Okay, welcome ladies and gentlemen to the last day of the JP Morgan Healthcare Conference. My name is Stijn Lanssens, and I'm very happy to introduce the team of Molecular Partners. We'll be taking you to their presentation, mostly Patrick, but then we have Martin, Michael, and Michael here as well. After the presentation, there's time for some Q&A, so feel free to save your questions for the end, and I'll leave it to the team. Patrick.
Thanks. Thanks for the kind introduction, and also thanks for hosting this conference. It's always a pleasure to start the year here and feel the pulse, and I think last year we were all hoping for a turnaround, and I think here I see now much more confidence for that turnaround. After a few difficult years in biotech, I think we can look forward to 2026, and for us, it was also very fortunate as Aktis Oncology did an amazing job in their IPO, and Aktis is a radiotherapy company, and we got a lot of positive feedback for that field and also many questions, so big congrats, but also thanks to Matt and his team for opening the IPO window again and re-energizing the interest in radiotherapy.
My talk today will be mostly on radio, and I will put in a few other thoughts for us, but it's really about radiotherapy and MP0712, our DLL3-targeted DARPin. That's going to drive the value next year, and that's where I want the attention of the audience, but then also of our investors over the year to focus while we are doing additional things. For that's the forward-looking, I will be making forward-looking statements, so here's my disclaimer. And for those who are, hello? For those who are new to the story, just a short intro to what we are doing and how we are doing that. We are a Swiss-based, Swiss- and U.S.-listed company. We have $100+ million or CHF in U.S. dollars or Swiss francs, and we invest that to bring DARPin candidates forward.
DARPins are designed to anchor in repeat proteins, and what the field likes to call them at this point in time, especially in radiotherapy, is mini proteins. And compared to, let's say, peptides, the mini protein has one advantage: that it has a class behavior. So what we learned from the first program, we actually can apply to the next programs going forward. How does a workflow look for Molecular Partners? We start with our libraries. We have different libraries for different applications. We select binders. That's that one arrow, but behind that, there's display technologies, computational designs, deep data mining, and it has really, especially AI and deep data mining has revolutionized how we do this. We find more binders. We find better solutions to build candidates. The candidates are always focused to solve a patient problem. So we start with usually a clinically validated problem.
We are not looking for new targets. We're not looking for new biology. We take a defined problem and build, engineer a solution. So it's always understanding the problem, the biology, finding the solution in our space. Ideally, this solution is unique to what we do, which gives us differentiation value for patients, but then also value for shareholders. If I look at our pipeline, I see a lot. There's many arrows there. But if I look where the value creation will happen this year, it is rather simple. I mean, the focus is on 712. So I think that's what we will be doing, and that's where most of the data will be coming out. It has a knock-on effect on the whole radio franchise, and it is directly useful, as I talked about, the class behavior that we can design better and better solutions going forward.
Before going into 712, I do want to distract you with two programs that I need to throw in here. I will start with MP0 317, then do MP0 533, then come to radio. 317, I think most of us, including myself, would have classified that as a dead program. We didn't see much activity. For the Monty Pythonists, maybe dead as a blue Norwegian parrot. But it got awakened, and it got awakened by investigators. Investigators saw the data of the phase one, and let me quickly show you how that looked. I draw your attention to these images. You see pretreatment and posttreatment. You see 317 is, you see the cartoon below, it is a local agonist. It binds to FAP, and then it activates, upon binding, CD40, which is on immune cells, T- cells, macrophages to stimulate the immune system.
So it can stimulate an environment that is immunosuppressive to become active again. You see that on the cycle two day eight picture, how actually we can now see, we can measure 317 in the tumor and the activation of the immune cells. And this activation did not lead to single-agent activity, unfortunately, in the phase one trial, but it did activate investigators that were also on the trial to think about how one would use it. And so it was mostly a group around Christophe Borg in France, and big thanks to him in his center to come up with a trial to test 317.
