Ladies and gentlemen, welcome to the Lundbeck Fiscal Year 2020 Results Conference Call. For the first part of this call, all participants will be in a listen-only mode, and afterwards, there'll be a question and answer session. Today, I'm pleased to present Deborah Dunsire, President and CEO, Anders Götzsche, Executive Vice President and CFO, and Johan Luthman, Executive Vice President of Research and Development. Speakers, please begin. Hello everyone, welcome to the Lundbeck Full Year 2020 Results Conference. As you've heard, I'm joined today by Anders and Johan, but also have Jacob Tolstrup, our Head of Commercial Operations, and Peter Anastasiou, our Head of North American Operations, with us to answer your questions. Next slide, please. You've seen this disclaimer many times before. I won't read through it. Let's go to the next slide. 2020 is a year that I am extremely proud to be part of Lundbeck for. We have accomplished so much in the midst of a global pandemic and faced with significant currency headwinds. Our employees came together to ensure seamless delivery of all our products around the world throughout the year, that enabled us, in spite of the challenges, to deliver revenue growth within our guidance range of +4% and reaching DKK 17.7 billion in line with our guidance. We also were able to save during the year. We weren't able to promote normally, and that resulted in savings that we could bring to the bottom line. Our core EBIT improved to DKK 4.4 billion with a margin of 25.1%. We grew our brands. Our strategic brands grew in total 13%, and we launched VYEPTI in the U.S. in the midst of the pandemic and were able to move that brand forward, not as we would have liked, indeed, but to get a lot done during the year. We've also had additional approvals in Canada and the UAE and initiated the regulatory review in Europe. REXULTI is on track for the interim readout of the phase III study in agitation in Alzheimer's disease, and that will come in Q2. It was great to be able to get the patients in for that interim analysis, even in spite of the difficulties the pandemic has implemented on our clinical trials. The COVID-19 impact, it's been across the business in many different ways, limiting patients from seeing physicians, limiting our promotion around the world, limiting our clinical trials. The people of Lundbeck came together to make things happen, and we've been able to move forward regardless. We couldn't, unfortunately, do anything about the significant currency headwinds in the second half of the year, and that has had an impact that Anders will go through in more detail. It is a year we're very proud of. Next slide, please. When we look at the underlying performance for the major strategic brands, Brintellix grew to DKK 3.1 billion, and you can see that it grew 13% versus full year 2019, so at a slower rate. You see the impact of the first and second half, very strong growth in the first half and the impact of the pandemic restrictions impacting the second half. The market shares have been stable and, in some markets, even increasing. REXULTI also had a very strong growth year and achieved DKK 2.6 billion. We've continued to launch that brand in other markets, recently launching in Brazil and Italy. The biggest business, of course, is still in the U.S. and also Canada, where we have the major depressive disorder indication as an adjunct therapy. ABILIFY MAINTENA was very resilient through the COVID pandemic and grew well at achieving DKK 2.2 billion in sales. The LAI market, I think, has been growing well in the pandemic as LAIs allow patients to come in less frequently, so ABILIFY MAINTENA benefited from that. We shouldn't forget NORTHERA achieving DKK 2.5 billion in sales with a growth of 10%. Next slide, please. Focusing a little bit more on VYEPTI, fourth quarter demand doubled compared to third quarter demand, showing that this brand is continuing its momentum even though it is challenged by the limitations of the pandemic. We've had very positive testimonials from both patients and the physicians providing VYEPTI to their patients that it really delivers on that powerful, fast, and sustained relief from chronic and frequent episodic migraine. The work we did in our U.S. operations to really get the bedrock of reimbursement in place for VYEPTI was quite remarkable in a virtual setting. We've had the average sales price is now published, and the permanent J-code was effective from October 1st. We had, by the end of the year, 130 million Americans covered lives by their insurance, providing access to VYEPTI with no branded step edits. We've seen utilization not only in those people, but in people whose plans required branded step edits. They had to go through other brands because VYEPTI can deliver relief where other brands have failed. We also see that at the end of this graph here, the normal reset at the beginning of a year as the deductible resets for people in their new insurance year. We're confident that VYEPTI has the potential we expected when we made the acquisition of Alder, but of course, it has been impacted by the pandemic. Moving to the next slide, please. This is a brand that we own globally, and the global rollout is beginning, and we're also rolling this brand into different indications. There's a very big market for prophylactic migraine treatments around the world, and we expect it to grow considerably in the coming years. It's a market that has been served by older generic therapies for so long, and they are inadequate. We do anticipate that there is a lot of headroom for growth in the prevention of migraine market. As I said, we've achieved approval in three markets, the U.S. Canada, UAE, and actually updating today, we have now submitted for approval in 12 markets around the world, the latest being Thailand. We importantly submitted to the European Medicines Agency in December, right on track. They have accepted Lundbeck's application for the marketing authorization. We anticipate that approval in the first quarter of 2022. We've started the trial ALLEVIATE for the second indication in episodic cluster headache. Johan will talk a bit more about that. Got also our Asian development activities underway with trials starting in China and pharmacokinetic trials starting in Japan. We're very excited about the potential for VYEPTI to expand globally and then expand into further indications. Next slide, please. Anders, over to you. Thank you, Deborah. Our five largest products have been quite resilient, growing 10% in 2020, and that is indeed a strong achievement considering the pandemic, but also the currency headwinds we have experienced during the year. The four key product delivered double-digit growth in 2020, despite the impact from the limitations we have seen due to the pandemic. There has been less patient interactions with healthcare providers, and we also have had a reduced ability to conduct normal promotion activities. The lower activity level and the patient interactions with healthcare providers has reduced the new to brand prescriptions, which has impacted the growth negatively, especially in the second half, as Deborah also alluded to in the previous slides. It is important to highlight that we have seen strong recovery and also uptake in periods where countries have opened up and society has been more back to normal. Next slide, please. For 