Ladies and gentlemen, welcome to the Lundbeck Update Conference Call. I would like to remind you that all participants will be in listen-only mode, and the conference is being recorded. The presentation will be followed by a Q&A session. You can register for questions at any time by pressing star and one on your telephone. For operator assistance, please press star and zero. The conference must not be recorded for publication or broadcast. At this time, it's my pleasure to hand over to Johan Luthman. Please go ahead. Thank you very much, and welcome everyone. Good afternoon, good morning, or maybe good evening to this investor call that we're holding in conjunction with American Headache Society meeting in Orlando, Florida. I'm here at the meeting and had the pleasure to talk through some of the meetings so far with some of the key opinion leaders this morning. I'm going to have this call together with Maria Alfaiate, our Executive Vice President for Corporate Portfolio and Product Strategy at Lundbeck. We're going to talk primarily about the PROCEED data from our bocunebart migraine treatment program. Before I go through the minutiae here, I'd just like to remind you about a few things about this program. The molecule was originally called Lu AG09222, and the clinical evaluation really was initiated through a trial that we concluded some years ago, the so-called HOPE trial, where we had headline results in April 2023, and a publication that came out in New England Journal of Medicine in 2024. Encouraged by the data we obtained in the proof of concept phase II-A study HOPE, we started the so-called PROCEED trial, which was a much more comprehensive phase II-B trial that we initiated in March 2024, and we obtained headline results in February 12th this year, 2026. Now we are at the American Headache Society presenting some of the data to the migraine specialists in the field. The presentation was primarily done by Jessica Ailani, who is a Professor at Georgetown University. She was also having an opening presentation where she mentioned it. There were actually three opening presentations of several that mentioned the PROCEED data. Then there was also a poster session where Jessica went through much more in detail yesterday evening, the data. Before we go into the conversation here about the program, I'd like just to remind you that this discussion today contains forward-looking statements which are subject to change. Let's go to the next slide, please. Thank you, Johan, for introducing the topic. Yeah. I'd like to leave over to Maria. Thank you. Good morning. Good afternoon, everyone. To set the scene, and as Johan already mentioned, with the PROCEED trial, we have further proof that our focused innovative strategy is producing a rich and differentiated pipeline. Bocunebart is now the first and only PACAP biologic to reach this stage in development. This is a mechanism that is distinct from and complementary to the established one of the CGRP class. This is significant across three dimensions. Firstly, there is another strategic proof point for our strategy and for the R&D transformation that Johan and his team started seven years ago. We now have two positive phase II readouts for bocunebart, the HOPE phase II-A trial that reported in 2024 and now the phase II adaptive trial PROCEED. These are milestones that reflect a remarkable positive momentum across the pipeline that you have seen from us in 2024, 2025, and now in 2026. The second dimension is the level of innovation with the first-in-class mechanism of bocunebart. There has been no new mechanism reaching this stage in migraine prevention in more than 10 years. You will remember that the last meaningful innovation came with the CGRP class, where VYEPTI is currently showing fantastic results, both scientifically and also commercially. With bocunebart, we now have a strong lead with the first novel mechanism in over a decade. As Johan will explain, the science behind it gives us real conviction that PACAP can deliver benefits that currently other treatments do not. The third dimension is what really can drive incremental long-term value, as we now see a strong opportunity in building a franchise for leadership in severe migraine prevention. The global migraine prevention market is sizable and is estimated at more than $12 billion globally by 2031. With VYEPTI as the most powerful anti-CGRP and bocunebart as the first- in- class anti-PACAP, we have a clear path to a differentiated migraine franchise with strong IV-led synergies. Next slide, please. We know that despite the genuine progress that we have seen over the last decade, the unmet need in migraine remains significant. From a disease burden perspective, migraine is still the number two cause of years lived with disability globally, and it is the leading cause of disability worldwide for young women. Many patients like Carlos, portrayed on the slide, report migraine as physical pain, but as much more than that. Many sufferers will attest to how the dread of the next attack takes over their life. It limits careers, social interactions, relationships, and also the ability to plan the simplest things. Critically, the treatment gap remains wide. The introduction of the anti-CGRP class was a real step forward. We know that between 40% and 70% of patients on CGRP-targeting medication continue to strive for optimal control and continue to suffer from other symptoms. That is a very substantial population of patients who are already on advanced therapy, but who are still not achieving the outcomes they want. This is the unmet need that PACAP inhibition, and bocunebart specifically, is positioned to address. Let me now hand over to Johan on the next slide for the science behind bocunebart. Thank you very much, Maria. Why bocunebart? Well, first I like to take you down a little bit in history around migraine here. Maria alluded to this. There is a long time ago, a new mechanism of action showed an effect in migraine. It actually was 2004 when the CGRP class was first shown to work in early gepant studies. A lot has happened during those 20 years. We are now looking at, finally, I would say, a new mechanism that seems to be working in migraine prevention, which is a new concept that has evolved during the last 10- 15 years. Bocunebart is a monoclonal antibody that neutralizes PACAP, and that is, of course, for a longer name, pituitary adenylate cyclase-activating polypeptide. Bocunebart is binding PACAP directly. It's binding to the ligand here that activates a number of receptors. Bocunebart prevents activation of those downstream receptors, blocking signaling that contributes to migraine pathophysiology. Of course, one may ask, what is PACAP doing that's different from CGRP? PACAP is a richer