H. Lundbeck A/S ($HLUNB)

Ladies and gentlemen, welcome to the Lundbeck Update Conference Call. [Operator Instructions] 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 are holding in conjunction with Anaren Headache Society meeting in Orlando, Florida. I'm here at the meeting and had the pleasure to talk through some of the meeting so far with some of the key opinion leaders this morning. I'm going to have this call together with Maria Sete, our Executive Vice President of the Corporate portfolio and Product Strategy at nonback. And we're going to talk primarily about the pro data or Konark, Myantreatment program. And before I go through the minutia here, I just like to remind you about a few things about this program. The molecule was really called LAB09222. And the clinical evaluation really was initiated through a trial that we concluded some years ago, this called HOPE trial, where we had headline results in April 2023. And publication that came out in New England Journal of Medicine in 2024. But encouraged by the data we obtained in the proof-of-concept Phase IIa study, hope, we started this called proceed trial. -- which was a much more comprehensive Phase IIb trial that we initiated in March 2024. And we obtained headline results in February 12 this year, 2026 and now we are at the American Headache Society presenting some of the data to the margin specialists in the field. And the presentation was primarily done by Jessica Alianne, who is a Professor the organ University. And see as also having an opening presentation where she mentioned this, there were actually 3 opening presentations of several that mentioned the pros data. And then there was also a poster session where Jessica went through much more in detail yesterday evening the data. So 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. But let's go to the next slide, please.

So thank you, Johan, for introducing the topic.

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 pickup biologic to reach this stage in development. This is a mechanism that is distinct from and complementary to the established 1 of the CGRP class. This is significant across 3 dimensions. Firstly, there is another strategic proof point for our strategy and for the R&D transformation that Johan and he started 7 years ago. We now have 2 positive Phase II readouts for Bokunebart, the HOPE Phase IIa trial that reported in 2024, and now the Phase II adaptive trial proceeds -- these are milestones that reflect our 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 Bonaparte. There has been no new mechanism reaching the state in migraine prevention in more than 10 years, and you will remember that the last meaningful innovation came with the CGRP class, whereby FT is currently showing fantastic results. both scientifically and also commercially. With Bokunebart, we now have a strong lead with the first model mechanism in over a decade. And as Johan will explain the science behind it gives us real conviction that leadership and 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 NTC GRP and Bokunebart as the first class person plus entry picked up, we have a clear path to a differentiated migraine franchise with strong. Next slide, please. These burden perspective, migraine is still the #2 cause of years lift visibility globally, and it is a leading cause of disability worldwide beyond women. Many patients like Carlos for trade on the slide reports migraine as physical pain but as much more than that, many sufferers will attest to how the bread of the next attack picks over their life. It limits careers, social interactions, relationships and also the ability to plan the simple things. Critically, the treatment gap remains wide. The introduction of the anti-CGRPs was a real step forward. But we know that between 40% and 70% of patients on CGRP targeting medication continue to strive for optimal control and continue to suffer from Aesynt. 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 pickup inhibition and Bokunebart specifically is positioned to address. And let me now hand over to Johan on the next slide for the science behind Bokunebart.

