Molecular Partners AG Price & Performance (MOLN)

Thanks, Seth.

For the intro and kicking off the call. And please again go to our website and grab the presentation and we will be referring to a slide number that we're on and the slide number that I will kick off with is Slide number five. Well, welcome from my side. Great to have you all on this call. Before diving into the highlights, twenty fourth we did put on the twenty years Molecular partners logo because it is our twenty years anniversary and it coincides with being ten years listed on the Swiss and then later on the U. S. Stock exchange. And it has been twenty years of a quest to make drug that matter for patients. And we have never gone away from that and this has really brought us where we are. And if we look back, it has not been a straight line. It is hard work, for specific results. And twice, we actually reached clinical PoQ, with the wet AMD drug, Evikipar, and with the COVID drug in Solvibl. And I think the call today is really to highlight where we are and how we're lining up our new programs to be in a position to have more of such readouts in the future.

So let's look at the highlights 2024 and what we have done it was a year of execution to get our programs closer to that clinical readout. Let me start with the radio DARPAIN franchise where we have TLL TLL3 targeting seven twelve that is our lead compound passing all IND enabling studies and ready to go into clinics and Michael will be talking about that. We also selected a new target. And I mean, if we say selected a target, it also means that we have data. We don't just took a target and it is mesothelin and we will touch on that too. And maybe most importantly, the third bullet point is the expansion of our Oronomed collaboration. And as you know, in the radio field, we bring the vector but we still need access to an isotope. And isotope supplies is challenging. And with this collaboration, we have secured tens slots of for products, real products, not just candidates, product for lead-two twelve, one of the most promising ISO important things of last year that we have secured that access to side, it is five thirty three where a year ago, we had mediocre or underwhelming results and it was a year of understanding those, working with our Philippe will talk about that how we have tackled target mediated drop disposition problem and are very curious and also see what the future will bring.

On the switch side, there was a bit of a change. A year ago, we were moving six to one that was the NK Engager and switched. We have call it upgraded that to the T cell switch and we will talk about that as we move. There's another program, three seventeen. It is less of strategic focus today, but still we finalized the Phase one. We are very good safety. We saw biological activity and we will be moving this one forward in combination with the PD-one in investigator initiated trial. We ourselves did decide that we would not invest that much, but we still see a potential future for it. And there is support from the investigators to move it forward. And last but not least, we did a small financing round late last year to bring in our friends from HVM a very strong reputable Swiss investor, and the round was also back by existings like PBF and SOVRETA, adding €20,000,000 to our treasure chest, which makes us well capitalized with the runway into 2027. Also, well beyond those inflection points that I was pointing out before. So with that, let's move to the next slide and now on Slide [indiscernible] Come again?

Which is this one?

Yes. So with this one, the pipeline. It's not number five. Now it's five. So, okay. Thanks for that. So on Slide five, Let me quickly start with what is missing on this slide. And what is less important. The one line that is missing is the Novartis collaboration. So you remember three years ago, we entered into a collaboration we made DARPAINS against those two targets and moved them into research. Over the years, they did not progress that fast. The results were there, but I think both Novartis and Molecular partners and so they did not see the strategic interest in the target This happens. And maybe an explanation is all those research targets that we're moving, we never talk about before it is a candidate for exactly this reason because Austin you don't move a target forward. In this case, because it was the Novartis collaboration, they were there. Novartis now after three years, that was the research term, decided not to move forward. We agree with that. We would also not move forward. So that line is missing. There is no technological setback It was just not the right targets in the right time. They might come back But as of now, this is not where we or Novartis would invest.

The other one that we are not actively moving forward is six to one. A nice molecule in HCT. So stem cell transplant We said that is not our focus interest to success of five thirty three and also the success of the radio franchise is much more relevant and important. So that is one that we can sort of put on hold and opt for part time. Now where are we focusing? This is Type three-three and the radio franchise. And I will hand over to Philippe later, our Chief Medic to talk about five thirty three in AML and all the progress And Michael Stump will be walking you through the radio work on seven twelve and the latest from mesothelin and our collaboration with [indiscernible] So before we go there, I'll hand over to Robert to give us the overview of the financial situations. Over to you, Robert. Thank you, Patrick. I hope you can all hear me well. Good morning and good afternoon to everyone on the call.

