Molecular Partners AG (MOLN) 2023 Q4 法說會逐字稿

Good day and welcome to the Molecular Partners Fourth Quarter and Full Year 2023 Results Conference Call. (Operator Instructions) 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, and welcome, everybody, good morning and good afternoon to the 2023 full year earnings call for Molecular Partners. My name is Seth Lewis, Senior Vice President of Investor Relations. I wanted to just go over a little bit of housekeeping before we begin. Obviously we are speaking today in reference to the press release, which was issued after the close of market yesterday, as well as the full year annual results, which are in the annual report, which can be found on our website, MolecularPartners.com, and we will be making reference in prepared remarks today to the presentation, which slides are also available under the Investors section of our website MolecularPartners.com.

If you are following along in the presentation, I will refer to you that we are going to make certain forward-looking statements today, and I would refer you to our latest filings and most recent filings with the SEC and with the (inaudible)for the sake of the replay today, we are recording this on March 15, 2023. If you are on slide 3, I just wanted to take you through the agenda briefly.

We are joined today by multiple members of our management team, including Patrick Amstutz, our CEO, who will take you through both the highlights of '23 and the outlook for 2024. Robert Hendriks, our Senior Vice President of Finance, who will go over some of our financial numbers; Philippe Legenne, who is our acting Chief Medical Officer, who will touch on our MP0533 program in AMLMDS; and Anne Goubier, our Senior Vice President of Research and Early Development, who will discuss the switch DARPin technology as well as our cKIT program; and Danny Steiner, our Senior Vice President, Research and Technology, who will touch on the radio DARPin platform and the DLL3 program.

With that, I will pass the call over to Patrick. Please go ahead.

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. And it is a special pleasure today to be here, not only with the usual suspects, Robert and set who are usually joining these calls, but also to Philippe 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. That's a special pleasure to see the team coming together and move Molecular Partners forward.

I'm now moving to slide number four, and I'll start with a short recap of what we do and how we do with. The DARPin is a novel therapeutic modality and novel class that we have validated in more than 2,500 patients in seven clinical with seven clinical compounds. And the DARPins are different to other modalities. So, not antibodies, not small molecules. There are the size, maybe a 10th of an antibody, and they're really well applicable for multi specific.

And our quest is to use the DARPin difference 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 need. So, true patient value means high medical need, and we termed the early clinical readout that you can translate into similar agent activity as what we move a drug into development.

We also will want to know if it works or not. And as we are working in many different fields, we love to work with partners that we don't have to reinvent the wheel and that is why that named Molecular Partners and our strategy on partnering with those or collaborating with the world-class partners is part of the strategy.

On moving to slide number 5, '23 was an exceptionally productive year with progress on literally all of our programs, and 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, it's MP0533 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 those cohort six. On the switch platform, we were able to nominate the first target and we're working towards the candidate, and we'll talk to that and we are absolutely excited as the switch concept is something that is very dark and unique.

And you will see we will be able to targets that are not easily accessible other ways. On the radiotherapy side, this is a whole field, Molecular Partners is heavily investing in. There is two key breakthroughs after last year. One is the reduction in kidney retention or accumulation and we were able to now increase tumor uptake by engineering to 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 are working with them. Those are two distinct targets that are exclusive to Novartis. 317, we have advanced through Phase one. We have dosed several patients and could see a favorable and strong safety profile and we have biological proof of concept showing activation of antigen-presenting cells and remodeling of the tumor microenvironment. And we ended the year with CHF187 million, and this brings us well into '26, 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 for the call 317, I did speak about that 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 we'll talk about the switch DARPin and explain that Antonio 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. We did, I'd like to run you briefly through the key figures of last year's financials and the guidance also for the year '24. My name is Robert Hendriks, and I'm SVP Finance at MP. The numbers I present here are stated in million CHF, and I'm on page 8 at the moment. Three numbers, it's suppose, like the 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 radio leaving therapies, as indicated part of this number is a recharge of research FTE. And the other part is the recognition over time of the upfront of $20 million that we received on the December '21 agreement.

Under that lost element, we still have around CHF4 million to be recognized in '24. The revenue number in '22, as you may recall, largely related to the funds we received from Novartis in early '22 upon their exercise of the option in (inaudible) the license agreement.