biology than the CGRP biology. PACAP has both overlapping and distinct roles versus CGRP. It's involved in vasodilation. It's actually also part of the parasympathetic nervous system, in addition to the primary sensory neurons. Through the primary sensory neurons, of course, it's involved in neurogenic inflammation and also as all pain signaling and central sensitization. It has an effect on numerous pathways that CGRP does not reach. It offers, from the biology side, a differentiated therapeutic angle, and that is exactly the kind of biology that we think is complementary and not competing with the CGRP treatment paradigm. I would also like to talk a little bit about the competitive landscape here, as there are some programs in the past that have not seemed to work out on PACAP inhibition. Most importantly, we like to talk about that the first program in this space was actually a PAC1 blocker. Looking at one of the three receptors, maybe four receptors that are involved in PACAP signaling. That was a much more narrow approach to it. Bocunebart is intervening through all these receptors by blocking the ligand itself upstream, which is much broader footprint, and then, of course, has the ability to affect all PACAP-driven migraine biology. With the molecule, bocunebart, we have one that's engineered really to test out and block the system, and we have a good pharmacokinetic profile that allows for sustained prevention. With both HOPE and PROCEED, we have now clinically validated the PACAP ligand approach for the first time. We also see that this is not only a scientific achievement, but it also gives us good, interesting data in terms of effect on patients with chronic and episodic migraine. Let me then turn over to some more data directly on the program we presented now. Next slide, please. Through the headline data, PROCEED, which we presented in detail at the American Headache Society, as I mentioned this week, yesterday. PROCEED was a phase II-B trial. It was a dose-ranging trial and a dose-finding trial, also dose rationalization finding study. Very broad study with a patient population with hard-to-treat migraines. They have failed one to four prior treatments. This is a population that already puts PACAP at the test in terms of its differentiation and its ability to really work on the more severe migraines where the need is greatest. The primary endpoint, as often in migraine studies, was the monthly migraine days over weeks 1 to 12 versus placebo. The headline data are really clear. PROCEED IV met its primary endpoint. bocunebart at an IV dose, as we call A here, with 84 patients, was statistically significant in reducing monthly migraine days versus placebo over a 12-week treatment period. We also looked at two additional doses IV, which we call B and C here. We showed in those two dose groups also a beneficial effect numerically in terms of reductions versus placebo. Those two groups did not reach statistical significance. From a safety point of view, bocunebart was well-tolerated with really no significant findings whatsoever. New safety signals was identified in the PROCEED trial. That safety profile is really consistent what we've seen before with this molecule in, for example, the HOPE trial. It's within the framework what we expect and hope to see within a class drug in the migraine prevention field. Taken together with the HOPE data, we have now two out of two positive phase II studies, as Maria highlighted, which is a strong basis to take this program forward. Not only PROCEED further validates the PACAP pathway, but it also strengthen our confidence in bocunebart as a potential first-in-class PACAP targeting therapy in migraine prevention. Let me go a little deeper into some aspects that were actually presented a little bit more by Jessica yesterday. That is really where the hardest migraine sits in the chronic patients and the results we've seen. Can I have the next slide, please? Thank you. Chronic migraine is the migraines where you have numerous attacks per month, and it doesn't really come in isolation. It builds up over time as a consequence of migraine biology fluctuating and worsening over time, and the pattern is well-described and well-understood. Frequent migraine attacks reduce the recovery time between episodes. That incomplete recovery tends to sensitize the brain for further attacks, and in pain like in many other CNS indications, you have a sort of a rewiring of the system, and that increases its excitability, not only in the peripheral nervous system, but also within the central nervous system. That drives further and further attacks. It's kind of a vicious cycle where you like to stop it before it goes too far. That's what we call the episodic migraine, but when you come to chronic migraine, you have really difficult to treat population. This was really what we did in the study, in PROCEED study, because we looked at prior treatment failures. PACAP is well-placed in this biology. It has a role in central sensitization and in the pathway that drive transition from episodic to chronic migraine. The therapeutic hypothesis is that bocunebart is neutralizing the PACAP, as we try to illustrate here. The PACAP biology is that it comes and goes in conjunction with the attack, we like to place some kind of umbrella over all these attacks with a PACAP treatment to press it down under the trigger point for causing a migraine attack. The more that occurs, the more chronicity you get in the disease, and the more you can suppress it below the point of inducing an attack, the more treatment you're soon to get. That's why we really strategically are positioning this program in the most severe chronic migraine, where the need is still the biggest. That's the segment where we think PACAP inhibition plays the biggest role. Next slide, please. The chronic migraine data here that we obtain in PROCEED are really very encouraging. What you see in this slide is now a pooled data set across both the HOPE and PROCEED trial. All the different treatment groups we had, the sub-Q in PROCEED, the IV in PROCEED, but also the IV from HOPE trial. This is a much larger data set that now focus and narrows down on 214 placebo patients and 354 bocunebart patients that had chronic migraine. In this chronic migraine subgroup, bocunebart delivered a reduction of 5.9 monthly migraine days versus 3.6 days for placebo at 12 weeks. This is more than two additional monthly migraine days reduction over time, 2.3, with a p value of less than 0.001. A very robust statistical signal in this subgroup and very relevant subgroup. Importantly, this effect is consistent across other key clinical endpoints on monthly headache days, which is capturing a more broader headache burden. We see a reduction of 6.9 days