I'll draw your attention here to the chart, and that's a chart, and it is really a dismal chart if you want, in colorectal carcinoma, where after one year with just chemo, you see 10% of patients are actually still alive, and the curve then becomes flat. If you add a PD-1 to it, in this case, Durvalumab, you see you maybe add 10% to that, and you get to 20-something percent at 12 months. And the idea here is that this is really an immune suppressive environment and could one now, by adding 317, change this and give the PD-1 a chance to work. That's what they want to try. There's going to be 11 centers in France. They will recruit 75 patients, randomize them, 25 standard of care, 50 317+ standard of care, and we will expect first results 2027 and beyond. So very nice trial.
Very grateful for these investigators to actually do this. We only have to provide the drug, and we have all the upside for us and our shareholders. So this might be a bit of a role model also for the next program, which is 533. 533, we just presented a poster at ASH. Let me just quickly introduce the molecule here. We see it's a multispecific DARPin. The green, the orange, and the yellow DARPin bind CD33, CD70, and CD123. And the blue DARPin here would be a T cell engager. So you bind the AML cell in orange, recruit the blue T- cell to kill. You might ask, why do we need three of these? That goes back to the disease. We're targeting AML, and AML is a heterogeneous disease, if you want. The cells have very different origins.
It's very different to a B- cell malignancy where you can take a CD19, a CD20, Blincyto, and you're done. Blincyto is great because you actually chase those last clones. You can actually really almost cure the disease, and this is unheard of in AML. So what we need is a disease not to, we need a product not to debulk. There are different therapies to debulk, but we need something to eradicate the last clones, and that's what this drug is designed for. Multispecific to address the polyclonality or multiclonality of the disease, T- cell engager to give high potency and then kill these target cells. The data, these are top two cohorts. We have cohort eight and nine. And the first thing that comes out is it only works, and that in the design, in low disease burden patients.
So it's for killing the last clones that are still there. It's not to debulk. If we recruit the patient too late, we have no chance. In the low disease burden patients, we see nice responses. And if we look closer, we also see that we target many of the clones, so it's a polyclonal response. In this chart, you don't see the, let's say, worst mutation, which is a TP53, but we also have activity in those patients. Given the focus in radio, we will not be investing very much more into this program. We will finish the phase one and then possibly, and there are a few attractive options, move this into an IIT following the logic and the route of 317. Good. So distraction is over. Now we're coming to the core bit, the focus part of the talk, which is the radiotherapy part.
How does radiotherapy work? You have on the one side, and this can be different, usually these are cyclic peptides. In our case, it's a DARPin, a vector. The vector has a linker, a chelator, and is then loaded with a radioisotope, and we are focused on alpha isotopes. What we bring is not the isotope or the linker. We partner for that. In our case, I'll have that on the next slide with Orano Med. We are experts in the vector and the half-life engineering, and especially half-life engineering is very important in this field in our view. So one word before going into that in more detail on the isotope. Here we partner with the leader in lead. Lead is 212. That's a radioactive form of lead. It decays in a better than two alpha decays. Very potent, very fast decay, really killing tumor cells fast and actively.
We are not investing our money in the supply of that, building that. Orano Med is the world leader. We're grateful for that. We leave that to the partner. We work more on the DARPIN side and on the product development side. Not only big thanks to Orano Med, also to our advisory team. We have Ken, James, Jason, and Michael here. They have been very helpful for us. For us, it's a new field and that we don't have to reinvent the wheel. We are fortunate to be able to count on the support of this group and other groups. And I would like to point out that it is very a collaborative field to work in. As we're all pioneering a new class of drugs, we are treating patients with very high medical need. So it's nice to work in this field and support each other.
And we see much more of a support than a competition behavior. So big thanks for that. Now a bit more specific from the general to the specific, 712, which is our first candidate to enter the clinic in small cell lung cancer. 712 targets DLL3, and DLL3 is now a validated target as tarlatamab is approved, a T- cell engager by Amgen. It has a response rate of 40% and around 10 months duration of activity. There's more to follow. At the same time, and we also have T- cell engagers in our pipeline, it also has rather a high level of side effects. The alternative there is ADCs. They have a higher response rate, likely because you don't depend on the activity of the immune system, on the fitness of your T- cells. The problem there is that small cell lung cancer is a very chemo-resistant tumor.
