Good day, and welcome to the Molecular Partners Fourth Quarter and Full Year 2023 Results Conference Call. All participants will be in a listen-only mode. After today’s presentation there will be an opportunity to ask questions. Please note this event is being recorded. I would now like to turn the conference over to Seth Lewis, Senior Vice President, Investor Relations. Please go ahead.

Thank you, Betsy. Welcome, everyone, to the 2023 full year earnings call for Molecular Partners. My name is Seth Lewis, Senior Vice President of Investor Relations. Before we start, I want to cover a bit of housekeeping. We are discussing the press release issued after the market closed yesterday, alongside the full year annual results available in the annual report on our website, molecularpartners.com. We'll refer to a presentation today, with the slides also accessible in the Investors section of our website. If you're following along with the presentation, please note we’ll be making some forward-looking statements. I encourage you to review our latest filings with the SEC and ESSEC. For the record, this call is being recorded on March 15, 2023. If you are on Slide 3, I will briefly outline the agenda. We are joined by several members of our management team, including our CEO Patrick Amstutz, who will highlight 2023 and provide the outlook for 2024, Robert Hendriks, our Senior Vice President of Finance, who will review our financial figures, Philippe Legenne, Acting Chief Medical Officer, who will discuss our MPO533 program in AML MDS, Anne Goubier, Senior Vice President of Research and Early Development, who will cover the Switch-DARPin technology and our c-Kit program, and Daniel Steiner, Senior Vice President of Research and Technology, who will address the Radio-DARPin platform and the DLL3 program. Now, I will hand the call over to Patrick. Please proceed.

Thank you, Seth for the introduction and kicking off our full year earnings call. And also a warm welcome from my side to all the audience on this call. It is a special pleasure today to be here, not only with the usual suspects, Robert and Seth, who are usually joining these calls, but also to have Philippe, Anne, and Danny on the call with me as they are the ones who are really driving the progress of our programs and they will be speaking about that progress here today, and that's a special pleasure to see the team coming together and moving Molecular Partners forward. I'm now moving to Slide number 4, and I will start with a short recap of what we do and how we do it. The DARPin is a novel therapeutic modality, a novel class that we have validated in more than 2,500 patients with seven clinical compounds. The DARPins are different from other modalities, so not antibodies, not small molecules. They are the size, maybe a tenth of an antibody, and they're really well applicable for multi-specifics. Our quest is to use the DARPin indifference to turn that into differentiated drugs. So what we do is, we create unique DARPin solutions to clinically validated problems that are of high medical needs. True patient value means high medical needs. We termed the early clinical readout that you can translate into similar agent activity as when we will move a drug into development, we also will want to know if it works or not fast. As we are working in many different fields, we love to work with partners that we don't have to reinvent the wheel. That is why the main goal of Molecular Partners and our strategy on partnering with those or collaborating with world-class partners is part of the strategy. 2023 was an exceptionally productive year with progress on literally all of our programs. Those who are working in our field know that that's usually not the case. Often one has a setback in one or the other program, but this year every single one was moving forward at speed and producing the results we were looking for. First and foremost is MPO533, our tetra-specific T cell-engager. A year ago, roughly, we dosed the first patient. At ASH, we reported good safety and efficacy of the first four cohorts, and today we are recruiting, or we have fully recruited cohort 6. On the Switch platform, we were able to nominate the first target, and we're working towards a candidate, and we'll talk to that. We are absolutely excited as the Switch concept is something that is very DARPin unique and you will see we will be able to target targets that are not easily accessible through other ways. On the radiotherapy side, this is a whole field Molecular Partners is heavily investing in, with two key breakthroughs of the last year. One is the reduction in kidney retention or accumulation and we were able to now increase tumor uptake by engineering the half-life. We were able to strike a collaboration with Orano Med, providing lead also for our lead asset DLL3, and we have progressed with Novartis on the targets and programs we're working with them. These are two distinct targets that are exclusive to Novartis. 317, we have advanced through Phase 1. We have dosed several patients and could see a favorable and strong safety profile. We have biological proof-of-concept showing activation of antigen-presenting cells and remodeling of the tumor microenvironment. We end the year with $187 million, bringing us well into 2026, meaning we are capitalized to reach key value inflection points. Moving to Slide number 6, this is the pipeline chart and sort of is my agenda for the next call. 317, I did speak about, that's the antigen-presenting cell activator. This molecule has little single agent activity. It is ideally combined with other IO drugs. That's why this is on the partnering track and I will talk to that in the summary, but we will not cover it in the presentation itself. 533, Philippe will talk about and will talk about the Switch-DARPin and explain that, and Danny will cover the radio piece. With that before we go there, I will hand over to Robert to share the financial overview.