I'd like to run you briefly through the key figures of last year. And the guidance for the year 2025. My name is Robert Hendriksen, and I'm the SVP of Finance here at MP. The numbers that I will present are stated in CHF 1,000,000 More detail can be found in the press release. As well as in the appendix to this presentation. Yesterday, we also published our full annual report in a 20 F So plenty of opportunity to dive into more detail. The entire presentation is also available on the website. Moving now to Slide number seven on the key figures. There are a few numbers that I'd like to highlight here. First of all, the revenue number five and seven Patrick has just mentioned, this is exclusively coming in both of these years Novartis collaboration In 2024, we recognized the last part of the upfronts that we had received back in '22. And there is no more revenue to be coming from this collaboration. So that's on the revenue. Then the operating expenses at €66,000,000 well within the guidance that we we gave That was €65,000,000 to €70 Just a high level breakdown without too much detail around 4074% of these costs are R and D related so pushing [indiscernible] the products through the pipeline there.

The overall cost have been fairly stable over the years. The third number just to highlight if you look at the overview, is the net financial result. Clearly, we benefited from high interest rates on our U. S. Dollar denominated deposits, This number is clearly volatile by design. And this year, think we, as I said, benefited from the FX rate, the interest rate, and through the small raise we did in October, we gained another $20,000,000 So that added to the the dollar pool that we have. With that, an intro also to the cash balance at the end of the year. Ending with €149,000,000 down from €187,000,000 at the end of last year. So resulting in a year on year cash investment of around 38,000,000 million dollars taken into account the receipts from the capital raise in October, The cash burn therefore for the year is around CHF54 million dollars This December 2024 balance of 149,000,000 will carry us well into 2027. And we consider this continues to put us in a privileged position in the industry And also I'd like to remind here that the company has been and remains without debt. All these numbers combined on this page, we feel these numbers tell that [indiscernible] financial story of MPN24 and show the continued solid financial state of the company.

Then moving on to the next slide, just a few words on the guidance for '25. So We will not guide on revenue or any other metric In terms of total operating expenses, we do guide for a total of $55,000,000 to $65,000,000 of which around $7,000,000 are expected to be non cash.

And as always, this guidance is subject to the progress and changes in our pipeline and excludes any potential payments related to partnerships. So to summarize and conclude here, what is relevant to remember from these numbers, I would say, is the continued financial base solid financial base entering into $25,000,000 that will allow us to continue to invest in our pipeline and to bring drugs to patients. [indiscernible] Thank you for your attention. I will be happy to take any questions during the Q and A later. And with that, I'd like to hand over to Michael Stump, who will talk about our radio DARPAIN programs.

Over to you, Mickey. Thanks very much, Robert.

Morning, good afternoon, everyone. I hope you can also hear me well. I really very happy and proud about the progress and all the achievements the various teams have made in the year. 2024. And let me first of all already acknowledge our collaboration possible. I'll speak a bit more in detail later. And 2025 is really the year with the first clinical data from the Radiodarpine and LED And that's why I'm so excited to be here. Things are moving forward. And let's quickly look back, but also then let's look a bit forward together. So moving on to Slide 10. I'm pretty sure you have heard about the DARPAINs before, so the big blue picture there, that's where we put a lot of effort into understanding what's the ideal properties of the radiopharmaceutical. It involved some protein engineering, it also certainly involves the linker chelator and of course we also explore half life expanders. Most importantly, however, for the patients benefit is the alpha emitting therapeutic isotopes, so that's the two twelve version of lead. Which has proven clinical efficacy, thanks to our collaborators from olanomet. Gives release to a lot of high energy immediate double stranded DNA damage.

And because it has a relatively short half life, it also seems to have an ideal waste management The safety profile so far so good. Of course, we need to explore further in patients. So all in all, we think that the darpins are the ideal partner for lead and that's what we are going to establish in the future. So moving on to Slide 11, let's quickly have a closer look at why Oronomid is really one of the meters in the targeted alpha therapy field. They are one of the pioneers And I think the very, very big reason to mention here is they have the supply chain under control with virtually unlimited starting materials. You see a picture [indiscernible] That's where it starts with. So there is really unlimited supply. Ronan had also recently validated their approach by an agreement with Sanofi which is of course one of the pharmaceutical players in the field. And that included their lead asset, the AlfaMedix program, which has shown very nice clinical data presented last year at ASCO. And of course, there are a couple of technical advantages That's how our teams chose to focus on that. Again, the short half life, it makes it relatively easy for patient administration.