Thank you very much, Maria. So why the Kona bar? Well, first, I'd like to take you down a little bit in history around mine it's Maria alluded to this. There is a long time ago, new mechanism action, showed an effect in margin. It actually was 2004 when the CGRP class was first shown to work in Japan studies or early depend studies. And a lot have happened during those 10 years, and we are now looking at finally, I would say, a new mechanism that seems to be working in Milan prevention, which is a new concept that has evolved during the last 15 years. Bocunebart is a monoclonal antibody that neutralizes takeup. And that is, of course, for a longer name, Peter and a late high-case activating polypeptide. And Bocunebart is binding PACAP directly. So it's finding to the ligan here that activates the number of receptors. And the coneva prevents activation of those dancing receptors blocking signaling that contributes to migrantsology. So of course, 1 may ask what is Pacapdoing that's different from CGRP. And Pais richer biology than the CGRP biology. Pakap has both overlapping and distinct growth versus CDP. It's involved in vasodilatation. It's actually also a part of the parent sympathetic nerve system in addition to the primary sensory neurons. But through the primary sensor in euros, of course, it's involved in organic inflammation and also it's all pain signaling and central sense sensitization. So it has an effect on numerous pathways that CGRP does not reach. So it offers on the -- from the biology side, a differentiated therapeutic angle. And that is exactly the kind of by already 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 the some programs in the past that have not seemed to work out a takeup inhibition. And most importantly, we'd like to talk about that. The first program in this space was actually a PAC1 blocker -- so looking at 1 of the 3 receptors, maybe 4 receptors that are involved in PACAP signaling. So that was a much more narrow approach to it. But Konevard 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 pace-driven migrant biology. So with the molecule, the convaran 1 that's engineered really to test out and block the system and we have a good pharmakinetic profile that allows for sustained prevention. So we both hope and proceed, we have now clinically validated the take-up ligand approach for the first time. And we also see that this is not only in scientific achievements, but it also gives us a good interesting data in terms of effect on patients with electronic in episodic migraine. So let me then turn over to some more data directly on the program we presented now. Next slide, please. Yes. So through the headline data, we proceed, which we presented in detail at the American Head of Society, as I mentioned this yesterday, this week yesterday. We see what's the Phase IIb trial? And was a dose-ranging trial and a dose finding trial but also dose routelesation finding study. So a very broad study -- but with the patient population with heartier migrants, they have said prior 1 to 4 prior treatments -- so this is a population that already puts take-up at a test in terms of its differentiation and its ability to really work on the more severe migrants where the need is greatest. The primary end point is often studies was the monthly margin days over weeks 1 to 12 versus placebo. And the headline data are really clear proceed I met its primary end point. Bocunebart at an IV dose, as we call A here with 84 patients was statistically significant in reducing monthly margin days. versus placebo over a 12-week treatment period. We also looked at 2 additional doses, IV, which we call B and C here, and we showed in those groups also a beneficial effect america in terms of reductions versus placebo, but those 2 groups did not reach statistical significance. From a safety point of view, Becanovart was well tolerated with really no significant findings whatsoever and new safety thing as also identified in the PROCEED trial. So that safety profile is really consistent to what we've seen before with this molecule in, for example, the whole trial. So it's within framework, what we expect and hope to see with in a cat drug in the migraine prevention field. So taken together with the HOPE data, we have now 2 positive Phase II studies that Maria highlighted, which is a strong basis to take this program forward. not only proceed further validate to take a pathway, but it also strengthened our confidence in the Cobar as a potential first-in-class PACAP targeting for PMI prevention. So let me go a little deeper into some aspects that were actually presented a little bit more by Jessica yesterday. And that is really where the hardest magnets in the chronic patients and the results we've seen. So can I have the next slide, please? Thank you. So chronic migraine is the migraine where you have numerous attacks per month. And it doesn't really come in isolation. It builds up over time as a consequence of in biology fluctuating and versioning over time. And the pattern is well described and well understood and fixed margin attracts reduce the recovery time between episodes. That in complete recovery tends to sempitize bring for further attacks. And in pain like in other -- many other CNS indications, you have a sort of a rebuying of the system, and that increases the flexibility not only in the preferred system but also within the central nervous system. And that drives further and further attacks. So it's kind of addition cycle or you like to stop it before it goes so far. That's what we call the episodic migraine, but when you come to chronic migraine, you have a really difficult to treat population. And this was really what we did in the study, Pacira study because we looked at prior treatment failures. So take-up is well placed in this biology. It has a role in central anticipation and in the pathway that drive transition from episodic to chronic migraine. The therapeutic hypothesis is that riconovart is neutralizing the peaks as we try to illustrate here. The pickup biology is fast. It comes and goes in conjunction with attack. -- but we like to play some kind of umbrella over all these attacks with a pickup treatment. Pretty down under the trigger point for causing amianattack. And the more that occurs the more front agents and the more you can suppress it below the point of inducing an attack the more treatment you assume to get. That's why we really strategically are positioning this program in the most severe chronic margin where the need is still the biggest. And that's the segment where we think take-up inhibition plays the biggest role. So next slide, please. The chronic migraine data here that we obtain and proceed are really very encouraging. And 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 is subcu and in proceeded the IV imposed, but also the IV from HOPE trial. So this is a much larger data set that now focus and narrow stone on 14 placebo patients and 354 Bocunebart patients that had chronic migraine. And in this chronic magnesite convert delivered a reduction of monthly migraine days versus 3.6 days for placebo at 12 weeks. This is more than 2 or different Moneymakin reduction over time, 2.3 with a p value of less than 0.001. So a very robust statistical signal in this subgroup and very relevant group. And importantly, this effect is consistent across other key clinical endpoints on monthly headache days, which has captured a more broader headache burden. We see a reduction of 6.9 days for the contact of 4.3 days for Paseo. On monthly margin as requiring acute medication, a measure of the depth of the response we see 5.2 days reduction for Beconabart versus 3.5 days for placebo. In quality of life, which is a very critical measure in magnates measured here by the so-called MSQ test, we see a change from baseline of 3.4 for the convert versus 7.8% for placebo. These are the kind of autos that massively it to those patients and the matter is in a real life situation, fewer margin days, fewer days require acute medication and a meaningful improvement in how they can function. So taken together, this data gave us a strong conviction that the coneva can deliver a clinically meaningful benefit in chronic marge. From a safety perspective, the profile remains clean and consistent what we've seen before, as I mentioned earlier. So now with the combined a very comprehensive data set from PROCEED and HOPE. We have now positive data and very encouraging data in particularly chronic severe mega patients. So we are Phase III ready, and we look forward to discuss the development path with regulators in the coming months. With that, I'd like to hand over to Maria again. Next slide.

