Good day, and welcome to the Molecular Partners call and webcast. At this time, all participants are on listen-only mode. After the speaker's presentation, there'll be a question- and- answer session. To ask a question, please press star one one. If your question hasn't been answered and you'd like to remove yourself from the queue, please press star one one again. As a reminder, this call may be recorded. I would now like to turn the call over to Seth Lewis, Head of Investor Relations and Strategy. Please go ahead. Thank you, and welcome to today's call. My name is Seth Lewis, Head of Investor Relations and Strategy, and this morning, we're following up on the data presented this weekend at the Theranostics World Conference in South Africa for MP0712, our DLL3 targeting radiotherapeutic. This data reflects clinical imaging and dosimetry data that was conducted as part of a named patient access program under the Legal Framework for Compassionate Care in South Africa, also referred to as Section 21 of the Medicines and Related Substances Act. This was done under the supervision of Dr. Mike Sathekge, Professor and Head of Nuclear Medicine at University of Pretoria and Steve Biko Academic Hospital, and President and CEO of Nuclear Medicine Research Infrastructure, or NuMeRI. We will start today's call with several prepared slides and then open up for question- and- answer session. Please be reminded that management will be making certain forward-looking statements throughout the call. We're joined today by Patrick Amstutz, CEO; Michael Stumpp, Executive Vice President of Projects; Philippe Legenne, Chief Medical Officer; and Professor Ken Herrmann. Ken currently acts as Chair of the Department of Nuclear Medicine at University of Essen in Germany, Chair of EANM Oncology and Theranostics Committee, and serves as Section Editor of the Journal of Nuclear Medicine, and serves as the Chairman of the Scientific Advisory Board here at Molecular Partners. At this time, I will turn the call over to Patrick Amstutz. Please go ahead. Thanks, Seth, for the kind intro, and from my end, a special thanks to Ken for joining this call and giving a medical perspective on our data. I also do want to thank Mike Sathekge for his work. He's not on our slide. He cannot be with us today as he has his conference still ongoing and many commitments. But I also want to thank and congratulate Komal from his team, because with the work and some of the data presented today, she and her team won the poster prize in South Africa. We decided to do this conference call as the conference is not readily and easily available for everyone. So we are using this call to make sure that our shareholders, but also other interested, interested parties, can look at the data, share data, and that we can discuss it after we have presented the few slides to come. I'm going to the next slide, number four, and this is a short recap, what we're talking about. We're talking about radiotherapy, and in radiotherapy, we, Molecular Partners, are working on a vector. We also engineer half-life, and our partners, Orano Med, bring the isotope. It's a true collaboration, a 50/50 collaboration, and we carry out research and development together. Most importantly, Orano Med is a leading company in the lead space, so we at Molecular Partners invest on the vector side and on the product side, while we can rely on Orano Med for everything to do with lead. I'm moving on to slide number five, as we sometimes get the questions, "Why are you going with radio into small cell lung cancer and DLL3?" I think that the answer is that at this point in time, yes, DLL3 is a validated target with T-cell engagers, and there are antibody drug conjugates. At the same time, we do see a clear need for radiotherapy, given that neither T-cell engagers or ADCs will cure cancer in these patients. The T-cell engagers have a good profile, but they do maybe lack the broad response rate of an ADC. They come with side effects, as we know, as we also develop T-cell engagers, and at the same time, they have a very good response duration. Antibody drug conjugates are, at the same time, have a higher response rate. This can work well in many patients. At the same moment, due to the chemo resistance, that the response duration is often limited. Given those two good options, we think there is the need for an additional one that works on DLL3, and I will come to the targets and the specific trick that we need to apply there, and has less, let's call it, resistance, and at the same time, works well in this disease, given that small cell lung cancer is known to be radio sensitive. So we believe all three options will be used, can be used in concert and possibly even in combination. So let's just quickly go into the next slide and explaining a specific trick we use for targeting DLL3. One point we had to understand, and we were a bit anxious in the beginning, was: how can we target DLL3 with this very low copy number? As experts on the call, you will all know that the other target that is most known is PSMA, is characterized by high copy numbers. We're talking more than 100 x more copies per cell. This is what we had to tackle. The trick was to add half-life to our targeting agent, the DARPin, targeting DLL3, as internalization and falling off and replenishment, the apparent copy number of DLL3 is much higher. One cycle only, so full internalization takes less than 30 minutes. Within 24 hours, we actually see almost the same number of copies of DLL3 as you would see on a PSMA high copy number, cell line or tumor. Given this trick, it was possible to reach in preclinical models, very high, tumor, accumulation in test animals. Today, we