Thank you, Patrick. With that, I'd like to run you briefly through the key figures of last year's financials and the guidance also for the year 2024. My name is Robert Hendriks and I'm the SVP Finance at MP. The numbers I present here are stated in million Swiss francs and I'm on Page 8 at the moment. Three numbers, it's a full slide, but three numbers in particular. First one would be the revenue. The revenue of CHF7 million this year is exclusively related to the agreement we have with Novartis on the RadioLigand Therapies as indicated. Part of this number is a recharge of research FTE and the other part is a recognition over time of the upfront of $20 million that we received under the December 21 agreement. Under that last element, we still have around CHF4 million to be recognized in 2024. The revenue number in 2022, as you may recall, largely related to the funds we received from Novartis in early 2022, upon their exercise of the option under the Ensovibep license agreement. The second number I'd like to point out would be the operating expenses total of CHF68 million. The guidance that we provided during last year was CHF65 million to CHF70 million, and the expenses ended right in the middle there. For further breakdown, the R&D share of this number amounts to CHF49 million, and the SG&A number to CHF19 million. You can see that the overall costs have been reasonably stable over recent years. It's fair to say that the reduction of just over CHF4.9 million last year related largely to a lower expense for the listing of the company in the U.S. as well as a natural attrition in headcount. The third number, as already pointed out, would be the cash balance of CHF187 million. You can see that's down from CHF249 at the end of last year, so an effective burn of CHF62 million. This amount will carry us well into 2026 and we consider this continues to put us in a privileged position in the industry. I'd also like to add and remind here that the company remains without any debt. We feel that these three numbers tell the financial history of MP and 2023 and the solid financial state of the company. If I then move on to Slide 9 on the guidance. We will guide on the operating expenses only, not on revenue or any other metric. We do guide for a total of CHF70 million to CHF80 million of which around CHF8 million are non-cash. For clarity, this guidance is as always subject to the progress and changes of our pipeline and excludes any potential payments related to partnerships. To summarize and conclude, what I think is most relevant to recall from this overview is the continued solid financial base entering into the year 2024 that will allow us to continue to invest in our pipeline and to bring drugs to patients. Thank you for your attention. Happy to take any questions during Q&A later. And with that, I hand it to Philippe, who will provide an update on MPO533.

Thank you very much, Robert. Good morning and afternoon to everyone. I am Philippe Legenne, the Acting Chief Medical Officer at Molecular Partners. I'm pleased to provide an update on our MPO533 program in AML, including insights from the dose escalation trial. As we consider AML, it is essential to recognize that it remains one of the most lethal cancers. While there are often initial responses and reductions in blasts, the persistence of leukemic stem cells leads to frequent and rapid relapses. A significant hurdle in designing therapies for AML is the absence of a single clear target in individual AML blasts and leukemic stem cells. However, there is an opportunity to differentiate AML cells from healthy cells, such as hematopoietic stem cells, through their co-expression of specific targets like CD33, CD123, or CD70. We have developed the MPO533 DARPin treatment as the first tetra-specific T cell-engager that binds to the tumor antigens CD33, CD123, and CD70 on AML cells, as well as CD33 on effector T cells. MPO533 is intended to promote T cell-mediated killing, particularly when two or three target antigens, CD33, CD123, or CD70, are co-expressed. This design is expected to help preserve healthy cells, creating a broader therapeutic window compared to other T cell engager therapies. MPO533 has the potential to target all AML cells, including blasts and leukemic stem cells, despite their heterogeneity, which could lead to long-term disease control. As we look at our findings on MOLM-13 cells, the graph illustrates the lower potency on cells expressing a single antigen compared to a potency that is 100 times greater when antigens are co-expressed. This data, along with further preclinical experiments and AML patient samples, will be published in the coming weeks. Currently, the dose escalation study in patients with relapsed/refractory AML and high-risk MDS is ongoing and has successfully recruited participants at the first six dose levels.

Yes, we hear you.