They don't have to stay very long until they are so called cleaned. Waste management, resin asset and the very high energy release from the alpha and mid a clean decay chain. So lots of reasons to believe that this is the ideal isotope for us. We didn't stop there. This partnership was greatly expanded and that's what really changed Nate last year in the beginning of the year. We announced it around JP Morgan. So it's a global partnership expansion more and above and beyond what we had before. Are now basically together the 10 products protein moiety. And the first one has been designated MPL-seven 12. I'll talk in more detail. That's our DLL3 program. We have also announced the mesothelin, our second dialpin program together with the one hundred and fifty fifth cost share and split. Beyond that, we have two MPO programs, number five and six here, where there is an opt in and then we have another four MPO programs. So we have a very rich supply chain. So to say now for lead based programs. So let's go one step closer. On the Slide 13. Our first program, the we are really very, very actively involved in development right now.

This is the seven twelve program with a focus on DLL3, Most patients initially we will be treating our small cell lung cancer patients. Is a very high unmet medical need, relatively low five year overall survival. And most importantly, the target was validated last year by the approval of Hentgen's tarlatumab in DELTA. So we believe there is room to do to get results above and beyond tarlatumumab. But it's also a proven pathway for approval. If you look again at the light picture seven twelve, the pudarapine that we added some albumin binding half life extension two. So it's composed of three essential parts the DARPA binding TFL3, the albumin binding loyalty and the lead two twelve radioisotope. [indiscernible] on to the preclinical results, just to be very brief here. And please feel free to ask questions. This was presented late last year. A very potent molecule and the potency is very important because the target is actually expressed at a relatively low level You see the brownish stain at the left, so there are different tumors, but the human small cell lung cancer tumors we have stained came with a relatively faint brown color, which means in the molecule that is very, very potent.

CTC in the middle, that's the biodistribution, we get except [indiscernible] and much above my kidney. So we also feel we have a good safety window. And very nice to see the Xtampograph study on the right that we saw complete and durable regression in that very relevant model. At a dose that is probably the right dose clinically. So with that, I think we can look at what the clinical program will be like So there are many parts to the program. And as you can there is a green box that's the Phase zero component. Focused on imaging. And from the imaging, you can calculate then the doses for the various organ. And this together should build confidence that we reach relevant therapeutic levels in the tumor lesion. Called dosimetry probably about 10 patients in The U. S. Should be enough And we anticipate these studies to start in the second half of the year. The initial Phase two Phase zero imaging will be complemented by a therapeutic part Phase onetwoa study in patients, the first part dose escalation with the main objective to establish the safety and the recommended Phase two dose. Thinking of about 15 to 20 patients Of course, we need to get the buy in from the FDA.

And then the Part two will be the dose expansion where we hope we can also go a bit beyond the small cell lung cancer patients including neuroendocrine carcinoma and of course looking then for responses response rate, which will lead them and we don't know exactly when in the future to a registration study. Of course, there could be more than one registration study depending on the integration and the line and maybe other factors Moving on to now something completely different, our second program just in a nutshell. I'm very excited about this one because it has a true DARPAIN differentiation. We have found DARPAINs that are very specific for the membrane proximal epitope. Shown here in pink and therefore not disturbed by a lot of very high levels of SHAT mesothelin that has hampered previous approach [indiscernible] very small differences. And again, it's a darbene with a half life extension and MET-two 12.

This will take some time to finish the preclinical development and the manufacturing, But hopefully, we can also report on that progress during the year. Note that there will be a poster at AACR which is I believe late April with more preclinical data. And just to conclude my part, there is one important biochemical distinction You see here a graph in the middle on Slide 17. Where we have added SHAT mesothelin in high concentrations. And the distal darpine, which binds an epitope we don't like so much, So it's also then inhibited by SHAKNESSYVIN. We're [indiscernible] epitope, and that's totally maintained by insurers throughout the whole activity race tested. And again, this will be shown at AACR twenty twenty five in late April. So again, very excited what the teams are doing together with Euronimet, fantastic collaboration partner and very excited to look both back but especially forward throughout this year to have first patient result from these programs. Thank you very much. And with that, I hand over to my new colleague, Philippe, who is running the whole from the medical side. Will talk today about five sixty three program. Thank you all.

Progress of our five thirty three Darpin Can you hear me? Yes, we can hear you now. You're good. Go.

Okay.