can then also show you that this is true for humans, and that will be part of this webcast. Here, I will take the opportunity to move to the next slide, seven, and I see here that we have the imaging part. We do first imaging with Lead-203, that can be followed by treatment with Lead-212. The 203 imaging we have now done, and we will present the patient data in South Africa. Here I would hand over to Michael to lead us through the data. Thanks, Michael. Thanks, Patrick. Also, welcome from my side. I'm together here with my colleague, Philippe, in actually South Africa, and we attended over the last four days, with a fantastic conference in a very nice country, great guests, great friends, and of course, also meeting Mike and the whole team. So really happy to be on the call and report back. So as Patrick said, we are in the process of summarizing the data for you all, so please feel free to ask questions, we, we should have time. So what we wanted to do first, and this goes back almost a year, is to assess how patients in South Africa, under the special S 21 regulation, show what our drug is doing. And as you all know, the phase I is ongoing as we speak in the U.S. So what you can see on slide seven is both the imaging, but then also later, the treatment part, and we will today focus on the imaging side. Let's move to slide eight. This is a slide you likely have seen before. This is a patient who is characterized by metastatic small cell lung cancer. So likely the best surrogate or the best picture for patients we will recruit also in the United States. Allow me to start quickly. On the right side of the picture, you have both the colorful overlay of the SPECT and the CT, as well as then the gray part, which is the maximum intensity projection. What you see highlighted by the blue arrows are the four liver metastases, and they were actually unknown at the time of diagnosis. So the patient could be upstaged and probably then treated with slightly more precision. The primary lesion is indicated by the red arrow. That's part of the mediastinum, so part of the lung. Yeah. As all other patients, we dosed with 185 megabecquerels of Lead-203. That's the standard dose, just to be able to do the imaging. You see a time course. At four hours, you see most of all the heart, that's part of the design. You see some of the larger blood vessels that then gradually disappear over the first 24 hours, and the lesions appear more and more. Of note, and I think this is what, what sort of was most gratifying, neither the liver nor the kidneys are lighting up strongly, especially if you focus over time. You will also see this in the next slide. Then we have more patients. They basically all derive the same insight on the healthy organ side. With this, I would move to slide 9. What is shown in slide nine is now a time-resolved summary of all the time points from that patient. On top in the dashed line, you see the tumor lesions, blue highlight the liver lesions or the metastases. They are characterized by a higher specific uptake, so the activity is given in% per gram, so it's like a concentration. The tumor, the primary tumor, is shown in red dashed line. And watch all the healthy organs, they basically all start a washout around about 24 hours, and that's where the tumors then also get more and more visible. And the protein, as Patrick just said before, the DARPin is accumulating, probably driven by internalization and retention. So in summary, we have continued uptake during the imaging period. We have higher uptake in the liver metastases, and we have washed out from healthy organs, all nicely visible here. That's why we are there to say it's a good profile; let's go to phase I. Moving on to slide 10. This is now just the maximum intensity projections of two more patients. So the patient we just looked at together is the one on the very left; now the red arrow is again shown here. The second patient in the middle is a small cell lung cancer patient without metastasis. So the three arrows indicate all the primary tumor, which was not so easy to resolve because it's close to the area where the heart is. And the third one is actually a bladder cancer, metastatic urothelial cancer patient, and the two arrows highlight the two metastases that were found in the, basically, lower pelvic. What you also see, bottom left, is then the SUVs, and this is important because it gives you a feeling of the, the contrast or the intensity of the lesion over the background organ. Typically, in fact, you go with SUV mean, this is a technical reason, so you're averaging the whole area. You could also calculate an SUV max. The numbers are given, so the numbers are very, very high, but SUV mean is in a range where we absolutely want it to be. Round about, say, eight-10 is probably the therapeutically relevant range.... If you look on the top right, you have both the mediastinal lesions and the metastatic lesions, even over the whole time course, every patient was imaged at multiple time points, and then the whole image analysis quantification was undertaken by our collaborators at, Radboud. They're really a state-of-the-art provider for doing this relatively complicated mathematics, and of course, guided also by the, the team in South Africa. All the lesions go up, as we said, so they quickly go up, and then they keep going up, but what is especially important, they quickly go up within the first 24 hours. So we have progressive uptake, reaching probably about 80% in the first 24 hours. There is strong tumor retention. We basically don't see decline in most lesions, and that's exactly what we're now going to look at again in the phase I. We also will do imaging, and