Welcome to the Molecular Partners presentation at the J.P. Morgan Healthcare Conference. I'm Richard Vosser, European Pharma Analyst at J.P. Morgan. It's my great pleasure to present and welcome Patrick Amstutz, the CEO of Molecular Partners, to the presentation today. If you have a question after Patrick's presentation, then please put your hand up and wait for a microphone, and we'll take your question. Patrick, welcome to the conference. Good to see you.
Thanks, Richard, for the kind intro. We were just exchanging that this is our number ninth presentation. Next year will be ten, so next year we'll definitely have to do some special celebration here together.
Warm welcome to everyone here in the room, but also those on the webcast. I want to thank my coworkers also sitting here, as they have given me a very nice challenge. The last year, they have worked so hard that I will have a hard time to put all the good results into the 25 minutes that I have today. So fasten your seatbelts, and off we go. Disclaimer: as usual, I'll be making forward-looking statements.
For some, a recap, and it's almost wrong to say that DARPins are a novel modality if I say that we've been here 10 years, but we're always finding new applications for DARPins, and we're discovering things that we haven't seen and engineering DARPins that we haven't engineered, and that's really what this is about. It's not small molecules, it's not antibody, it's, it's something else.
And I don't want to say in between, it's really something different. We have 7 clinical compounds, so we know quite a bit how they behave in humans, and that is always informing also our next programs. And as I said, it's all about using the uniqueness, the differentiation, the DARPin platform or the DARPin thing. And my talk will be a lot about how we are using the uniqueness to generate patient value. And it is the patient value which drives us.
That's our purpose, and we couple that with a need for early clinical readouts. In the past, we had few molecules that needed to be combined, that did not have single agent activity, and that becomes very difficult to develop.
Our mandate today is really every molecule that I will be showing you today has single agent activity, also bringing clinical value early on. As we are diverse in what we do, and we don't want to reinvent what others are doing good or better, we really like to partner with the world-class expert, and you'll also see that we have released a new partnership in the radio-DARPin space. The highlights are also my agenda.
I'll kick off with MP0533, a tetraspecific T cell engager, and I will update you of the data that we had at ASH and a bit of the status of the program. Then the Switch-DARPin, that's a new one. I will be talking about a c-Kit molecule for HSCT. The other part, if you have a AML franchise or pipeline, is the DARPin, the radio-DARPin space. We will update on that, made good progress, especially in Q4 of this year.
317 , I'll skip for today, and I just want to kind of remind ourselves that we're in a very strong position on cash, and that goes back to Ensovibep, our COVID DARPin, where we had a very nice option fee from Novartis, and it's not on the pipeline chart anymore, but actually everything we're doing, we are now funding with the success of that molecule.
We have updated the pipeline chart, and I just want to draw your attention to the new kids on the block, the Switch-DARPin. It's a c-Kit CD16a, CD47, and also in the radio space, we are now spelling out a bit more lines, and there are actually more than those three as we have more targets moving forward. I'll dive into 533 first.
That's the call it most advanced one, that single agent active molecule. You see it here. I like the picture. You see three DARPins binding an AML cell, a tumor cell. The blue DARPin is engaging with a T cell, and then you have another two DARPins that are binding HSA for half-life engineering. And I, with the team, we were at ASH, and we really got reminded how deadly and how poor the outcomes in this disease are, especially if you are of older age. And it goes back to really a lack of good targets and a high risk of clonal escape.
If we take a bit closer look at that, one can see, and that goes back to the hypothesis that we are following here, that there are targets, and we're talking here CD33, CD70, CD123, and they are also expressed on healthy cells.
But our translational team came up with the hypothesis that they then looked in a lot of databases to verify that you see co-expression of these cells, of these targets on AML cells, also leukemic stem cells, especially CD70, while the healthy cells are mostly mono-expressing these targets. The idea now is to have our tetra or tri-specific times CD3 that has lower affinity to the mono targets, so it will not kill the healthy cells, while it will engage AML cells and kill those much more effective than healthy cells.