So I restart So again thanks Mickey first. And I am very happy to share an update on the progress of our five thirty three DARPAIN, which we are developing in 19, basically, let's remember, it's important to remember that AML is a very challenging disease. Because of the heterogeneity of the cell population as well as the difficulty to kill the leukinib stem cells which tend to persist despite treatments and they drive the recurrence. So we have designed five thirty three as the first TTRASPI specific T cell engager that recognizes DML blast and the LSCs [indiscernible] the co expression of either CD33, CD123 or CD70. And kills them when they express at least two of the three TAA simultaneously. By doing that, this multi specific approach has the potential to open the therapeutic index and particularly kills the lung cancer stem cells more effectively than a single would do. Moving to Slide 20, So this slide describes the clinical journey that we have started two years ago When I reported last year, we were still in the blue left part of the schematic. We are now reporting on the orange middle one and we will be initiating soon a new amendment corresponding to the green. [indiscernible] In the initial dose escalation cohorts, on the left, the blue, we were able to understand the manageable safety profile of the drug up to Court seven and obtain signals of efficacy However, too low and not durable enough.

Then what we did is we identified with a group of international experts that we had in fact too much loss of exposure likely due to the multi target antigen sync. Let's remember, we are targeting free antigens. Two twenty three. And so at that time, we initiated a first amendment to accelerate the step up dosing and densify the regimen by adding an additional dose during the first fifteen days at day 12. And I'll show you the results of that. And basically that we have now significantly increased the efficacy and we are now very encouraged to further accelerate that step up dosing and have a more frequent administration, particularly during the first cycle. This new amendment corresponds to the green schematic and has been submitted to regulators. Moving to Slide 21. You can see on the left swimmer plot corresponding to the blue part of the dose escalation during which we saw some initial responses however, not enough and not doable enough, as I already said. On the right part, you can see that the outcome after the initial amendment and the initial step up dosing and one level of densification And you can see that this now appears to be very promising with three CRs out of eight patients that were treated past day 12.

Moving to the next slide, which is a waterfall, That slide in a way that visual adds one level of granularity to the document to document the blast reduction on top of the full year LN criteria. And we can see here that the drug had effect with approximately half of the patients having reduction in blast even during the dose escalation. However, the new amended cohort certainly has more. And also this helps understand that most of the patients that have blast reduction had a lower disease burden at baseline as is frequently seen for effect for T cell engagers. Moving to the next slide, [indiscernible] it's a key slide. Because when we discussed the blue curve representing Court six with our experts, they were even surprised that we had had even responders and blast reduction because as you can see, there were only very few concentration peaks in the effective dose range on the eight, the 15 and the 20. So very little stimulation or effective stimulation to generate that blast reduction or initial responses. And this is what is very interesting is that in the recent amendment, so corresponding to the orange curve, we see that there that in those orange curve, the concentration effective ranges at the eight, twelve and fifteen for significantly more time [indiscernible] And we hypothesized that this component supports the higher activity that we see in this new cohort.

So based on that learnings, we have now built on this finding and are further densifying the dose and also introduce a B cell depletion pre medication to also reduce the proportion of patients who were developing ADAs at the end of the first cycle. So we basically, it's a two pronged approach. Densification to generate deeper response, more responses, and abysmal depletion to make sure that we have a maximum of patients that have long exposure beyond the first cycles. So Slide 24, describe the further amendments which is currently in review.

And we anticipate to initiate it soon and communicate outcome of those new cohorts by the end of the year coming. Okay? So I'd like to expand a bit on this now. Meaning that the first experience regarding T cell engager has driven us to develop further the platform and we have initiated programs in solid tumors where it is key to manage the on target of tumor risk of toxicity. And you may know that there has been some good level of excitement recently on that topic with development from companies like Janex. So Slide 26 is an example of how we are integrating the concept of masking the CD3 binders in absence of TAAs. As well as the concept of co activation to mitigate the risk of T cell exhaustion. So it's two scientific concepts integrated. And more precisely, you can see on the left schematic that this darpine has the CD3 mask circulation And on the right, that when engaged with the first TAE like here mesothelin, similarly with a second TAE like Epcam, this will free the CD2 binding to the T cell. And the CD2 co activation does potentiate the immune mobilization. So this is a very sophisticated approach, highly relevant, we think.

And again, some others are analogy there's analogy to what all of us doing, but we think that we are doing it in a very sophisticated manner. And will share further detail of this interesting approach at the upcoming AACR. So on this, I want to thank you. And I will pass again the phone to Patrick.