Second number, I'd like to point out would be the operating expenses total of CHF68. The guidance that we provided during last year was CHF65 to CHF70 and the expenses, and that's right in the middle there. For sort of break down, the R&D share of this number amount to CHF49 million in SG&A number to CHF19 million. You can see that the overall cost 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 US, as well as a natural attrition in headcounts. The third number, as already pointed out, would be the cash balance of CHF187 million. You can see that's down from the CHF249 end of last year. So an effective burn of CHF62 million. This mark will carry us well into '26 and we consider this continues to put us in a privileged position in the industry. Also like to add and remind here that the company remains without any debt. We feel that these three number, the financial history of 2023 and the solid financial state of the company.

If I then move on to slide 9 on the guidance, I will, we will guide on the operating expenses only, not on revenue or any other metric. We do guide for a total of CHF70 to CHF80 million, of which around CHF8 million are non-cash. For clarity, this guidance is 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 '24 that will allow us to continue to invest in our pipeline and to bring drugs to patients.

Thank you for your attention and happy to take any questions during Q&A later. And with that, I hand to Philippe, who will provide an update on MP0533.

Thank you very much, Robert, and good morning and afternoon to all, I am Philippe Legenne, the acting Chief Medical Officer at Molecular Partners. I'm happy to share an update on our MP0533 program in AML, including some learning from the dose escalation trial.

Looking now at slide 11, I want to remind us that AML remains one of the most deadly cancers, where despite initial frequent responses and reductions in blasts, the persistence of leukemic stem cells drives the frequency and quick relapses. A major challenge for design of therapies in AML is that individual AML blasts and leukemic stem cells lack a single green target. However, the opportunity is that AML cells can be differentiated from healthy cells like hematopoietic stem cells, but the core expression of specific agents or specific targets like CD33, CD123, or CD70.

Moving to slide 12, we have design, MP0533 DARPin treatments as the first to specific T cell engager binding to tumor antigens, CD33, CD123 and CD70 on the AML cell and to CD33 on the effector T cells. MP0533 is designed to induce T cell mediated killing preferentially when two or three target antigens, it is 33,CD123 or CD70 are co-expressed.

First such design MP0533 is hypothesized to preserve the healthy cells since opening a broader therapeutic window that has been seen for other detail, (inaudible) therapies. MP0533 has the potential to cure all AML cells, the blasts and the leukemic stem cells despite heterogeneity translating into long-term disease control.

Moving to slide 13, we can see that this scientific hypothesis of creating a therapeutic window is demonstrated on MOLM-13 cells. Describing on the graph, the low potency of on single antigen expressing cells versus 100 times more potency when antigens are core expressed on the cells.

This data alongside with additional preclinical experiments. Sorry, there is just (inaudible) passing just one second, please. Okay, so, I was just saying that these data alongside with additional preclinical experiments, including AML patient samples, will publish in the next coming weeks.

Focusing on slide 14 now. These CP101 dose escalation study in patients with relapsed refractory AML and high-risk MDS is ongoing and has now recruited the first six dose levels across--, can you hear me? (multiple speakers) So, I was just saying that, you know, the study, the Phase one 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 for coherts, as Patrick mentioned earlier on.

Moving to slide 15, this slide refers to the safety profile of this population of elderly heavily pretreated 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 cohorts [three of those levels and those level four]patient achieved AML response of MLFS,MCR.

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 dose is even higher as the safety profile has been so far manageable.

And we want to evaluate how higher dose could impact target saturation and onset of response further. We also want to evaluate the impact of adding another dose at the 12, you can see in the blue square to seek that, if we can increase the impact on the MSLs 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 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 our DARPins can further change the game for AML by significantly enhancing the therapeutic outcome of hematopoietic stem cell(inaudible)

Let's move to slide 19, as you know, HSCT (inaudible), that's a lot of patients relapse and conditioning regimen up highly toxic and compressing GvHD, organ sales,(inaudible) secondary malignancies. So, one can apply reduce in intensity conditioning, but then the risk of relapse is higher. So,(inaudible)solution and delivering a safer and more potent conditioning regimen for HSCT with the potential to transform treatment impairment and other conditions.

So, in order to understand this well, let's keep slide 20 and go directly to slide 21. The key issue with your and conditioning regimen is that they are not targeted leading to bystander toxicity and ultimately lower potency. So, our solution is to target cKIT expressed on hematopoietic stem cells and leukemic stem cells. The challenge here is that as we know, blocking c-Kit binding to its is not enough for the hematopoietic stem cell depletion, you need to induce killing of the sticky position.