for bocunebart compared to 4.3 days for placebo. On monthly migraine days requiring acute medication, a measure of the depth of the response, we see 5.2 days reduction for the bocunebart versus 3.5 days for placebo. In quality of life, which is a very critical measure in migraine patients, measured here by the so-called MSQ test, we see a change from baseline of 23.4 points for the bocunebart versus 7.8 for placebo. These are the kind of outcomes that matters really to those patients, and that matters in a real-life situation. Fewer migraine days, fewer days requiring acute medication, and a meaningful improvement in how they can function. Taken together, this data gave us a strong conviction that bocunebart can deliver clinically meaningful benefit in chronic migraine. From a safety perspective, the profile remains clean and consistent, what we've seen before, as I mentioned earlier. Now with the combined very comprehensive data set from PROCEED and HOPE, we have now positive data and very encouraging data in particularly chronic severe migraine patients. We are basically ready, and we look forward to discuss development paths with regulators in the coming months. With that, I'd like to hand over to Maria again. Next slide. Thank you very much, Johan. I'll bring the conversation back to the patient community. The size of this underserved population of chronic migraine patients and the magnitude of their unmet need is what makes this such a compelling opportunity and such a compelling commercial proposition. We know that worldwide, around 80 million people currently live with chronic migraine. By definition, this is the severe end of the migraine spectrum. 15 or more headache days per month with profound impacts on disability, employment, and also quality of life. In our priority geographies, the U.S., major core European countries, U.K., and Japan, we estimate around 12 million chronic migraine patients to-date. Within that population, around 30%-45% of those on preventative treatment receive a migraine-specific advanced therapy. Something like an anti-CGRP or botulinum toxin A. That equates to approximately 1.5 million-2 million patients on advanced preventative treatments in our priority markets. This is a critical insight. Even within this treated and well-managed population, there is a very large gap. In the U.S. alone, as of today, 40% of patients on an anti-CGRP have already cycled through more than one anti-CGRP agent. Looking at the class, as few as 20% of patients currently on an anti-CGRP achieve a 75% reduction in mean monthly migraine days. That leaves an underserved population of approximately 6,000-1.2 million patients in our priority market who are on advanced therapy but are still not achieving optimal control. This is the addressable opportunity for bocunebart. It is precisely the segment where current therapies are not delivering the outcomes that patients want, and it is precisely the segment where a differentiated mechanism upstream of CGRP and hitting different parts of the migraine biology, as Johan just mentioned, has the strongest case to deliver value. Next slide, please. This is also another step on the path to franchise leadership, and this also gets us excited about the opportunity. It's also what sets Lundbeck apart in the migraine space. The strategy is simple. Two complementary mechanisms, anti-PACAP and anti-CGRP. One market-leading commercial engine to deliver these therapies to patients. VYEPTI, our foundational asset, is the most powerful anti-CGRP available, and it is delivering exceptional momentum as you know. 59% global growth in 2025, continued strong execution in the U.S. and in Europe and international operations, and the upcoming launches in Asia, Korea, Japan, and China all keeps us firmly on the path of our previously guided global peak sales of $1.4 billion. All supported by continued evidence generation, driving new patient starts, and supporting earlier line usage. Bocunebart is our expansion asset. It's on track to be the first-in-class anti-PACAP designed to complement VYEPTI and extend our reach into patients where current treatment options are not providing optimal benefits. Both assets are delivered IV and will go through exactly the same infrastructure that we have purposely built for VYEPTI. Trusted relationships with the headache specialist community and a field force that understands the workflow, the access dynamics of IV preventative treatment, and an infusion footprint that very few competitors can match. Two differentiated mechanisms, one market-leading commercial engine. This is what allows us to credibly aim for severe migraine leadership. With that, let's move to the takeaways and next steps. Next slide, please. I would like to clarify the three points that you should leave this call with. First, PROCEED gives us a phase III-ready, first-in-class anti-PACAP preventative agent. The clinical outcome shows meaningful efficacy in people who currently lack effective therapies for migraine, and the safety profile remains clean. With HOPE and PROCEED both positive, the bocunebart program is now in a strong position to progress to pivotal development. Second, our focus on chronic migraine continues Lundbeck's commitment to serving patients with severe migraine. Chronic migraine is where the need is greatest, where the biology of PACAP is most relevant, and where the commercial opportunity is most compelling. Third, with VYEPTI and bocunebart together, we are building a differentiated migraine franchise. Two complementary mechanisms, one market-leading commercial infrastructure. This is a position that very few companies in the migraine space can credibly claim. Our next steps, our immediate priority, as Johan also mentioned, is regulatory interactions on the phase III design and program. We expect to provide an update on those interactions and with the potential initiation of the phase III, in the second half of 2026. On the back of this, we are also planning a dedicated investor presentation later this year where we will go deeper into the franchise strategy and also the commercial opportunity. We will share details and timing in due course. With that, Johan and I would like to thank you for participating, and we can now open for Q&A. We will now begin the question- and- answer session. Anyone who wishes to ask a question may press star and one on their telephone. You'll hear a tone to confirm that you have entered the queue. If you wish to remove yourself from the question queue, you may press star and two. Questioners on the phone are requested to disable the loudspeaker mode while asking a question. In the interest of time, please limit yourselves to three questions. Anyone who has a question may press star and one at this time. The