We do hear you. Yes.

There's some very strange sound coming up. Okay, there's a beep. Okay, so I was just saying that the study, the Phase 1, has now recruited the first six dose levels across nine sites and four countries and the preliminary data was reported at ASH 2023 from the first four cohorts, as Patrick mentioned earlier on. Moving to Slide 15, this slide refers to the safety profile of this population of elderly, heavily-patients with comorbidities, but this has been manageable. The most frequent treatment-related adverse events reported are infusion-related reactions and cytokine release syndrome with no DLTs reported to date. This is important to mention. Slide 16 reports evidence of clinical activity which was presented at the last ASH and you can see that in each cohort, 3 of those levels 3 and those level 4, the patient achieved ELN response of MLFS and CR. Slide 17 summarizes the near future and some upcoming changes to our study design. Indeed, we are planning to initiate soon the last seventh dose level upon the Dose Escalation Committee review. We are also submitting an amendment allowing to increase the doses even higher as the safety profile has been so far manageable. We want to evaluate how higher doses could impact target saturation and onset of response further. We also want to evaluate the impact of adding another dose at day 12, you can see the little square, to seek if we can increase the impact on the ML cells as early as possible. We look forward to sharing with you an update on the program at the end of H1 and more data later coming up in 2024. I'm now handing out to my colleague Anne, who will update you on the Project 580, which is aiming at a complementary need in the treatment cycle of AML patients. Thanks.

Thanks, Philippe. And good morning or good afternoon, everyone. In the coming slide, I will show you how DARPin’s can further change the game for AML by significantly enhancing the therapeutic outcome of hematopoietic stem cell transfer. As we move to Slide 19, as you know, HSCT is potentially creative for ML patients, but a lot of patients relapse, and conditioning regimens are highly toxic, encompassing GVHD, organ failure, sterility, or secondary malignancies. So, one can apply reduced intensity conditioning, but then the risk of relapse is higher. Our DARPin solution aims at delivering a safer and more potent conditioning regimen for HSCT, with the potential to transform treatment in AML and other conditions. In order to understand how this works, let's skip slide 20 and go directly to slide 21. The key issue with current conditioning regimens is that they are not targeted, leading to bystander toxicity and ultimately lower potency. Our solution is to target c-Kits, which are early expressed on hematopoietic stem cells and leukemic stem cells. The challenge here is that as we know, blocking c-Kit's binding to each ligand is not enough for the hematopoietic stem cell depletion. You need to induce killing of the c-Kit-positive cells. For this, we are leveraging our CD16-engager proprietary platform, which owns the potential to be safer than a CD3-engager or ADC, and to be more potent than an antibody by targeting the activating Fs receptors and not the inhibitory receptors. One challenge remains that the macrophages are limited in their activity by the don't-eat-me signal delivered by CD47. The solution to that seems obvious, which is blocking CD47. But as you know, CD47 blocking therapy has been limited due to the high toxicity linked to the expression of CD47 on T cells. Our solution is conditional CD47 blocking, which will ensure that CD47 is blocked only on c-Kit-positive cells. We are leveraging our Switch-DARPin technology, which ensures that CD47 remains masked when c-Kit is not expressed, and that CD47 is blocked when c-Kit is expressed. I will not go into detail about the mechanism, and if you are curious about it, I invite you to go to our website. There is an educational video that clearly explains the depth of the mechanisms. But now let's move from the theory to real data. In the coming two slides, I will show you that the Switch-DARPin is indeed safer and more potent. Slide 22 highlights the power of the Switch-DARPin for conditional blocking of CD47. What you are looking at here is the percentage of free CD47 on cells. This means that this line decreases when CD47 is blocked. When you look at the light blue line, which represents c-kit negative cells, you can immediately see that there is no CD47 blockade until very high concentrations. This tells us that at physiological concentration, the molecule will be inactive and thus safe. The dark blue line illustrates the c-Kit positive cells. Here, you can see that CD47 blockage starts at very low concentration. When you compare the light blue and the dark blue, you can see the depth of the therapeutic safety window, which is here more than three logs in concentration between the c-Kit positive and c-Kit negative cells. The conditional blocking of CD47 ensures a high safety profile. Now, how about efficacy? Slide 23 shows the therapeutic potential of our c-Kit switch target. I would like you to focus first on the dark green bar, which illustrates the phagocytosis induced by the IgG1 antibody. As expected, an anti-c-Kit IgG1 antibody does induce phagocytosis. But you can immediately see that this phagocytosis is limited in intensity, especially compared to the dark blue line, which represents the Switch-DARPin. This indicates that we can expect a much deeper hematopoietic stem cell and leukemic stem cell depletion in patients with DARPin as compared to an IgG1 antibody. Of course, you could combine this antibody with a CD47 blocking antibody like Magrolimab. But as discussed earlier, you will face a high toxicity there. Additionally, as you can see here, comparing the light green to the dark blue, you are not as potent as what we see with the dark green, most likely linked to the fact that in the dark green, both CD47 and c-Kit targeting are in the same molecule, thus both benefit from anti-CD16. This data shows us that we have a molecule that is not only safer but also more potent than anything we can obtain even with a combination. The next step is the efficacy study. The beauty of this study is that it is perfectly translatable to the human setting, from the building regime to the safety and efficacy against HSC. We're expecting data from this study in the second half of this year and planning to be in the clinic in 2025. With this, I'm very pleased to hand over to Danny, who will introduce you to another groundbreaking aspect of DARPin technology, the Radio-DARPin.