Thank you very much, Johan. And 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 impact on visibility, 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% to 45% of those on preventative treatment receive a migraine-specific advanced therapy. So something like an anti-CGRP or bottle immune toxin A. That equates to approximately 1.5 million to 2 million patients on advanced preventative treatments in our priority markets. And there is -- 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 a CGRP have already cycled through more than 1 anti-CGRP agent. Looking at the class as few as 20% of patients currently on an anti-CGRwe achieved a 75% reduction in mean monthly migraine days. That leaves an underserved population of approximately 6,000 to 1.2 million patients in our priority markets who are on advanced therapy but are still not achieving optimal control. This is the addressable opportunity for Bokonabat. 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 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 Lumbee parts in the migraine space. The strategy is simple: 2 complementary mechanisms, anti-tick 1 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. 9% 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 USD 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 T pickup designed to complement Bai and extend our reach into patients where current treatment options are not providing optimal benefit. Both assets are delivered and we'll go through exactly the same infrastructure that we have purposely built for Vyepti, trusted relationships with a 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, 1 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 3 points that you should leave this call with. First, Proceed gives us a Phase III-ready pins anti-piup preventative agents. 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 Bokun Bart 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 super migraine. -- chronic migraine is where the need is greatest, where the biology of pickup is most relevant and where the commercial opportunity is most compelling. And third, with Vaezi and Dukinopart together, we are building a differentiated migraine franchise, 2 complementary mechanisms, 1 market-leading commercial infrastructure, -- this is a position that very few companies in the migraine space can credibly plan. Our next step, 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 2020. 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, John and I would like to thank you for participating, and we can now open for Q&A.

[Operator Instructions] The first question comes from the line of Marc Goodman from Leerink Partners.

Yes. Could you talk about the percent of CGR failures that were treated here. Obviously, we're kind of looking at the VI-eppy data and saying, "Oh, IFPs great data, a little stronger than this. But obviously, this is for patients who failed by Epi -- so who has failed by FD filled out the CGRPs, Give us a sense of that and what the other kind of breakdown is the type of patients. And I mean you said there were 1 to 4. So if you can give us any sense of that? And -- do you have any responder rate analysis? Just curious on that. And then also on this dose -- you talked about a B and C. Is dose A, the most potent dose? Is that the highest dose? I mean, was there a dose response? If you could just give us a sense here.