then we will, of course, start the treatment. Most likely, all of the U.S. patients will be heavily treated in their former malignancies. Good. Moving on to slide 11. Where are we on the healthy organs? That's, I think, the main value of dosimetry. We can quantify of all the patients, the healthy organs. We picked two of them, the kidneys and the red marrow, because those are, that's what we knew from animals, the most likely, potentially dose-limiting organs. If you watch the two graphs on the left, I think what is really noteworthy, all the curves give us the same message. They go up for the first maybe 24 hours, and then start to go down with a very nice, close clustering. So there is no difficulty to read this. Same for the red marrow. Of course, there are some differences, but the message is the same. They go up quickly, and then they go down. When you take now all this information and transform this into absorbed doses, you can arrive with the following graphs on the right. So we've given for the initial clinical phase I dose, the 1 × 75 megabecquerels, the absorbed doses in gray of Lead-212 for both the kidney and the red marrow, and this is well within the EBRT limits. EBRT limits were, of course, established for external beams. We probably are not correctly sort of reflecting this with the alpha emitters, but it's a good guidance, and FDA also agreed with us that this is the appropriate starting dose. Once you dose repeatedly, of course, these numbers will go up, but we are confident that the red marrow, as we know from animals, will recover, and we can continue to dose, potentially also exceeding the EBRT limits. If you focus on the rightmost graph, this is for the highest starting dose we are intending to give 200 megabecquerel. Kidneys are still well below the 23 gray limit. The red marrow is within the range, but we are also approaching the two grays, so therefore, we will watch very carefully the hematological recovery. Very good. Brings me to the phase I design. This is also a slide you may have seen before, so we are dose escalate in small cell lung cancer patients simply because they have a well-known and high uniform DLL3 expression, so we can quickly accrue and dose escalate from 75 to 100, 550, and potentially 200 megabecquerels. All the details are given before we then open the non-, the neuroendocrine cancer patients here, indicated in green. And that should lead us to a recommended phase II dose, more or less in one year from now, which should allow then Philippe's team to do a phase II dose expansion box. Good. Ken, take us away. So next slide, slide 13. So thank you very much. So my name is Ken, I'm a med physician based in Essen, Germany. Looking at the first-in-human biodistribution is always a very important, yeah, very important step. There is a moment when you want to decide more or less to, as a bird, by moving forward with the clinic or not. The overall headline of my slide only, it takes away everything, all boxes are checked, and I will explain you why I think like that. So first of all, human biodistribution is very favorable. We see very little background uptake. We see a little bit uptake in physiological organs, like, for example, in the kidneys, and in the liver. I'm going to discuss a bit more about it, how this evolves over time. But overall, nice, crisp uptake in the tumor. Don't forget, these are SPECT images. These are not PET images. They are by definition, a little more, less crisp than, for example, PET images, but overall, this looks, I think, very exciting. The second thing is, the tumor uptake we see is also visible at very late imaging time points. Depending on the patient and on the scans shown, you can see this goes up to 120, 168 hours. So really five to seven days of residual strong tumor uptake. This is really nice because this only means that we will get a significant good dose in the tumor, which is also important as when we look at the normal organs, actually, the other way around, they seem to wash out. They seem to wash out over time, which means that when you look at the area under the curve, this separation between the dose and the normal organs and the dose and the tumor, is, this, separation is getting bigger over time. So this is absolutely favorable. Then, Mike already quickly talked about the normal organ doses, and I think it's very important to mention the limits come initially from EBRT. We are now actually extrapolating from imaging into therapy. Nevertheless, if you take all these into account, it's absolutely safe to start with the starting dose, and we have a very high likelihood that we won't see any significant toxicity, even with the highest starting activity. And then again, we of course have to monitor, especially when we talk about the bone marrow. It's very easy to monitor the real response of the healthy organs, because there we can very easily monitor, for example, the thrombocytes. So in the end, I think all boxes are checked to really now go into the, I think, really exciting part, to go now into therapy and perform the therapeutic trial. But long story short is, I think the data package, the things we have seen from the great group from Mike Sathekge in South Africa, is absolutely encouraging to move with the therapeutic product into humans as soon as possible. Thank you. Thanks, Ken, and I appreciate that you'll stick around and join us during Q&A as well. I'll turn to the next slide now and hand back to Patrick, I believe. Yeah, thanks. Uh, thanks, Seth, and thanks, Ken. And I do want to point out, before I come to the conclusion, that this is very unique to radio, and theranostic approaches, that you can get data, as we just looked