What you see here on this slide is the call it preclinical proof of concept of that mode of action. You see, we built a Venn diagram knocking out the individual targets. In green, you have mono expressing cells, in red, dual and triple, and you see how we're opening that window of targeting, and this data was presented at ASH 2022.
What we now presented at ASH 2023 was data of the first 4 cohorts of the trial. So we just started a year ago. We're now in dose range 6, so that's a bit of an update, as we have now passed dose range 5. We're safe, we're well-tolerated, going up as I speak, and that is also a testament to the clinical power of our company and the execution of it. We have a step-up dosing, just to remind you.
We start with a bit lower dose. That is because we do see T cell activation. That brings me to the next slide. We have IRRs and CRS as main side effect, and I would even say it's not a side effect, it's actually an effect of activation of T cells.
Anne and her team could also show that it goes in line with T cell activation, so we can measure that, so it's actually activity. This is the snapshot of the first four cohorts, and you see, we actually have two responders, one in dose range three, the other in dose range four. I remind you, these are both sub-therapeutic, suboptimal dose ranges, but it also shows you that this molecule really works.
I can remind you that this is the first tetraspecific T cell engager and also the first non-antibody-based T cell engager ever into the clinics, showing activity. This then opens other approaches, including Switch-DARPin on CD3 that I will be talking about. We will have more to come in the coming years, and what I wanna do now is go to our next program, which is preclinical.
It's actually pre-candidate, but introduce you for the first time to a program in HSCT. When we are or when we were working on 533 , we did realize that 533 will help, but it will also not solve all the problems, especially as those patients would ideally profit from transplant. It's those patients that have a high-risk clone or are elderly and frail that cannot profit from transplant.
So the challenge is to create an induction regimen that goes deep, kills the high-risk clones, and is very safe that most patients should be able to profit. We came up with an idea for that program that has the following logic: We target c-Kit on hematopoietic stem cells and leukemic stem cells. It's a target that has been known.
We know that simple antagonists are not good enough, while ADCs are maybe too toxic. So we need a strong, effective mode of action to kill the cells that is benign on safety. So we chose a CD16a DARPin for engagement of NK and macrophages, and at the same time, that is a good mode of action, but it will be limited by CD47.
CD47 is the "don't eat me" signal on all cells, and that will prevent the activity, so we need something to block CD47. But as CD47 is on healthy cells, it has so far never been successfully really targeted. So we needed to create a mode of action that allows that to happen.
For that, I would like to introduce you to the either/or or Switch-DARPin. And I'll keep this a bit simple here, but in principle, DARPins are like molecular hands, and you have a right hand and a left hand. You can bind, let's say, fruit, a banana and an orange, and you have both in both hands.
If you now fuse those two hands together, in one hand, your hands will have to decide, "Do I now hold the banana or the orange?" Or whatever you have selected for, and you have an either/or, a gate. And what we have done is to create exactly that gate that has to decide between c-Kit and a DARPin that binds CD47. And this is the basis of the switch.
So we have this molecule. In gray, you have the switch. It binds to CD47 DARPin. We have another c-Kit to target this to the cell and the CD16 as activity. And as this is a bit complex to follow, we have a little cartoon. You can go to our homepage and watch it. And so what happens is the c-Kit will bring it to the cells.
This is still the closed confirmation, but the affinity from the switch to the CD47 DARPin is not so high, so it will open and close and breathe, and in that moment, the c-Kit part will bind to c-Kit, and the CD47 DARPin is free to bind to CD47. Then again, CD16 can engage macrophages.
They will not be blocked by CD47 and will engage and kill these cells. And we had a few investor meetings, and people were saying: "That's crazy. That will never work." And then I'll quote Anne, "The data shows you that it works." And the order of magnitude you see here, you have the light blue line. These are c-Kit-negative cells, so there is no c-Kit to sort of bind and open, and you see you need a lot of DARPin to then still see some blocking of CD47.
If you now add c-Kit to those cells, so these are not knockouts, but c-Kit-positive cells, you see already small amounts allow you to bind, to open and block CD47. So this is sort of the preclinical proof of concept of the first Switch-DARPin that we will now perfect and nominate a candidate first half of this year to hopefully then be in the clinics next year.