Thank you, Marc, for those questions. several of them. Let's start with the proportion of patients that's been on CGRP and the past failures. And -- we had a fairly low range. We're in the 10% to 15% patients that's been on the prior CGRP treatments any type. So we have a data set on this, not an extensive data set, but we have a good data set on it. I'd like to sort of just emphasize 1 aspect here. This is not the drug for biopsy failures. This is a drug for any failure that we see it. I would like to proceed with it. And that's broader label, of course. We will not particularly study this specific against 1 particular drug or drug class. We like to have this as goes to treatment for those that fail any type of prior treatments. So yes, there were 1 to 4 prior failures on average. We didn't present that much in detail, but let's say they've been at our average about 2 prior sale treatments that occasionally include ERP. Responder rates analysis, et cetera, we will come back to that in upcoming meetings. These are aspects of the data we present today or already yesterday. -- at the meeting, and we will have at upcoming conferences going into more details on the different aspects of the ProCata. The ABC, which 1 is the most potent, which order do come, we have actually purposefully and not reveal any of that. And my apologies for that, but we are actually in the process of building a very strong understanding about the PK relationship here and we are building further on our proprietary portfolio around this program. So at this stage, we cannot unfortunately reveal any details on the exact doses and the ranking of the different doses. Let's say did I cover all your questions at it Marc?

Yes. Yes. So just to be clear, the answer to the first question was 10% to 15% of patients for CGRP failures.

Yes, in that broad range. We have a little bit difference between, of course, HOPE and PROCEED. But proceed was that we were aiming for a maximum of 15% and we got a little less. So somewhat below 15%. .

The next question comes from the line of Kirsty Ross-Stewart from BNP Paribas.

Just a question on the pooled data. I mean, you present all of the doses and formulations, but understand that you're moving forward to Phase III with the formulations. So just interested if you can give us any color on what we would see in the pool data with the IV formulation only. And can you confirm as well that in that full data that dose group A was the maximally effective dose in line with what you saw in the kind of broader proceed trial? And then second question, just how does narrowing the targeted population impact your expectations for the opportunity for the asset and now you're targeting chronic to be migraine. I think you've previously said you expect payout to be bit like in its opportunity. So just wondering if that still holds.

Thanks for those questions. In terms of the poll data, yes, you're really speaking on 1 thing that I didn't emphasize so much in the data presentation, but this is all the data, meaning all the pool data across Hope and proceed in the chronic population, independent of dose or road administration. So this is somewhat diluted as you may suspect. So the same arms, some treatment paradigms for electrification in the chronic population. So in some manner, we made a sort of value a little bit what presenting here, but do you think it's very, very difficult 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. But obviously, there are doses that are more payable than other doses there. So the jump from 3.6 million with asbuptoER5.9 million, the 2.3 delta in Monthean. It's, of course, a very strong response. But in certain subgroup analysis, we might see more. Now you're getting the scale numbers, so 1 has also to be very careful with that. And that's why we do the pooling of everything together. But this pooled mixed sort of response population in chronic migraine is a pretty robust response. I would like to say when you already trianteprior prevention treatments. In terms of narrowing the population. When it comes to most of the monoclonal antibodies, definitely -- 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. And in some manner, it makes sense where those drugs are currently placed in the treatment paradigm. Of course, we like to go a little higher up. So this is by far the dominating population. And this is also the population that is harder to treat. This is the population where you actually ended up having refractory patients as well. So we are always trying to go where the biggest, biggest medical need is, and that is an iconic population. And that is a very sizable population and Maria can do that a little bit. I don't know if you want to comment further on that, Maria, you know how we see the opportunity in chronic Magnation.

I can, Johan. And 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. So it is in line with our expectations. And once we are able to share more details on the commercial potential, we do later in the year, it will probably be clearer on why we see the value and what exactly the value is more from a collegial opportunity point of view, but there's no reason to think that this is not a good thing.

Can I just ask 1 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 mention on that because there are rather small populations. But obviously, it goes in that direction. That's clearly it.

We now have a question from the line of Charles Pitman from Barclays.