at, before you actually go into a phase I, before you have the big investments, you know, where you're starting from. And I think that is unique to this field and is one, big excitement here, but also good for investors as we can, before we choose to invest into a full phase I, two, we know where we are, and we can stop early. A very important thing and ability that this field allows, and we can capitalize on at Molecular Partners. So maybe I'll just conclude and call it simple terms. First, we see nice tumor uptake, and also that was a question. We see fast, rapid tumor uptake, which is important for lead, as lead will be active in the first 48 hours. We see a good biodistribution in healthy organs, so low, and as Ken pointed out, the bone marrow is the part we need to monitor most, and the good thing is we can monitor bone marrow well. And that's why we are allowed by FDA to go to the EBRT limit at the 200 megabecquerel dose, and then see how far we get. Hopefully, several doses in reasonable time. Reasonable would be dosing every four-six weeks. And I think, as we said, we can start at a reasonably high starting dose. Maybe Ken can also share a bit, in the Q&A, how he sees small cell lung cancer, as we do expect that this tumor to be rather radiosensitive and something where we could expect initial activity in the first two doses already. Brings me to the outlook. The phase I/II is open. We are ready for screening. I think first patients are identified and should enter screening literally in the coming weeks. We will update on safety in H1. As you heard, the blood parameter is an easy one to screen for, so we will give an update and hope to have activity as of Q2, Q3, Q4. So second half of the year, we want to show on activity. Response rate will obviously have to wait until we have those, the meaningful number of patients on the right level, and that will likely be more very late in 2026, early 2027. Before I come to the outlook and conclusions of the full pipeline, I do want to draw your attention for an opportunity that we learned about in this program. I mean, we were optimizing, obviously, for the lead window. I'm on slide 15, but as also Ken and Michael pointed out, the tumor retention is remarkable. We see very good tumor uptake and retention over many, many days, almost no dropping versus the clearance in the healthy organs over time. And this allows us to see also an actinium profile in such an approach. Given that we are a vector play, meaning we don't own and build lead or actinium facilities and distribution lines, we are agnostic. So in future projects, we can actually go forward, test both in parallel, and then with possibly even clinical data, decide with which isotope is the more favorable one for a specific DARPin. Keep in mind, it's always a multitude of factors. It's the target, internalization, biodistribution, it is the disease, and it is the vector and the half-life. We can tune all of this to come up with the ideal candidate. That brings me to the pipeline. Just recap, this year is all about seven-twelve, so we will, this is what we are driving. We're driving forward for patients, but also for shareholder value. 726, our ovarian program, will be progressing towards first-in-human. And then the other, and we have four boxes here, which depict four internal activities, and it's a bit schematic, so don't take us at our word. But you see some, you choose the isotope upfront, others, you keep open and choose later. This is more schematic at this point in time, but what should change is that mid-year, we do want to nominate one or two of these programs for future development and share the target and the plan. So a very exciting year ahead, focus on MP0712 and more to come. With that, I turn to maybe the most important slide, the acknowledgments. I do want to thank our entire team at Molecular Partners. Many, many hands have helped to get this molecule where it is. Very exciting moment. I want to thank our helpers and team. I call them our team at Orano Med, because without them, this would have not been possible. I also include Julien Torgue, who has left Orano Med, but he will definitely always earn a, an acknowledgment on this slide. Then the NuMeRI team, Mike, his team, for the very strong support, and I heard from my team that that collaboration is going well, and we want to build on it also in the future. I do thank Ken for joining us here and stepping in and also then taking questions. And my last thanks goes, obviously, to the patients and their families, especially in this trial. It was not always easy to be part of, and so big thanks to everyone who made this possible. With that, I thank you all for your attention, and we open for questions. Thank you. As a reminder, to ask a question, please press star one, one. Our first question comes from Jonathan Chang with Leerink Partners. Your line is open. Hi, this is Albert Agustinus on for Jonathan Chang. Congratulations on the data. My question is regarding the future safety data. I don't know if I missed this, but since red marrow and kidney are potential dosimetry organs, are there any adverse events that you're monitoring in this phase I study based on these organs, or that we should pay attention to for your next update? Mike or Philippe? I think the question is how we are monitoring the organs- Yes. of the interest. I wouldn't even yet say concern. I do think obviously, blood and bone marrow is number one. We're often getting a question, what is the dosimetry? Now we can share it. It is not so high, but it's still something we need to monitor. So maybe Philippe, just a quick word from your side, how we are monitoring the safety, especially on