Patrick Amstutz: Thanks Georgi. Both great questions. Happy to answer. So, let’s stay on the durability of 533, and it is actually the key design feature of this drug. And the problem of durability is also of other drugs clonal escape, because you are not killing all clones, that means you might reduce the tumor mass. But if 10% of your tumor cells are not killed, there you have your population that just goes back in two months afterwards, you are at the same starting point that you were. And so this mono targeting is actually exactly leading to this short-lived responses. We are trying to go broader with our tri-specific approach and include €“ and there is a bit of debate, we call it the leukemic stem cells or the precursor cells, because if you really get to them, if you really can kill those cells upstream that are causing the problem, you have at least the belief and the hope to have a much longer durability of your response because, a, you don’t have clonal escape because we are targeting three targets.
And b, you are sort of drying up what’s it called the stream or you have to source so that you really could kill those cells that are responsible for the relapse. And that is what we designed the molecule for. That’s where we have a lot of preclinical data that was presented at ASH, and that’s what we want to show in the clinics. Now, as I have said, the holy grade is obviously to follow the patients and see the non-relapsing patients that follow the time they don’t relapse. What you can also do is you can do bone marrow aspirates and check for MRD positivity or negativity so minimal residual disease. And if you are MRD negative, meaning there is no disease that is a good, call it, biomarker for your durability of response. So, that is something we are looking into as early as we can when we see a complete response.
So, to have a complete response, MRD negative, that’s the first thing we are hoping for. And then obviously, looking that translates into durable responses. And all on the design of the drug, so this is not by chance, if this happens, this is because we designed it to happen. On the DLL3 and I am also glad about that question, now going to Radio DARPin therapy. Most of our competitors are working with ligands. That’s why it’s called radioligand therapy. And take PSMA that target or other targets you were hinting to, these are targets that have groups where ligands combined really well. That’s one reason these companies that have radioligand therapy are all going against the same targets. With the DARPins, we are rather agnostic is it’s on the surface and it’s a protein that we can bind it.
So, we are hoping to expand the target space beyond what is, I would say, ligandable or addressable with ligands, so going to the broader space. And we have chosen DLL3 because of other also €“ because it’s €“ because certainly it’s high medical need, especially in small-cell lung cancer, but also in some prostate, and it is €“ the tumors are highly metastasized, so that one of the reasons. At the same time, we have a rather big initiative to identify new targets for DARPins. And as I have said, they are sort of a gating system that it should be something where that is more DARPin unique, I mean maybe not ideal for ligand. And it should be as clean as possible and in indications that have high need and have maybe a high level of metastases.
And then in indications where radiotherapy is used, so it’s sort of a Venn diagram we are building. And that is ongoing, definitely also something we can update over the year how our thinking of differentiation between radio DARPin and radioligand is coming along, but both great questions and both hinting to the differentiation activities that we are building into our pipeline.
Georgi Yordanov: Thank you so much.