first question comes from the line of Marc Goodman from Leerink Partners. Please go ahead. Yes, hi. Could you talk about the percent of CGRP failures that were treated here? Obviously, we're looking at the VYEPTI data and saying, oh, VYEPTI has great data, little stronger than this. Obviously, this is for patients who failed VYEPTI. Who has failed VYEPTI, who's failed other CGRPs? Give us a sense of that, what the other kind of breakdown is of the types of patients. You know what I mean? You said there were one to four. If you can give us any sense of that. Do you have any responder rate analysis? Just curious on that. Also on this dose, you talked about A, B, and C. Is dose A the most potent dose? Is that the highest dose? Was there a dose response? If you could just give us a sense here. Thanks. Yeah, thank you, Marc, for those questions, several of them. Let's start with the proportion of patients that's been on the CGRP and the past failures. We're at the fairly low range. We're under 10%-15% patients that's been on the prior CGRP treatments, any type. We have a data set on this, not an extensive data set, but we have a good data set on it. I like to just emphasize one aspect here. This is not a drug for VYEPTI failures. This is a drug for any failure that we see it, how we like to perceive it. That's a broader label, of course. We will not particularly study this as specific against one particular drug or drug class. We like to have this as a go-to treatment for those that fail any type of prior treatments. Yes, there were one to four prior failures on average. We didn't present that much in detail, but let's say there'd be another one average about two prior failed treatments that occasionally include CGRP. Responder rates, analysis, et cetera, we will come back to that in upcoming meetings. These are aspects of the data we present today, or rather yesterday at the meeting. We will have at upcoming conferences going into more details of the different aspects of the PROCEED data. The A, B, C, which one is the most potent, which order do they come, we have actually purposefully not revealed any of that. My apologies for that, but we are actually in the process of building a very strong understanding about the PK/PD relationship here. We are building further on our proprietary portfolio around this program. At this stage, we cannot, unfortunately, reveal any details on the exact doses and the ranking of the different doses. Let's see now. Did I cover all your questions with it, Marc? Yes. Just to be clear, the answer to the first question was 10%-15% of patients were CGRP failures? Yes, in that ball range. We have a little difference between, of course, HOPE and PROCEED. PROCEED was we were aiming for a maximum of 15%, and we got a little less. Somewhat below 15%. Thanks. The next question comes from the line of Kirsty Ross-Stewart from BNP Paribas. Please go ahead. Hi. Johan, Maria, thanks for hosting the call. Just a question on the pooled data. You present all of the doses and formulations but understand that you're moving forward to phase III with the IV formulation. Just interested if you can give us any color on what we would see in the pooled data with the IV formulation only. Can you confirm as well that in that pooled data, that dose group A was the maximally effective dose in line with what you saw in the kind of broader PROCEED trial? Second question, just how does narrowing the targeted population impact your expectations for the opportunity for the asset? Now you're targeting chronic severe migraine. I think you've previously said you expect takeup to be VYEPTI-like in its opportunity. Just wondering if that still holds. Thanks. Thanks, Kirsty, for those questions. In terms of the pooled data, yes, you're really picking on one thing that I didn't emphasize so much in the data presentation. This is all the data, meaning all the pooled data across HOPE and PROCEED in the chronic population, independent on dose or route of administration. This is somewhat diluted, as you may suspect. Some arms, some treatment paradigms were less efficacious in the chronic population. In some manner, we may even sort of devalue a little bit what we're presenting here. We think it's very, very critical to see the whole population together because that is a much more bigger population and more in the size you probably wouldn't use in a phase III program. Obviously, there are doses that are more favorable than other doses. The jump from 3.6 days with placebo up to 5.9 days, the 2.3 days delta in monthly migraine days is, of course, a very strong response. In certain subgroup analysis, we might see more. Now you're getting to smaller numbers, so one has also to be very careful with that, and that's why we do the pooling of everything together. 2.3 days in this pooled, mixed sort of response population in chronic migraine is a pretty robust response, I would like to say, when you already tried month or four prior prevention treatments. In terms of narrowing the population, yeah. When it comes to most of the monoclonal antibodies, definitely VYEPTI, the majority of the patients we see are chronic patients. It's really the go-to drug when you have more severe and more chronic migraine. In some way, it makes sense where those drugs are currently placed in the treatment paradigm. Of course, we like to go a little higher up. This is by far the dominating population. This is also the population that is hardest to treat. This is the population where you eventually end up having refractory patients as well. We are always trying to go where the biggest medical need is, and that is in the chronic population, and that is a very sizable population. Maria went through that a little bit. I don't know if you want to comment further on that, Maria, and how we see the opportunity in chronic migraine patients. Yeah. I can, Johan. Thank you. Thank you, Kirsty, for the question. We don't see this as a limitation. As Johan just said, this is exactly where the biggest unmet need is, and this is exactly what drives the value. It is in line with our expectations, and once we are able to share more details on the commercial potential with you later in the year, it will probably be clearer on why we see the value and what exactly the value is, more from a commercial opportunity point of view. There's no reason to think that this is not a good thing. Thanks. Johan, can I just ask one clarification on the pooled data? Are you able to confirm whether dose group A was also the maximum effective dose you saw when you look at that data, or is it too small population for you to draw a conclusion? I don't like to venture on that because they are rather small populations. Obviously, it goes in that direction. That's clearly