So amazing engineering on a really important problem to solve in this space. We're not limited only obviously, with this switch concept to the CD47, CD16 combo, but you can use that. You can exchange c-Kit for whatever targets you want and build the molecule you like.
We also have that now on CD3, so we have a CD3 mask, and we have a whole suite of effectors, including CD2, CD28, 4-1BB, to super boost T cell engagers, and we'll also be nominating maybe a candidate there, and we are open for collaborations with other partners if you have a mode of action in mind that this would solve. Good.
Short break. And now to something completely different: the radio-DARPin space. So radio-DARPins are— Why do I say completely different? We're, we're not building here on the multi-specificity, on the Switch-DARPin concepts, on T cell engagers. Here we're really building on two benefits of DARPins: the small size and the very high stability. Radiotherapies, I think we're all aware that's definitely the hot space at the moment. We saw all these acquisitions, and it's clear they are highly effective.
You have the psychology that you see what you treat. The supply chains are being solved. We saw BMS acquiring Rayze, we saw Lilly acquiring Point. There's massive investments going in here. We see increased use, and where we think the remaining need is, is the vectors, and I'll come to what the vector is. It's not that we're just starting this now.
We've been doing this now for more than two years, and it started with a collaboration with Novartis that reminded us during the COVID collaboration, how well DARPins would be suited for this. So what you see here on the left-hand side is the setup of such a radiotherapy. You have a vector, a linker, a chelator, and the isotope, and we'll be focusing on the vector.
The idea is to deliver a lot to the tumor and keep it minimal in the blood and the kidney. Those are the organs you need to spare. If, and I'm now on the left-hand side of this slide, if you can use a small molecular weight targeting vector, do it. It will be perfect. It will leave the body, it will give you high accumulation in the tumor.
It's really a way to go. At the same time, you'll need a target with a groove, and you'll need to bind tightly and specifically, and we do believe that that's much more difficult, and that's why the whole field is collapsing on a few targets. The untapped potential, you have to use protein-protein binders, including antibodies or small proteins.
Antibodies have too long a half-life, so you'll go for smaller proteins, and we believe DARPins are ideal. Why so? And I'm here on the efficacy side, the small size and the high affinity allow your loading the tumor. The safety, you will be fast out, and you will be selective in the tissue, and we can target the whole broad target range.
And still, there are a few things we had to really overcome. First and foremost, the kidney. DARPins are reabsorbed in the kidney, and I'll talk about that. Second, you have to load more on the tumor, and if you do number one and two well, repeatedly, you own a platform to build a full pipeline, and you have a real engine to fuel what you're doing. What you see here is the kidney problem.
Left-hand side, the DARPin, it's G3, a HER2 binder. It's fused to technetium. You see the tumor, and you see the kidney lighting up massive amounts. What is happening? The DARPin goes through the kidney, it's excreted, but it's reabsorbed, as the body does not want to lose proteins, and it does not want to lose peptides.
Everything valuable is kept back. What we have done is we have created a Stealth DARPin. We have re-engineered the surface that it is not recognized in the reabsorption mechanism, in the brush border, but it actually then is secreted into the urine. We have published data on this, and you see we have kidney reduction of 80%-90%, while the tumor is around 5%.
At the same time, this is only sort of the tip of the iceberg, as in the beginning, and this is the first time we actually published data on DLL3, so this is highly meaningful for our pipeline. You see, it was not just one engineering round. It was two, three, sometimes even four rounds of engineering.
You had to re-engineer the surface, test it in mice, and then you had to learn from that and do the next round. So it took us roughly a year to get the DLL3 low-kidney stealth DARPins, and you see here three of those. We also have other targets, and we're always integrating the learning. And here you see out of four parental DARPins with one engineering round, we are now there. So we have learned a lot. We're filing IP here on this approach.
So from here forward, we should be much faster to build the pipeline, and this is really the part of the engine. So now we're in the kidney, in the low kidney, in the 10% range, maybe 20% range kidney. We also now have to load the tumor more. And if you take a stealth naked DARPin, I was telling you before, we're on the 5% range, and that is not quite enough.
