Okay, everyone, so welcome to the London Jefferies Healthcare Conference. My name is Amy Li. I am a biotech analyst at Jefferies, and today we have the pleasure of hosting MorphoSys. Joining us is Lucy Crabtree, CFO, and then Julia Neugebauer, Head of IR. I will before we begin, I will just pass it to them to introduce themselves, and then provide opening remarks. Sure. So, yeah, Lucy Crabtree, pleasure to be here today. I started MorphoSys as CFO three months ago on the August 7th, so fresh in post. You know, incredibly excited to be at MorphoSys. You know, clearly, we've got a big event in the coming weeks with the top-line results from the MANIFEST-2 study expected. I think, you know, in general, the myelofibrosis community is in desperate need for more effective and well-tolerated medicines, and we're very excited about the potential for Pelabresib, our small molecule BET inhibitor, to deliver on this need. Great. Yeah. Yeah, thanks for having us. Julia Neugebauer, scientist by training. With MorphoSys for more than 16 years now, and Head of Investor Relations. Excellent. So let's start with Pelabresib, as I know this may be top of mind for everyone. So just stepping back, looking at the broader landscape in Myelofibrosis, can you go over what the standard of care is? And how do you expect Pela to fit into the current standard of care? Yeah. So at the moment, the current standard of care, sorry, mixed up. I've just come off a red-eye from Boston, so is JAK inhibition. You know, JAK inhibition benefits half of patients in the Myelofibrosis community. You know, physicians have vocalized, KOLs have vocalized the need for more efficacious and well-tolerated therapies. Yeah, I mean, you know, based on our phase II study, the MANIFEST study, you know, we're pretty excited about the potential for Pelabresib to show exactly that. Would you add anything, Julia? No, absolutely. Excellent. So just looking at the BET inhibitor mechanism of action, how does it compare to current therapies that are currently approved or in development for Myelofibrosis? How is that mechanism synergistic with JAKs, and, I guess just how do you think that it could treat Myelofibrosis broadly on symptoms, disease, pathophysiology, et cetera, et cetera? So, well, leveraging epigenetics, I mean, you know, Pelabresib is a small molecule therapy that, you know, is selective for, for BET inhibition. I think BET inhibition and, and the JAK-STAT pathway, which, is clearly where the, JAK inhibitors fit in, you know, are, instrumental in the pathology of Myelofibrosis. So I think, you know, that in combination, should speak to a powerful effect in, in treating the underlying, cause of, of Myelofibrosis. Okay, excellent. So moving on to MANIFEST-2, can you go over what your internal bar for is on, SVR35 as well as TSS50 at week 24? Sure. So, I mean, you know, moving back to our original phase II MANIFEST study, for SVR35, we, we saw a 68% effect for SVR35, and for TSS50, this was 56%. You know, I think, you know, that speaks to a nice profile of candidate for a therapy in Myelofibrosis. Okay, great. Now we have seen other trials fail on symptoms, so the main question is on TSS50, one, do you expect to hit on symptoms based on your current phase II data? And then, two, if you could talk a little bit about, you know, was the miss for AbbVie surprising? I think they've had some very early disclosures in their abstract that looks almost as if symptoms was trending the other way. So in terms of mechanistically, how is a BET inhibitor better in terms of some of these trends that we're seeing in symptoms from phase II to phase III? And then, of course, you know, what they did. Were you expecting them to miss, any sort of color would be very helpful. Sure. So, I mean, first of all, I'll talk to our study. You know, we're confident in the outcome of the MANIFEST-2 study. Our study is well-powered, you know, we have 431 patients randomized, which is nearly double that of other recent first-line Myelofibrosis combination studies. So I think, you know, the size of our study is important. You know, based on our experience and what we've seen in terms of precedent studies and how RUX has performed historically, I think what we see is a degree of consistency, right? Mm-hmm. You know, I speak to, and Julia, maybe you can allude to the TRANSFORM study. You know, I think all that combined, you know, we're hopeful, and we expect to see a consistency between, you know, our phase II study and our phase III study. You know, certainly for TSS50 and SVR35. ... Yeah. No, absolutely. I mean, to