so, right. Okay. Thank you. Thanks, both. We now have a question from the line of Charles Pitman-King from Barclays. Please go ahead. Hi, guys. Thanks so much for taking my questions. Charles Pitman-King from Barclays. Firstly, just in terms of just trying to place versus peers, the lower number of migraine days reported versus some of the CGRPs. Just wondering if, Johan, you put this down to the difference in MOA or whether or not you put it more down to the fact that you are trying to treat a heavily refractory patient population. If it is the patient population that you would look to justifying this, how do you then explain the relatively in-line placebo reduction in migraine days by a similar degree versus peer CGRP trials? Secondly, I'm interested in any physician feedback you've had so far. Just given the kind of limited feasibility of this asset being chosen as a first-line treatment, and as you highlight, you're going for the kind of refractory patient population. I'm just wondering how you think about the commercial positioning. Do you see the migraine market shifting to a kind of switch dynamic post one or two CGRP failures, or will take up be positioned as an additive product? Following on with that last comment, in terms of the combo data that you reported in the release this morning, you mentioned that you have data for combination with either ubrogepant and triptans. I'm just wondering what data you have or are working on to show combo effect with CGRPs. Thank you. Just a clarification. Your last question is about monoclonal CGRPs then, right? Not only your PACAP? Correct. Yeah. Correct. Okay. Thanks. A lot of good questions there. Yeah. When it comes to the mechanism action and effect in this population, we had a speculation here rather than a real firm data set that there is something very special going on here with the chronicity and how the disease thrives in this population. Is this dependent on PACAP itself at a different mechanism, or is this a generalized mechanism that can play also a role when you treat the CGRP? Yeah, there are many reasons to believe that PACAP, through its broader role, could play that sort of more modifying role. I just like to be a little careful. I mentioned refractory patients, that's the ultimate patient that is not responding to anything. Basically, not even CGRP. That is population we have not specifically studied here. We're really going to the very severe ones that are definitely at the risk of ending up being refractory. Refractory is that you understand you tried all preventive therapies, and you're not responding. That is a very hard-to-treat population, but we like to be in that space as well. We have not studied directly refractory patients. We studied those with very strong chronicity with that subgroup analysis. Yes, there is the placebo response with all these treatments, and as you know, it's part of the real response. Is this 2.3 days impressive about placebo? Yeah, I would actually think so. It's definitely what you see in the good old days when we did preventive treatments in chronic patients without prior treatments in treatment-naive patients. Obviously, some of the feedback we got here and some of the scientific dialogue here is, wouldn't it be nice to see how this drug works in treatment-naive patients that haven't got it, and that's a good scientific question. Luckily, I would say CGRP patients have never tried a preventive drug before, it could be nice to also study this drug in a treatment-naive population at some time point. There are feedbacks on the switching dynamics, also feedback generally at the meeting here. I would say, from what I heard and what I've been seeing here, generally very positive comments about that this is a new mechanism, that it's moving forward. I think many people expressed basically often impatience when will we get started with the phase III. When it comes to specifically switching. Yeah, when you get into the chronic stage and you're not responding well, you are switching quite a bit, if you really go to high-end specialists at least. Will this be a drug you cycle through trying various things? No. We hope that you have a specific effect of this drug in the hard-to-treat patients. Combo data. Yeah, we did the gepant. We can, of course, look at the combo data on mAb versus mAb. We are looking now primarily at people that are traveling from gepant to gepant failures, and may even want to stay on the gepant and still get on the monoclonal antibody. Are we doing those drug-drug interaction studies primarily because we think we will influence the peak concentration or the PK behavior of the drug? Not really. We're looking mostly for safety here. Obviously, eventually it could be interesting to see whether PACAP works safely and nice in combination with monoclonal antibodies. That's a very unusual treatment paradigm. You probably will not run simultaneously on two monoclonal antibodies. I don't know, Maria, if you'd like to comment further on commercial scenarios here. I can. We know that despite the fact that anti-CGRPs are very effective, only 30% roughly of the eligible population is currently being treated. This can be because, with some agents, there is lack of efficacy because there are other components to migraine, as we just mentioned, other than just the headache, because there may be loss of response to the treatment, as Johan also alluded to. There is a central sensitization. We do see a place for PACAP. In reality, it can be used when an anti-CGRP is no longer efficacious or when any other drug is no longer efficacious. Because this is a different pathway, there's also no reason to imagine that it could not be used in concomitant use, similarly to what physicians do with other treatments. At this point in time, we will not be able to communicate yet on our commercial positioning. Yeah. Maybe I didn't fully address your question about first- line. Obviously, we're not aiming for first- line at this stage. Not even VYEPTI is the first- line. Of course, there is good reason why you like to start very early with the more potent treatments. This is a drug you go to when you at least tried a few others. That's how we position it right now. Great. Thank you. The next question comes from the line of Shan Hama from Jefferies. Please go ahead. Hi. Thank you so much for taking my questions. Three from me. Could you then clarify if the phase III population will be 100% chronic migraine patients, so no episodic at all? That's my first question. Secondly, I know you can't say much about the doses, but were there baseline misbalances between dose A, B, and C? As in, was there more chronic in one group and less chronic in the other? Just wanting to think about how that's distributed across the dose