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spk01: Ladies and gentlemen, good afternoon or good morning. My name is Julia Neubauer, Head of Investor Relations at Mophosis, and it is my pleasure to welcome you to our third quarter 2023 financial and results conference call. With me on the call today are Jean-Paul Kress, our Chief Executive Officer, Tim DeMuth, our Chief Research and Development Officer, and Lucy Crabtree, our Chief Financial Officer. Before we begin, I'd like to remind you on slide two that some of the statements made during the call today are forward-looking statements, including statements regarding our expectations for the commercialization of our products and our development plans, and expectations for the compounds in our pipeline, as well as the development plans of our collaboration partners. These forward-looking statements are subject to a number of risk certainties that may cause our actual results to differ materially, including those described in Morphosis 20F and annual report, all for the year ended December 31st, 2022, and from time to time in other SEC documents of morphosis. It is important to keep in mind that our statement in this webcast speak as of today. On slide three, you find the agenda for today's call. Jean-Paul will begin with an overview and give an outlook. After that, Tim will share an update on our clinical development work, and then Lucy will provide a summary of our third quarter 2023 financial results. Following our prepared remarks, we will open the call for your questions. With that, I hand the call over to Jean-Paul.
spk11: Thank you, Julia. Good morning and good afternoon, everyone. Thanks for joining us today. We are very excited that the top-line results from our Phase III Manifest-II study of Pelabrasib in combination with Rixolitinib in first-line myelofibrosis will be available by the end of November. Shortly after, We will present detailed findings from the study at the 2023 ASH annual meeting during an oral presentation on Sunday, December 10th. Pelabrasib, our investigational best inhibitor, has the potential to meaningfully improve upon the current standard of care for myelofibrosis. Right now, we believe we have the best new molecule to treat this disease. Our phase two manifest study showed the strong efficacy and safety profile of Pelabrasib in myelofibrosis, with deep and durable improvements in spleen volume and symptom reduction at 24, 48, and 60 weeks. Further to this, in the manifest study, changes in biomarkers correlated with improvements in certain clinical measures of treatment success, suggesting a potential disease-modifying effect of Pelabrasid. These Phase II data underscore the strength of this combination therapy, and we remain very confident in the outcome of the Manifest-II study. Combination treatment is the highly anticipated next step to address the inadequate splint size reduction, symptom control, and lack of response durability observed with JAK inhibitors in myelofibrosis, the current standard of care. Our market research shows that the majority of US community and academic-based physicians view combination therapy as the way of the future in myelofibrosis. The Pelabrasib and Ruxolitinib combination therapy was ranked among the highest in top product attributes driving treatment decisions against Ruxolitinib, Momelotinib, and the Navitoclax and Ruxolitinib combination. These physicians commented on Pelabrasib's impressive efficacy and were pleased that the combination was well-tolerated and appeared to have a benefit for anemia. This reaffirms the excitement we continue to hear from physicians around Pelabrasib, reflecting the dire need for more effective and well-tolerated therapies to treat myelofibrosis. Moving to Monjuvi. Monjuvi, our CD19-targeting immunotherapy, continues to be prescribed to certain adult patients with relaxed or refractory DLBCL. In the third quarter, Monjuvi net sales were 23.4 million US dollars. This represents a 5% year-over-year growth and is on track with our 2023 guidance, allowing us to narrow our full-year 2023 guidance target. Beyond its currently approved indication, the largest potential upside for Montjuvi is in the first-line DLBCL setting, which we are investigating in our Phase III false-mine study. Data from that trial which randomized nearly 900 patients, are projected for the second half of 2025. Monjuvi is also being explored in the phase three in-mind study in relapsed refractory follicular lymphoma and marginal zone lymphoma, which is being run by our partner Insight. These data will be available in 2024. The strong U.S. commercial infrastructure we have in place for Monjuvie would also enable the smooth launch of Pelabracine, as we have encountered a large overlap in treating physicians for DLD-CL and myelofibrosis, especially in the community setting.