your question, were we surprised by the results? Absolutely not. I think they—what they showed was really totally in line with what they've shown in phase II study for SVR35. I mean, it was the exact same number they saw. For the TSS50, that was the metric they had disclosed in the phase II study. I think they always had been sort of in line/underwhelmingly compared to RUX historical studies. That's now what they've disclosed in their phase III study. So again, no surprise. I think the other nice data point we got out of the abstract is that the RUX monotherapy arm, and now we have a very recent data point from a very recent study, has not really changed compared to older studies. I think that was another nice learning for us from the data that we saw. Okay, excellent. In the RUX monotherapy arm, are you talking about SVR35 or TSS50, or both? Actually, both. I mean, SVR35, it was probably even on the lower end of the range that we've seen before. And then these 11 points, they saw an absolute change, so they didn't give us the TSS50, just the absolute change. But when you compare that- They didn't give us this baseline either. Yeah. Yeah. They didn't give us the baseline, so we can just... I mean, there's a bit of guessing here, but when you compare that, for example, to simplify it, it was a nine, 9-ish points reduction. So we believe the 11-point reduction is really in line with that. Okay, excellent. And then just in terms of the FDA requirements for approval, are both TSS50 and SVR35 required? And then, I guess, what other endpoints would they look at? Would they look at OS and PFS, or is it mostly on those two initial endpoints for approval? So look, you know, SVR35 and symptom improvement are absolutely, you know, the two endpoints we're looking for in this study. You know, I will say, I think recent approvals in Myelofibrosis speak to the pragmatism showed by the FDA on an agent that's needed in an area of high unmet need. And, you know, I think in that context, the totality of the data is important. We're looking at numerous meaningful endpoints, you know, as well as obviously SVR35 and TSS50. That includes absolute change and a percentage change in TSS, you know, alongside PFS, OS, et cetera. So, you know, look, you know, SVR35 and TSS50 are our, you know, our two endpoints. But, you know, I think we're encouraged with the recent approval in the Myelofibrosis space based on mixed clinical results. Excellent. And I know this is too early to talk about regulatory discussions, 'cause I'm sure you, you know, you'll go with, you know, see the data and then go, but is there any sort of potential flexibility around that TSS50 symptoms? We've seen some of the TSS50, you know, trend down over time. So is that 24-week a hard endpoint? I know you guys are doing some stratification factors as well, based on, you know, population. Any sort of initial color would be super helpful. Again, I mean, it's too early to comment. Right. I think, you know, I would just reinforce the fact that we're encouraged with- Right ... with the recent approval in this space. You know, I will point to navitoclax as well. You know, they recently sort of presented some data in an ASH abstract- Mm-hmm ... on absolute TSS. Yep. You know, different from sort of TSS50. But, you know, I think looking in general, you know, our base case is that we're confident with our study based on MANIFEST and. But we do think the totality of the data will be important, too. Mm-hmm. Yeah. Excellent. I mean, adding to that, TSS50 is a very binary way of looking at symptoms. So while symptoms are gonna be important, the breadth and depth of the symptom response also is something that the regulators will look at. Okay, excellent. That's super helpful. And then in terms of historical rates of symptoms, what is your internal expectation? I think historically, some of the RUX and JAKs have shown anywhere between 39%-44% TSS50 at week 24. Internally, do you think you guys could come depending on, you know, your baseline population, the N, will you come on the higher range, the lower range, or anywhere in between? I think it's too early for us to speculate. Right. You know, we'll, we'll see when we see the data. Okay. Okay, that's fair. And then in terms of your AE profile, can you go over, some of the, you know, the safety you've seen to date as compared to, the JAKs, as well as some of these other agents in development? Are you seeing any sort of additive tox? And then, I guess, in terms of your titration for RUX, in your phase II, Arm three, was there any issues, tox-related, from