2020, the gross and net sales amounted to 4%. Thereby we are actually meeting the expectations that we laid out in the market in the beginning of year before the pandemic actually started. To achieve 4% in an unprecedented year, we are super happy with that. The core gross margin increased with one percentage points during the year to approximately 86%. The reported gross margin was a bit lower than we expected. That is of course due to the additional amortizations on REXULTI of approximately DKK 300 million. The increase in SG&A and also R&D is a consequence of two things, the foliglurax write-down of DKK 800 million, as you're aware of, and then investments in additional clinical trials for VYEPTI, and also additional sales and promotion activities as we started the launch of VYEPTI in April 2020. If we adjust for this, the cost development would have been flat between 2019 and 2020. When we look at the underlying performance without these investments and the write-down, our reported EBIT margin would actually have been above 25%. It's also important to emphasize that we delivered a very solid core EBIT of DKK 4.6 billion, which is also the reason for the strong cash flow, which I will come back to in a minute. The effective tax rate for 2020 has been a positive surprise as it ended much lower than anticipated due to a couple of positive impacts. It was increase in Danish R&D tax incentives. It was faster integration of the acquisition and faster utilization of NOLs, and also a positive tax impact on transfers of IP rights to Denmark. All we are pleased with the financial performance for 2020, which is also seen in this slide. Please turn to slide nine. As you know, Lundbeck has more than 50% of our business in the U.S. We have 24% in international markets. The rest is coming from Europe. Our main currencies are U.S. dollar, Chinese yuan, Canadian dollar. These three exchange rate together constitutes about 70% of our currency exposure. We have seen declines across all these, including some very steep depreciations on some of the more exotic currencies during the year. The impact on sales from depreciations in currencies was very visible in the fourth quarter. Reported revenue from the U.S. was negatively impacted with seven percentage points, and in international markets, the impact was negatively or was a impact of nine percentage points negatively. The depreciation of currencies is expected to impact Lundbeck's revenue with approximately DKK 800 million in 2021. It's also important to highlight that our assessment, based on the currency rates we have now, is that a 5% change in the US dollar will impact Lundbeck's revenue in a range between DKK 250 million-DKK 300 million. Next slide, please. As you can see from the left-hand side of the slide, free cash flow in 2020 was very solid and is a testament to the strong underlying growth and performance by the business. To the right at the slide, you can see that acquisitions made in 2019 increased the net debt to around DKK 6.6 billion. That debt has, during 2020, due to the strong cash flow, been reduced to DKK 4.1 billion at the end of 2020, leading to a net debt to EBITDA ratio a bit less than one. We expect that the net debt during the year will end, or at the end of 2021, will end in a range between DKK 3 billion-DKK 3.5 billion. Next slide, please. We believe that 2021 will continue to be impacted by the pandemic, and we assume a gradual return to a more normal market situation by mid-2021. We expect to regain momentum with double-digit growth for the key brands during the second half of 2021. We delivered approximately DKK 17.7 billion in 2020, or revenue of DKK 17.7 billion. In 2021, we expect revenue to be in a range between DKK 16.3 billion-DKK 16.9 billion. We have tried to illustrate the moving parts in the bottom of the slide. As you can see, we have maintained our expectation around 50% decline in NORTHERA sales due to loss of exclusivity, which is approximately a decline of DKK 1.3 billion. The other key brands are expected to show high single-digit to double-digit growth during 2021. We expect that the mature brands will decline around 10%, and that is due to two things. It's continued generic erosion, and then it's VBP in China. The net effect of that is a total gross in revenue of around DKK 800 million-DKK 900 million for the key brands and the mature brands in local currency. We assume, as I said before, negative currency effect of around DKK 800 million and a hedging effect that goes in the opposite direction of DKK 200 million, which means the net effect will be around DKK 600 million in 2021. Reported EBIT, we guide DKK 1.8 billion-DKK 2.3 billion, despite having elevated investments, both from a SG&A perspective, but also from an R&D perspective in 2021 compared to 2020 or last year. For the full year, you should expect financing items to be a net expense of DKK 250 million-DKK 350 million, depending on currency development. With that, I will like to hand over to Johan for going through the R&D pipeline. Thank you, Anders. Please turn to slide 12. While we continue to maximize our brands, including by running critical life cycle activities, we are simultaneously focused on filling the pipeline with innovative programs, with an increasing focus on niche and rare diseases affecting more defined subpopulations of people where the unmet medical need is the highest. With regards to VYEPTI, some of the recent activities I like to highlight are that we started a phase III clinical study in episodic cluster headache. We also submitted, by the end of the last year, the European Marketing Authorization application for the preventive treatment of migraine in adults, which means that we can expect the CHMP review by end of the year, and the formal EU Commission approval of VYEPTI in Europe around a year from now. By the end of last year, VYEPTI was approved in UAE as our second approved market, followed by the very recent approval in Canada. In addition to the present three approvals, we have to date submitted VYEPTI to 12 regulatory authorities for review. We plan to submit to over 10 other authorities during 2021. For brexpiprazole in agitation and Alzheimer's disease, we have, as communicated earlier, somewhat changed the study with the introduction of an interim analysis. We have completed the recruitment of the patients needed for this planned interim analysis. It's on track for the second quarter. I'll come back to some more details of that program in a minute. We continue to progress innovative programs in our research organizations in Valby and La Jolla to build up a steady and dynamic early-stage pipeline. While our early development programs are endowed with a systematic experimental medicine approach, we also diligently, swiftly close down less promising programs if we do not see what we expect to see. We continue to see a very fluid situation related to the COVID-19 pandemic. Many of our trial sites closed initially, then opened up, and now some are closing down again. This is primarily impacting study starts, especially in the early development studies where we depend on very few sites. Nevertheless, overall, we have a strong, sustainable phase I set of assets. For example, we have a strong momentum in the PACAP and MAG lipase inhibitor programs. Next slide, please. As I mentioned previously, in the ongoing agitation and