So ADCs are, let's say, chemo and steroids. It still will likely be resistance to that, and you will have a much shorter duration of action. And that's what we see in the first clinical trials. And here radiotherapy comes in. I hope we can have the activity of the T- cell engagers in the durability with the response rates of the antibodies and the side effect profile that might actually be better than both. So that's the promise of radiotherapy in small cell lung cancer. 18 months ago, we published these results. That was at SNMMI. And you see here what you do is dosimetry. You dose your drug to a mouse. You look at all the organs, and what you're looking for is a positive tumor-to-kidney ratio. Usually, it's tumor-to-kidney because these proteins are excreted via the kidney. We saw nice activity.
And at the same time, especially when Dani, he's on the stage here, presents, he always gets the question, "So why do you get so much on the tumor?" And why does he get the question? It's because DLL3 is a very low-density target. So a cell, a typical cell in a human that with this disease only has a few hundred counts on the cell surface compared to all hundred thousands of HER2 that even can go to a million. How on earth can we get so much in? And I want to draw your attention then also to the blood value because we had seen by engineering a longer half-life, that's how we could boost the uptake. We didn't totally know why, but we saw a correlation of when we added half-life, much more went into the tumor.
And the team then looked at this and came up with a very good hypothesis that we believe. And it is the following. It builds on internalization. What you see here is you spike the DARPin. It has a fluorophore in this case, so we can measure. And we see within less than 30 minutes, all of that DARPin is internalized into the cell. And you can make nice pictures. And here the DARPin is in green. And you see the DARPin is not on the cell surface. It's internalized. This has not been described in this way, while it is logical because ADCs work and they need to be internalized. Now the interesting part was that if we then added DARPin to the solution, this internalization kept on sucking in, almost catalytic, the DARPin into the cell. So we're loading the cell over time.
If we would have only just given one bolus, that's that orange line to the right. That's the maximum you can get if you don't have half-life engineering. But with half-life engineering, we can load the cell and reach a much higher activity. That's the cartoon. That's how this now works. We bind, we internalize, we likely fall off, and the DLL3 is replenished to the surface. Now the other interesting part is we can actually follow this also in humans. And while our phase I is just opening now and the first patients are being screened as we speak, we were able to get some patient images upfront. And so the beauty in radiotherapy is you have a theranostic pair, so you can do imaging and treatment. In the imaging part, that's the upper part of the cartoon, we use Lead-203, so it has no therapeutic activity.
We can image, we see where the drug goes, we see the tumor, and then in a second part, we take the same vector, replace 203 with 212, and treat. You can do this in all sites, and we started this on a named patient access program in South Africa with Mike Sathekge, and what I will present you on the next slide is sort of an appetizer or teaser to the data that he will be presenting end of the month at the TWC conference in South Africa, and I think that's where our investors will definitely look, and we will be present, and I think that's when all the data will be released, and the image I will be showing you on the next slide is sort of an appetizer to that. The phase one two will be the same. You will be first imaging and then dosing.
As I said, we will be opening eight sites. First site is open in the U.S. to move forward. Let's look at the patient that we dosed. We chose one because we thought this is most relevant for the patient profiles we will see in the U.S. because this is actually something we found. We found metastasis in the liver, which is very characteristic for these types of patients, while other patients did not show that characteristic. It's a smoker, it's small cell lung cancer, and we dosed. Let me quickly move through. Here. Let's see at the four-hour time point to start at the beginning. What you see there is not the tumor. That's the heart. That's the blood pool. As I told you, we have engineered the half-life of the drug to actually be a reservoir to load the tumor.
And that's what you see at four hours. You might ask, is that not a safety risk? The good thing here is alpha particles decay and only kill neighboring cells. So a clean decay in the blood is likely safe. That's a calculated risk we take. And the one organ, if you want, we have to follow is the bone marrow to see how much do we hit the bone marrow. The good thing is actually the blood values, they come back, they recover. And that is going to be the question on safety and the four-hour time point. If we now jump to 116, so we sort of let the blood pool leave and see what is left. And there you see now the primary lesion, the lung lesion, and you see four or five metastases in the liver. And you see the precision of targeting.