titrating up? Any color would be helpful. So I'll start with maybe two sound bites, and I'll pass them to Julia. You know, I look, first of all, in the MANIFEST study, you know, our discontinuation rate was low, you know, in terms of emerging AEs, you know, low grade. So we were very encouraged by the safety profile in that MANIFEST study. You know, the other thing I will speak to is obviously, you know, RUX, RUX alone, you see, you know, a drop in hemoglobin levels, in combination in our MANIFEST study, you know, we saw a significant improvement in anemia. So, you know, I would hope and expect to see that replicated in MANIFEST-2. Do you wanna touch on the other points? Yeah. No, I agree. I mean, that—I think that's super important and super rare that you see better safety profile in the combination compared to the monotherapy. But to your question on the RUX dosing, so I mean, RUX is dosed as per label, we just start a bit lower in the first cycle, so there is the option to titrate up and down. What we've seen in the, in the MANIFEST study is a median dose of 10, which is totally in line with, for example, the JUMP study. So we're really—the patients are really getting the real-world dose in our combination, and I think that's something that's also very important and very encouraging to see. Okay, excellent. And then I believe the ASH abstract has some early disclosures on how many patients you recruited, and at the cutoff, how many patients, you know, are on therapy. What does that—it looks like, you know, it was somewhere around... Let's see. It was 383 out—you enrolled 431, and then at the time of the cutoff, mid-year, it was around 383 patients. Do you—is that—can we use that to proxy a current discontinuation rate? I know this is, you know, at the time of cutoff, not at the time of 24 weeks, but any—I mean, is that encouraging to you? How does that compare to your phase II, and is that, you know, like, can we use that to kind of proxy discontinuation rate so far? No, that's absolutely encouraging, and, I mean, as you said, you cannot really directly use that to calculate discontinuation rate because it's at cutoff. But I think when you would calculate that, I mean, the number even that you get out of that will be very encouraging. So also that is in line with what we've seen in phase II study and with what Lucy has already alluded to, that, I mean, that speaks also for the safety profile that we believe we can see with this combination. Okay, excellent. And then in terms of the data disclosures for MANIFEST-2, I know you guys have an ASH presentation, December 11th. Is that where we expect to get top-line data? No, look, I mean, the data, when it becomes available to us, will be disclosed via an ad hoc- Okay. -press release. You know, in that ad hoc, you can expect the primary and key secondary endpoints, a general statement on safety findings, and, you know, due to the ASH embargo policies, the remainder of that will. You can expect to come at ASH. Okay, okay. So there is a potential we could get a top line whenever it becomes available between now and ASH? Yeah. That's super helpful. Yeah. And then just moving on, in terms of, you know, the market, when do you expect Pelabresib to get onto the market, assuming positive data? Our expectation, if you follow standard timelines, will be 2025. 2025. Okay, got it. Can you break that down in terms of the components? Well, I mean, look, we're not going to comment on, you know- Right ... approval timelines in any specificity. We'll, you know, we'll update as and when we're able to, but you know, you can assume on a positive outcome, which we hope and expect, we would be looking to file as soon as possible, and you know, based on the approval timelines, we'd expect to get Pelabresib onto the market in 2025. Okay, excellent. And then in terms of your commercialization strategy, right now, on the sales force, how much overlap do you have with your current sales force and Monjuvi? Well, I think this is an important point. You know, we're not coming from a standing start with Monjuvi, you know, commercialized in the US. We've got an existing US commercial infrastructure. Mm-hmm. And you know, there is a high degree of overlap between you know, the target audience. You know, we've historically you know, spoken to around 80% overlap. I mean- Okay. So, you know, again, you know, with our experience with Monjuvi- Yeah ... we're not a first-time launcher. We have an existing infrastructure. There's, you know, a high degree of synergy. I think we're well positioned. Okay, perfect. Can you