And for this, we are leveraging CD60 (inaudible), a complete platform, which all the potential to be (inaudible) ADC, and to be more potent than an antibody by targeting the activating (inaudible). One challenge is that the macrophages are limited reserve activity by the don't eat me signal delivery by CD47.

So, the solution to that is since OBS, which is blocking CD47. But as you know, CD47 go to therapy have been limited due to the high toxicity linked to the expression of CD47 on (inaudible). So, our solution is a conditional CD47 blocking, which will ensure that CD47 is blocked (inaudible) And for this, we are leveraging our switch DARPin technology, which makes sure that CD47 remain masked CD47 blocking dopamine remain masked when CD47 is not expressed, and that's CD47 is blocks when expressed. So, I will not go into details into beginning them. And just curious about is I invite you to go to our website. There is a big additional and very clear video that explains the depth of the mechanism.

But now let's move from the (inaudible) In the coming two slides, I will show you a switch DARPin is indeed safer and more potent. So, slide 22 highlights the power of the switch DARPin for conditional blocking of CD40 symptoms. What I'm looking at here is the percentage of free CD47 onset. So, what it means is that these lines decrease went to the 47 is blocked.

So, when you look at the light blue line, which is negative and can immediately see that there is no CD47 blockade on the very high concentrations. So, this tell us that at physiological concentrations, the molecule will be in active and safe. The dark blue line, (inaudible) is a positive sales. And here you can see that CD47 look at that and very low concentration.

So, when you compare the light blue and the dark blue, there you see the depth of the therapeutic safety window, which is here more than three log in concentration between the second positive and negative sense. So, the condition and blocking of release of (inaudible) ensure high safety profile.

Now (inaudible). The slide 23 shows the therapeutic potential of our (inaudible). And I would like to focus first on the dark green bar. And this illustrates the progressive disease induced by IgG1 antibody. So, as expected, the note, I think it's IgG1 antibody does induce phagocytosis, but you can immediately see that (inaudible) is limited in intensity, especially compared to the dark blue line, which represents the switch DARPin.

And this tells us that we can expect a much deeper hematopoietic stem cells and leukemic stem cell depletion in patients with adapting as compared to (inaudible) antibody. So, of course, you could combine this antibody with a CD47 blocking antibody like Magrolimab. But as discussed earlier, we face a high safety others.

And on top of this, as you can see here, comparing the light green to dark blue, you are not as important as what we see with adapting most likely linked to the fact that ended up in both CD47 and CD16 are in the same molecule and the new (inaudible) sign-ups and both been (inaudible) 16. So, this data showed us that we have a molecule that is not only safer, but also more potent that anything is going to obtain even with the combination.

So, next up is assignment (inaudible) study and the beauty of this study is that it is perfectly correlated to the human setting from the dosing regimen 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.

And with this, I'm very pleased to hand over to Danny, who will introduce you to another ground breaking aspect of that in technology Radio DARPin.

Perfect. Thank you very much, 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 DAARPin therapy platform and respective pipeline assets. So, as you probably know all of you know, the field of radiotherapeutics is experiencing a lot of excitement push driven all by strong clinical efficacy and good tolerability data.

And that first compounds on the market or a new emerging compounds 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 type of space to be common. And that's exactly where we saw the benefit of the (inaudible)the opportunity to come in in this direction.

If you move to slide 25. So, just for those of you who are not familiar with radiotherapeutics. The ideal properties of a radio therapy product candidates are to deliver radios at the radio isotope selectively to the tumor, while sparing healthy tissue. And there's a special focus on kidneys and bone marrow, bone marrow being very tightly connected to blood levels, which are the most those frequently dose-limiting organs.

If you move to slide 26, apologies. So, on the left hand side, if you had a target in mind with the cavity where a low molecular weight compound vector with high affinity and specificity can be identified. This is perfect. It is the ideal targeting moiety. The problem is that there is very limited target, where this [exists], where the possibility and hold up.

So, to open up the Target space, the most proven class of a class of protein binders, where you can generate high affinity and specificity binding proteins that bind surfaces of a broad range of tumor targets into these class belongs to monoclonal antibodies and antibody fragments and all other small protein. The problem here is that all of these protein binders have key limitations for the effective and safe to use as radio therapeutic vectors.