You see, we are not stuck in the kidney. We leave very rapidly, and we have a very good tumor to organ or healthy organ distribution. So very promising data for us. And so that's sort of the hint we're giving here. And the full data will be released in South Africa TWC, where you will also get the exact values over time. So what are we doing next? We're starting the phase I dose escalation. We do start with a 75-megabecquerel dose, which is very in line with what others have done, if at all, on the higher end. And that's because we could do the dosimetry in South Africa and the mouse work showing that also this blood tox is very reversible and likely not dose limiting, going up to 200 in four-dose cohorts.
If that looks good and when that looks good, we go into a fast-to-market strategy. That's the second-line or small cell lung cancer trial there. And we can go also first-line, ideally in combination. That would then be with a PD-1 and branch beyond small cell lung cancer to find other indications as DLL3 is not only found in lung cancer. The timing of this is a question we get. Our goal is to recruit a cohort per quarter. So we will see the updosing. We will have safety results. We will have likely, let's say, case studies, second half of the year of activity, and be able to update the market as we move. In this, you see that is sort of this slide to keep in mind. A big year for us, first activity in a patient population that needs more durable treatment that is safe.
This is the slide to keep in mind. We obviously didn't stop with that. We have other targets, and I just picked out this one. That's the second up, MP0 726. This targets mesothelin. Mesothelin has a different problem. It is cut from the cell membrane, and you have a big shed portion. What remains on the cell is just the membrane proximal epitope, very small. Now the team has selected DARPins that now binds to this specific part of the protein and does not get stuck or sponged away or inhibited by the shed mesothelin, as shown in the graph. And then again, you see we did some half-life engineering here too, as this is also internalized, albeit a bit slower. And you also see a very nice tumor-to-healthy organ ratio. And that brings me to sort of the last slide of the almost outlook of what we're doing.
You see in the chart we have 712, 726 on the top. We're working on four additional targets that we want to select one or two mid this year for development. The point here is we have chosen those that we can then start to do combinations of these in the next projects to do multi-specific to address tumor heterogeneity. As I told you, this alpha does not travel far. If you don't have a very good distribution of your target, you can profit a lot from targeting more than one target. I'll sort of come to an end here just by highlighting how we think about this. We start with the patient need. We have then the target, the disease in mind, the surface internalization, the off-target expression. We design the ideal vector, including half-life, and then choose the right isotope.
As you saw, we have 10 slots of lead. We don't have to always use lead. We are, in principle, we're open to other isotopes as our, let's say, value we bring to the table is the biology and the vector, and that is then paired with the best solution on the isotope side, and with that, we really think we're uniquely positioned to build the pipeline, and I think I will actually recap very simply here before I open for questions. Focus this year is all about 712, first in human results. I think first stop is January, so just two weeks from now, first time to look at the dosimetry data, safety first half of the year, cohort one and two, activity second half of the year, and with that, a validation of the product, but also the platform. We're well capitalized with $116 million.
That's CHF 93 million in cash. We have a great team to execute what we want to do. With that, I come to an end, and then I'll take some questions. And but before then, I want to thank you all for coming here, for those on the webcast joining us. I do want to thank my team that was here with me the last few days at JP Morgan, having all those investor and partnering discussions, the team at home. I do want to thank also the Orano Med team that was also here promoting our cause and their cause. I thank our advisors, especially the clinicians that come up with these great ideas and trial designs and support IITs, something that is really helping patients where we as a company cannot go. And obviously, all the patients and their families in our trials.
With that, I come to an end, and I would be open for questions.
Any questions for you?
We have a microphone in the back. I think that will be.
I'll actually just use this one. Thanks for taking my questions, and thanks for the presentation. Zane Abraham, JP Morgan. My first question is just on the DLL3 in terms of, and you've provided hopefully the data cadence that we should see this year in terms of safety in the first half of this year. And you alluded to the fact that from the imaging data that we're seeing, it does look like it accumulates more broadly in the blood, but the alpha decay time might mean that it's only a signal in the bone marrow to really think about where you were not seeing a signal on hematological toxicity.