Alzheimer's study, we have recruited the 255 subjects needed for the interim analysis, and I'm therefore confident that we can conduct the planned interim analysis sometime during the second quarter. The main analysis is a pooled analysis of the two and three milligram doses. With the upcoming analysis, it might be worthwhile to recap on what has been published prior from the two conducted phase III studies on brexpiprazole in patients with agitation and Alzheimer's dementia. The program was initiated to assess the efficacy of brexpiprazole on agitation measures, as well as safety and tolerability in two 12-week randomized, double-blind, placebo-controlled parallel arm studies. One of these studies, Study 283, was a fixed-dose study conducted at 81 sites and in seven countries and recruited 433 patients. The second study, Study 284, was a flexible-dose study with 0.5 mg- 2 mg per day of brexpiprazole or placebo and conducted at 62 sites in nine countries, recruiting 270 patients in a care facility or community-based setting. In Study 283, brexpiprazole 2 mg per day demonstrated statistically significant greater improvement in the Cohen-Mansfield Agitation Inventory total score from baseline to week 12 compared to placebo at a level that is also considered to be clinically meaningful. In Study 284, brexpiprazole 0.5mg -2 mg per day did not achieve statistical superiority over placebo. However, a benefit was observed in the post hoc analysis among patients titrated to the maximum brexpiprazole dose of 2 mg per day compared with placebo patients. Combined with our broad knowledge about the molecule, it's therefore my view that brexpiprazole has the potential to be efficacious, safe, and well-tolerated in the treatment of agitation in Alzheimer's disease. Next slide, please. This is our current pipeline. We have aligned the products according to our strategically prioritized biological clusters. In development, we are currently active in three out of four of those clusters. During the second half of 2021, we plan to start Phase II programs, one on PACAP in migraine and another planned on A2422, our alpha-synuclein monoclonal antibody in multiple system atrophy, or MSA for short. We also expect to have Phase I read out of REXULTI in borderline personality disorder in the second half. With that, I'd like to turn over to Deborah again. Thanks, Johan. Next slide, please. As you know, at Lundbeck, our purpose is to tirelessly dedicate ourselves to restoring brain health so every person can be their best. While we do that, we want to do it as part of a global community committed to moving the world forward. We support the sustainable development goals. We make an impact on a number of them. A very important one that we are focusing on is our commitment to carbon neutrality. We have committed to the Paris Climate Agreement and aim to be carbon neutral definitely by 2050 or before. We have new science-based targets approved that we're talking about in our sustainability report to keep moving us along that journey. In 2020, we made significant progress reducing our CO2 emissions in spite of the fact that we are increasing production volumes. 14% cut in the carbon emissions from our production versus 2019 even. We've exceeded our annual target by 4%. We're a company that's working hard to become carbon neutral. We made these reductions even without purchased certificates of origin in 2020, and it's our goal to continue to do that. We also have made progress in creating a workforce that's even more diverse and an environment where people can be their best that is inclusive of all as we make progress against the Sustainable Development Goals five and 10, looking at gender equality and the reduction of inequalities generally. We're a company where discrimination is not tolerated. We've also formed a donation partnership with International Health Partners to help bring our medicines to places that don't have access to medicines for brain disease or mental health. We're constantly looking to reduce the stigma associated with mental health so that people facing brain disease can get equal parity of care. Next slide, please. We released today our sustainability report for 2020, and you'll find that on our website, and you'll see that Lundbeck has significantly improved our ESG ratings during 2020. In this new reporting format, we list our information on what we're doing according to the Task Force on Climate-related Financial Disclosures, the TCFD reference index, so that you, as investors, can easily track our commitments and our goals regarding sustainability. We were very proud this year to be listed for the fifth year in a row as an A-list company by the Carbon Disclosure Project for our work on climate. Next slide, please. Turning to looking to the future, we've made significant progress on our expand and invest to grow journey, you know that we expanded our disease operating space in 2019. During 2020, focused our internal discovery in four very promising areas of biology to yield new medicines for neuroscience. In the future, where we'd like to go with that is always addressing the highest unmet medical needs, which are typically specialist indications. We want to be able to bring that innovation forward for patients in those select segments that allow us to bring transformative improvement in brain health. We want to do it in selected patient populations where we've got biomarkers to measure the progress and give us predictability, or where we may be able to use a biomarker to select a group of patients where we can focus a medicine on that disease. That gives us more tractability in development and helps us reduce the size of our development programs. When we focus on bringing forward transformative medicines in these niche psychiatry, niche neurology indications, we also know that it helps us have a focused footprint around the world. As a mid-sized company, it enables us to be able to afford the commercial footprint to bring those medicines as Lundbeck around the world. We're looking to be able to bring our medicines to all countries, given the transformation that we're looking for. You know that we have great medicines. TRINTELLIX is a phenomenal drug. There are some countries we can't launch it because we can't get pricing. We want to change that as we go into the future. Next slide, please. Here's the trajectory, expanding the disease operating space, focusing our internal discovery in the most promising areas, and then focusing as we develop medicines in indications in niche neurology, rare disease neurology, and niche psychiatry. Next slide, please. We're on a journey. We are very ambitious. We look to be number one in brain health. That will come through providing those transformative outcomes to patients in the most high unmet medical need areas in neurology and psychiatry. We want to be recognized by patients and other stakeholders as their partner, their number one partner in brain health. We want to be recognized for having a pipeline filled with premier neuroscience and having a commercial organization that partners with healthcare providers and patients around the world on those targeted areas of niche neurology, niche psychiatry, and rare disease neurology. We're working to become a more digitally enabled company to be able to use data and digital to improve patient outcomes. Never forgetting that we're