For antibodies, the high long systemic half-life, high Life is leading to bone marrow toxicities and decided leading to a limited tumor penetration. And for the small proteins, we are limited by key accumulation and global tumor update. So, please remember those two elements, high key uptake and low tumor and high key accumulation and low tumor uptake. This is the dimensions, where we felt looking into the molecular properties and biological mechanisms behind this, the team has a strong conviction that the DARPin platform is ideally suited to executive building on the new unique properties of DARPin to overcome these challenges.

So, if you move to slide 27, so this is just like showing you the engine that the team has built for building our radiotherapy therapeutic candidates. Starting from the left hand side, the starting point is that for all our project building a diverse set of high-affinity DARPins against a specific target of of which, where you see, and that's always the lower (inaudible) likely accumulates in the tumor, but at the same time, still have very high kidney levels.

So, in the next step, we address the first limitation to keep. So, what we've been building is what we call Stealth design, which I will show you more a bit of data on the next two slides, where we reduced the kidney level down to below 25%. As a next step, we are addressing the second limitation. So, we're bringing up the tumor load by using our half-life toolbox, specifically built for rated European therapeutics, increasing the tumor uptake, while keeping the systemic exposure low.

And if needed at a loss that, we are increasing activity of the respected scientist to ensure tumor retention. So, the normal two aspect of the radiotherapy therapeutics and (inaudible)step number two and step number three, and I'm going to show you a bit more of a bit of data to these two points.

So, if you move to slide 27, please focus first on the upper right side,(inaudible) where you see this is what we call a normal or parental typing. What happens if that DAPRin is excreted into the by the kidney, it gets into the primary you're right here at all other proteins as well. It's reabsorb to get a lot of radioactivity into the kidney disease causing kidney damage.

What we've been building on is the extremely robust architecture of the DARPin scaffold, heavily reengineered the whole backbone and we call this the stealth diabetes. And this is now basically not recognized by these cells into kidney anymore and the DARPin activities, which is directly excreted into the urine.

If you move to slide 29, I'm showing you some in-vivo data supporting the strong kidney, reducing effect of the cell therapy. So, if you look at the left-hand side first, this is the example of our front room run a program on DLL3. So, we successfully engineered three out of three DARPins in three to four iterative and engineering round each of them taking three to four months, including all the production down to the in-vivo testing.

Now, if you move over to the right-hand side, you see after integrating all these learnings from the first programs, we manage for a new tumor antigens, for three out of four DARPins within a single round, we managed to bring them down to low levels. So, what I wanted to take home from this is that we really established a robust, reliable engineering solution to bring it down to low levels.

So, moving over to the second challenge, I am showing you how we addressed the key limitation of tumor uptake. And this is where we used systemic half-life expansion to increase tumor uptake.

Focusing on the left hand side, so you always see two examples here on(inaudible) and DLL3, on the left hand, side, you had like to make it Stealth DARPin, which shows a tumor accumulation in the single-digit percent range, very low blood level or non detectable blood levels at these time points and then if you go over to the right-hand side, we applied different half-life extension moieties leading to very low or low or medium and decreasing systemic exposure. And this nicely drives the tumor uptake up to 30% and on the tumor. And please keep in mind, all of these molecules has much lower systemic exposure compared to an antibody.

So, quickly summarizing. So, the cell therapy produced key accumulation and the half-life extension for increasing tumor uptake is the basis of our radio DARPin therapeutics and engine and basically the basis to build our pipeline. In our pipeline, we have two targets, if Novartis and(inaudible), including DLL3 and quickly expanding on our animate, extremely happy with the collaboration that we've already started one and a half years ago.

Amazing team, great capabilities, great expertise and also there is like very strong data emerging on lead to two one two as a radionuclide of choice in this specific case. And then we have additional targets, which we are moving ourselves, which are not partnered at this current point in time. So, we are looking very much forward to sharing more data at key upcoming conferences in the next month to come.

And I'm finishing here, happy to answer questions during the Q&A session and handing over to Patrick for the outlook.

Thanks, Danny, for the exciting overview that we have on the radio space. And before opening for questions, let's just look at the outlook. It's a really exciting year that we have ahead. I will start with the first and foremost most exciting one, which is 533, our AML drug. We're excited to look into the first data with you of those cohorts 56 and a taste of 7 still in the first half.

Obviously the protocol amendment push that we get that through that, we can then go to higher doses and share with you what we are developing in very close collaboration with our KOLs at a strategy that goes beyond relapsed refractory, but where would else would one apply this molecule?