remind us how many reps you currently have? We've not disclosed that publicly. Ah! Okay, okay, got it. Is the assumption that you will be hiring more for this potential launch? I think you can assume we'd look to optimize our infrastructure, but I think the important point is that, you know, again, it's not a standing start. We're not having to build this from scratch, and you're not gonna see, you know, a huge uptick in our level of SG&A, you know, as we- Right ... lead into a potential launch. Okay, okay. Excellent. And then, if you think about, I guess, if you think about the commercialization potential of Pela in Myelofibrosis, do you think physicians will-- I guess, how do you expect physicians will use Pela? Is-- will it be in combination with other JAKs? Like, would, would it be with RUX, as you ran the trial in? Would it be with other JAKs, you know, on top of-- in addition to RUX? And then any sort of rationale, and color would be helpful. Well, look, I mean, our study is a combination with Ruxolitinib. Mm-hmm. You know, it's standard of care. So you can imagine that's gonna be our priority. It doesn't... You know, we do think, you know, in principle, and with the mechanism of action being a BET inhibitor, you know, this is a therapy that could be potentially JAK agnostic. But, you know, in terms of our study and an approval, it will be in combination with Ruxolitinib. Okay, understood. That's super helpful. And then in terms of second-line, I know you have early second-line refractory data from phase II. Are you planning on running a phase III? And also, would you consider collaboration agreements to run some of these combo trials in the more refractory setting? ... So look, you know, our study is first-line. You know, that is a meaningful opportunity, not least the unmet need, but also in, you know, from an economical perspective, it's a meaningful opportunity. I think getting Pela on top of RUX to patients sooner, we believe is the key focus and, you know, should be the focus. So you know, we're not planning any second-line studies as yet, right? I mean, the focus at the moment is pela first-line Myelofibrosis. Okay, understood. If you were to look across the landscape, what combination potentials do you see for Pela in Myelofibrosis, outside of just the JAKs? Well, I can only speak to—you know, the approved JAKs. You know, there's more than one approved JAK. You know, that could be an opportunity downstream. You know, and as always, I mean, in terms of—you know, your earlier point in terms of partnerships, I mean, you know, we are focused on pela. We're focused on delivering value with pela, and we're also focused on keeping a lean and efficient cost base as well, and I think that's all I can really speak to. Okay. Am I done, I think? That's, that's super helpful. In terms of, I guess, just going over LOE and exclusivity for Pelabresib, it looks like the composition of matter may be expiring in 2032 in the U.S. Please correct me if I'm wrong. That's correct, yep. And then you guys, I guess, what other method-of-use patents do you have, or, you know, formulation, et cetera, extending that exclusivity? And in terms of patent term extensions, have you made any comments on if you plan to file one with the composition of matter MOU? And then just general expectations on, you know, when this could go off. Well, method of use is 2039. Have we made any comments on other- No, I mean, I think we just made the comment that you could look into some standard options for extensions of the lifespan of the patent- Okay. But we've not been specific on that. Okay. Okay, perfect. I guess, I just want to save a little bit of time for some of your other programs as well, 'cause I know you guys are excited about them. Come on. Yeah. So, beyond Pelabresib, can you talk about what other pipeline assets excite you the most, and why? So, I mean, obviously, we have an approved asset, Monjuvi, in relapsed refractory DLBCL. You know, we're pretty excited about the potential for Monjuvi and additional indications. You know, we're running it from the frontMIND study in first-line DLBCL. I mean, first-line DLBCL is clearly a you know, a large opportunity, 30,000 patients a year diagnosed. You know, that data is due to read out in 2025. We're developing that alongside Incyte. We're also running a study in relapse refractory follicular lymphoma and marginal zone lymphoma due to read out in 2024. So, you know, I think with Monjuvi, where we expect the growth to come from will be those additional indications, and we're pretty excited. You know, in terms