Charles Pitman from Barclays. So firstly, just in terms of just trying to pace versus peers the lower number of mine grain days reported versus some of the CGRP is -- just wondering if your and you put this down to the difference in or whether or not you get 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 new migraine days by a similar degree versus hit the 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 to the kind of refractory page population. I'm just wondering how you think about the commercial positioning. Will -- do you see the migraine market shifting to a kind of switch dynamic post 1 or 2 CGRP failures or will take up be positioned as an additive product. And then following up with that last comment. In terms of the combo data that you reported in the release this morning, you mentioned that you look -- that you have data for combination with ubrogepant and triptans, but I was just wondering what data you have or are working on show come effect with CGRPs.

Just a clarification. Your last question is about monoclonal CDR, right? Not only the 10.

Yes. Correct.

Okay. good questions. Yes. When it comes to the mechanism of 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 clinicity and how the disease drives in this population. Is this dependent on Pakap itself at a different mechanism? Or is this a generalized mechanism that can play also a role when you treat. Yes, there are many reasons to believe that takeup to its broader role could play that sort of more modifying role. I just like to be a little careful, I mentioned refractory patients, that that's the ultimate patient that is not responding to anything basically not even CGRP and that is the population we have not specifically studied here, but we're really going to the very severe ones that are definitely at the risk of ending up being refractory refractories, as you understand, you tried all preventive therapies and you're not responding. That is a very, very hard to keep population, but we like to be in that space as well. we have not studied directly refractory patients. It studied those with very strong conicity with that subdue analysis. Yes, there is a placebo response with all the treatments and as you know, it's part of the real response and is this 2.3 impressive about placebo, Yes, I would actually think so. it's definitely what you see in the good old days when we did the preemptive treatment in chronic patients without prior treatments and treatment by patients. And 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 -- how this drug works in treatment-naive patients that haven't got it. And that's a good thanks. Luckily, I would say senior patients have never tried a preventive drug before, but it could be nice to also study this drug in a treatment by population and sometime point. I mean there are feedbacks or on the switching dynamics but also feedback generally at the meeting here. And I would say it's been what I heard and what I've been seeing here generally a very positive comment about that it's a new mechanism, but it's moving forward. And I think many people expect basically open in patients when will get started with Phase -- when it comes to specific restriction, yes, 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 these things, No. We hope that you have a specific effect of this drug in the heart to treat patients. Conbo data, yes, we did the Japan. We can, of course, look at the combo data on mAb versus man. But we are looking now primarily at people that are traveling for from Japan to pad failures and they even want to stay on the Japan and still get on the monoclonal antibody. Are we doing those drug-drug interaction studies primarily because we think we will influence the big concentration or the PK behavior of the drug, not really, we're looking mostly for safety here. So obviously, eventually, it could be interesting to see whether takeup works safely and niche in combination with monoclonal antibodies. But that's a very unusual treatment paradigm. You probably will not run simultaneously on 2 monoclonal antibodies. I don't know, Maria, if you like to comment further on commercial scenarios here.

Yes, I can. So we know that despite the fact that NTC GRPs are very effective, only 30% roughly of the allergic population is currently being treated. This can be because with some agents, there is like of efficacy because there are other components to migraine, as we just mentioned other than just the headache because there may be a loss of response to the treatment, as Johan also alluded to. -- there is a central sensitization. So we do see a place for pickup. In reality, it can be used when an anti-CGRP is no longer efficacious or when any other drug is no longer efficacious, but because this is a different pathway, there's also no reason to imagine that it could not be used in concomitant similarly to what physicians do with other treatments. At this point in time, we will not be able to communicate yet on our commercial position.

And maybe as maybe we didn't fully address your question about first line. I mean obviously, we're not aiming for first line at this stage, not even yet is the first line. Of course, there is a good reason why you like to start very early with the more potent treatments. But this is a drug you go to when you at least try a few others. That's how we position it right now. .

The next question comes from the line of Shan Hama from Jefferies.

Three from me. So could you then clarify if the Phase III population will be 100% chronic migraine patients. So I sold it at all. That's my first question. And then Secondly, I know you can't say much about the doses, but are there baseline is balances between this A, B and C and then was that more chronic in 1 group and less chronic and the other just wanting to think about how that's distributed across the dose groups. And then lastly, can you provide either 50% or 75% responder rates, particularly in the chronic migraine group.