Thanks, Philippe, for these very nice and explanations and also showing us how we have worked through some challenging settings and findings. To give especially five thirty three the best chance to succeed and help these patients Let's have a look what we can expect in P25. I will start on the radio side. And I think there, as Michael pointed out, we are really excited by the perspective to share that the first clinical data of of seven twelve, the Radial BLL3 program We do start with imaging, as he explained, that it's a Phase zero approach. And then we can do dosimetry and have clinical results in efficacy and safety in 2026. And let me just take a minute here because in most instances, you're Phase zero imaging is maybe not that relevant. This is different here. We will have the understanding of how much of the drug will be in the tumor and how much will be on the healthy organs And for those who are less familiar in the story, the one organ we're really zooming into and excited to then see results is the kidney. Because most of these approaches have high kidney absorption. So we'll be first and foremost looking for a tumor to kidney ratio and should that be positive in the dosimetry that is an exciting moment to move the program forward.

So the imaging holds real value for molecular partners and the whole radiodarpine pipeline. Meza will go forward, we will update that at AACR. And we will definitely not stand still, but add additional programs that are some fully owned by us, others likely also move forward by Oronomed. Moving to five thirty three, as we just heard from Philippe, we are now at this moment where we can test maybe the optimized or even optimal dosing for this compound in a deadly disease. So that is a highly exciting moment for us. That's the reason we go to work to test our drug in the setting where it helps patients.

And we will be able to update with more data from cohort one in H1 and for sure in H2 this new amendment that Philippe talking about will be in place and be delivering results guiding us on response rate and especially also on duration of On the switch side, as I said, we are there moving forward mesothelin or maybe another one where still looking at a few. We're also opening for partnering be it six twenty one or or also on the T cells because we will not have the bandwidth to move all options that these new platforms give alone. Cash situation is strong, almost boring for us. But I think boring in this market is a good thing. As many biotechs are struggling for funding and we are in a position we can execute our plans, move forward bring value to patients that will then also move into value for shareholders. Now before opening for questions, this is a moment to also thank you for dialing in. Thank the the presenters that I had on the call and stay obviously just present the tip of the iceberg of the molecular partners team. And that team really makes all this work.

All those hours, all those troubleshooting, all those coordination meet moving things forward, Big thanks to everyone at Molecular Partners. Highly and full of gratitude to be able to be part of that team. We don't do this alone. We do this with partners think the name or Anomet was said many times, big thanks there. Also to Novartis, without Novartis, we would not be in this call. We would have not moved forward in radiotherapy. And it is maybe more on a personal side fact that we're not continuing that one, but I'm sure there will be opportunities also with Novartis to move things forward in the future. The troubleshooting not only [indiscernible] experts that know our drugs, big thanks to them I do think the last and possibly most important thanks goes to the patients that are in our trial that are part of them and allow us actually to test these drugs early on to see if they actually do what we want them to do. With that, thanks for everyone dialing in, especially also the analysts. That cover us for these many years. For those ten years. Some of them have been doing it for ten years.

Big thanks for that. And looking forward to your questions.

The first question comes from Jonathan Chang with Leerink Partners. Please go ahead. Hi, guys. Thanks for taking my questions.

First question on MP-seven 12, Can you provide more color on where you are in the IND submission process and preparations for study initiation? And how should we be thinking about the initial clinical data by year end? And then second, question, can you discuss why you think mesothelin is a good target for radio Dartmouth? Thank you.

Mickey, are you on? Because I think that is goes directly to your area of expertise. Yes.

Yes, I can start and then please continue. So thanks, Trondsten, for the question. I'd love to sit down with you in more detail and go over but just give you the top line. So as I said, late last year, we started 2025 with the GMP manufacturing. That has moved forward really nicely. Of course, are a lot of technical challenges to be overcome including logistics. Q2, so next quarter will be the sufficient submissions, maybe there are several ones to the FDA. And that's where hopefully then in Q3, we can open the first part of the program, the imaging part. And in the net of part of the year, so I'm not exactly sure where we will be, will then have the first therapeutic doses. If FDA agrees to our proposal to start close to therapeutic dose rates. We should see something maybe in the first two dose cohorts. And as you know, probably tumor shrinkage and then also the duration of it will probably take a bit of time. So early twenty twenty six will be then the the clinical data from the therapeutic part. Submission in Q2 anticipated.