spk07: Beyond our pivotal programs, we are pleased with the progress of Tulmimetostat,
spk11: our investigational next-generation dual inhibitor of EZH2 and EZH1. In September 2023, the FDA granted fast-track designation for tulmimetostats for the treatment of patients with advanced, recurrent, or metastatic ARID1A-mutated endometrial cancer whose disease has progressed following at least one prior line of treatment. Continued exploration of this promising asset in our Phase I-II study across tumor types, now with an additional lower-dose cohort, will inform our future development plans. Our key partner programs, developed via our legacy antibody technology platform, are also progressing well, Ultragenyx and Mereo Biopharma recently announced interim phase 2 data demonstrating that Sestrusumab significantly reduced fracture rates in patients with osteogenesis imperfecta. Antof Therapeutics revealed that its phase 2 study of Abelacimab in patients with atrial fibrillation was stopped early due to overwhelming positive results, highly significant reductions in bleeding events versus standard of care. While not central to our business strategy, these programs offer potential upside and provide us with options for non-dilutive financing. I would now like to turn the call over to Tim to provide a development update. Tim, over to you.
spk09: Thank you, Jean-Paul. Good morning and good afternoon, everyone. We're eager to release top-line results from the Phase 3 Manifest-2 study as soon as they become available. These data will be released by the end of November. We will disclose these results via an ad hoc company press release, which will include the primary and key secondary endpoints, screen volume and symptom reduction at week 24, as well as a general statement on safety findings. Beyond SVR35 and TSS50, Manifest-2 is assessing several other important clinical endpoints, including absolute change and percent change in total symptom score, progression-free survival, overall survival, and duration of the splenic and total symptom score responses, among others. These endpoints reflect the challenges that patients with myelofibrosis encounter daily, helping us to better evaluate the efficacy and tolerability of the Pelabrasib and Raxolitinib combination. We remain confident that the comprehensive MANIFEST-2 data package will provide impactful insight now and over time into the potential benefits of this first-line therapy for patients with myelofibrosis. We are also very pleased that shortly after we release the Manifest-2 top-line results, we will have the opportunity to present the detailed findings from the study during an oral session at the 2023 ASH annual meeting on Sunday, December 10th. With ASH being the world's largest professional society, serving both clinicians and scientists focused on hematologic cancers, this is the perfect stage to present these highly anticipated pivotal trial results. Seven additional abstracts on Pelabrasib and tefacidamab were also accepted at ASH 2023. While our primary focus for Pelabrasib is in first-line myelofibrosis, we see strong additional opportunities for this investigational medicine beyond this indication. At the 2023 ASCO and IHA Annual Meeting, we presented positive results from Arm 4 of the Phase 2 Manifest Study, which is investigating Pelabrasib as a monotherapy in patients with high-risk essential thrombocytemia, also known as ET, whose disease is refractory or intolerant to hydroxyurea. These robust proof-of-concept results support Pallabrasib's expansion into other myeloid diseases. As such, we will continue our ongoing evaluation of Pallabrasib in ET in the manifest study. We will also initiate a phase two study in lower-risk myelodysplastic syndrome, also known as MDS, in 2024. Patients with MDS experience progressive anemia that can require regular blood transfusions or subcutaneous injections, often diminishing quality of life. Furthermore, patients have low long-term response rates to currently available treatments, reflecting a need for new therapeutic options. The outcomes of these assessments in ET and MDS will inform our Phase 3 development plan. With that, I will now turn the call over to Lucy.