So Dani and his team have tested, he just told me, around 30+ different half-life extension approaches. And I'm saying approaches because there is a few variabilities in there. And we discriminate between those that have low level to medium level. So we're talking hours to a few hours half-life of these clones.
Now you see nicely how we're bringing this up to 10-ish% for low, and then medium half-life is 20-30%. On the right-hand side, the far right, that's the DLL3, that's obviously our favorite, where the blood levels are low and the tumor is now nicely approaching the 25, almost 30%.
I think we're in very good state there to marry these both dimensions, low kidney, high tumor, to have a first candidate on DLL3. As I said, if you now marry both of these, you can build a pipeline, and that's what we're doing. We're applying it to the two Novartis targets, X and Y here. They are exclusive with Novartis.
We have a suite of own targets, the light blue ones that we are moving forward, and we just announced a collaboration with Orano Med to access lead, as obviously we don't have radioisotopes, so we will be working with the experts, and it's a real pleasure to be working with that group. It's not that we start today.
Everything I showed you on DLL3 was already done, and we said once we're approaching candidate, that's when we need to sign the agreement. And the relationship builds and we have more candidates, we can also add more candidates into that collaboration. And it's not that they are only lead suppliers, they also really know their business. They have their own pipeline with small molecules, with peptides, and they really like the DARPin approach. It's just a few words on that.
As I said, it's a really true collaboration. It's 50/50. We share everything, the ups and the downs. They bring lead, we bring DARPins, and for the first candidate, we have the commercialization rights. Good. So another breath, deep breath before we come to the outlook, and then I would ask my colleagues to join me on stage for the Q&A. But I think we're really entering a very rich year for Molecular Partners.
And the first foremost, recap 533, so now we're entering the therapeutic relevant doses. We'll definitely give an update in the first half of the year. Safety seems to be trending really well, so let's hope for that, that we can go to the top doses and maybe even beyond. We'll also open an IND there, so we're highly excited to see how 533 develops this year.
Switch-DARPin, first candidate we're moving forward, should be nominated first half of this year to be in the clinics next year, and hopefully, it actually will, even be able to produce first clinical results then. I'll also point out that the cyno model is very translatable for then the human outcome, as we will also be killing, stem cells, hematopoietic stem cells in the cyno model.
So I think it's one of those assets that the cyno model will be very guiding. We have the radio space. There is more to come. First candidate, additional targets, additional candidates. I mean, that's really on its own a, a full franchise that we're broadening, and we're also, as you just saw, are broadening the access to these, isotopes with the collaboration with Orano Med. Three seventeen, I did not talk about.
It's winding down the phase 1, so last patient has been dosed, data will be collected. It's a tumor-local CD40 agonist. It activates antigen-presenting cells, and we are in some partnership discussions there for combination trials as that's where it belongs. Just repeat myself, we're well-financed with cash into 2026, funding everything I have shown you here, and obviously, excited to now open for questions and ask Anne and Dani to join me on stage.
Before I do that, I do want to thank all of you for coming here and attending. I think this is, it's nice that you're here. I want to thank my team here with me, but also those at home for the passion, the work, and the progress they have demonstrated.
Our partners, Orano Med, but also all the clinical sites, and obviously all the patients in our trials that make this possible, and that's, in the end, the purpose of our doing, helping these patients to fight their disease. With that, thanks, and open for questions.
Thanks, Patrick. Thanks very much, Patrick. So we're, we're now entering the Q&A phase. If anyone's got a question, please put their hand up. Maybe I'll, maybe I'll start. Maybe we can start with MP0533, and just as we look at... I mean, you've had some efficacy in some of the non-therapeutically active or expected to be non-therapeutically active dose cohorts. What should we be looking for as you move into the, you know, dose cohort 6, et cetera, and some of the therapeutic, what sort of response rates or what, what should we be looking for?
Yeah, no, that's a great question. What I can share with you that the two responders, they had a low disease burden, so there was some logic that they did respond. So if you add a T-cell engager, you have three compartments. One is the number of the tumor cells, then you have the number of T-cells, and in the end, your drug.