part of a global community, we need to be on track to being carbon neutral by 2050 and deliver sustainable growth in revenue and profitability so that we can address all our stakeholders' needs. We look forward to communicating with you over the years ahead on our journey to be number one in brain health. Next slide, please. When we look at the news flow coming this year, the first half, we've already achieved one goal, which was the Canadian approval of VYEPTI. We're looking forward to in the middle of the year, Australia. The interim analysis for REXULTI in Alzheimer's agitation in Q2. In the second half of the year, the MSA trial with our[uncertain] the alpha-synuclein antibody, kicking off. We'll start the phase II with our PACAP antibody and migraine and then hope to finalize the study with REXULTI in borderline personality disorder, as long as clinical trials can accelerate the accrual and as the pandemic lifts. First half of 2022, it'll be a big milestone to have VYEPTI approval in the EU and then finalizing the post-traumatic stress disorder trial with REXULTI. Next slide, please. I think we probably are done with presenting, and now we can go to your questions. Thank you. Ladies and gentlemen, if you do wish to ask a question, please press zero and then one on your telephone keypad now. First question is from Wimal Kapadia from Bernstein. Please go ahead. Your line is open. Oh, great. Thank you very much for taking my questions. Wimal Kapadia from Bernstein. Can I just ask about the upcoming interim for REXULTI and Alzheimer's agitation? Firstly, what is the bar at interim? I am assuming reasonably high. Just tied to that, what are management expecting in terms of primary outcome, in terms of CMAI reduction? Is a good benchmark the previous six-dose study where we saw close to 20-point change? Secondly, can I just push a little bit on the target population? Clearly there are a large number of patients, but how does Lundbeck think of which are the most likely to receive the products? I am really just curious to hear how you think about the dynamics, both in the care home institutionalized setting, where on-label drug use is very important, but also in the community setting, where carers are really trying to delay institutionalization. My second question is just on VYEPTI. You flagged in your release that the manufacturing has been shown to be more cost-effective and thus production costs will be lower going forward. Could you just help us better understand that in terms of accretion dilution versus the group COGS, and what that could mean moving forward in terms of benefit? Thank you. Okay. Wimal, that sounded like a lot more than two questions, but I'll kick off with the target population and hand over to Johan to talk about the trial. We know that agitation is the symptom that causes people to have to move out of community care into care homes, and it's very difficult to manage even in those settings. We'd anticipate that this would be able to be used in both settings. We showed a very good tolerability profile in the previous two studies, and so we anticipate it could be used in the community to maybe enable people to stay with their families for longer, but also be used in the care homes to make the management of patients much better, both for patient and staff in those settings. We really look across both. Johan, perhaps you can comment on the other parts of the question. Yeah. Just one more word about the population. The population we're studying in this particular trial that's ongoing, it's actually the same population we studied in the two previous trials, and this is a mix of about 50/50 people that are institutionalized in nursing homes primarily, and people that are outpatients living at home. That is the population we're targeting also in the trial and document in this trial work. In terms of the interim, obviously this is a very classical interim. There are three possibilities here, success, futility, or trial continues. As you may recall, we talked about the trial going out to 330 subjects now. The interim is at 255 subjects. The bar, we don't go into details of the statistics here, but the futility bar is set pretty high because there is really no reason to believe that we will hit futility. We have previous data from the two previous trials. In terms of the primary outcome measure and the size effect, we're actually aiming for similar effect as in the previous trials. The effect size is what is considered, as I mentioned before, clinically meaningful effect. The absolute effect is also similar to what you saw in the previous trials. That's what we're aiming for. We are going to see the results by Q2. Obviously, we can only communicate details, whether it's a progression of the trial or to a different outcome, success and futility at that time point. On the VYEPTI question, perhaps, Anders, you can. What we have said before is that we have had a pretty nice improvement in our COGS for producing VYEPTI. Of course, it's not something that we are willing to go into if it changes the accretion dilution. What we can say is that what we have said in the past is that the gross margin that we have for Lundbeck around 78%-80%, that will not be changed by launching VYEPTI. That is the indication we have said before. Great. Thank you very much. Next question is from James Gordon from JP Morgan. Please go ahead. Your line is open. Hello. This is James Gordon from JP Morgan. Thanks for taking the questions. One on the Alzheimer's agitation and also just one on prescription trends in U.S. growth. On Alzheimer's agitation, if you repeated the efficacy you saw in the previous two Phase III's with the 2 mg dose in Phase III, would it be fair to assume that that would clear the statistical hurdle that you have at the interim? Also, could you just remind us, I think one of the interesting differences is that the current Phase III has a different geographic enrollment. You've taken out the Russian enrollment. That was a bit of an issue in the two pr evious trials. If you look at the previous trials and you did take out the Russian enrollment, how much better does the efficacy look there? Do you still think that is a big confounder for those previous trials, please? The second question was just REXULTI and TRINTELLIX and the post-COVID-19 rebound. I know there was a bit of an issue from COVID-19 in 2020 for these drugs in the U.S. but earlier this year it sounded like you were seeing some encouraging trends. Have those continued and could they be double-digit growers in the U.S. again this year? Great, James. Thanks for the questions. I'll have Johan start with the Alzheimer's agitation, and then I will move to Peter for the commentary on what we saw in the fourth quarter and what we're seeing in the first. Yeah, if I got your question right, you're really after will it be sufficient at the interim with progressing, for example, with filing. We have a good understanding with the regulators that this would be the case. This, as I said, is a pooled analysis of 2 mg and 3 mg. We have, as I said, 255 subjects. It's a two to one, we have sufficient subjects dosed at that time point, including the critical 3 mg dose that is there really to create the headroom for safety. Probably that's what you're asking if I got your question right. Can you confirm that was what you were after? That's right, because