the red marrow. So red marrow is one of the, if I could say, standard organs that we monitor in clinical trials. We will do weekly, you know, a blood draw to make sure that lymphocyte, ANC, and white blood cells, you know, stay as they should be. We expect, in fact, it's a sign that the drug is doing something, that at some point we would see a drop. We anticipate that it will recover within two weeks, three weeks, and that patients can be redosed. So there's no specific concerns about this, and it's one of the most monitorable, if I may say, organs that there is. So, this is not, you know, from an investigator standpoint, this is not the most complicated one to monitor. And let's also remember that in the world of small cell lung cancer and other neuroendocrine tumors, the treaters are used to work with, you know, drugs that reduce bone marrow, and are used to see them recover. So, this is not, you know, something which is not unexpected and something that is, you know, creating a bit of anxiety for the moment. Does that address the question? Yes. Thank you very much. Thank you. Our next question comes from Charles Zhu with LifeSci Capital. Your line is open. Hello, everyone. Congratulations on this update, and thanks for taking our questions. First, I'll start off with a comment. I really appreciate, in context of your biodistribution data, the mention or the openness of looking at Actinium-225. I am curious, though, with respect to the Lead-212, MP-0712, and can you comment on the on the radioactivity delivered window that you would expect to see? I'm looking at, for example, on slide nine, at 24 hours, the tumors seem to have, through 24 hours, you know, like, only somewhat higher uptake relative to some of the healthy tissues. I call out 24 hours specifically because that's where lead unleashes 80% of its activity. So kind of wanted to get your sense there. Thank you. Michael, or should I take it? I, I think it's a very fair question, and I'll hand over to Michael and then maybe do some, some remarks afterwards. Yes, thanks, Charles. Excellent question. Absolutely, and that's why we also want to show the data and be fully transparent. What is not easy to learn from dosimetry is how the tissue will react, so the famous radiosensitivity. I personally believe the tumor cells, you know, small cell lung cancer, are dividing rapidly. With that, area under the curve in the first 24 or even 48 hours, they will probably find it difficult to survive because, you know, the alpha decay produces double-strand DNA break, whereas healthy organs who are not dividing rapidly are probably fine. So I think it's a good sign that eventually the tumor curves go above the healthy values. Hopefully, for our future programs, we can even increase that window. Back to you, Patrick. Yeah, no, and I think, Charles, you make a good point, and there, there's even an internal betting, what isotope would have been or is better. So I think the fair answer is we don't know. And we gave lead a very good chance, given the high energy we can deposit. And if you look at, at the dosimetry and the healthy organs, we can give a very good amount, so we will give a lethal amount to these tumors. Having said that, if you would just take a very simple tumor to healthy organ equation, obviously actinium looks favorable on that dimension, not meaning that that will lead to a better outcome for patients. So the mathematics are clear, they, they would place on actinium, but if you like the lead profile, lead has a good chance to work on this one, as does actinium. Maybe I'll hand over to Ken, as he has sort of seen most and also knows both. I don't think it's an either/or here, it would be much more an end. ... No, I absolutely agree it's important as a, for any program to stay radionuclide agnostic, right? So, and then be open. I really think here, it's very smart to start off with lead because of the short half-life. However, if, for example, we see the potential therapeutic index is not significant enough, because to the points, Charles, you correctly alluded, it's always an option to switch to actinium. Right now, I wouldn't be surprised if we see pretty good responses based on lead and the first two, three half-lives. But in the end, this is exactly why I said it's super important now not to spend much more time imaging, but really now going into the treatment and look for the real toxicity profile, which, again, kidney and bone marrow is absolutely standard, so it's nothing really outside of what we would expect. And then the second thing is look how do we see responses? Because we should not over-interpret too much dosimetry, to be fully honest. Yeah, so. Thanks, Ken. And maybe just one comment, because not everybody has looked at the, the patient data. And, you know, at the 24 hours when we had one patient, we often got the question, how much is actually already on the tumor? And I think given the data we showed today, most, so 80%-ish, has reached the tumor at 24 hours. So we do think we have a, a very good profile there. Thanks, Charles. Thank you. Thank you. Our next question comes from Chiara Montironi with Van Lanschot Kempen. Your line is open. Hello, team. Thanks for taking my question. Congratulations with the update and good questions, everyone. So I just wanted to follow up a bit more on the safety. Can you basically remind us how many doses will the patient undergo, and which strategies can be implemented to monitor the hematological recovery to avoid bone marrow toxicity? I think that goes to Philippe or Michael. No, I'm happy to take that again. So we'll watch many organs, by the way, you know, but we'll watch first, you know, hemotox risk. And