And obviously, by adding more, we hope to combine more, and it will also be a lot of learning. And just in the end, what we're looking for is a response rate about 30%. That's what we were aiming for, and on the other side, the response duration should be beyond 3 months. That's sort of the range.
If you then talk to the doctors, they're actually they see this a bit more nuanced, as they say, "Hey, the safety is great. It helps patient where I have nothing." So for them, I think the response rate could be even less, as long as the value for the patient is given and the safety is given.
And then I'll look towards Anne, as her team is doing a lot of translational work, and we're measuring the target expression, we're measuring T-cell activation to see if there is any type of stratification we can do, and to enrich the response rate, and obviously doing combination trials, as we have seen very nice synergy with Aza-Ven in preclinical models that make a lot of sense.
When we were at ASH, I can tell you there was deep and broad interest in the molecule, as magrolimab has just fallen off, and there is high medical needs. So if we continue to see activity, there will be a path forward for the molecule.
I mean, just on that path forward, next steps. So you see efficacy, next steps, broaden the patient population. You talked about the IND in the U.S. Is that do a sort of phase 1b or phase II trial, with once you've found the dose?
Absolutely. So we'll be dose escalating to as high as we can, as we do think-
Mm-hmm
... that, there is a window there, and so far, the safety is great. We will then just need more patients to be measuring exactly what I said before. At the moment, we have two patients. This is guesswork. We'll - we will - that response. So to really broaden the number of responses, to understand better which patients do respond, to guide what are the next steps.
At the same time, we are now discussing with the key clinicians in the field, what - how could such next steps then be looking? And I think that's then really for towards maybe ASH this year, when we have more data that we can really engage with the community what is needed. And it's in simple, it's the last line, and it's the earlier lines for a deeper response early on.
Partnering after that?
Um-
Sort of phase II-ish partnering or?
I think the partnering strategy follows, as always, with us, the data. So if the data is strong enough and we find a subpopulation that we can progress further, so if it's above 30% response rate and it's a clear path, and we maybe even can stratify, let's go. If it's below and it needs a combination, then it's more partnership. So the data will also inform the strategy.
Makes sense. Any questions? Maybe thinking about the Orano Med deal, and... So I suppose first question, you know, what led you to think about Orano Med? What led you to think led to twelve? You've obviously got the Novartis partnership, but you want your own-
Sure.
But that's the thing. We'll start there.
I'm very fortunate to have Dani here with me. Dani is our mastermind on the radio space, and I will pass the question to him to answer why lead and why Orano Med-
Yeah
... because both are good questions, and Dani is very versed to answer both.
Yeah, I'm happy to start from the lead side. So for me, it's like, of course, there's all the questions about which radioisotope to use. Do you use alpha, beta, long-lived, short-lived? And lead has, for me, certain properties, and I maybe quickly explain. Lead is a very short half-life of roughly 10 hours-
Mm-hmm
... and is leading to an alpha decay, or is leading to particles that are emitting alpha inside in vivo. So by itself, it's not an alpha particle generator, only the decay chain is leading to that. So this has the short half-life for me on the efficacy side, has the advantage you deposit a lot of energy on the tumor in a very short time frame, and if you look at the lead and the actinium DOTATATE data, it's very convincing what you see in terms of response rate with lead-212.
Then the second element the short half-life brings is the waste disposal. So whatever is excreted, if in very short timeline, you don't need to collect the waste, and you don't need to take care of that one. And the third element, which I like about lead, is like the clean decay chain.
It has first a beta decay, where your radionuclide still stays attached to the molecule, and then a very rapid alpha decay to the final stable lead-208. This is very different to other radionuclides, where you have a high energy decay followed by other high energy alpha decays, but much delayed, which means you have free radionuclide that still emits high energy within the body.
So that's the three elements that, for me, why I like lead or why we like lead. The other element is then, of course, having the partner that has all the supply available and the supply chain established, and that's where Orano Med came into the game because Orano Med's mother company is Orano, nuclear power plant company in France, with all the endless supply of the raw materials.
So that's been the elements, and then, of course, additionally, Orano Med being an extremely good collaboration partner, extremely dedicated, extremely knowledgeable, and a very strong R&D team.