I'm aware that when you take an interim, there can be a statistical penalty. Even it's not just about how many patients you've got, but if you're splitting the alpha, and sometimes the regulator or company themself sets a higher hurdle for success at an interim versus the final result. My question is, effectively, do you need even better efficacy than you saw previously because it's an interim? Or the extra patient you enrolled boosts the power sufficiently that even though it's an interim, you only just need to repeat what you showed in previous trials for 2 mg? No. Without going into details there, we're looking for the same treatment effect across the study at its total end, 330, and at the interim. That's as much as I can comment on that bit. Thank you. The bar is higher. The bar is higher, yes. Yes. The bar is higher at the interim. Obviously, with fewer subjects, you have more variability, and that's taken into account. It's a pretty robust approach to the interim as well as the final readout if we have to go that far. The geography, taking Russia- Geography. Yeah, you're wary about that. We had Russian sites in the previous program. We don't have that now. This is a U.S. and Ukraine-based study where we have experience. In terms of taking out different subgroups, et cetera, in the previous study, obviously Russia is a well-known problem in Alzheimer trials. If you look at the totality of the data versus taking out the Russian sites, there are differences. I think the most important thing is now with the ongoing trial, we have a good set of sites, high-quality sites, and we have experience with those sites before from the two previous trials. We're pretty confident that we're picking the right geographies this time. To put a fine point on it, the flexible dose trial from 0.5 mg -2mg without the Russian sites, the overall intent to treat was positive. Yeah. That's a post-hoc analysis, so we can't claim anything from that. We have excluded the Russian sites. Peter, would you take the question on what we saw when the society was opening up in the fourth quarter, and then what we're seeing in the first? Yeah. Thanks for the question, James. The short answer to your question is yes, we believe we will get back to double-digit growth with those brands. It's very dependent on COVID about when that happens. As Deborah mentioned, in Q3, Q4, where we saw the lockdowns ease, patient volumes were coming back, our reps were getting close to back to full promotion, although about a third of those calls were coming from virtual versus face-to-face, but we were approximating some normalcy. We saw the NBRX trends go back to their pre-COVID levels. That's why we have the confidence that as this thing lifts, that those brands are going to recover. The big question is when. I think in the first quarter, we've seen much lower ability than the fourth quarter to be able to be out promoting, and that's also, of course, affecting patients' willingness to come in to physicians and physicians' offices being open. I think we're seeing not as deep a impact in the first quarter as the second quarter of 2020, where it was a much harder lockdown, but we have less availability to go out than we did in the fourth quarter. If I can add then, so when you look at the phasing of the growth for the strategic brands in 2021, you should definitely expect also due to the strong currency or the strong dollar in the beginning of the year, that the growth will be muted in the first couple of quarters, and then it will gain momentum in the second half of 2021. Thank you. Next question is from Trung Huynh from Credit Suisse. Please go ahead. Your line is open. Hi, guys. Trung from Credit Suisse. I have a few on guidance, just one on the TRINTELLIX patent proceedings. On guidance, if you have a look at the 2021 guidance at the sales level, it looks quite conservative. I was just wondering what the pushes or pulls you expect to get to that upper end, more importantly, that lower end of your guidance. For 2021, what are your expectations for that other pharma portfolio? Looks like consensus has a decline of 8%. Do you think that's an appropriate decline? On the EBIT level, just touching on Wimal's question, there's clearly an increase in costs coming through here. I wonder if you could just take us through some of those other aspects of the cost structure beyond COGS that we should expect to the group in 2021. On the TRINTELLIX patent infringement proceedings, I see they've started. You've settled with eight people. There's a remaining six. I was previously expecting a decision in the first half of this year, but your release today suggests a decision within seven months after the trial. Is an expectation for that decision in the second half of this year now, or even in 2022? Is there any comment you can make about the case? Thanks. Okay. Anders will take all the numbers questions. Okay. Our expectations for the cost ratios in 2021 is that we anticipate that the cost of sales will be in a range of 20%-23%. We anticipate that the SG&A will be in a range of 41%-46%, and then that the R&D will be between 22%-24%. It is important to say, then you can take the mid-range, and then you get what is the mid of the guidance we are giving here. If you look into the SG&A costs, we will use more money on VYEPTI in 2021 compared to 2020, but then we will make some savings on other costs. VYEPTI is basically the only reason for increase in SG&A. The rest will be absorbed by efficiencies. When you look into R&D, it's pretty straightforward that if you compare with 2020, if you take out the foliglurax, you are more or less on the midst of the ratio. Within the portfolio, there will be a substantial additional spend for VYEPTI due to cluster headache, the trial for that, the DELIVER study, and then we will reduce the spending on other programs. Did you ask about other revenue or other pharmaceuticals? Other pharma. Yeah. We had anticipated to be declining a bit more than 10%. That is of course due to pricing. What we have seen in 2020 is, of course, the mature brand showed a really, really strong performance. It is a bit difficult to predict what will the performance in 2021 be. The underlying structural performance should indicate 5%-10% decline because you will see generics coming in. Of course, you also have the VBP in China that is taking out some DKK 150 million or something like that. That is definitely meaning that the mature brand portfolio will have a decline around 10% or more, and the totality of the mature brand portfolio will decline 10% because we have the VBP on top. Did I cover all the financial questions? Guidance. Yeah. What is the take to hit the top and hit the bottom end? Thanks. What are the puts and takes? Thanks, Deborah. It's definitely to go to the bottom of the revenue guidance, or the lower end, then it's we will be hit more by the pandemic, that we will not regain momentum, that the pandemic will not lift in the second quarter, and we will not see a rebound into single-digit, double-digit growth in the second half. That could be a reason. A reason could also be if NORTHERA is declining more than 50%, and that is basically the two biggest uncertainties. As Peter alluded to, we have seen a very, very strong uptake when we are back in the market and in the field, then BRX is regaining momentum immediately. That is also why we have a