published in the US, there's no such restriction in respect to carriership of APOE gene. So we await now the evaluation by the FDA and other regulators for this about the clarity AD data, which provide a much better data set in terms of determining benefit risk in APOE for homozygotes.

Okay, thanks very much. Thank you.

Thank you, Joseph.

The next question comes from Patrick Ling from DNB. Please go ahead.

Thank you. Just a few questions. Just to follow up on the first one regarding royalties. What's your agreement with ASI when it comes to when you will receive royalties? Is it the same quarter of sales is generated or is it the quarter after?

That is the quarter after the sales have taken place. So we will get a report from... So there will be one quarter or a little more than one quarter delay before we get the payment.

Okay, and when will it be booked from an accounting perspective?

That depends on when we get the information. We are not yet through this with ASI. So we have to come back with that next quarter.

Okay, so potentially next quarter we could get the royalties both for the second quarter, if you have any, and for the first quarter? We don't know that yet. Okay. Then I had a follow-up question on one of the comments that you gave, Gunilla, regarding the royalty agreement. Can you just clarify what happens after 15 years if they decide not to extend the royalty agreement?

Then it comes back to Biotic.

Okay, so they cannot continue to sell it, so you will receive the product back. Great. Okay, great. Thank you. Then I had a question on the AHEAD 345 trial. If you know anything about recruitment there, when it's expected that the trial is fully recruited, or how far they have got into this 1,400 patients as of now?

So I think it's fair to say that the study started in the US and it has been expanded broader and broader around the world. So it's also now ongoing in Japan and Australia, Singapore and some different places in Europe. We're hoping it will come to Sweden soon. And the it's recruitment is going quite well. But we have not yet gotten all the patients included. So there is still some time to get all the patients included. I don't know, Thomas, if you want to say anything more? No. I think one really important thing was also last year when they also now started to have blood biomarkers as a screening tool to come into the trial. And that has really simplified and facilitated the recruitment part. since you screen many patients and some of them get the very positive news that they do not have amyloid. And for those who have amyloid, the next part is to find out how much they have, if they have intermediate or clearly elevated levels that decides if they go into A3 or A4-5.

Okay, great. Then my last question, I think that this might be for Johan as well. You talked about your operating expenses now in the first quarter and you said that there were some costs associated with the milestones. Maybe you can elaborate a little bit on that?

Yeah, we had an agreement with LifeArk in the UK and we paid a milestone payment to them which was linked to the milestone that we received from ASI, the 25 million milestone payment. And then we had some payments to our staff under a remunerating program for the staff as the FBRT receives milestone payments. Also the employees will get a share of it.

And is that something that we should expect? I mean assuming that you get the full approval for example now in Q3. If you get a milestone associated with that, which I would expect you to get, should we expect some additional costs associated with that as well? No.

I think it's very important to clarify, Patrik, that the remaining milestones that we have are linked to Japan and Europe. And as you saw, I mean, the regulatory milestones is one for U.S., one for Japan, and one for Europe. And we have already got the one for U.S. So the next one to look forward to will be Japan and then Europe if it continues to go up. I think it's important that we clarify.

Okay. That's great.

Great. Good. Thank you. Thomas is pointing that the staff will get some remunerations when we get milestones.

Okay. Okay, great. Good. Thank you, guys. That's all for me.

Thank you, Patrik.

The next question comes from Fredrik Thor from Red Eye. Please go ahead.

Hello, and thank you. I was wondering a bit about the ADTD presentation about the relationship between patients with on anticoagulants and the aria frequency. Could you elaborate a bit on that and what does this mean for the previous hypothesis that maybe the risk could be higher in this patient group?

So what this analysis shows is that in terms of the risk level of having such an event there is no implication of being on antiplatelets or anticoagulants. However, if you get a major hemorrhage, there is a greater impact of that if you are on such treatment potentially. So what these data do not tell us is that there is no risk consideration in terms of initiating leucanumab treatment for subjects who have antiplatelets or anticoagulants. I think it's very important that if the regulated decision is to provide full approval, that prescribers are given the insight in terms of having a conversation with subjects who are on such treatments so that they are aware that the consequence, if there is an area event associated with bleeding, may be worse if you have that type of concomitant treatment. But as of yet, we have a limited data set based on controlled clinical studies. It's important to build on that evidence once leucanumab is more broadly available to further assess the potential risk if you have those type of concomitant treatments.

Okay, thank you. And I was also wondering a bit about the market potential in China. Could you maybe develop a bit on that market? What type of

Approach approach as I could tell you maybe how already the market is for for the kind of Yeah, now I think that China is very difficult to To estimate in in any way, I think not We are happy to see that as I am the Chinese authorities are Really working on on the kind of mouth for the patients But I don't think that we can say anything about how big an uptake could be in China. We know that the population is very, very large, but it's very difficult to judge China. So I see that as a very positive upside, but it's difficult to foresee.

And a final question for markets beyond these four. What's the status here, the rest of the world beyond? Excellent question.

Thank you, Fredrik. And we will provide more information about other parts in the world when that becomes relevant. The focus so far has been those four major markets that we talked about right now. But of course, there are other important markets that ASA is working on and will provide more information when that is relevant.

OK, yeah, that's all for me. Thank you.

Thank you.

As a reminder, if you wish to ask a question, please dial star five on your telephone keypad.

So if there are no more questions, then I think I just want to conclude that we have had a great start this year and that we have a very exciting year ahead of us. And I thank you so much for your attention and for the great questions.