Perfect. Thank you very much, Anne, and welcome everyone from my side for this call. So it's a pleasure to, on behalf of the team, give you an update on our Radio-DARPin therapy platform and respective pipeline assets. As you probably all know, the field of radiotherapeutics is experiencing a lot of excitement, pushed by strong clinical efficacy and good tolerability data that first compounds on the market or a new emerging compound deliver. What is limiting the expansion of this amazing promise to other cancer types is vectors that are matching targeted radiotherapeutics requirements and allow a broad target space to be common. That’s exactly where we saw the benefit of the opportunity to come in with this DARPin. If you move to Slide 25, for those of you who are not familiar with radiotherapy, the ideal properties of a radiotherapy product candidate are to deliver the radioisotope selectively to the tumor while sparing healthy tissue. There is special focus on kidneys and bone marrow. Bone marrow being very tightly connected to blood levels, which are the most dose-limiting organs. If you move to Slide 26, so on the left-hand side, if you have a target in mind with a cavity where a low molecular weight compound vector with high affinity and specificity can be identified, this is perfect. This is the ideal targeting moiety. The problem is that there are very limited targets where this exists, where this possibility holds true. To open up the target space, the most proven class is protein-protein binders where you can generate high-affinity and specific binding proteins that bind surfaces of a broad range of tumor targets. Monoclonal antibodies and antibody fragments fall into this category. Unfortunately, all of these protein-protein binders have key limitations for the effective and safe use as radiotherapeutic vectors. For antibodies, the high or long systemic half-life leads to bone marrow toxicities, and the size leads to limited tumor penetration. And for the small proteins, they are limited by kidney accumulation and lower tumor uptake. So please remember those two elements: high kidney uptake and low tumor uptake. This is the dimension where we felt looking into the molecular properties and biological mechanisms behind this, the team had a strong conviction that the DARPin platform is ideally suited to exactly build on the unique properties of the DARPin to overcome these challenges. If you move to slide 27, this is just a demonstration of the engine the team has built for creating our radio-DARPin therapeutic candidates. Starting from the left-hand side, as for all our projects, building a diverse set of high-affinity DARPins against a specific target, which, when you see in the lower graph, these DARPins are nicely accumulating in the tumor but at the same time still have very high kidney levels. In the next step, we address the first limitation, the kidney. So, what we've been building is what we call a stealth design, as I will show you more data on the next two slides, where we reduce the kidney level down to below 25%. As a next step, we are addressing the second limitation, bringing up the tumor load by using our half-life toolbox specifically built for radio-DARPin therapeutics, increasing the tumor uptake while keeping the systemic exposure low. If needed, as a last step, we will increase the affinity of the respective binders to ensure tumor retention. The novel two aspects of the radio-DARPin therapeutic engine are these two middle ones, and I'm going to present a bit of data related to these two points. If you move to Slide 28, please focus first on the upper right side cartoon where you see an example of a normal or parental-DARPin. When this DARPin gets excreted by the kidney, it enters the primary urine, as all other proteins do. It is then reabsorbed and consequently causes kidney damage due to the accumulation of radioactivity. What we've developed is the highly robust architecture of the DARPin scaffold; heavily re-engineered the entire backbone to create what we call the stealth DARPin. This design is not recognized by the kidney cells anymore, allowing the DARPin with radioactivity to be directly excluded into the urine. If you move to Slide 29, I’m showing you in vivo data supporting the strong kidney-reducing effect of the stealth-DARPin. On the left-hand side, this is the example of our front-runner program on DLL3. We successfully engineered three out of three DARPins in three to four iterative engineering rounds, each taking three to four months, including all the production down to in vivo testing. Moving over to the right side, you see after incorporating all these learnings from the first program, we managed to bring three out of four DARPins down to low kidney levels within a single round. What I wanted you to take home from this is that we have established a robust, reliable engineering solution to lower kidney levels significantly. Now, regarding the second challenge, I'm showing you how we addressed the key limitation of tumor uptake. Focusing on the left side, you will see examples on HER2 and DLL3. On the left-hand side, we have the naked -stealth-DARPin, which shows tumor accumulation in the single-digit percent range along with very low blood levels that are non-detectable at these time points. On the right side, we have applied different half-life extensions leading to either low, medium, or increased systemic exposure, successfully driving the tumor uptake up to 30% while maintaining much lower systemic exposure compared to an antibody. In summary, the stealth-DARPin addresses kidney accumulation, and the half-life extension improves tumor uptake, forming the basis of our radio-DARPin therapeutic engine and pipeline. In our pipeline, we have two targets with Novartis, and two targets with Orano Med, including DLL3, while also rapidly expanding in Orano Med. We are extremely pleased with the collaboration we've initiated over a year and a half ago, thanks to the outstanding team and their expertise. Strong data is emerging from lead 212 as the radio client of choice in this particular case. We also have additional targets that we are moving ourselves, which are not currently partnered. We look forward to sharing further data at key upcoming conferences in the next months. I’m finishing here, happy to answer questions in the Q&A session, and I’ll hand over to Patrick for the outlook.