groups. Lastly, can you provide either 50% or 75% responder rates, particularly in the chronic migraine group? Thanks so much. Thank you. The first question, you wanted us to clarify exactly. Can you try to ask your first question again so I get it fully? Yeah, of course. I was just wondering whether in the phase III study it would be 100% episodic migraine patients. Okay. Now I get it. Yeah, we have not revealed what we're doing in phase III yet, and it's also pending, as Maria outlined here, on regulatory interactions. We are particularly interested in the chronic population, so that gives you a hint where we like to go with this. Yes, episodic populations are on the track to get chronic. As I said several times here, we really like to go where the biggest medical need is still, in spite of the CGRP class, in spite of drugs like VYEPTI, and that is in the very severe chronic patients. That's where many of the patients end up already with drugs like VYEPTI, and we like to play in the same space, basically, as VYEPTI. Yeah, when it comes to the doses, I didn't reveal the doses, were they evenly balanced in terms of episodic and chronic? The answer is yes, they were well-balanced. There was no bias. If you try to read in did group A have more chronic patients or something like that, no, that's not the case. It was quite evenly well-balanced across the different doses. Yeah, the responder rates, I know you're all eager to hear that, we're not presenting this at this time point. We'll come back to that when we have further data presentations in this work. Thank you. I like to emphasize that this, again, is a group that has failed prior treatment. One should probably not expect response rates that are up at the top rate of drugs that have been tested in treatment-naive patients. Was that okay? Yes, that was a good point. Yeah, thanks. We now have a question from the line of Xiang Deng from UBS. Please go ahead. Thank you for taking that question. Just sort of coming back to Johan, one of your previous comments on the combo trial. Interestingly, at least the poster you're sharing is actually a combo with the oral triptan. You were saying, sorry, if I got it correctly, you said it's unlikely for patients to try two antibodies together. Just wondering if you could elaborate a bit on why that is the case, because given the high unmet need, we're looking at 10- 15 days of migraine days. Let's say if you combine this with VYEPTI, which is also an IV, if you actually have synchronized administration, that could actually be, in terms of convenience, there's actually no negatives added. Just wondering if you could elaborate on that comment, please. The second part is. Yeah. Yeah. Sorry, go ahead. Sorry. We can start with that one. No. Please ask your second question. Yeah. The second one is just wondering, so this is with prior therapies, one to four prior therapies. Just wondering, other than CGRPs, what are the other kind of typical treatment that's actually used here? Because other than triptan, is there anything else? Yeah. Thank you. Okay. Yeah, thanks a lot. Going back to the combo, yes, of course, scientifically, at some time point, one would probably like to see if there is an additive effect of a CGRP mAb, for example, and the counterpart. I was more commenting on how we like to proceed right now, and if, for example, in our clinical trials here, it's the oral pills or whatever, oral drugs is by far the most dominant drugs even in the more severe population. There's probably not so many patients that will be on monoclonals at this time point that will be included in the program moving forward. From a safety perspective, we don't think this is a challenge for us and should not be studied. Scientifically, yes, it will be great to look at this, and these are obviously things we're thinking about for future things. Now we should look at what we have. We have the PROCEED and HOPE data that are really looking at bocunebart in a scenario with prior oral treatment failures. This is where we like now to deliver phase III. For lifecycle management, we obviously may consider very different combinations here. We're sitting very well positioned here because we have a CGRP monoclonal. We have the bocunebart, and you can probably guess that we're also working on other things in the preclinical arena here for the future. We like to stay in this field and really understand how much benefit you get with overlapping therapies. That's not on the rail immediately for us here. Gepants may be much more common in the phase III trials, and that's why we do this drug-drug interaction, drug-drug safety study. Yeah, what kind of prior treatments did they fail on? It's the usual battery, and also they're more off-label, antiepileptics and all these drugs. It's a mixed bag, triptans are not generally considered preventive treatments. We're talking about those that are off-label use for preventive purposes. Some, of course, are triptans but some are also the, as I mentioned, the general antiepileptics therapies and others that are used for migraine prevention. It's a very mixed bag of several different drugs, four or five different drugs even. All right. Thank you very much. By the way, subgroup analysis probably doesn't really make sense because it's historical data. They've been some time back on one drug, and they shifted to another. It gets very complex and very small subsegments to look at. We now have a question from the line of Peter Hugreffe Ankersen from Nordea. Please go ahead. Hi, it's Peter Hugreffe from Nordea. Thank you so much for taking my questions and also congratulations with the outcomes. Firstly, just on the phase II trial and the response curve, it seems that at least the response hasn't kind of plateaued at 12 weeks. Are there any learnings from the eight weeks follow-up, or is that purely safety? Can you also kind of confirm the hypothesis that it hasn't plateaued? That's the first thing. Secondly, in terms of the phase III trial design, I know you haven't really revealed anything, but can you just kind of help us speculating a bit around the trial duration, the dose selection, and also right now, have you initiated the regulatory discussions, or is it only just yourself trying to kind of find out how to position this before you start the discussions? Thank you. Yeah. Thanks, Peter, for those questions. Thanks for the congratulations. We definitely think this is a really great data set. We are very encouraged by this data set. You observe something here in the curve that obviously we also noted. It seems like we haven't settled yet at 12 weeks. This is obviously something we pay a great deal of interest in. We might have a bigger interest looking more further out and see how this can sort of pan out longer