And there is clear need in this indication, and we're starting to understand how we would also move forward beyond relapsed refractory. On the switch or CK side, it's clear. We are striving fast towards candidate selection. We will talk about that still in the first half of this year.

Then as Anne has pointed out. It's all about the nonhuman primate study. We will report the data second half of this year, and I think this is maybe the most translatable days toward value we ever had at Molecular Partners. So, we are convinced that, if we see strong data in nonhuman primates, the risk or the ability to translate that the risk is low.

The ability is high to translate that into patient value next year, meaning in '25 already. From Danny, we heard on the radio platform, it's all about the first candidates we want DLL3 also first half of this year that we can then move into IND-enabling studies and see that first in human data next year. We will add, as Tony said, the platform is ready, we are moving forward, add new targets and additional candidates.

And in that side, it's also a mandate to us to broaden the collaborations and move the ones we have forward. 317, where we think, we have recruited the last patients where we're still kind of in the trial, but we are expecting to close that clean the data, open the data room for partnering and advance those. And just to remind you on our cash position, we are well financed with CHF187 million in cash.

That brings us into '26, capturing all those value inflection points that I pointed out. With this, I want to thank you that have been 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.

It is hard work and also a great team spirit. The work here is a pleasure and the hard work comes easily, if 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.

And with that, I would end the presentation part and open the floor for Q&A.

Yes, we will now begin the question and answer session. (Operator Instructions)

Richard Vosser, JPMorgan.

Hi. Thanks for taking my questions. Two, on MP0533 please. Just whether you could give us any additional color, I suppose the first question on, what you're seeing and what has led to the what is more important and leading to the further dose expansion, whether it's you know that the safety profile is clearly very benign, which is great. But, you know, is there a sense that efficacy need higher doses. So, just some context of that, if you can

The second question, maybe just sort of an idea of how much higher the doses are, if you can say about that? And certainly, when should we think about a that Phase three, Phase two enabling decision? Is that more in '25 or is that more in in the second half of '24, just some color there would be helpful. Thanks very much.

No, thanks, Richard, for the fair and good question. So, maybe just a bit color on the doses and when we started the trial and obviously and then Philippe can then follow up on that. But the highest dose was calculated. And with that, knowing that we would only reach around 80% receptor occupancy in the bone marrow. You have to know in the blood is one thing, but then you have to penetrate into the bone marrow where you expect also the leukemic stem cells and others.

And so so we're just kind of looking at other T cell engagers that were 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 go to 90 or above, which gives you then hopefully an even 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 continued to see activity of the drug, but to seek to understand, if the dose response is there and we get a better and deeper and prolonged killing of the cells. We cannot comment today and we also said we would not piecemeal the data. So, you'll have to be patient until we give that update.

And that will be obviously where we will be looking. And keep in mind is also about this MRD. So, minimal residual disease. So, we will be following the clone. So, the clonality of disease and see if we can be killing the high risk clones as those are the ones which drive relapse fast. So, it's more than just the response rate. It's really understanding what the drug is doing also in the bone marrow.

Maybe I'll quickly pause there on that one. It may be, Anne, she is nodding her head, I think I covered well (multiple speakers). So, may be out on top of that add why Philippe was pointing out that we want to dose escalate or kind of dose escalate ended in faster. So, you know, we have a step up dosing and we are adding an additional step in there to reach the higher dose faster. And that is something in the first patients you saw we had efficacy and we saw a deepening over time.

Now one point that has been pointed out by our KOLs. Could you go in an earlier line (inaudible) to kill remaining cells after you have a complete response, but you are still MRD-positive, so you still have some leukemic cells and leukemic stem cells, could we kill those fast?

And obviously, this could even be before transplant. And there you don't have three months, where you want to wait. So, you need to be fast. So, this is already implementing some feedback. We're getting from the KOLs for an earlier line, where this would ideally be in two, three weeks, we have the full effect efficacy.

And that's why we are excited to be able to look into that to a steeper dose escalation. And that also goes back to your first question. I mean, we see a good safety. So, that's one of the key drivers that we can do that. So, we think that molecule allows us to explore kind of where the wells are on safety and we do see CRS. I can also tell you we do see T cell activation. So, we have the biomarkers there. So, all of that is hinting that the molecule is doing its job. We need to find out how we can tune, how we use it to get the best patient benefit.