Thanks, Danny, for the exciting overview that we have on the radio space. Before opening for questions, let's just look at the outlook. It's an exciting year ahead. I will start with the first and foremost most exciting one, which is 5.33, our AML drug. We're excited to look into the first data with you from those cohorts 5, 6 and a taste of 7 still in the first half. Certainly, the protocol amendment will allow us to push that through so that we can get to higher doses and share with you what we are developing in very close collaboration with our KOLs, a strategy that goes beyond just relapsed/refractory cases but exploring where else we might apply this molecule. There's a clear need in this indication and we are starting to understand how we would also move forward beyond relapsed/refractory patients. On the Switch or CK side, we are quickly moving towards candidate selection. We will discuss that still in the first half of this year. As Anne has pointed out, it’s all about the non-human primate study, and we will report data in the second half of this year. I think this is perhaps the most translatable data we’ve ever had at Molecular Partners, and we are convinced that strong data in non-human primates translates well into patient value next year, meaning in 2025 already. From Danny, we heard about the radio platform being ready; we will move forward and add new targets and additional candidates. This also mandates us to broaden collaborations and move the ones we have forward. As for 317, we have recruited the last patients where we’re still in the trial; we are expecting to close that, clean the data, and open the data room for partnering advancement. Just to remind you about our cash position: we are well financed with CHF187 million in cash, which will carry us into 2026, allowing us to capture all those value inflection points I mentioned. With this, I want to thank you for listening to the call. I want to thank the team here. I want to thank Seth, Robert, Philippe, Danny, and Anne for presenting today. I want to thank the entire Molecular Partners team. It has been an exceptional year. Hard work, and also great team spirit. To work here is a pleasure, and hard work comes easily when you work in a great team. I do want to thank all our partners and especially our KOLs running the trials and the patients in those trials. With that, I would end the presentation part and open the floor for questions.

We will now begin the question-and-answer session. The first question today comes from Richard Vosser with JP Morgan. Please go ahead.

Hi, thank you for taking my questions. I have two regarding MPO533. Could you provide any insights on what is driving the further dose expansion? While the safety profile appears very favorable, is there a belief that efficacy might require higher doses? Additionally, could you share how much higher the doses will be? Lastly, when should we anticipate the decision for the Phase 2 enabling study? Will it be more in 2025, or in the second half of 2024? Any details would be appreciated. Thank you.