spk05: Thank you, Tim, and good morning and good afternoon to everyone. We're pleased to share our financial results for the third quarter and first nine months of 2023. Monjuvi sales were $23.4 million in the third quarter of 2023 and $67.8 million for the first nine months of 2023, reflecting a year-over-year growth of 5% and 6% respectively, allowing us to narrow our revenue guidance for the full year 2023. We also recorded €1.2 million or $1.3 million in royalty revenue from Minjuvi sales outside of the US from our partner Insight in the third quarter of this year. Recall that the results of the second quarter of this year included a one-time effect coming from previously deferred revenues related to Insight's early access program in France. Total revenues in the third quarter of 2023 were 63.8 million euros compared to 95.8 million euros in the same period a year ago. The year-over-year decrease resulted primarily from lower revenues from licenses compared to the prior year. Recall that Q3 2022 benefited from the out-licensing agreements with HyBio. Total cost of sales was 15.1 million euros in the third quarter of 2023, compared to 8.1 million euros a year ago. Cost of sales specific to Monjuvi US product sales was 7.5 million euros in the third quarter of 2023, compared to 4.5 million euros in the third quarter for 2022. Turning to operating expenses. R&D expenses in the third quarter of 2023 decreased to 63.2 million euros compared to 77.8 million euros for the third quarter of 2022. Also, selling expenses decreased to 19.9 million euros in the third quarter of 2023 compared to 23.5 million euros for the same period in 2022. The year-over-year decline was driven by streamlining and focusing of selling efforts. G&A expenses in the third quarter of 2023 were €15 million, compared to €15.6 million in the third quarter of 2022. For the third quarter of 2023, we reported a consolidated net loss of €119.6 million, compared to a net loss of €122.9 million in the third quarter of 2022. Turning to our balance sheet, we ended the third quarter of 2023 with cash and investments of 642.2 million euros, compared to 907.2 million euros at the end of 2022. This provides us with a cash runway into 2025, which is more than 12 months beyond the pivotal readout for the collaborative. Turning to our guidance for 2023, On October 25th, we provided an updated financial guidance, narrowing the guidance for Monjuvi net product sales and now expecting it to be in the range of $85 to $95 million. Following the recognition of one-time write-offs for raw material used in the production of Monjuvi, we now expect gross margin for Monjuvi US net product sales to be approximately 75%. All other aspects of our guidance remain the same. With that, I'll now turn the call back over to Jean-Paul.
spk11: Before we open up the line for questions, I want to conclude with a few words. 2023 has been marked by exceptional progress at Morphosis. We have over-delivered on our key priorities and have a very strong cash position, allowing us to continue this great momentum in the final weeks of the year and beyond. Elabrasib represents an opportunity to meaningfully improve the standard of care for patients with myelofibrosis, a community in dire need of more effective and well-tolerated treatment options. We very much look forward to sharing the results of the manifesto study with you soon. With that, I'd like to open the call for questions. Operator, please open the line.
spk03: Ladies and gentlemen, at this time we will begin the question and answer session. Anyone who wishes to ask a question may press star followed by one on their touchstone telephone. If you wish to remove yourself from the question queue, you may press star followed by two. In the interest of time, please limit yourself to two questions only. If you're using speaker equipment today, please leave the handset before making your selections. Anyone who has a question may press star followed by one at this time. The first question comes from the line of Derek Archila with Wells Fargo. Please go ahead.
spk00: Hey, good morning, everyone, and thanks for taking the questions, and congrats on the progress here. So just two questions from us. I guess, you know, first, in the MANIFEST-2 trial, you know, it looks like you enrolled more patients with intermediate 1 myelofibrosis, you know, than you had kind of seen in cohorts. kind of get your thoughts on how that might impact the trial, you know, in terms of SVR35 and TSS50. And then also just second question, you know, just looking at, you know, some of these myelofibrosis trials, you know, it looks to us, you know, the mean change in TSS is highly variable across studies. This was most recently demonstrated with the Nevetoclax trial, but also with ruxolitinib. So, you know, what do you think is really the main driver of this, you know, variability? Thanks.