Your I believe third question, mister Silin, why is it a good target? Excellent question. Of course, we are hoping it will be a good target. There is certainly a high medical need in the ovarian cancer patients. And mesothelin expression is very high there. Whether it will be perfect for an alpha emitter now of molecule we need to establish, it looks good pre clinically. But whether it will then work, that depends to the on future data. There are a number of programs also using other modalities. But I hope with the alpha radiation of lead we can tackle these two results.

Yes. No. And we often get the question on mesothelin because it let's say in public it's a bad target because others have failed on it and are not moving. I think as what we do is we go back and we triangulate the data and it's also a phrase we use internally. We like to work on clinically validated problems. And in this case, as you said, Michael, ovarian is immune more silent. So you don't have that much effect You often have chemo resistance, so and also not the highest response rate for ADCs. And MESO was in principle a good target for the shedding and the high level of free target made it a very difficult approach for radiotherapy because you don't want to be binding SHAD target being in the body everywhere and having an on target of tumor effect. So this is the hypothesis that ovarian will be radiosensitive when delivering an alpha via mesothelin. The target very difficult for peptides to do. So we don't expect anyone from the peptide field to be able to crack that one. So it is dark and unique and differentiated. And that's the thesis that we will have to prove.

If it works, good thing is I do think we are very differentiated versus other radio approaches.

Understood. Thanks for taking the questions.

Thanks, gentlemen.

The next question comes from Richard Vosser with JPMorgan. Please go ahead.

Hi, thanks for taking my questions. I wondered if you could just explore learnings taken from the Novartis programs before they were discontinued? What you could take there? And also whether there were any issues with the DARTIN hitting the target or was this, as you said, just the targets don't work or they've been deemphasized? And then a second question just on you mentioned the key for seven twelve is the kidney ratio. To target ratio. So what could be if you could help us with a good level on that ratio that we should be looking for when we see the data? And you'll be looking for?

Thanks very much.

Thanks, Richard. I'll start off with Novartis one. And then I'll hand over to Michael. I think when we started this three years ago, and that was really our first steps into radio. And we learned a lot by sharing and learning what profile makes a good radiotherapeutic. So tumor to kidney and Michael will come to that. Half life and this is all also gauge to which isotope you need and you apply. And there Novartis is obviously lutetium and more recently Actinium. While we are going towards lead. For different reasons. The learnings, I mean, I can't be too detail oriented here, but the one thing we all agree in this field is you have to test many candidates, meaning many different sequences to find the to have the right models up and running and different models will give you different insights. And it was very helpful to compare notes on the models, how to run the models, how to use the models. And at the same time find what can you learn and what can you not learn from these models. And I think have to understand this field is still in the early days. And for the DLL3 I think we were in iteration seven or eight.

So that's the seventh generation that we have. With Novartis, just given the the broad pipeline they have and the way they operate, we think never made it by on level three. So it was maybe not that fast cycling. Do think and I'm fair to say, I've said that on stage that that was also learning for Novartis. That was one reason they acquired Mariana to have potlabs faster to be able to cycle faster to test more in shorter time.

At the same time, the targets they picked, which were very reasonable three years ago, did not like have the data or the excitement building. Like DLL3 when we started was also not present. And then with tarlotsamab and all the excitement, it validated itself. These targets are still as unknown, I would say, as they were three years ago and nothing has built around them. So when you come to this moment, say, should we invest another three, four cycles Maybe it will yield, maybe not. On a target that today neither Novartis and Als puts to the top of the list. We sort of together said, let's end it here, see how this goes on and then rather reengage when we actually have a candidate. I mean, this is a research phase. But the learning was really good. Collaboration was good. Scientifically speaking, I think both teams really liked that. And we'll see where it goes. I think I can also say that Novartis wants to see clinical data on lead. Now we're talking about the isotope. They have obviously seen Oronomid. But for Novartis to add a third isotope to their ward chest that would need clinic data.

That's at least what they're saying publicly. Maybe, Mihi, could you be a bit could you take seven twelve tumor kidney Yes.

Richard, and also here next time we meet, let's take the time and sit together look at the piece of paper or the laptop screen. I think the challenge is in animals, it's relatively perfect. So you can control everything. You can give a number. And pre clinically, you've probably seen this before, we like to go above one, so ideally two:one tumor to kidney. Then of course sometimes there is a question which time point do you integrate over many time points. So animal models relatively easy in patients. We need to learn clinically whether there is exactly the same translation In the end, it boils down to the therapeutic dose we can deliver. So ideally, we have, as Patrick said, more more of the uptake in the tumors, but I'm pretty sure it depends on the tumor size, the blood perfusion. Whereas the kidney will be probably relatively similar from patient to patient. So if we can deliver a therapeutically relevant dose to the tumors, and we're speaking in the order of one hundred megaacral per dose, and the kidney stay below the safety limit that is at the moment accepted. So several grades. But it's exactly one of the questions we don't know for sure whether [indiscernible] has the same limit.