So that's been the convincing element, working with them now for 1 year and being very convinced that's the right path for us to go. And we are establishing the whole platform, not only for lead, we're establishing it in general, so we will be able to add additional collaborations going beyond lead. That's just the first step for us now.
So potentially better off-target toxicity, potentially from another alpha particle emitter or-
To be shown-
Mm-hmm
... too little clinical data out there, so today, but the initial data looks very convincing from our perspective.
I suppose that half-life, it does beg the question of logistics. I have to go there.
Sure. Yes.
You know, the Novartis themselves have made a big play of the logistical challenges, and we have seen this before for some of the first radionuclides. I think Biovent, which had to be generated in the hospital. So how do you... It may be an Orano Med question, really, but how do you see the logistics?
So, spot on, spot on question, and there it's like... And Michael would be the person to answer.
Yeah.
He's been at Novartis, and he's been involved in the whole AAA, acquisition and, and those elements. So it's like, there Orano Med has established a centralized process, and they can deliver within the 24-hour time frame. So if you double the, let's say, the radioactive load on your initial product-
Mm-hmm
... and you can deliver to the U.S. sites within those 24-hour time frame, you're set to go. They are establishing the same in Europe. They probably need to establish a separate U.K. site for the reasons of being able to deliver in these sites.
So we're very confident that they are on the way to have that all established, and they've been showing with the RadioMedix study they can deliver with a very high probability of success within that timeframe. So we are very confident having Orano Med on board for these aspects.
Maybe I'll just echo what Dani said in between the lines. So if you take 100 DARPins and then load them with lead, you're only loading a very small subset. So if you load more DARPins, you just by doubling that, if you have 5% loaded, you go to 10%, you just have 10 hours half-life one.
Just the half-life.
It's not that 100% are loaded at start, so you can actually play with that ratio.
And I suppose on the DLL3, you know, you highlighted for the DARPin side of things, you know, that you what looked to me like you've solved the kidney and you've now got accumulation of the tumor. So I suppose next steps now, conjugation, that's already done?
That's all done.
So we're, yeah, next steps overall then.
So, we're not the only ones working on DLL3. So, what you saw, and this is a lot of real wet lab work. It's... So what we'll do is we now have one solid, call it lead idea. We'll test a bit around that if we get something better, because we do want space between us and competition to have really high tumor, low kidney, and a good stable molecule. So we gave ourselves first half of this year to finalize that and then be in the clinics a year later.
From a, I mean, you can see the drug. You can obviously target, you can see the drug working with these radionuclides. So, you know, you have to... What do you need to progress to the next level? So you do dose finding, and then?
That's a great question, and we're also looking into that. If you do start with more of an imaging trial to see before you actually go to the therapeutic application, it's a beautiful idea. We will be looking into both.
In an extreme case, and that's one reason we're very interested in the whole field, if you find a way to be fast, and you can actually do for early fast in humans, you could look at different candidates even in a diagnostic setting, and then only choose which one you want to turn into a therapeutic. So that's obviously one scenario for the future that makes this field so attractive that you can sort of do with the imaging in human research.
And I suppose, you know, you highlighted that you would lead marketing, but, you know, there's a ways to go for there. So how should we be thinking about, you know, phase 2, phase 3? I know it's a bit far, but, you know, we can go there.
No, it's a, it's a good question because obviously we are selecting these targets also for targets in indications where we believe radio works. So we're talking small cell lung cancer, we're talking some neuroendocrine prostate cancer. So these are indications where this type of approach works.
And obviously, who commercialises this in the end, we will obviously see when we'll cross that bridge when we're there. But with first in human, you can go really fast, and we saw that with Rayze Bio. They went from incorporating the company, I think 4 years later, they have their phase, and they started more or less from scratch. They're, they're in phase 3. So this is, actually has been done, the path has been shown to work, and I think we're, we're not starting from zero today.
And obviously, there's a partnership with Novartis, and you can't presumably say too much about it. But, you know, in terms of solving their problems, how's that partnership going? Where are we? What can we think about in terms of next steps?