spk09: Hi, Derek. This is Tim. On the population in the manifest phase two study and potential differences on SVR and TSS50, when we look at the JCO manuscript, ARM3, we see very clearly that there is no difference in SVR response between the INT1 and the INT2 slash high population. confidence intervals are completely overlapping. The data for TSS50 has not been published. However, there is a waterfall plot in the JCO manuscript where you can derive numericals for patients with the respective risk categories. If you put then the confidence intervals around those, you will see that they are also completely overlapping while, yes, there may be small numerical differences. However, those are clearly related to the very small sample size. On the variability, as you call it, on mean change in TSS baseline parameters between different historical studies and one of the more recent ones, in our perspective, this is really within the natural fluctuation of baseline scores. And I would even say that In the most recent Phase III readouts that you're referring to, the 11-point change, absolute TSS change from baseline in the RAC solidness arm appears to be very well within the range of what one would expect from historical RACs control arms. If I put this together with the SVR response rates that was reported for that RACs arm which is exactly in the line of what one would have expected, we actually feel very, very confident in the fact that a Phase III is a very good replica of Phase II results.
spk07: Got it. Thank you very much. Look forward to the data. Thank you. The next question comes from the line of Shandeng with UBS.
spk03: Please go ahead.
spk08: Hey, thank you for taking my questions. Two, please, if I may. The first one is just wondering if you could confirm whether you have got the data in-house or not at this moment. And secondly, it's on TSS50, please. Just wondering, you know, what sort of efficacy do you think that you need to hit statistical significance? Just any color on your confidence on hitting TSF50, that would be great. Thank you very much.
spk09: This is Tim again. On the first question, do we have data in-house? The answer is very clearly no, we don't have data in-house. And as we mentioned in the prepared remarks, As soon as we have the data, it will be made available through that ad hoc press release, and we said the data would come by the end of November. Second question, confidence on TSS50 results. I would go back to what I mentioned previously. First of all, phase two in myelofibrosis, as we learned very recently, is very predictive of Phase III readouts with respect to SVR, with the recent Phase III hitting on the decimal point on SVR response for the treatment arm and the control arm. And as we just discussed on the Wells Fargo question, also TSS seems to be very well behaved on the RUX control arm vis-a-vis historical control, giving us confidence in our phase three readout. Additionally, just to reiterate what we said before, and you are very well aware of that, when morphosis took over the MANIFEST-2 study from Constellation, we increased the sample size from 310 to 400 patients. We over-enrolled to 431, and with that, we are very well set up for a what we anticipate a positive readout of the study. On the last question regarding powering, we said previously that we have not disclosed the powering assumptions. That's the 56% TSS response rate in manifest RM3 and a historical RUX performance within expectations. We do feel confident in our readout.
spk07: Thank you very much. Here. The next question comes from the line of Jason Butler with JMP.
spk03: Please go ahead.
spk02: Hi. Thanks for taking the questions, and let me add my congrats on the progress as well. Assuming positive results from Manifest 2, can you just walk us through the steps from that point to regulatory submissions Are there ancillary studies that need to be completed? And is there anything time-gating to submission? And then second question for me is just on reimbursement. Can you just talk about the work that you've done to prepare to get patient access for collaborative and any learnings or leverage from the Monjuvi experience? Thank you.
spk11: Hey, Jason. This is Jean-Paul. Thanks for your question. On the regulatory pathway, we are totally ready to roll the ball here. We've been having many interactions with the FDA and EMA as customary and as you can expect. We'll be ready to share the relevant data and the globality of the data. That's also what I wanted to insist on. Beyond the two endpoints we mentioned, we have many other data sets that we will share with the regulators because it's our experience and our observation that the agencies have evolved and have been evolving lately with, you know, the way to apprehend this disease as we've seen, for example, with Momelotinib. So, the totality of the data is also something very important. We've been mentioning that and we have a rich set of data. I would, for example, quote the anemia data, which, as you know, are very impressive in our phase two, and we anticipate that in our phase three we will also have a very good score on that one. And this is very important to put in the package. So we will be ready to file swiftly with the totality of the data and the rich set of data we are preparing. We already have and will have with the phase three. both on the efficacy and the safety side. Now on the reimbursement aspect, well, it's all based on the data. It's a value-based approach. With what we know from Phase 2 already, we know that we have, we're building value here for the patients, and that's what is recognized by the payers. We will be leveraging that in our discussions later on with the with the payers in the U.S. and ex-U.S., and we believe that with incremental, significantly incremental value brought by the product for the patients on many aspects we've been discussing several times, we can sustain a strong reimbursement and pricing commensurate of the innovation we bring in here.