term. That plays also in the space where I mentioned that there is something mixed on the patient here of the disease. It's almost an element of continuous modification of the disease process. We are intrigued and also quite optimistically looking at that increasing the separation of the treatment effect over time. That's definitely something we are looking at for the further long-term data that we have already in the trial, but also for eventually for the exploration. That's an interesting observation, clearly. Phase III data design, where are we? First of all, in terms of trial duration, et cetera, we have a proposal that is submitted to the regulators, we have not had active interactions yet. We are in the process of having initiated the process for this, it takes, unfortunately, a while until we get to the actual conversation with them. You can sort of assume that we will like to deliver on what we really found positive and strong out of the phase II data. Obviously, most of the enrolled population is part of it. Already at 12 weeks, we already have a significant effect in the chronic and the A subgroup in the PROCEED program. We will try to not over-complicate it for phase III. We have the program at risk again. I think we have already very encouraging data in a very interesting subgroup of treatment failures, prior treatment failures. If I may, Johan, just because, Peter, I don't know if your question was around just the science behind having more than one dose or the commercial opportunity, like what we see with VYEPTI. As Johan said, the science will guide us first, but if your question was around commercial potential, this is something that we will also explore following the analysis of the data and the discussions with the different regulators. No, I guess, the two doses with VYEPTI kind of is serving you well right now because of the linear pricing, right? Yes that's, of course, also inherent in the question whether that is part of the speculation or rather go with one big and then, of course, choose to price around that as well. Yeah. Absolutely. This is a huge difference also in the U.S. market versus other markets. There are two parameters here, dose selection and duration selection. I'd like to remind you this is monthly IV infusions that we've done so far. That's also something that we are mulling over how to address. This not yet plateauing effect is also pointing that there could be a reason to explore dosing intervals also a little bit more. Much appreciated. Yeah. Okay. Yeah. Thank you so much. Thank you. The next question comes from the line of Alex Moore from Bank of America. Please go ahead. Hi there. Thanks for taking my questions. Just a quick one. A step down in efficacy has been seen in phase II-A study relative to phase II-A. Could you maybe just elaborate on what the key drivers of that could have been potentially related to mix of chronic versus acute patients in the two studies, and any sort of differences in severity, particularly monthly migraine days at baseline? Any comment to what you think drove differential accuracy between those two studies? Secondly, you mentioned that chronic migraine is sort of the bigger unmet need within migraine prevention. Can you roughly size or have any data to hand on the rough split of acute versus chronic? Thank you. I'm not sure I captured. It was a little breaking up the first part. You talked about the differentiation between which studies? I'm not sure I captured it fully. Sorry. I was just talking about the exit from phase II-B PROCEED at 1.38 monthly migraine day reduction versus placebo compared to 2.0 day seen in phase II-A HOPE study. Please remember each arm is entirely small arms. In migraine, you have several hundreds per arm. there might be little fluctuation here, but I think the most important thing is that we're traveling at something that is around two or more. Right? it may be slightly different between the different studies. That's definitely clinically meaningful in a population like this that is not responding well. I don't think we should read too much into it. Then of course, differentiation monthly migraine days at baseline, et cetera. When you go to the chronic population, and we didn't really present that here, but how many do we really have in that group? This is what you usually see in those trials, I would say. It's traveling with 15- 16- 17 monthly days in the chronic groups. Let's see. the key drivers for this. I'm not sure I understood really that either. Sorry. The question was mainly just on what the key drivers between the difference in efficacy between the phase II-B and phase II-A studies were on. Was it mainly on? No. Quite plainly, I think it's just a little bit variability between the studies because the populations are very similar, the geographies are very similar. HOPE, we didn't have Japanese patients. PROCEED, we had Japanese patients, but we don't really see any difference there. I don't think there is really something we can find in terms of key drivers. Yeah. The trials were not designed to be compared like for like. There are these nuances, as Johan just said. Regarding treatment window, regarding the percentage of patients enrolled in the trial that were chronic, so the trials cannot be compared like for like. Should I take the second question on the approximate split of chronic versus episodic migraine? Yeah. Please do that. Thank you. We estimate that in real world, from an epi point of view, the approximate split of chronic versus episodic migraine is roughly two-thirds episodic and one-third chronic. More patients have episodic migraine. However, and again, to remind you, the later line treatments are more chronic migraine, and this is exactly the population we're going up against. Also, the value of these treatments and the price points that will be used for reference are higher for chronic migraine. Just to give you a bit of an illustration, we currently estimate that of the population on VYEPTI and other anti-CGRPs, more than 80% of patients are chronic migraine. I hope this is helpful. Yeah. Alex, I like just to emphasize one more thing. Let me go back to that prior point that I should have really emphasized. HOPE and PROCEED were very similar populations, yes. Obviously, HOPE was just one treatment. We looked at one month, PROCEED is a repeated treatment out to three months, right? There is a little bit slight difference there as well. Peter from Nordea pointed out that we may have expanding effect over time, that could explain also that little difference. Again, I think we should be very careful with those small numbers between the different studies. Cool. Thank you very much. Yeah. As a reminder, if you wish to register for a question, please press star and one on your