And Patrick, just one thought there and then we can alone and move on to the next question. But then also, Tim, one last piece of Rich's question as far as dosing, while we haven't disclosed dosing I think it's fair to say. And we have said before that where we are now in dosing, we are either at or above where others have gotten to when it comes to bispecific antibodies with T-cell engagers, certainly, but I think additional (inaudible) But I wanted to (inaudible)

I often miss the obvious one. So, thanks for pointing that(multiple speakers) Richard Vosser, what will be gating. And I think there we there's definitely two things. One is what is gating to go on in relapsed refractory. And we have clear cutoff criteria there. And I was talking about the clonality and how we kill those clones, and that will be likely a gating mechanism to move to earlier lines or not. We're working on that. This will be part of the update later this year. That we really share the strategy now heard a bit in which direction we are thinking. And I can tell you it's a very good and close collaboration with the KOLs.

Richard I hope that was covering your point.

I think we got it. I think, operator, to give another question.

(Operator Instructions)

Mike Nadel [Covage], TD. Cowen.

Thanks for the questions. I have one on MP0533 and then one on the switch DARPin platform. So, for MP0533, when we get the updated interim data from the Phase one 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? And 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? So, the first targets would seem to be relatively derisked, 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 quickly over to Philippe. But I think we, I personally see two cutoffs. And if we or where we will stand in the first half versus second half and the dose escalation we will see. But we always communicated that for relapsed refractory setting. So, the patients we see today, that's where we are aiming for a roughly 30% response rate with well beyond three months disease control.

As I was pointing out, if you want to move to earlier setting, it's really about this MR deconversion, can we also kill the difficult to kill clones? So, those are the in very short, the elements we're looking for. And maybe Philippe can have your closer as you make a comment on (technical difficulty) are key to these KOLs on a daily basis.

Yes, so thank you, Patrick, and thanks for the question. First of all, you know, I want to just want to reiterate that what is really a position of strength is that the agent seems to be very well manageable and tolerated so far. So, it shows CRS , it shows IRRs, but enough to make us confident that it's doing something, but not enough to do a little enough that we are still within safe boundaries. So, that's dispersed position of strength. And this is why we want to keep optimizing it.

You know we want to densify in the first cycle and we want to go higher to make sure that we give a chance to as many as many patient as possible to [reply]. So, because, we again, we see activity, but we want to see maximum of activity in most cohorts.

In terms also want to say we are working on fairly large dose escalation cohorts, six to nine, nine patients so far. So, those can give us some good level of earnings. And then the question is when are we going to get them new to the next important relevant batch of data? And it's still is a bit tricky. So, to say, because, in fact, we are hoping to go higher, as we said already. And it will depend, you know, at some point potentially it will hit the DLT.

So, then we can expand immediately or at some point, we'll see that it's not worth going higher because, in fact, you have saturated, you know, all the targets and we have maxed out what we think is reasonable go for activation. So, but all of that, as you know, it takes a few months before we get the final, I could say translation of data that can really guide us for that. So, it depends a bit on what we are going to see in cohort seven, potentially eight, nine, you know, or even higher, but to really understand when we can figure the expansion and also the movements into the earlier line, which is a goal. Thanks

Thanks, Philip.

And then the last question I think was for much more in the switch and blue-sky scenario. I think it's a wonderful question to ask somebody at early development. So I'm excited to hear your thoughts.

Yes, you already rightly pointed out, c-Kit DARPins, which is just a starting point. And of course, there is a broad applicability for this platform, you can think of it from a data point of view because, here on the second digital first step now you can think that you apply these platforms and gates. So, you need to target to be expressed to initiate your therapeutic activity.

So, for metallic point of view, you can revive, well-known targets that has been stopped or has been limited due to the expression on (inaudible) So, I mean a good example is, for example, EpCAM was just kind of target where the annuity blades are expressed on a large tumor cells. They are very highly expressed, but they are limited by the fact that the (inaudible)And so thanks to the switch, we can allow gating and make sure that we didn't do the killing of cancer cells.

The second thing you can do with this platform is allow different effect on modality and make them safe vaccines, just about CTCL, engage on making sure that your T cells are engaged only when your targets are expressed or again also allows using co-stimulation, if we think buying (inaudible), which carriers very high toxicity risk.

Now (inaudible)and we think that this will be activated only when a set of targets are expressed. So, you are opening a broad suite of applications that honestly, even beyond that, we can't do anything ourselves. So, this is where also we will be looking for partners to completely exploit the switch platform.

Yes, thanks.