strong belief that we will regain double-digit growth with the key brands because there's a strong need for the products in the market. Great. I think the other thing we don't hope that we'll see more of is currency decline. That's another wild card. Yeah, that's also why we gave you some indication of what a change in U.S. dollar is actually meaning with the 5% sensitivity. Then it's also important that the hedging we have, guidance we have given you, of course, the hedging will impact Q1 and Q2 mostly because that is where we had the high U.S. dollar rates last year. Right. To the Trintellix patent, obviously the strongest patent for any product is the compound patent, and that's the 2026, 2027 expiry. The court case, we are litigating the other very important innovations that we've put around Trintellix. The outcome of that is what's being litigated in the court case. We don't provide guidance on ongoing litigation. We have innovated around Trintellix. We will defend those patents accordingly. As to when we'll see an outcome of that, we can't tell. We do know that there had been delays because of the pandemic leading up to this. There may be more. I wouldn't really hazard a guess as to whether we'll see it this year or early next. Very clear, guys. Thank you. Next question is from the line of Michael Novod from Nordea Markets. Please go ahead. Your line is open. Thank you very much. It's Michael Novod from Nordea. Maybe a bit of a strategic question to sort of your European launch and rest of world launch of VYEPTI. There's been a lot of focus whether you could do more M&A. Maybe you could talk a bit about whether you could consider doing more product in-licensing for drugs that are very close already on the market in order to support the range of products that your sales force is going to target the market with, given that you are probably going to invest anyway in significant promotion activities for VYEPTI. More of a strategic question to that. Secondly, we've seen your ABILIFY MAINTENA two months formulation, and we're waiting for production ramp-up. What about the brexpiprazole long-acting version? I know you have one in the pipeline as well. How do you see the progress for that? If that's successful, how would that also fit into a potential Alzheimer's agitation indication, and also regarding the length of the IP protection for a long-acting injectable of REXULTI? Thanks. Whew. Wow, that's a tour. Jacob is going to start with VYEPTI, rest of the world, and then thinking about how we build the portfolio in the rest of the world. Yeah. Hopefully I'm answering correctly, Michael. Just to start on VYEPTI, as you know, we'll be starting the end of this year in the first markets outside of North America, which is obviously exciting. The first launch will be the Arab Emirates, and then we'll move into Europe in early 2022. That will be a phased rollout of VYEPTI over some time, some years, as you are normally well aware of for Europe. It's also a different launch for us this time compared to what you've seen in the past, that this is more of a hospital-based, few clinics opportunity since it is an IV product. That also means that we were positioning it towards a specific segment of micro-inpatient where we believe the benefit speaks the most and where we have good data also compared to the other CGRPs in the market. For the strategic point of it is that we will have VYEPTI launching in 2022, rolling out over the next two to three years after that in Europe. At the same time, we will, in 2024, lose ABILIFY MAINTENA to exclusivity. That still means that we will have two large-scale promotable brands in Europe, and we would obviously like to add to that portfolio. That is where we come to the BD part of that question, that we are constantly looking for opportunities to add to our product portfolio. We have been looking at opportunities that are very close to market or even on market, basically, during 2020, and I am sure we will continue to look for those in 2021. You are absolutely right. It would be good to add something more to our portfolio in Europe where we have a full-scale infrastructure. Yeah, we'll continue to look externally things that might have global rights. We've said that we'll look for license, we'll look for partnership, we'll look for M&A. We would be prepared to do regional deals. It's a question about finding the right strategic fit for us at the right price. There are a number of things that are a little bit priced to perfection right now, we'll be disciplined in how we invest. Definitely looking to supplement from external innovation. Johan, maybe I can ask you to comment on the Brex LAI. Well, first of all, the ABILIFY MAINTENA two month, we delivered very good clinical data that we think are supportive, and that gives you the answer to the brexpiprazole. One needs good data. This is a very early-stage program. Obviously, in collaboration with Otsuka, we're exploring a lot of formulation and possibilities, but it's too early to tell in that program. We're exploring different options, formulations, and we have ongoing clinical studies to see whether we can deliver upon the pretty challenging demand to put some long-acting molecules into the right space and format. I think if we do find a formulation that works, it's been a challenge. Brexpiprazole and aripiprazole don't formulate in the same way. They are different products. It's been a lot more challenging with brexpiprazole. That would carry its own protection around that formulation, and we would anticipate bringing it forward in a number of different indications. You're perfectly right. A longer-acting formulation in an agitated Alzheimer or dementia population would be a benefit. I think we could see lots of different possibilities there. First of all, we need the formulation to deliver the parameters that make it worth investing in. Okay. Can you say whether you're seeing progress in the formulation work on BRX? That was my feeling in recent discussions that you've seen some progress in this formulation work. It's too early to tell, quite frankly. We are still running a number. We have gone through a number of formulation and tests, and as Deborah alluded to, not every molecule is made the same way, and there are some technical challenges with this molecule, quite frankly, to make it long acting. In terms of the question of different indications, I may add to what Deborah said, that traditionally, this kind of class of molecule has not been very big for long acting because the tolerability is an issue. Obviously, we hope to be able to deliver better tolerability, which we've seen in the two previous trials in agitation and Alzheimer's. It's an area where you usually have stayed away from long-acting injectable because of the tolerability challenges. Okay, super. Thanks a lot. Next question is from Michael Leuchten from UBS. Please go ahead, your line is open. Hi. Thank you. It's Michael at UBS. Two questions, one for Anders and one for Deborah. Anders, you referred to tax benefits from the acquired companies. I just wondered if that's something that's a one-off just from the tuck-in, or if that's an ongoing process that could help you with your tax rate going forward. For Deborah, I think in Q2, maybe Q3, you talked about how the mental health issues coming out of the pandemic might lead to a benefit for you, but patients