So we will have the discussion with the FDA. We'll propose our escalation rationale. And I'm pretty sure it will be similar to preclinical data, but I would not look for a specific number because tumors in patients are very different. So on average, I hope it's above the kidney value. But maybe in the end, it's about therapeutic dose.

Excellent.

Thank you.

The next question comes from Mike Delkovich with TD Hi, thanks so much for the questions. I have two.

When it comes to DLL3 and radiotherapy, do we know you mentioned the kidneys, which I believe is nonspecific. Off tumor uptake. Do we know are there any on target off tumor DLL3 expressing organs we should be concerned about when we see the first imaging or dosimetry data? That's my first question. And then my second question is on the SwitchDARpen platform. This is very unique and very promising. How do you think about partnering in terms of the scope and scale? Would you be pursuing a partner for an individual molecule or more kind of platform wide? Thank you.

Maybe, Felix, take the first question on the other three. And I'll be happy to talk a bit on the platform or candidate partnering.

Yes.

So thanks, Mike. [indiscernible] DLF region is a clean target. That's why there is so much excitement about it, I would want to say. And experts are very excited, in fact, based on the recent accumulation of experience, which has a conveyed on the antibody. On the ABCs or on the radiopharma approaches. So is a body of experience, which is still early but rapidly shaping. And I think for what we know, from the programs is that we pituitary gland, is the only place which is has some level or a mini level of deleveraging expression. All the rest is clean. And when we looked at the tadalatamab experience, for example, they did not have any specific safety profile And of course, we checked on the pituitary gland, and there hasn't been any adverse event that makes think that that would be an issue. But of course, technically, if I could say, there is a little expression there outside of the tumor. So that will be the one that we'll watch Although again, we are not very worried because there hadn't been a problem, we would have seen it already. So that's so very clean target. And we are confident obviously and as we're preparing our protocol obviously what are the adverse events of special interest and that this is short.

For us, but also for the others.

And maybe just to add because there is a big hype on DLL3. So I think on the target, people totally agree that that is call it, validated and a very good target to go after. And we just had dinner with a PI that is in many trials And for me, what was reassuring to hear is that the different modalities and we're talking T cell engagers, ADCs and radiotherapy that he he also said there is a need for all of them. None of them will cure as of now. And the sequence and how we can actually develop them is was very exciting. For him. And he actually sees a big place for the radiotherapy there. Even a bit in the earlier line to help the others move forward. But thanks for the question.

I'll take also the partnering one.

And the question is great. I mean, some partners like to work on a candidate. These are either companies that have a specific need. Let's say you're just take this as an example, you are in breast cancer and then you want a breast cancer target and candidate for the pipeline and ideally then we have a candidate there. You sort of are the missing piece in the puzzle. As you don't know and kind of in which puzzle you're you fit well, that is sort of an opportunistic one. You obviously look who's what do we have, which candidate do we have and where would they fit. That is one part of the partnering versus the other. The big pharmas obviously take long shots. They see that they want to fill their pipeline over time. And often they say, okay, your targets are a nice showcase, but can you do these? And both discussions are valuable. Obviously, if you have to start from scratch, that's then eighteen months, thirty yes, two to four years of research and development as we just saw with Novartis collaboration. Usually, they come with a good upfront because there is high risk. So you have to also commit something there.

Versus a candidate that is ready to be in the clinics within the next eighteen months that is exciting. At the same time, it has that puzzle piece has to fit and we don't know sometimes where it fits. So both we are looking at We're looking into both. Discussions are ongoing. And we will see how they develop from here. Thank you so much.

The next question comes from Kiara Monteroni with Kempen. Please go ahead.

Hello, team. This is Tiara from Kempen. Thanks a lot for taking my question and congratulation with the update. On 07/12, I was wondering, the Phase zero and one will not run-in parallel, right? So did I understood correctly that the Phase one start is contingent upon good imaging data? Or am I wrong? Thank you.

He is not in line. I can take yes, go ahead, Michih.

Sorry, Philippe. Yes.