telephone. We now have a question from the line of Tobias Nissen from Danske Bank. Please go ahead. Perfectly. Thanks, Johan and Maria, for the presentation. I just have two fast ones here. You mainly speak on the chronic migraine here, but what did you see in the episodic and any signal at all, if you can talk a bit more into that? Just Johan, on the HOPE versus PROCEED trial here and the data, if you can talk into what surprised you the most, if any. Thanks. Yeah. I like to start with the surprise because I made a point that it's 20 years since last the migraine mechanism worked, and that was CGRP, and it was done in the Kingdom of Denmark. Yes, the [audio distortion], together with Boehringer Ingelheim, they had the Japan, the IV Japan. That's many years ago, and there was nothing given that this PACAP mechanism would work. I think already in April of 2023, we had a big surprise that this actually seemed to be working, because that was far from given. Of course, there's some overlapping biology, and there were really great prior data on infusing PACAP into migraine patients, inducing migraines, but this was far from given. That's the biggest surprise because we are not spoiled with positive proof of concepts on new mechanisms. You can work many years in pharma industry and not get any of those. I think that was the biggest surprise. In terms of between HOPE and PROCEED, I think there was a really good idea to do a very comprehensive PROCEED. I really like to build a robust platform for phase III. We have given you an indication where we think really the drug is speaking to us, and that is in the chronic population. You asked about the episodic population. Yes, we do see an effect, of course, in that population because we show the overall data, but we are really nailing down now the chronic population for many of the reasons Maria and I talked about. This is the patients with the biggest needs. That's actually where we like to go, but also where the patients like us to go. That's where actually we find most of the patients for those advanced treatments. Remember, this is high-end. This is IV, specialist-treated. This is not the pill for the GP. This is a very different population. That's actually in some manner a surprise that this drug mechanism seems to work where it's hardest. That we didn't believe, to be honest. We had no idea whether this is a weak mechanism or for the mild patients. We have worked many years on antidepressants. We had great SSRIs. Those drugs are normally not for the very severe depressive patients. Here you have the opposite a little bit. It looks like PACAP is for really the ones who need it most, which is really, in some manner, a positive surprise because normally it's harder to treat the more sick the populations are. We will reveal a little bit more what we see in the episodic. I think that's quite frankly less interesting. Maria commented on this several times. I don't know if you want to comment again, Maria. Yeah. As we said before, episodic, although it is a large population, in reality, it's not as interesting for many reasons, right? From a science point of view, they're fairly well-covered. Whereas we are interested in the populations where we can indeed bring clinical value, and these are the ones that are more refractory, more qualified, and that's why we are scientifically excited about the chronic migraine population. Of course, these are the ones that are left without alternatives, which is what makes us excited from a commercial point of view. Maybe I can just emphasize what Maria talked about before also. We are the ones with an IV infused mAb already. We have learned over six and a half years how to deal with that. We built an infrastructure internally, also externally how to deal with it. This, as I said, is the high-end treatment that is working for most physicians and most patients quite okay. We actually play where we are the best players also with this, to be honest, where we have the strongest experience. Perfect. That's very clear. Thank you. We have a follow-up question from the line of Kirsty Ross-Stewart from BNP Paribas. Please go ahead. Thank you for squeezing in another question from me. Wanted to pick up, Johan, on something that you said earlier, which is that you're kind of not targeting VYEPTI failures, but you're looking still in that prior treatment failures between two to four prior failures. From a commercial perspective, maybe it's a question for Maria, talking a little bit about the portfolio approach and what the plan is to ensure that PACAP doesn't cannibalize VYEPTI, because I understand that is moving up in the treatment paradigm, but it is still used as a kind of later line therapy option. Interested in that portfolio approach that you're taking. Any early thoughts there? Thank you for your question, Kirsty. I wouldn't want to comment too much yet on the commercial positioning as mentioned before. We have assumed that there will be very limited cannibalization. We do not intend to position bocunebart as a replacement for VYEPTI. It is a differentiated preventative approach. It targets a complementary migraine pathway. As you know, the two neuropeptides have overlapping but independent roles in migraine. What excites us about this is that there is heterogeneity in migraine treatment. Some patients don't respond to anti-CGRPs. Some patients need more than an anti-CGRP. The PACAP inhibition may address these disease-relevant signaling that is currently not covered by CGRP pathway therapies, therefore it supports a different prevention option. We expect bocunebart to add incremental value to our migraine franchise, not necessarily to replace VYEPTI. Okay. Thank you. Yeah. I think we have been going on for almost more than an hour here, so maybe could get the last questions here from any of the investors, analysts. Ladies and gentlemen, that was the last question. I would now like to turn the conference back over to Johan Luthman for any closing remarks. Okay. Yeah. Thanks for the interest and thanks for all the questions. It reflects what I think this is. This is an asset that is quite interesting and raises a lot of questions, and everyone wants to hear and learn more about it. We are in your box too. We also like to learn and hear more about it. For us, the next thing to hear about it is where it progress and planning our phase III and make sure that this works out also in a bigger setting. This is what we're looking forward to do now, and you will hear, as I said, at coming conferences, some more details. We're happy to share that. Again, my apologies for being a little cryptic with A, B, and C and other things, but there are reasons for that, proprietary reasons and IP reasons. With that, Thanks for all your interest.