have to go through the generics first. Is that part of the dynamic you're seeing early in the year with that slightly more dynamic behavior of your portfolio in the U.S., or is that yet to come, or is it just impossible to say because it's not something that can be analyzed? Thank you. Yeah. If I start with the tax question, you should expect that our reported tax rate from a structural point of view will be around 23% going forward. What we have done here is, of course, also to optimize our tax payments. For the next three to four years, you would see way lower cash tax rates. Of course, on a more long-term basis, it will be around 23%, but it is simply to optimize cash flow. It is not that you should expect that it has a sustainable impact on lowering the corporate tax rate. That will be around 23%. On the impact on mental health, we're still seeing that there's a tremendous discussion about the impact on mental health. As society opens, some of that diminishes. We've seen in multiple places a difficulty for patients to get in to see physicians to be diagnosed. So, a drop of IQVIA data in the U.S. suggests that there's a drop in new patients coming in to seek care by up to 40% in some categories. We would see that reverse. I think it's going to be dependent on how much of the mental health impact that the pandemic has had based on isolation, concern about jobs, those kind of things, whether that resolves when the pandemic resolves, or whether we see people coming through requesting care and going through the first generic SSRIs, SNRIs. I think the dynamism we saw in the fourth quarter; we see as a return to a much more normal. We don't see that as sort of a wave coming through after the pandemic. It's a normalization of patients seeing physicians. Thank you. Next question is from Peter Sehested from Handelsbanken. Please go ahead, your line is open. Yeah. It's Peter from Handelsbanken. Thanks for taking my questions. Apologize if they have been posed. If so, please say so. I'll just listen to the replay. I have three, if I may. Sabril performance in Q2 to Q4 has actually shown positive growth rates in constant exchange rate terms. Is that a trend that you see going into 2021 as well? This was my first question. On the upcoming interim analysis with the target sample 255, it basically corresponds to that upon which the two prior studies were designed, and they were designed with an 85% power and a 5% level. I guess that you are probably using a spending function here during the interim, which all else equal suggests that the BAF or efficacy is higher than that we have seen in the first two studies. My question is this: Is it correct interpreted that BAF efficacy is higher? Conversely, can you confirm that you're using a spending function here in the interim analysis? Secondly, with respect to agitation, I guess you're getting some sort of data exclusivity, but what is sort of the effective exclusivity period on this particular indication? Thank you very much. Okay. Anders is going to start with the Sabril question. Yeah. The annual growth you have seen in 2020 is more or less what we anticipate in 2021. That is with the assumption that only one generic is in the market. If more generics enters, and that might be the case, it, of course, can drop. The negative growth can be accelerated because then you don't know what the second generic will have of pricing strategy and all other stuff. If it's the same one generic play, then we assume it will be more or less the same negative growth rates. Yeah. On the interim analysis spending function. Obviously, there is a spending with any interim analysis, but the way it's structured is not a major penalty for it. Alpha hit, if that's what you're asking about. The overall trial is slightly increased in sample size, 330. That's for many reasons. First of all, we like to make sure that we have a strong trial at the end to really make sure that if the drug works, we detect it. It's not a big impact of the spending function. It's not very high. It's not a big impact on it. It's a handful of patients more, basically. In terms of the corresponding data and sample size, obviously at the interim, we have somewhat fewer patients than at the end of the study. Remember, I went through the number of patients we had in the previous studies, and those were split between different treatment arms, et cetera. Here we have a pooled analysis, which means that already at the interim, we're going to have a pretty sizable cohort of about 150 subjects versus placebo, so slightly more than that even. It's not a small sample size. The effects we are after in terms of statistical details, I'm not going to into details, but you can assume we're operating with similar assumptions. Right. There was the third question on agitation and exclusivity. Exclusivity, yeah. There is data exclusivity, but we also know that the compound patent is the strongest patent always. While we defend our patents, I think we would still guide you to the 2029 compound patent for REXULTI. Thank you very much. Next question is from Carsten Lønborg from SEB. Please go ahead. Your line is open. Thank you very much for taking the time here. I have a little bit of more of a conceptual question left. If I look at Lundbeck's average R&D to sales ratio over the last 15 years, it has, of course, jumped up and down. On average, it has been 22.5%. On top of this, you have made several acquisitions. Even on the back of these investments, it sort of feels like Lundbeck is not in tip-top shape. Before you accuse me of being too bearish, you are guiding for a relatively bleak outlook here in 2021. My question is, longer term, is 22%-24%, can I remember what it was you said, Anders? I think you said 22%-24%. Is that really enough to make Lundbeck an interesting case, not only the next couple of years, but also on the 10, 15-year horizon? That was the first question. Secondly, I was just interested in hearing whether there are some huge patient differences in the agitation trials we've seen already, the 283 and the 284 studies. Simply because when you look at the absolute responses, it seems like data is less impressive in 283 versus 284, where patients respond much more in terms of reduction in the scores. Okay. I'll start in saying we are a company that keeps looking at building strongly forward. I think we've had a great success in the past with molecules that have come out of our internal pipeline, Lexapro, TRINTELLIX, Cipralex, and with things that we've brought in from the outside, we've had a sustained compound annual growth rate over the last, I guess since 2007 or something, of 7.4%. We will continue to be able to do that in the future through a combination of the drugs that are moving through our own pipeline, and we have quite a robust phase I pipeline, and we're working in new biologies that will continue to yield an opportunity to bring new molecules forward. We will continue, as we have in the past, to make licenses, partnerships, acquisitions to supplement the growth, where we've been very successful in the past with the Ovation acquisition, the Chelsea acquisition. Like almost every other pharma company in the world, we're built on a combination of both internal and external innovation. Anders, I'll hand it over to you on the ratios. I think I will not go into any kind of speculation in R&D to sales ratios for