Thanks, Richard, for the fair and good question. So maybe just a bit of color on the doses. When we started the trial, we calculated the highest dose with the knowledge that we would only reach around 80% receptor occupancy in the bone marrow. You need to know that the blood is one thing, but then you have to penetrate into the bone marrow where you expect also the leukemic stem cells. So, we're just kind of looking at other T cell engagers that have been held back by safety. We designed the trial and the top dose was 80% receptor occupancy. So the news that we can go to higher doses is definitely helpful because you want to go beyond that. You want to reach 90% or above, which gives you then hopefully a more complete killing of these cancer cells, especially the leukemic stem cells. Now, if this is needed or not, it's too early to say. We're in dose range six. We continue to see activity of the drug, but to better understand if the dose response is there and if we achieve deeper and prolonged killing of these cells, we cannot comment today. We also said we would not piecemeal the data, so you'll have to be patient until we give that update. This will be a point of focus, particularly looking at MRD, or minimal residual disease, to follow the clones and see if we can be killing the high-risk clones, as those are the ones driving relapse quickly. It's more than just the response rates; it is truly understanding what the drug does in the bone marrow. Maybe I'll quickly pause there on that one. Maybe Anne can follow up on that.

Yes, I'm nodding my head. I think you've covered it well.

Just one thought there. I think it’s fair to say that where we are now in dosing, we are either at or above where others have gotten to with bi-specific antibodies with T cell engagers, certainly.

No, I often miss the obvious ones. Thanks for pointing it out. The last point of Richard was regarding what will gate our decision. There are definitely two things to consider here. First, what will be gating for moving towards relapsed/refractory? We have clear cutoff criteria there regarding clonality and how we kill those clones. This will likely guide our decision moving into earlier lines as well. We’re working on that, and this will be part of the update later this year when we share our strategy. You’ve heard a bit about the directions we’re considering, and I can tell you it's a very focused and close collaboration with our KOLs. Richard, I hope that was covering your points.

I think we got it. Operator, I think we have another question.

Your next question comes from Mike Nedelcovych with TD Cowen. Please go ahead.

Thanks for the questions. I have one on MPO533 and then one on the Switch-DARPin platform. For MPO533, when we get the updated interim data from the Phase 1 trial in the first half of this year, what are you hoping to see? What level of efficacy in a given dose cohort would you consider a success? On the expanded dose cohorts, is there a chance that we get those data by ASH at the end of this year, or is that more likely to be a 2025 event? And on the Switch-DARPin platform, can you describe the broader strategy for the platform? The first targets would seem to be relatively de-risked, but perhaps a smaller indication. What are other good targets for this approach in a blue sky scenario? What indications might you go after?

Thanks for the question. I think I'll just hit the first one and then hand it over quickly to Philippe. I see two cutoffs. Where we will stand in the first half versus the second half in the dose escalation we will see. We've always communicated that for relapsed/refractory settings, we aim for a roughly 30% response rate with well beyond three months' disease control. If we want to move to earlier settings, it’s really all about MRD conversion. Can we also kill the difficult-to-kill clones? So those are in very short the elements we are looking for. Maybe, Philippe, you can add more detail on safety.

Yes, thank you, Patrick, and thanks for the question. First of all, I want to reiterate that what is really our position of strength is that the agent seems to be very manageable and well-tolerated thus far. It shows CRS; it shows IRRs, but enough to make us confident that it's doing something, yet not enough to exceed safe boundaries. We want to keep optimizing it to ensure that as many patients as possible can respond. We're working with large cohorts, six to nine patients, so we hope this provides good learning. When we can expect the next important and relevant batch of data is still a bit tricky to say because we hope to go higher. At some point, we will potentially hit the DLT, so then we can expand immediately. Alternatively, we might see that it's not worth going higher because we have saturated all targets. It will take a few months before we get final translational data to guide us for that. We aim to present valuable updates as we make progress.

Thanks, Philippe. The last question was for Anne regarding the Switch and blue-sky scenario. I’m excited to hear your thoughts.