again, they are weekly, you know, measurements. Patients will have blood draws every week, will be followed every week during the course of the treatment. So we will be able to really monitor what's the, you know, what's the time to formula reduction, if any, and what's the time to recovery. So with that, on that one, again, we are pretty on top of it. It's standard practice, so we should be able to do that. Your first question was about many—how many cycles? And by the standard is what we are planning for is four cycles. We could, you know, based on risk, on benefit risk, we could go up to six. But But standard, what we are targeting are four for the moment. And yeah. And again, what we also anticipate is that we want to see effect, you know, after the second at some point, when we get into the higher, you know, the higher dose or the most effective dose. Thanks, Philippe. Yeah, clear. And, if I, if I may, another question, any take on the fact that the uptake is higher on the, liver mets versus the primary tumor? Happy to give a first step, hand over to experts, maybe Ken. For us, we saw that, and then we were a bit surprised, and then we went back to our ad board and the experts, and they confirmed that they have seen exactly the same with other modalities in small cell lung cancer. So it seems that the metastasis take up more radioactivity on such vectors. This has been described, there's publications, I'm sure Michael can point us to the right ones, but that actually the metastasis are better in uptake of this radioactivity and vector. Having said that, in the U.S., we expect actually much more metastasis, and all patients will be of that profile. We will have very seldom a single tumor without metastasis. Maybe Michael, a word from you. Thanks, Patrick. Happy also to hear them from Ken. So I think all of us have seen these amazing pictures from prostate cancer patients. You have hundreds or even more micrometastasis. With SPECT, we only see lesions that have a certain size, probably around about a centimeter. And you can easily imagine that they are sort of fresh or younger tissue. The primary tumor is somewhat older, there may be necrosis. Then how about vascularization? How about the DLL3 expression? All of that, of course, are unknown, and ideally, for an alpha emitter, you kill within the vicinity of where your drug is, so probably that's the better profile, a heavily metastasized patient, high density of radioactivity on the lesion. Ken, anything from you? No, I think it's super important. This is SPECT, right? This is SPECT imaging. SPECT is much more specific, equals less sensitive than PET. You should not compare this one to one with what you have seen for prostate cancer. With prostate cancer, you always see PET scans. When you want to compare this, you need to compare this with a good old Octreoscan in the times of meta one. To be honest, what we see here is really hot uptake. It's really intense uptake, number one. Number two is I also suspect a significant size difference between the mediastinal lesion and the liver lesion. Again, what we see here is actually a maximum intensity projection, most likely, or maybe only a whole body scan. So this is not very granular. So I think right now, the key message is we see intense uptake in both the primary tumor as well as in the liver mets. Anyway, if the liver mets really would be higher than the rest, I wouldn't even mind, because these are usually the ones which kill the patient. But I wouldn't be surprised if this is predominantly just a size volume relationship. Super clear. Thanks, everyone. Thanks, Ken. Thanks, Chiara. Thank you. Our next question comes from Bill Maughan with Clear Street. Your line is open. Hey, good morning, and thank you. So early in the presentation, you mentioned other DLL3 targeting modalities. So, given, you know, the updated data, where do you think is the most likely place, either in sequence or combination, that your product will slot into the treatment paradigm? And second question is on the dose escalation. Now, with what you know about dosimetry, when do you expect to start seeing efficacy signals, and where do you really expect for your prime therapeutic window to be? Thank you. Thanks. I will take the first one, and I think the first answer is, obviously, we are moving this program forward in the U.S., so this will be a, call it, last line, second/third-line treatment. We will have patients that have seen other DLL3 agents, likely tarlatamab as the approved drug. Luckily, there is reports that it's not DLL3 loss that leads to resistance there, so we think we will have activity. And that line is sort of your fast to market, given the remaining high medical need in that population. So I think in that sense, I think we will for design test post tarlatamab. Now, there's two points I want to make. First, as you heard, these are likely four cycles of treatment, and doctors like that because four cycles, four months, and you're done, done. So this, they can also put in between cycles or lines because it's more an intervention. So we have spoken to doctors. They very much like that, that maybe after a first line, they can use this before going somewhere else. That's one point. And the other is, one of my hopes is that this can then go in a combination, especially with IO, IO being either a PD-1 and/or a T-cell engager. That's where I think the biological logic is highest, because with an alpha-like lead, you create a lot of inflammation, a lot of damage to the tumor, and you create an inflammation, and it's a very hot tumor after that, where a PD-1 and/or a T-cell engager would profit from. So I really think first line combo is ideal from