the next 10, 15 years. What we have said is that we believe that the next six to eight years will deliver nice growth numbers. We also believe that we'll see a margin expansion. We need a margin expansion after having invested heavily in VYEPTI, as we said when we made the Alder acquisition. You would see a substantial margin improvement of both reported and core EBIT. I think it's important to emphasize that the core margin for this year is 25%, and it will expand over the next couple of years. That is what we're aiming for, and then another time we can look into data for the next 15 years. Johan. Maybe I can comment on that percentage also a little bit first. Obviously, 15 years from now things have changed tremendously in how we run trials, what we do, and what populations. You heard about our strategy when we go more to niche and rare diseases. That means that you have different clinical pathways. You have different requirements on the study. I wouldn't say there are lower bars in any way, but sometimes smaller studies, more directed studies. You can get more bang for the bucks, if I may say so, also out of R&D with the strategic change. In terms of the graphs, I guess you're looking at Study 283 and 284, and the graphs, and you see that they look slightly different in the outcome there. For someone who's been in this business a long time with psychometric readouts like the CMAI score, this is what you normally see between studies. I think it's actually more encouraging to see that there's a robust treatment effect in both of those studies. The absolute differences, yeah. They are slightly different here. There's also the influence of, as we talked about, different countries and geographies that could also have an effect. It's well known in Alzheimer trials that you have country differences. As I told you, we had seven countries and nine countries in the two different studies, and this is just basically what you expect randomly across two studies like this. The inclusion criteria were aimed to be identical between the two studies. As also the third study we're running. Remember that the 284 is a post hoc subset analysis. Yes. Right. Yes. So. Yeah. Thanks for that. That's very important to see. Good. Next question unfortunately needs to be the last one. Next up. Okay. Yep. The final question is from Marc Goodman from SVB Leerink. Please go ahead. Your line is open. Yeah. Hi, a couple questions. Number one, can you just talk about your alpha-synuclein and how it differs? Biogen announced that they had stopped theirs, and obviously Roche had some disappointments last year. Just so we understand the difference in the products, in the way that you approach it. Second, on borderline disorder, can you just give us a sense of how enrollment has been? I'm just trying to get a sense of how much demand there is for that type of therapy. I'm just trying to get an understanding of that market. Maybe you can tease out if COVID's had a major impact or if you believe everything is pretty exciting there as far as demand. Then just on VYEPTI, is there any way you could just give us the actual number of patients that were on the product, and a sense of was January stronger than December, which was stronger than the previous month? Just any type of trend from a pure patient perspective. Thanks. Great. Johan's going to start talking about our alpha-synuclein and the borderline enrollment, and then Peter will comment on VYEPTI. I will preface it by saying we won't be giving you actual patient numbers. For alpha-synuclein, yeah, I understand your question because it was just very recently Biogen announced that they were stopping that program. That's the Neurimmune antibody, cinpanemab. It's actually a binder to the 1 to 10 domain residues of the alpha-synuclein molecule. A very different binding domain than we are targeting with this one. We are actually at the C-terminal domain with our antibody, which is mechanistically a very big difference. Prasinezumab, the Roche molecule, is targeting about the same area as we are. We're kind of in that ball range more mechanistically. As you may know, the Roche PASADENA study showed some interesting data on the UPDRS score, particularly at the higher doses. They showed also some effect on progression over time. They are very different molecules, basically, and that's how we view them right now. In borderline, yeah. That's a study that was hit quite a bit by the pandemic. It was also at an early stage of the startup of the trial. Otsuka and we have jointly worked very hard in trying to regain the momentum of the study. We are not really clear on the timelines. We're talking about delays, obviously. We don't know exactly how long delays we're going to face because the efforts done recently seem to have an impact on the study. We're regaining momentum. With recent events in the U.S. and the study is a U.S. based one, it's very hard to tell really where we are. I think in terms of using the study to think about the ultimate size of the market and demand, I don't think it's going to give you a clear picture. Borderline is a very difficult disease. There's nothing approved for it. It's almost a diagnosis of exclusion, and a difficult patient group to treat. This is, I think, it's a very challenging bar for the study, but a high unmet need. Peter, do you want to comment on VYEPTI? Yeah. Thanks for the question, Marc, as Deborah said, won't give specific information on patients, but I will point out what we said in the release. That is that each quarter we have doubled the amount of demand and volume that we've been on the market. A good growth trajectory, albeit off of a lower base. In the fourth quarter, as we were starting to get some normalcy, as we were starting to get patient volumes come back, one might even argue that there was a little bit of an acceleration in the fourth quarter, as you can see on the demand curve that Deborah showed in the deck. All that is progressing well. The types of patients we're typically getting are, like in many launches, a little bit sicker at the beginning because people are trying new therapies on partial responders. I think it's particularly true here. Because of the pandemic, the risk-benefit ratio of patients who are willing to come out and get treatment tends to be those patients who are a little bit sicker. As doctors are getting experience and the drug is delivering, even in these sicker patients that have been unresponsive or partially responding to other therapies, they're getting good results. We're getting very good feedback from both the patient and the physician community. I expect as the product becomes more familiar with customers, as patient volumes continue to come back, that that'll move earlier in the algorithm. Great. Are these patients on CGRP already? Peter? Yeah, some have been. Certainly, some have been. I mean, almost everybody has been on a previous preventative of one of the older therapies. That's required by payers. Yes, we've received patients who have tried and have had dissatisfactory outcomes with other CGRPs. Unfortunately, I will have to call the end of the meeting, as we have another meeting bang onto this. Thank you everybody for your interest. Again, I'll just summarize by saying I'm so proud of the year that Lundbeck delivered in 2020, and we look forward to continuing to grow the business in 2021. Thank you.