The first question, you wanted us to clarify exactly what the episodic -- can you try to ask your first question again, so I get it with [indiscernible] so I was just wondering whether in the Phase III study, it would be 100% episodic migraine patients. Okay. Now I get it. Yes, I mean, have not revealed what we're doing in Phase III yet, and it's also pending as Maria outlined here on the regulatory interactions. But we are particularly interested in the chronic population. So that gives you a inhere like to go with this. And yes, episodic populations are on the track to get chronic. But as I've said several times here, we really like to go over the biggest medical need is still inside of the CGRP class in spite of drugs like FT, and that is in the very severe chronic patients. And that's where many of the patients end up already where we drive like by DM. We like to play in the same space basically Yes, when it comes to the doses, yes, I didn't reveal the doses, but were evenly balanced in terms of episodic and chronic, and the asset, they were well signed up. So there was no bias. If you try to read in, did the 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. Yes, the responder rate, I know you're all eager to hear that, but we're not presenting this at this time point, we come back to that when we have further data presentations in this for -- but I'd like to emphasize that this, again, it's a group that has failed prior business. So 1 should probably not expect responder rates that are up at the top rate of drugs that have been tested in treatment-naive patients. that okay?

We now have a question from the line of Xian Deng from UBS.

So just sort of coming back to Johan, 1 of your previous comments on the combo trial, Interestingly, that you actually -- at least the poster you're sharing is actually a combo with the oral -- and you were seeing -- sorry, if I get got correctly, it's unlikely for patients to take to antibodies together, -- but 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 to 15 days of migraine days. So -- and let's say, if you come on with BT, which is also an IV, if you actually have synchronized administration, that could actually be -- in terms of convenience, that's actually no negative added. So just wondering if you could elaborate on that comment, please. Sorry, go ahead. sorry, if we can start with that one.

No, no, please ask your second question.

Yes. So the second 1 is just wondering -- so this is with prior therapies, 1 to 4 prior therapies. So just wondering, other than CGRP, what are the -- just the other kind of typical treatment that's actually used here because other than Tristan, is there anything else SP572775931 Yes. .

Yes. Thanks a lot. Yes, going back to the combo, yes, of course, scientifically at some time point on probably like to see if there is an additive effect of CDP, for example, and the 1 I was more commenting on the how we like to proceed right now. And for example, in our clinical trials here, it prorate or whatever oral drugs is by far the most dominant drugs even in the more severe population. So there are probably not so many patients that will be on monoclonals at this time point that will be included in the program going forward. So from a safety perspective, we don't think this is a channel for us and it should not be started. . 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 -- but Cunard in a scenario with prior oral treatment tailors. And this is where we like now to deliver a Phase III. For life cycle management, we obviously may consider very different combinations here. And we're sitting very well positioned here because we have a CGRP monoclonal -- we have in the convaran -- you can probably guess that we're also working on other things in the preclinical arena here for the future. So we like to say in this field, I really understand how much benefit to get with all lapping series. But that's not on the way immediately for us here. Japan may be much more common in the Phase III trial. And that's why we do this drug-drug interaction, tragedies safety study. yes, what kind of prior treatments did they fail on Yes, it's the usual battery and also them are off label to coat and all these drugs. So it's a mixed bag and since are not generally considered preventive treatment. So we're talking about those that are off-label use for preventive purposes. So some, of course, are treatment, but some are also the -- as I mentioned, the general malt therapies and others that are used for male production. So it's a very mixed bag of several different drugs -- 4 or 5 different track. And by the way, subgroup analysis probably doesn't really make sense because the historical data, there have been some time back on 1 drug and they shifted to another. So it gets very, very complex and very, very small subsegment to look at.

We now have a question from the line of Peter Ankersen from Nordea. Please go ahead.

It's Peter Hakes from Nordea. 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 8 weeks follow-up? Or is that purely safety? And can you also kind of confirm the hypothesis that it hasn't plate. So that's the first thing. Then 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.