A lot for the question. It's a really good one because we are proposing to the FDA that it should not depend on each other. We want to do them in parallel. We have the required animal data to argue for the parallel start. But in the end, of course, we will listen and have to live with what FDA decides. So stay a bit with us. Ideally, in parallel, but it's a regulatory question. So and if that is, I think we'll probably keep them together just a few months apart because patients like to be treated and not just image. So also for the patient, we keep them closely staggered.

Yes, of course. Thanks a lot. Really helpful. Welcome.

Thank you.

And the last question today will come from Yoris Zimmerman with Octavian. Please go ahead.

Yes. Hi, Patrick and Tim. Thanks for the presentation and for the opportunity to ask questions. I have a short one, I guess, on just on the structure your deal with Autonomy. If you could elaborate a little bit on how those different programs are split between the two companies? I mean, you've nicely depicted that on Slide 12, I guess.

Just to understand, so the later programs will be fully owned by you and then there is two with opt ins. But who will take the commercial lead for those? And then also for three and four, is it correct that this will be mainly led by Autonomy? Yes. No, thanks for the question. And I'll do a short recap of how this all came about. So we started a collaboration on an NTA with Auronimed on the DLS redarpin. And so that was sort of call it the honeymoon. And we had made very good progress on it then we said, okay, let's move forward. At that point in time, we did a deal with actually three targets or three products of these were both fifty-fifty. We got first The idea was they would take the second and then the third, we would see how how that develops. I think we had underestimated the speed and productivity of what we were doing. And so what had happened is that we took the first but then miss Ocelin came about and we had to approach them and say, actually, we have a second And then there was an imbalance. So we said, okay, then let's add a force that we get one and two and they can have three and four in the fifty-fifty, but commercial leads for one and two are with us.

In the meantime, they were successful in their Phase two and did a massive deal with Sanofi bringing in $400,000,000 for late stage development and commercial supply, So they have a clear mandate now to put that money to work, build the manufacture [indiscernible] [indiscernible] And it's sort of I would say it is clear where their focus is.

And so we were like, okay, we have one and two, you have three and four and your focus is late stage, let's sit together because we cannot wait until your programs. We want to do more. And then is where this win win situation happened where we said, okay, let's add six. Molecular partners can move them forward and add early clinical Phase zero ish data for Anumet can opt in into two, while four will remain with us. So I'm not going to go into all the details, but you see we are helping each other. They have time focus, money to build the late stage We are working a bit more on the early stage and they also get then with the opt in what they need to build their pipeline. So for me, it's a beautiful example of a win win situation And I do think on value, this has gone very much under the radar. That we have 10 products worth of lead supply with the most advanced and credible partner you can have. So big thanks to them. Indirectly also big thanks to Sanofi for putting all that money to work. And we're ready One point also, these are these are commercial products.

So if number eight would fail, in Phase three, even then we can go back and replace it. So these slots are up to commercial stage. So if you want, this is a thirty-forty target setting you can do. We don't have to. We can also do other isotopes. But I would say for lead, we have access to whatever we need. Thanks very much. That makes a lot of sense. Maybe a very quick follow-up. You mentioned the high productivity. So how should we think of timelines and frequency of you and Autonomy disclosing the additional programs? Yes, that's a good question. And that's sort of like you never communicate too much what you're doing in research because it is so so risky. And then if I will give you an update on our pipeline today in research and a year later, a lot has changed. That's why it's always we're careful. But I think it's fair to say that my guess is we'll have two new targets that we will be talking about this year. And also new, call them technologies that we're testing. So it's not that we are waiting in radio and sitting there but we're also evolving our platform for next generation as we go.

So I think in all fairness, roughly two targets per year is likely a productivity that is fair. Pending the results of seven twelve obviously, we can ramp up more. Their clinical data will be key.

If that looks as we hope for, then let's move forward. And two more.

Thank you so much. Thanks.

This concludes our question and answer session. I would like to turn the conference back over to Patrick Amstrutz, CEO for any closing remarks. [indiscernible] Twenty years Molecular partners, twenty years innovating and bringing drugs forward.

I'm also proud on the timing. This is almost Swiss timing. We're right on the hour as we had planned. So also thanks and thanks for all the great questions. We're off to an exciting year. We'll keep you updated as we collect the data. We'll also work closely with you to give you the what you need to also I'll end with a big thanks to my team treating physicians and especially the patients. See you all soon. We're at many conference. Going forward. So reach out and we'll be in contact.

The conference has now concluded. Thank you for attending today's presentation. [indiscernible]