Maybe providing a bit more detail on what gives you confidence that you might not see a high level of blood toxicity and putting it into perspective with the safety profile a little bit more, that you alluded to for Imdelltra, would be helpful. That would be the first question.
Yeah, sure. I will be also very happy to give this question then to Michael. From the preclinical work and from the dosimetry that will be released, we feel confident that we will have a safe dose. I think Michael can speak to that question.
Yep. Yep. Microphone three. Thanks a lot for your question. As Patrick said, Dr. Mike Sathekge will present in detail on this on the TWC conference.
What you probably understand is from all these patients that have been dosed, you do a very precise dosimetry, take every image, characterize every organ, the volume, the radioactivity, and then calculate a time-activity curve from that, basically the organ exposure. Then you look at the external beam radiation limits. Then you can derive basically a safety margin. It's not obvious from the pictures because they are adjusted to the contrast of the image. But if you look, for example, what Patrick said at the tumor-to-non-tumor, and kidney is always a good one, the blackest spot is in the liver and not the kidney. So the kidney gets less. But of course, you need to take the integral over time.
And for Lead, a couple of days are relevant, but for other isotopes, even longer time courses drive this even to a better therapeutic index.
Makes sense. Very helpful. And just contrasting versus Imdelltra, where do you expect to see the safety benefit for you versus Imdelltra potentially?
Safety benefit, of course, we haven't exposed the patient yet with Lead-212, but since the radioactivity decays very quickly, I think the blood values recover extremely quickly. We have seen that in animals. And in a four-week dosing interval, I guess the patients will have only minimal experience of side effects and then have a good time for most of the time in the cycle. And hopefully, we can continue to dose them without any additional toxicity. So I'm very confident that there will be a good safety profile, especially at the lower dose levels.
Very helpful. And last question I had.
Maybe just to add, I mean, we work also with T-cell engagers and with radio. And I think let's just talk about the class. And I mean, T-cell engagers have heavy cytokine release syndrome. The patient feels ill and does not feel well. On radiotherapy, the patient feels almost no side effects. So the side effects come much later. You can have kidney toxicities, but they come much later. And so I think just from the patient experience, it's a big difference if you're in the T-cell world or the radio world. And that you can go back to prostate and compare that. So if that applies, which it should to lung, I think that's where the safety benefit comes in the patient quality of life.
That's very clear. And then the last question was on the activity signal that we might see the second half of this year. What should we look out for? Will we see response rate data? Can we see a little bit more than response rate?
Yeah. So I think the response rate for a robust response rate, we need a robust number. And so we will not be able to give the full response rates. What I was hinting to is case studies. We will see patients that respond. That's the aim. I think the duration hopefully will take longer than end of the year as the patients still should be profiting. And the rate maybe end of the year will get a first hint of that. I think just we also will be careful on how we represent the data.
If you go out too early, it is not doing the work justice. So we'll be very thoughtful about how presenting that. I do think case studies is the way I see other companies presenting their data. And I think that's also what we will be doing.
Very clear. Thank you.
I think I had one question. Can you give a bit more details on the Orano Med partnership and how do you see that evolving going forward? And maybe comment on any potential other partnerships that.
Sure. So the Orano Med partnership, I'll just maybe go high level. Maybe Dani adds one or two words there. So on the Orano Med partnership, we have, when we go a few years back, we had to choose an isotope provider as we don't invest our money there. And we had the choice between in alpha. There was no choice.
It was clear: alpha, actinium, or lead. Orano Med really rose to the prime partner as they have a quasi-unlimited supply of lead because they have mined. They are a daughter company of Orano, the French nuclear power company, and they have 22,000 barrels of thorium in France. So they can more or less supply the world. What happened in the meantime is that they went into a phase or had a very nice phase two data, partnered with Sanofi, and Sanofi has also added around $300 million-$400 million to build that infrastructure. Now our partner not only has the capacity on the lead side, they also have the cash to make it work, and they want to do that for their frontrunners. By the time we get there, the infrastructure should be established while we are moving forward our asset.