Yes. Thanks, Peter, for those questions. And thanks for the congratulations. We actually -- we definitely think it's a really great data set. So 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 plateaued yet at 12 weeks. And 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. In that case, also in the space where I mentioned that there is something reconception here of the disease. And it's almost an element of continuous modification of the disease process. So we are intrigued and also quite optimistically looking at that increasing separation of the treatment effect over time. So that's definitely something we are looking at for further long-term data that we have already in the trial, but also or eventually further exploration. So that's an interesting observation, clearly. Phase III data design, where are we? Well, first of all, in terms of trial duration, et cetera, -- we have a proposal that is committed to the regulators, and we have not had active interactions yet. We are in the process of having initiated the process for this, and it takes, unfortunately, while until we get to the actual conversation with -- but you can sort of assume that we will like to deliver on what we really found positive and strong as for the Phase II data. So obviously, most of the electronic population is part of it. Already at 12 weeks. We already have a significant effect in tectonic and the subgroup in the PROCEED program. we will try to not complicated overcomplicated it for Phase III. So we have the program at least again. I think we have already very, very encouraging data in a very interesting subgroup treatment. -- tailors, patent failures.

If I may, Johan just because Peter, I don't know if your question was around just a science behind having more than 1 dose of the commercial opportunity, like what we see with biopsy. 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 discussions with the analysis of the base and the discussions with the different regulatory.

I guess the 2 doses with Ypiois serving you well right now because of the no pricing, right? So I guess that's , of course, also inherent in the question whether that is part of the speculation not go with 1 big and then, of course, choose the price around that as well.

Yes. Absolutely. This is a huge difference also in the U.S. market versus other markets. I mean there are 2 parameters here. The dose selection and duration selection. And I'd like to remind you this is monthly IV injection that the IV infusions that we've done so far. So that's also something that we our mining or how to address. And this not yet gating effect is also pointing that there could be a reason to explore dosing into is also a little bit more.

The next question comes from the line of Alex Moore from Bank of America. .

Just a quick one. a step-down in efficacy you can see in Phase II study relative to Phase IIa. Can 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 2 studies? And any sort of differences in severity, particularly may migraine days at baseline. Any comment to what you think drove differential between those 2 studies? Actually, you mentioned that chronic migraine is sort of the last or the bigger unmet need within migraine prevention. But can you roughly size or how many data to hand on the rough split of acute versus chronic.

Yes. I'm not sure I captured what's a little breaking up the first part. You talked about the differentiation between which studies. I'm not sure I captured it fully.

I was just talking about the Phase IIb PROCEED at 1.38 monthly migraine day reduction versus placebo compared to 2.0 seen in Phase IIa HOPE study?

Okay. Yes. I mean, please remember, each arm is entirely small arms. I mean, in my annual hundreds per -- so there might be a little fluctuation here. But I think the most important thing is that we're traveling at something that is around 2 or more, right, then it may be slightly different between the different studies. That's definitely clinically meaningful in a population like this that is not responding well. So I don't think we should read too much into it. Then, of course, differentiation mostly magenta baseline, et cetera. This is -- 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 route. We see then are the key drivers with it. So I'm not sure I understood really that either, sorry. .

The question was mainly just on what the key drivers between the different in efficacy between the Phase IIb and Phase III studies.

No. No. I mean there is really quite claim, I think it's just a little bit viability between the studies because the populations are very similar. -- geographies are very similar hope we didn't have Japanese patients proceed, we have Japanese patients, but we don't really see any difference side. So I don't think there is really something we can find is in terms of the key drivers. .

Yes, the trials were not designed to be compared like-for-like. There are these new ones under set. -- 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 epitotic migraine?

Yes, please do that.

Thank you. So we estimate that in real world, so from an API point of view, the approximate split of chronic versus episodic migraine is roughly 2/3 episodic and 1/3 chronic. So 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. And 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.

Yes. And Alex, I'd like just to emphasize 1 more thing, and I'll go back to that prior point that I should add really side open proceed were very similar populations yet. But obviously, hope was just on treatment. We looked at 1 month and proceed is repeated treatment out to 3 months, right? So there is a little bit slight difference there as well. So -- and Peter from Nordea, I pointed out that we may have expanding effect over time. So that could explain also that little difference. But again, I think we should be very careful with those small numbers we see in the difference by this. .

[Operator Instructions] We now have a question from the line of Tobias Nissan from Danske Bank.