of other assets, by the acquisition of Constellation a couple of years ago, we gained a second asset, Tulmimetostat, which is an EZH2 and EZH1 inhibitor. You know, that's shown promising results disclosed at ASCO earlier this year in a basket of solid tumor and lymphoma studies. We recently got breakthrough designation in endometrial carcinoma or endometrial cancer. And we're going to continue to look at that asset in, you know, some of these indications over time. So you know, I think that's, you know, an exciting second asset for us. And then, you know, speaking more broadly, you know, we also have exposure to key partnered assets or programs from the legacy MorphoSys. You know, I think I'll call out a couple of those. For example, Bimagrumab, which is now housed within Lilly and being developed in Lilly for obesity. Ianalumab, sorry, in autoimmune indications. That's being studied in a number of different autoimmune indications at Novartis. Setrusumab, for example, at AstraZeneca. So there's you know, some assets with significant potential we're not spending anything on. It's pure upside where we get low to mid-single-digit royalty exposure. And, you know, these are interesting partnered assets from the perspective of potential downstream monetization opportunities as well, right? So, I think, you know, all in all, we've got some meaningful opportunities within MorphoSys. Excellent, excellent. And then, of course, since you're the CFO, quick financials question. A question that I can answer. This is, this is fantastic. So what's your current cash position, and have you made any disclosures on your current cash runway? Yeah. So, at Q2, we had around EUR 670 million of cash. I mean, clearly, we're reporting our Q3 very shortly. And our guided cash runway is cash into 2025. Okay, excellent. I mean, looks like we have a couple more minutes, so we can maybe jump back to Pelabresib if you, Yeah. I'm sure everyone would like that. So in terms of your phase II to phase III, can you go over any major design changes? I know it looks like you guys are potentially recruiting more, DIPSS Int-1 patients, so potentially milder patients. How do you expect that to change, SVR35 and then TSS50? And then... I guess we could just start with that. ... Yeah. I mean, maybe just quickly mentioning the rationale for doing that. So yes, we intentionally wanted to include these patients. It's as per the RUX label, so there was an update to the Jakafi label. And we believe, we wanted to include as many patients as possible. All the intermediate-1 patients that we include need to be symptomatic. Obviously, that was an important threshold for us. We have some data from the phase II study, they're in this JCO publication, for SVR 35. When you look at the forest plot, you see that the, I mean, confidence intervals are overlapping, so we don't have any indication that this should differ. We've not published these data for TSS 50, but there's a waterfall plot and when you sort of deduct from that, it's small N numbers, but then also you could see that the confidence intervals are overlapping. Again, all of that is based on small N numbers we will see in the phase III study. But, yeah, that's probably what we can say for now. Okay. Okay, excellent. And then in terms of the RUX titration, I know you guys have disclosed, you know, the phase II very broadly, in terms of, you know, the starting dose, it's either, 10 or 15 or potentially five, depending on your baseline platelet. And then at a certain point, you could titrate up. Is that the same case for phase III, to the extent directionally that you can comment? And then is there any sort of opportunities to kind of titrate RUX up even further in your phase III trial? I mean, again, broadly speaking, I think for us, it was important that RUX is used as closely to the label as possible because, I mean, that's the ultimate goal, right? To give physicians something that they can just add on to the therapy they know. And so, yeah. No, and it's broadly in line with what we did in the phase II study, meaning starting a bit lower, in the initial cycle, and then just as physicians know, based on platelet counts, dose up or down. Okay. Okay, excellent. I think, with that, any closing remarks you want to share with everyone? No, look, I mean, I'm. I'll just reiterate what I said at the beginning, incredibly excited to be at MorphoSys. I'm three months in. I think we've got a fantastic opportunity ahead of us, and, you know, watch this space. Excellent. Well, thank you so much for your time today. Thank you so much, everyone.