At the same time, they have really good research, so we are doing this together. It's a 50/50 partnership on DLL3. It's important for us that it gets the prime attention of Orano Med, and in the future, we saw on the chart, you saw we have up to 10 products worth of either 50/50 or MP-owned slots for lead. Maybe Dani can talk a bit more about the process and how they do lead and why we think they are at this point the leader. At the same time, there's other lead companies, and the question is, how can we as a field democratize lead and actinium that many more patients get access to it,
so happy to quickly cover the question from a production process perspective.
Orano Med, as Patrick mentioned, is sitting on the stockpile of basically nuclear waste, which they are using as a source material to basically start to harvest. They call it milk, the Thorium-228, which is a starting material for building their generators. The generator is basically the system they elute on a daily basis, Lead-212. They need to elute this because it is so powerful. Otherwise, it would start to destroy the generator itself. They have a process established where they can on a daily basis now in different sites, and they're expanding these sites, elute therapeutic doses and big amounts of therapeutic doses now getting ready for Sanofi for phase 3 and then for the registration of compounds with Lead-212. Maybe just adding on the aspect Lead, we like it for the properties.
We like it for the short decay and allowing the immune system two days after you inject it to come back into the tumor. And this is very different compared to other long-lived isotopes. And for us, the focus now going forward, we've learned a lot during the last four years is to really say, think about the patient, the disease biology, the vector we are able to generate, and iterating all these aspects together to make the best possible compound, being it lead or being it going forward, actinium. And I think that really depends on, as I said, disease and vector profile we're able to generate in that setting. So we're getting way more agnostic in that sense and trying to not decide upfront, but trying to decide on the data we are generating during the program progression.
So can we expect an actinium partnership at some point as well, or?
Yes, sure, so if we just quickly stick with the 712, so DLL3 is internalized in 30 minutes. Let's say that was four or five hours. That means your ramp-up is much slower. You'll need a few days maybe to ramp up, and by then, lead is decayed. In that case, you will need actinium if you stick to the alpha strategy, so what Donny was saying will follow the science. Ideally, you choose only in your clinical setting, and if in the compassionate care setting, you can actually test both isotopes or actually don't have to test both. You do one imaging trial and then choose the isotope when you know what we're up for in the human setting.
I don't know of any other area where this is possible that you fine-tune your drug on clinical data. I think we're not there yet. I mean, at this point in time, we're working with lead. But in the future, we would love to have that flexibility, which is also then a uniqueness of Molecular Partners because we're not lead or actinium. We're a vector play. We make the best vectors with the optimized half-life, ideally multi-specific, then paired with the best isotope. If you think more strategically, what had happened in PSMA world, first was lutetium, then actinium, then lead. We want to get away from that. You get one vector, you have different isotopes, and you're not afraid to be scooped by the next better one because you have access to all.
Yeah. No, that's very interesting.
And any comments on the development part of the DLL3 program beyond lung cancer? Any other?
Yes, maybe Michael?
Yes, of course. Our team is working on this. Small cell lung cancer is the obvious entry point because we know there is a high and uniform DLL3 expression. So by far, most patients will be amenable for treatment. Beyond that, and it's also on the slides, there is the other neuroendocrine tumors, mostly outside the lung. There you need to look out for patients with DLL3 expression. But again, we have the imaging. That will be easy. And we haven't disclosed anything, but we are also working on interesting indications beyond these two because there will be a lot of potential treatment patients with DLL3 expression. So it seems to be a really, really good target.
So I'm so glad we are in this decade where DLL3 is basically on the rise. And hopefully, we can also combine with other potent principles to maximize survival for these patients.
And maybe just to add there, the imaging agent can even become pivotal because you can then select the best patients in an indication where not 80, 90, or even more patients have DLL3. But with imaging, you can actually pick out the best patients. And this see what you treat and treat what you see idea is then pivotal if you want.
Thank you.
Any other questions in the room? That seems not to be the case.