So Novartis has two targets, and the collaboration is such that all foreground improvements on DARPins, if they make them or we make them, are available to both parties. So that's why everything on the DARPin, we get access to. We did show you half-life engineering. We did show you some of these linker technologies that we are doing.
If we have a hit there, we'll have to discuss with Novartis, but maybe they also have a linker that we would like, and maybe there's really cross-licensing possibilities there. We have not crossed that bridge, I would say, and I'm looking towards Dani. I think our DLL3 candidate has overtaken their molecules by now, so we are a bit faster as they are, but they are obviously a great partner to have. And with more data, we can exchange more. I think for them, the two DARPins are also get to know the platform. We had to build the platform while we were working with them, so.
Yeah.
Maybe I can, I can add, we've been implementing, and you've been seeing on the slides, there is HER2 has been our workhorse initially, then we moved over to DLL3. We've been building a lot of the learnings on these two targets, and Novartis is now profiting in that sense that we're we can apply those learnings, which are we own in terms of IP, we can apply those to the Novartis program.
The same for the half-life engineering. I think there we've we've invested we've done massive investment in terms of building that platform, and also that's what we can now apply to the Novartis program. And we hope, hope, of course, we're successful on both of them and can move both of these targets and be also a partner of choice for radio-DARPin therapy for Novartis as a collaboration partner.
One more question here. Dani, in terms of other radioisotopes or other targets other than DLL3, do those get deprioritized now, so you focus just on-
No.
on DLL3, or, you know, do you work on the other things in parallel?
No, I think the beauty here is that we can actually move a whole suite of these targets because the engineering is much less complex than a tetraspecific Switch-DARPin, so I think that's the beauty. We will... You saw some of the arrows. We'll definitely have 5, 6 candidates or, or targets moving forward, and we will not be shy to move more than one of those towards the clinic.
... Let's be clear there, it's six targets we are moving at the current point in time. If there's candidates dropping out for whatever biological or technical reason, if we are able to move all of them in parallel, that's a question of investment of resources. But that's what is reflected on the slide, is the current status of the pipeline, what we're trying to do, maneuver in parallel. So that's where we are today.
And maybe a final question on Switch-DARPin. So, obviously, first program in AML, do you look to generate sort of proof of concept or proof of principle? Proof of concept may be later, but in AML first before moving out into other areas with Switch-DARPin or-
I'll start the answer and then hand over to Anne, as she's the master of the switch. So this was the first one we saw that is to be moved forward. At the same time, we do have the CD3 switch, so we'll likely move one in parallel, a T-cell engager switch that has a costim part to it, and we'll be looking also for partnerships, because there, we cannot move too many at once. But maybe, Anne, you can comment a bit on the thinking. But I think the c-Kit was attractive, and we'll move it first, but we'll not hold back with another one switch.
No, I mean, I don't see much to add. I mean, it opens a wealth of possibility, as you can imagine. I mean, beyond CD47, we have indeed CD3, and then we can broaden the program, but the idea was to first confirm that it does work, and you've seen it. It does.
Yeah.
My guess is that if we see good cyno data, we feel comfortable on the CD47, CD16 part-
Mm-hmm.
And then you really, you can exchange c-Kit with whatever target you like, and it would be the first time that the CD47 part is conditionally locally activated, so we're super excited about that. And today, first time we present some data on that.
Excellent. Any final questions? There's a question there at the back.
Thanks for the presentation. Given the vast differences between radioisotope half-lives, is your technology out there yet to match the isotope half-lives, you know, going from the different direction?
So matching isotope half-lives to possibly half-life of the drug, and I think it's a great question. I'll hand it to Dani, but it's part of the thinking. Yeah.
Yes. So our ambition is to build it for all different radioisotopes, being it short or long-lived, and the Novartis collaboration is anyway focusing on long-lived beta, beta emission or alpha emission, so we're building the platform for both. It's just like here we decided simply on the progress, on the collaboration together with Orano to go with that one first, but we are happy to add others to the pipeline, to our pipeline going forward.
Excellent. I think we're out of time, unfortunately. Thank you very much.
Thank you so much.
Thank you very much.