the mode of action, while we will have to test last line for a fast to market. In between, you have the opportunity to go to other indications next to small cell lung cancer. I guess I'll hand over the other question, too. Now, we're not in the same room, so I'll leave that open, who can take the second part? Yes. Philippe. So I can, I can start, and thanks, Bill, for, for both questions. Excellent question. That's, of course, what we all and the team are working on. In terms of when exactly to expect the fuel response, of course, we will do the experiment, we will learn. What I can sort of give, give to you is my personal impression. So we have, of course, done a number of mouse experiments. These cell lines respond extremely well. We have discussed with the FDA. We are really happy with the 75 megabecquerel starting dose. So just based on allometric scaling, we are exactly there, where the mice respond very well. We are even above where mice start to respond. And then, of course, it depends on the sensitivity of this particular cell line in this patient. We hear this also at the current conference from experts. Small cell lung cancer is expected to be radiosensitive. As we said before, we should see something, hopefully in the second dose cohort, round about 100 megabecquerel per cycle. Then, of course, the jury is out. Not every patient will respond, that's also clear. Its oncology is heterogeneous, but hopefully within the very early days of, or say early months of this year, we have the confidence then to continue. Thank you. Maybe, Ken, I mean, you had shared with us that you have seen radio in small cell lung cancer, and what you saw was encouraging? So yes, very limited data, but, in patients with very low doses, and in this case, I really mean tumor doses, not the doses given to the patient, but actually both. Low activity given and low tumor dose, still a very good response. Underlining that, I think we should not overemphasize the meaning of dosimetry. We really need to understand how something works in the clinic, and that's why it's so important now not to lose time and really... Yeah. Of course, the question of Bill is very smart. When do you want to see efficacies? That's something if people know this upfront, people probably are faster in a couple of groups. But I think we need to start observing very closely patients early on. Like I said, I've seen this for two competitive programs that you see efficacy actually potentially earlier than you sometimes think. Thanks, Ken.... Looks like... Our next question comes from Michael Nedelcovych with TD Cowen. Your line is open. Hi, thanks so much for the questions. I have a couple. My first question relates to the potential Actinium-225 effort. It sounds like your plan is to wait for clinical data with the Lead-212 Radio-DARPin in the second half of the year before potentially initiating a new trial with Actinium-225. So can you confirm if that's correct? And if so, are there any steps you could take between now and then to prepare for that eventuality, such as, for example, securing supply of Actinium-225? So that's my first question. My second question is on the dosimetry data. It looks like you've provided it for kidneys and bone marrow, but not tumor or metastases. Do you have the dosimetry data for the lesions? And if so, how do they compare to the healthy organs? Then my, my last question, if you don't mind, three, is on the dose limits for kidneys based on EBRT. How confident are you in the field about those dose limits as applies to radioligand therapy? Are there regulatory requirements that will require you to remain below those limits, or is it more, a decision based on sponsor preference? Thanks. So, so thanks, very great questions, and I will dodge the first one a bit, but also give you some update. Obviously, we know of the actinium type profiles in tarlatamab, so, so rest assured we're thinking in all dimensions here. What we're discussing here is mostly, let's call it a strategic path forward, also for other targets, how we think about this. We will definitely update on MP0712, and if there should be an actinium track there, rest assured that is something we can look into, and we, at this point in time, are not giving any timelines for that. I do want to add one word on the actinium supply. I mean, we at Molecular Partners at this point in time, will not build actinium, so that would again, be a partnership. Now, luckily for actinium, most large pharmas that are interested in radio have actinium supply, too. So that is one angle of it. The other is that actinium for your phase zero, phase I, is quite available these days. While for commercial it's different, but that's where anyway a different partner would be used. So at this point in time, we're not looking to build commercial actinium supply agreements or supply, but we are looking into how one does run, and I'll be general, early clinical trials with actinium, for molecules we're interested in. I'll hand over the question on the tumor to, I guess, Michael, he's closest to the data. Yes. And then maybe yourself or Philippe for the last question. Yes. So thanks, Michael. Excellent question as always. So we have done, of course, dosimetry on all organs, so it's a really long list, and you look into spleen and all the small organs, but it's just a long list, so there is nothing really to disclose. On the tumor side, of course, this is also something we did. We are still looking for benchmarks, but apparently the field has not really come to a consensus or publishes a lot. Also, at the conference Philippe and I attended, there were not a lot of numbers, but if you just look at what we have on slide