Kathleen Silverman, Leerink.

Hi, Team, thanks for the question. I am on for (inaudible) today. A bit of a tag on to Michael's question from TD Cowen, the scenarios for potential stock movement on the first half '24, [533] interim dose escalation data. If I break it into thinking at it as a layering and a floor. The layering being, what's your conviction in potentially seeing like some other CD3 T-cell engagers have seen about shape to respond or some have called it a step up respond. And do you think there's a reason to maybe think about seeing that at this dose cohort five level?

And then the last one, which I think you pretty much nailed is the floor scenario, which was Michael's question. So, in the relapse refractory data, knowing that durability will be immature and you are targeting getting eventually in a larger trial over three months as a threshold in this current cut that we'll see in the first half. Are you going to be sharing those directional signals like VMRD and the biomarkers of T-cell engagement? Thanks so much.

Yes, happy to go for on the first. I do think our molecule looks different than the other T-cell engagers. So, we also just on the safety side, we have really been able to dose to these doses that are above what competitors have been doing. So, we also hope to have a bit of different response profile, and to really be able to control disease.

And as you rightfully pointed out, we will not be obviously, it's just a matter of time be sitting on data of several months follow-up. And you also pointed out that MRD level can be a good surrogate marker on the depth of effect that then directly linked to duration. And yes, we will definitely want to update on what we have, but keep in mind a clonality of the disease. It always takes time. You have to follow it over time. So, it will be a limited dataset, but we want to share what we have and how that leads to the decision making at Molecular Partners to then further invest in the molecule, and it will be an interim update. Thanks.

[Tore cinnamon], Octavian.

Yes, hi, (inaudible). It's two a month from Octavian. Congratulations on all the progress, impressive, and thank you for taking the questions. One on the RDK platform and one on MP0317. On the RD T platform, you've announced two partnerships, but also you have two internal assets or targets. Can you shed a bit more detail from on your plans that you will follow up with the two internal targets and any potential partnering you see there?

And then on MP0317, where do you stand there and when can we expect the next update, any potential partnerships announcements? Thank you so much.

Thank you. And I'll quickly take 317 and then hand over to Danny to talk about the radio DARPin and our internal targets and isotopes and everything.

So, 317, as I said, we are literally finalizing the trial. We are filling the data room with all the data, and that should be open, I guess, as of next month, allowing interested parties and partners to look at that. I do remind ourselves that at the moment, the IO combinations are not at the peak. We were joking that a few years ago, this would be a multimillion or multi-hundred million dollar upfront.

Those times are not now. So, we are really looking for a partner that commits to the program, run several combination trials, and we're not going to try to optimize the selling price, but more that a partner can run these combination trials and it's always very difficult to to comment on timing.

With this, I would hand over to Danny to talk about kind of the internal undisclosed targets and our thoughts on sourcing of isotopes and other partnerships.

Thanks for the question. Maybe I start zooming out quickly on the target. So, our aim for picking the target is, of course, driven first from the medical need side, but also then there, we are assuming into targets, where we feel like those are very difficult to address targets with certain, I say, biological and molecular biology and requirements that need to be met in terms of specificity, what part of the time today address location of target expression.

So, all our elements play into this, and we are very carefully about nominating and picking those targets. So, we have internal programs ongoing, where we say like we lost to move them to a point where we say we are, like I say, almost like proof of mechanism, proof of that we could really match those profiles well. And then afterwards, we would love to keep that element of freedom to decide ourselves are those targets which are ideally suited for a short half-life, short range output (inaudible)like, let me really like lead from its profile or we'll be better to go into an expansion into other collaborations that we more build like on long-lived alpha emitters or even better images, if indicated by the respective tumor indication by the respective tumor biology. So, we keep it open for now, but we are definitely not only focused on (inaudible)

Thanks, Danny.

(Operator Instructions). This concludes our question and answer session. I would like to turn the conference back over to Patrick Amstutz any closing remarks.

So, again, I would like to thank my team here for all the work and all the great Q&A and shedding some light on the questions. I would like to thank you for your attention, all the good questions that we've got. I think it's clear, we're heading into a very data-rich period with a lot of also strategic work on the background, linking the data to decisions.

We will be working internally and be close to communicating with all of you to share what we have and how that forms the decision and especially the investment potential that we see for the cash we have and are truly excited to be bringing forward differentiated DARPin therapeutics for the patients that today have no good treatment options.

With that, I would like to end 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.