I have 2 fast ones here. You may speak on the chronic migraine here, but what did you see in the episodic and any signal at all if you can talk a little bit more into that -- and then just your hand on the home versus PROCEED trial here and the data you can talk into what surprised you the most, if any?

Yes. I'd like to start with a price because I made a point that is 20 years since last margin mechanist worked and that was CGRP, and it was done in the Kingdom of Denmark, Solesence Group together with Boeing in him, they had a Japan to Ivan. So that's many, many years ago. And there was nothing given that this takeout mechanism would work. So I think already in April 2022, we had a big surprise that this actually seems to be working. -- because that was far from given. Of course, there's some overlapping biologies, but -- and there are really great prior data on infusing PACAP into patients in using Iansiti was far from given. So that's the biggest price because we are not spoiled with the positive proof of concepts for new mechanisms. You can work many, many years in pharma industry and not get any of those. So I think that was the biggest surprise -- in terms of between hope and proceeds, I think there will -- there was a really, really good idea to do a very comprehensive proceed. And I really like to build a robust platform for Phase II. We have given you an indication where we think really the drug is speaking to us, and that is an economic population. You asked about 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 our tectonic population for many of the reasons Maria and I have talked about. This is the patients with the biggest need. That's actually where we like to go, but also reputations like us to go. And that's where actually we find most of the patients for those advanced treatments. Remember, this is the high end. This IV specialists treated. This is not the pill for the GP. This is a very, very different population. So that's actually in some manner, a surprise that this drug mechanist seems to work very hardest. That we didn't believe to go on that. We have no idea whether this is a weak mechanism or for the mild patients. We have worked many years on antidepressants. We had great series. Those drugs are normally not for the very, very severe depressive patients Here, you have the opposite a little bit. It looks like Pace is for really the ones who need it most, which is really in some manner positive surprise because normally, it's harder to treat, the harder treated the more sick population, so -- we will reveal a little bit more of what we see in the peso, but I think that's, quite frankly, less interesting. And Maria commented on this every time, so I don't know if you want to comment again, Maria.

Yes, 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. So as we are interested in the populations where we can indeed bring clinical value, and these are the ones that are more refractory, more produced. And that's why we are scientifically excited about the chronic migraine population. And then, of course, these are the ones that are left with us. I'll tee 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 map already. We have learned over years how to deal with that. We built an infrastructure internally, but also externally, how to deal with it. And this, as I said, is the higher-end treatment. That is working for most physicians and those patients quite okay. So we actually play where we are the best players also with this, to be honest, where we have the strongest experience. .

We have a follow-up question from the line of Kirsty Ross-Stewart from BNP Paribas.

Feather question from me. I just wanted to pick up your hand on something that you said earlier, which is that you're not targeting biopsy failures, but you're looking still in that prior treatment failure team 2 to 4 prior failures. So just from a commercial perspective, maybe it's a question for Maria, just talking a little bit about the portfolio approach and how -- what the plan is to ensure that pay cap doesn't cannibalize biopsy because I understand that is moving up in the treatment paradigm, but it is still used as a kind of later line therapy options, just interested in that portfolio approach that you're taking? Any early thoughts there?

Yes. So thank you for your question, Kristen. 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 on bad as a replacement for Vyepti. It is a differentiated preventative approach. We target a complementary and migrant pathway. As you know, the 2 neuropeptides have overlapping but independent roles in migraine. But we -- 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 RP -- so the pickup inhibition may address these disease-relevant signaling that is currently not covered by CGRP pathway therapies and therefore, it supports a different prevention options. . We expect Bocunebart to add incremental value to our migraine franchise, not necessarily to replace by epti.

Yes. I think we have been going on for almost more than an hour here. So maybe I could get to 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. Yes. 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 the rate is a lot of questions, and everyone wants to hear and learn more about it. And we are in your box, too. We also like to learn and hear more about it. And for us, the next thing to hear about it is really to progress and planning up our Phase III and make sure that this works out also in a bigger setting. So 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. And again, my apologies for being a little tricky with A, B and C and other things, but there are reasons for that propriety reasons and IP reason. So with that, thanks for all your interest.