nine, the curves, you can appreciate that the tumors are above the other organs. So that's probably as much as I want to say today. I wouldn't be led too much by the numbers because it's dosimetry, but the numbers we have are very attractive. Yes. I can confirm that. Again, when we discuss with all the experts working either on lead or actinium, currently, you know, it's difficult to get through dosimetry per tumor, per patient, and then those numbers, those benchmarks are not really out there yet. So, that's why it's a bit, you know, it's tricky to really fully answer your question on the tumor uptake. You had a question on the EBRT, the kidney. In the discussion that we had with the FDA, or whenever we ask any experts, you know, working in that, in that field, and maybe, Ken will give his perspective on it, you know, we usually start with the, the visual, 24 gray, EBRT, limit as a theoretical base for discussion. And then, we are happy, in fact, that we are pretty much always staying, below that one across all doses which we're planning to administer. And then there is, if I could say, negotiation, because there is negotiation, based on benefit risk, obviously, and, because we don't completely know how, alpha treatment compares to EBRT. So FDA is watching, is discussing, and, but is also open, and this is the type of discussion we have had. So based on our dosimetry, we are comfortable in how we are starting. And also, obviously, we are monitoring this closely, you know, through urine and blood measurements, regular ones, and also a specific biomarker, which we have included in the trial. So we think we are on the good side from that end. So I think the question is absolutely valid. On the other side, I'm obviously a bit concerned that we over interpret or try to over interpret the model we have. When we perform first human imaging at different time points, we want to get an idea. We want to get an idea at the time of express. We want to see if the tumor uptake as retained. We want to see, are there any organs we really have to additionally worry about? For example, I would not spend too much time on the doses. First of all, it can be really bleak numbers, then it's Lead-203. Next thing is Lead-212. And next question would be, if you want to see tumor dose, what tumor dose do you want to see? What are the tumor doses you want to see? To be honest, even for Pluvicto, Lutetium-177, which has been approved as the, as a multibillion-dollar drug, I could not answer you. So that's why here, I think the biggest question is, does this compound check all the boxes required to go into first human therapy? And, and, and now we really need to see how the clinical data is, and, and we all hope that the clinical data will speak for itself. And, and I think this is, this is the key. And again, yes, we have to watch the bone marrow, but again, very standard. Yes, we have to watch the kidney, very standard. Now let's go out, collect data, and hopefully cure a few patients. Very helpful. Thank you so much. Thanks. Thank you. Again, to ask a question, please press star one, one. Our next question comes from Georg Zimmermann with Octavian. Your line is open. Hi, this is Georg Zimmermann from Octavian. Not sure you can hear me. Yep, we hear you well. We hear you. Oh, perfect. So my main question has already been answered, and so I'll leave that one. Maybe just on the timelines. You mentioned that we have or can expect safety and first efficacy from the phase I/II-A trials still this year. Can you also give an outlook already on how that would progress from then onwards? We can try, and I think listening us to Ken and all the others in the call, I think this is where we just have we'll have to find out at what those levels will we see what. So everything can also come earlier, as we just heard. Where we are, let's say, and we are very deliberate to say we will see activity, so these are case study type activity because we will not have a response rate. For a response rate, you need X patients at the right dose, in the right setting, and I think that's when I would point towards the outlook, and that will be a year-plus from now. But that means we are heading towards a phase II. That means we will have a recommended phase II dose ready. That means we are almost in a phase II, so we are at a very different point, and I really want to take that. That's sort of the outlook. If we reach that, we are in a very different stage as a company. Then we are the leader, and that's the ambition we have. We're the leader in the alpha targeted therapy approach for DLL3 in small cell lung cancer. And that's our ambition, that in a year-plus from now, we are heading towards that, to move this to what Ken said, "Let's go out and cure some patients." So I think that's really how I would summarize that. So a year from now, heading towards recommended phase II dose would be an ambitious and highly valuable moment for us. Thanks, George. Thank you. Thank you. I'm showing no further questions at this time. I'd like to turn the call back over to Patrick Amstutz for closing remarks. Thanks. I I think that last question was a very nice closing remark. I mean, we are at the brink of this new chapter for Molecular Partners. We are a year-plus away to hopefully be the leader in the targeted alpha radio field for DLL3 small cell lung cancer. It's an exciting moment, and I will close to re-quote Ken, "Let's go out there and cure a few patients." I like that, and we will keep you all posted while we are on that quest. Special thanks to all of you and to Ken for joining this call. Thanks. Thank you for your participation. You may now disconnect. Good day. Thanks. You're welcome.