Yes, thanks. As you've rightly pointed out, c-Kit DARPin Switch is just a starting point. There is broad applicability for this platform. You can think of it from the target point of view, because here on the c-Kit, it's just a first step. You can apply this platform to various targets. For instance, a good example is EpCAM where they are beautiful, highly expressed targets on many tumor cells, but they are limited by the fact that they are also expressed on healthy cells. Thanks to the Switch, we can gate and ensure that we can induce killing of cancer cells without affecting the healthy cells. Moreover, you can create different effects on mortality, ensuring safe engagement of T cells only when your targets are expressed. You can also think about utilizing cost simulations with targets like CD28, which have a high toxicity risk, by activating them only when a set of two targets are expressed. This opens a broad field of applications and we are also seeking partnerships to fully exploit this Switch platform.

Thanks, Anne.

The next question comes from Kathleen Silverman with Leerink. Please go ahead.

Hi team. Thanks for the question. I am on for Daina today. A bit of a tag onto Michael's question from TD Cowan. The scenarios for potential stock movement on the first half 2024 533 interim dose escalation data. If I break it into layering and a floor, the layering being what's your conviction in potentially seeing other CD3 T cell engagers with a belt-shaped response or some have called it a step-up response. Do you think there's a reason to think about seeing that at the cohort 5 level? The floor scenario was Michael's question. So in the relapsed/refractory data, knowing that durability will be immature and you are targeting getting eventually in a larger trial over three months as the threshold. In this current cut that we'll see in the first half, will you be sharing those directional signals like the MRD and the biomarkers of T cell engagement? Thanks so much.

Yes, happy to address that. I do believe our molecule looks different than other T cell engagers. Our safety profile has allowed us to reach doses that others have not. We hope to see a different response profile, enabling us to control disease better. As you rightly pointed out, we will not have distinct data to relay regarding several months of follow-up, but MRD levels make for a good surrogate marker on the depth of effect that links to duration. Yes, we absolutely intend to update on what we have. However, remember that tracking the clonality of the disease requires ongoing following over time and will yield limited data for us for now. We aim to share as much as we can to inform decisions at Molecular Partners based on these data. This will be an interim update.

The next question comes from Joris Zimmermann with Octavian. Please go ahead.

Hi, Joris Zimmermann from Octavian. Congratulations on all the progress. Impressive. Thank you for taking the question. One on the RDT platform and one on MPO317. On the RDT platform, you've announced two partnerships, but you also have two internal assets or targets. Can you shed a bit more detail on your plans to follow up with the two internal targets and any potential partnerships you see there? Then on MPO317, where do you stand there, and when can we expect the next update, or any potential partnership announcements? Thank you so much.

Thank you. I’ll quickly take 317 and then hand over to Danny to talk about the radio-DARPin and our internal targets. For 317, as I said, we have been finalizing the trial. We are essentially filling the data room with all pertinent information, and that should be open shortly, allowing interested partners to review the findings. I would remind everyone that at the moment, IO-IO combinations are not peaking. A few years ago, this would have been a multi-million dollar upfront; those times are not now. We're looking for a partner who can fully commit to running multiple combination trials rather than simply trying to optimize the selling price. Timing is difficult to comment on. Now I'll pass to Danny to discuss our internal undisclosed targets and thoughts on sourcing isotopes and partnerships.

Thanks for the question. To zoom out quickly on the targets: our aim when selecting the target is driven first by medical needs, and then we zoom in on targets we believe may be difficult to address but meet certain biological or molecular biology requirements regarding specificity, location, and expression of the target. We are attentive when nominating these targets. We have internal programs ongoing where we hope to show proof of mechanism, ensuring that we can effectively match those profiles. Subsequently, we want to maintain the freedom to decide if these targets are suited for short half-life short-range alpha emitters like lead or if a collaboration is necessary for longer-lived alpha emitters depending on the tumor indication and biology. We remain open for now, but we are not solely focused on the length.

Thanks, Danny.

This concludes our question-and-answer session. I would like to turn the conference back over to Patrick Amstutz for any closing remarks.

Again, I would like to thank my team here for all the work and the great Q&A, providing clarity to the questions. I want to thank you for your attention and the quality of the questions we received. It’s clear we’re heading into a very data-rich period with lots of strategic work in the background linking the data to decisions. We will work internally and communicate closely with all of you as we share what we have and how that reflects on our decisions, especially concerning the investment potential we envision for the available cash. We are truly excited to bring forward differentiated DARPin therapeutics for patients without good treatment options today. With that, I would like to conclude the call. Thanks again. Take care, and speak soon.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.