spk07: Great. Thank you. We're excited to see the data.
spk03: We are too. Thanks. The next question comes from James Gordon with JP Morgan. Please go ahead.
spk10: Hello, James Gordon, JP Morgan. Thanks for taking the questions. Firstly, in the release last night, you suggested you saw the potential to meaningfully improve upon current first-line treatments. Can you just confirm that there is confidence in a Statsig benefit on both the SVR35 primary and TSS50 secondary? Second question was looking at the scheduling for the Manifest 2 data, Ash, had the organisers seen any element of the study result or were they totally blinded? And had you hoped for a more prominent session versus the Sunday session, like a presidential session or anything like that? And then third and final, just on funding, assuming Manifest 2 does deliver, and hopefully it does, how are you thinking about next funding steps for the company? So would you partner in some geographies or you'd raise equity? what would you do to fund some of the things you were laying out in the presentation?
spk07: Hey, James. This is Tim again.
spk09: So the study has the primary endpoint of screen volume reduction. And as secondary endpoints, we're looking at the improvement in symptomatology. And of course, they are connected to a p-value. On the question of the ASH manuscript, or the ASH abstract rather, we submitted the abstract as it appeared just very recently, so without data, which is highly unusual for ASH, as you know, to accept a data-free abstract. And for that, we are very, very pleased to have gotten a oral presentation And what counts for us is the opportunity to be able to share this data in an oral format with the scientific community. And again, we're really pleased to have gotten that opportunity from ASH.
spk11: On the partnering and financing question, James, so the great thing we still have received, and this is why we were so keen on acquiring Constellation at the time, 2021 is that it's not tied to any previous partnership that the company actually was thinking doing. So we have the whole slate. That being said, after the data, we will think about what kind of deployment we want. We are already in the U.S. The intention is to commercialize ourselves in the U.S. We have an experience among the organization with a very strong overlap with the myelofibrosis treaters. So this is very important, very different situation than when we launched Monjuvi four years ago. So we'll see. But, you know, you can always imagine non-dilutive possibilities for partnering XUS or this kind of thing. So more to come on that. It will be a great problem to have when we have the data. Then the financing, I'll pass on to Lucie.
spk05: Yeah. Hi, James. Of course, the priority is to ensure we continue to retain a strong balance sheet in the future. You know, that in turn, obviously, is important to make sure we continue to deliver value. And as you might expect, you know, we'll continue to weigh up all appropriate funding options available to us and we'll update as and when we can.
spk03: As a reminder, if you wish to register for a question, please press star followed by one. The next question comes from the line of Pippa Prichard with Morgan Stanley. Please go ahead.
spk04: Hi there. Thank you for taking my questions. Just a couple from me, please. So, firstly, on the Manifest 2 endpoints, you mentioned that there are other endpoints such as Absolute TSS, PSS, et cetera, that would be important to look at alongside TSS50 and SPR35. And I know that it's been mentioned before that the totality, breadth, and depth of data are important to look at and consider amongst other things. But the impression so far has been that a stat-sig TSS50 benefit needs to be seen for approval. So could you please expand on and remind us how flexible you believe regulatory authorities may be in the event that TSS50 may not be that sigged? Secondly, just a question related to slide number seven, where you mentioned that 13% of US physicians were hesitant to utilize Pella. Did they give any reason as to why they were hesitant? Was it cost? Was it efficacy? If you could give some color on that. And then a final one to squeeze in, just related to the question before on partnering. If you could let us know what you would look for in an ideal partner, should you choose the partner, that would be very useful. Thank you.
