Operator: The next question comes from Daina Graybosch with SVB Securities. Please go ahead.
Daina Graybosch: Hi. One question for me, in other T-cell engagers, there is often a pretty steep dose response curve. So, if you follow receptor occupancy, you see it jump up. And I wonder if you are targeting three different targets, how are you thinking about pharmacodynamic markers and when you will know that you should be in an active dose for where we should start to see clinical activity?
Patrick Amstutz: Yes. No, that’s €“ it’s start on, and it is something we are following. As you say, we have to try specific with the lower affinity, so it’s not quite as easy as it’s not one target. What we are doing is obviously €“ and that’s the good thing in AML, we can take patient samples as you go. So, it’s much easier than a solid tumor biopsy. And we are looking at target engagement. We are looking at T-cell activation. We are looking exactly at the questions you have. But your point you make, so how steep that sort of response curve will be, we will have to find out. We did not up for the most potent molecule because potency was seen with other T-cell engagers, but with the side effects were just too strong. So, the idea, hopefully is that we actually can find that window of engagement and killing without the side effects.
And we will update definitely with all the data we have, and we are measuring exactly what you were hinting at. So, how €“ and its receptors occupancy, if you want, or how many DARPins per cell and how active are the T-cells. Thanks Daina.
Operator: The next question comes from Yi Chen with H.C. Wainwright. Please go ahead.
Unidentified Analyst: Hey, Vikas Tyagi on behalf of Yi. Just a couple of quick questions on 533, any plans on €“ and please, I beg your pardon if you have already addressed this, but any plans on expanding the clinical sites to the U.S.? And then the other one on abicipar in AMD and DME, where does it stand as it relates to commercial activities? Thank you.
Patrick Amstutz: Yes. 533 and U.S. So, the initiation of the trial plan or the first part is planned for Europe at this point in time. So, we are first in Switzerland, then the Holland side. And I think it’s also Lithuania that we are planning to start up sites. With success, with good response rates, with complete responses, we would immediately want to go to the U.S. to include U.S. sites. Those plans are being built. We do plan for success on that program, for sure. And so that will be the next step after we have clinical data. Then abicipar, where does the program stand, let me quickly remind you so abicipar went to through two Phase 3 trials. It has stellar efficacy data activity data with three or every three months injection being as €“ then as a monthly Lucentis regime, so non-inferiority reached.
It had and they got a complete response letter on inflammation that was 15%. At the time, we had thought it was the impurity. So, we put a lot of activities on further purifying and we brought the 15% to below 10%, but then we hit a ceiling we could not explain. As we gave the program back and more recently, we have found the likely culprit of those 10%-ish, below 10% inflammation, which is the silicon oil that is used to lubricate the syringe that together with the DARPin, so it’s sort of an induced indirect impurity that causes DARPin aggregation. We see sub-physical particles that form or can form and then can lead to inflammation. The solution is rather simple to go for non-siliconized syringes, then you could move the program forward. There is some discussions ongoing with a potential path forward for this program.