spk11: Hey, Pippa, thanks for the questions. So on the first one, on the evolving landscape of myelofibrosis, including for the regular years, you know, it all starts with this very high unmet medical need with the same current standard of care for decades now and the appetite for new options. And again, as we've said several times, and we hear consistency, the combination in first line is number one. opportunity to improve the standard of care here. That's very important for all stakeholders, including the regulators and the agencies. And based on our ongoing interactions, our experience, the recent approvals we've observed, even with mixed clinical trial results, this tells us that regulators will look at the totality of the data, inclusive of efficacy and safety results. Very important to keep in mind. Now on the market research question and the physician feedback, we had a couple of those market research along the way since we acquired Constellation. And the great thing is that it has really, really evolved from two or three years ago when there was the novelty factor about combination. People were still a bit, you know, wondering how they would do that first line. And now we have an overwhelming... number of physicians, more than 80%, both in community hematology and academic setting, who are ready for the combination first line, which is great, and show how we have been imprinting the space with our engagement based on our phase two data. Your last question on partnering, again, here. When you partner, you let value go. so you have to be very cautious here. You know, I mean, we have the whole slate right now, so it's a great position to be in. Then we will know more later. And, again, if partnering would come into discussion, I mean, this is probably more for ex-U.S. because we believe that we have what we need in the U.S. But, you know, we'll keep you posted on this one.
spk04: Great. Thank you.
spk03: Thanks. The next question comes from the line of Manos Mastorakis with Deutsche Bank. Please go ahead.
spk06: Thank you very much. Just quickly wanted to clarify, if you could give a bit more color actually, how important you think it is to show both SVR35 and TSS50? So would an extremely positive outcome on one endpoint mitigate lower efficacy outcome on the other endpoint? and also a commercial one. So given the synergies in the sales force with Monjuvi and Pellebrev Sib, in a scenario of ideal positive results, would you expect to see further investment into the sales force? And thus, could we make an argument that Monjuvi sales could potentially benefit as a result? Thank you.
spk09: Hey, Manuel. This is Tim. As Chapal stated, Based on the discussions with regulators, the assumption is SBR35 and symptom improvement are important points that we'll look at. Ongoing interactions and experience from recent approvals in the myelofibrosis space with mixed results certainly tell us that regulators really appreciate the unmet needs in this patient population, and that's what they're responding to. In addition to spleen volume and symptomatology, we are also looking in the study at the changes, absolute as well as percent change in symptom score. We're looking at PFS, overall survival, and as I mentioned in the prepared remarks, duration of spleen and symptom response And we are confident that the comprehensive data sets that we will be able to share at the time will really demonstrate and underscore the potential of the combination therapy to regulators.
spk11: On your question, too, regarding cell-source synergies, as mentioned, there is a very high overlap between the treaters, more than 80 percent, especially in the community hematology side. We would most likely need to do some incremental investments to have the right share of voice and, you know, be just at the level of the opportunity here. But we're not going to start from scratch. It's qualitative and quantitative, qualitatively because we already know the targets and we have the relationships and the engagements well oiled. and also quantitative because it's not going to be a full buildup which would require more OPEX. You asked about the Montjuvi benefit. Well, for sure it's positive because you will have our reps out there and our medical affairs people having two products, which means the franchise, which means more commitment towards hematology and with these two products on the market who would definitely be as a leader, which is your choice.
spk07: Ladies and gentlemen, there was the last question.
spk03: I am back to you, Illinois Gebauer, for closing comments.
spk01: Ladies and gentlemen, this concludes today's conference call. If any of you would like to follow up, Morphosis Investor Relations team is available for the remainder of the day. Once again, thank you for joining. Have a great day and goodbye.
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