ProQR Therapeutics N.V. Ordinary Shares 12th Annual Cantor Fitzgerald Global Healthcare Conference

Yeah, absolutely. First of all, thank you for having us today. I'm happy to share some of the progress and the updates that we are having at ProQR. As you refer to this morning, we announced in a press release that our second RNA editing drug is now in the clinic. We've started dosing people in a clinical study of AX-0811, which is the fast follower improved molecule of AX-0810, for which we announced positive direct engagement data in June of this year. So really exciting to now have a second program into the clinic. It's the second of four that will enter the clinic in the near term. Over the next 12 months, we're going to have five different clinical trials reading out across those four programs. So a really exciting year ahead.

To further educate people on what's coming up with our program for AX-0811, we are indeed hosting an investor event at the end of this month in which we are going to outline the expectations for the AX-0811 clinical study that we today have started. In that event, we'll have a key opinion leader, Gideon Hirschfield, that will walk us through the rationale of this therapeutic strategy. We will review the AX-0810 data that we announced last June, and then we'll also review on the basis of our now new learnings on these bioasset endpoints, the expectations for the 811 readout that we expect before the January J.P. Morgan Healthcare Conference. We expect to have two cohorts of PD data before that time point. So really exciting. Lots coming up.

We will give expectations on what to see on the three different endpoints.

Nice. We are measuring conjugated bile acids, which are the toxic ones that actually cause the disease.

We are measuring TUDCA, which is a chemical bile acid that is not produced by the body, but we administer to measure the clearance rate thereof, and we are looking at total bile acids. Across those three, we are going to outline the priority order of how we rank them in terms of importance and also the threshold target that we are setting for each of those.

At this event, there will not be new data.

Okay. We will present the remaining data from the AX-0810 study at a scientific or medical conference later this year.

That will include cohort 3. So far, we have announced cohort 1 and 2, the 3 and the 6 milligram per kilogram doses respectively. Cohort 3 data will be announced together with the 12-week follow-up data of all 3 cohorts later over the course of this year.

I think it is really interesting times for RNA editing. This field, obviously, is a fairly young field. We only announced our initial programs in the pipeline just 3 years ago, and right now we are in the clinic with 2 of them and 2 more to follow very soon. There is a number of other players in the field that have progressed molecules into the clinic, some with more success than others. I think broadly as a field, we have learned a lot from all of those data points that have come out. I think most importantly, since the last time at the Cantor conference that we discussed this, we have now established that Axiomer RNA editing using ADAR with editing oligonucleotides is able to edit in a dose-dependent manner in a consistent way across different endpoints.

We have seen across 3 different endpoints in human that there is, in a dose-dependent way, concordant responses after editing at the different dose levels. We also noticed that those are mimicking exactly what we have seen in the preclinical space, and that is really important from a platform perspective because it tells us that our preclinical models that we use, the primary human hepatocyte in vitro model, but also the humanized mouse model are predictive of what we can subsequently see in the clinic. That is relevant as it helps us to translate the next batch of programs and project where their editing will land once we are in the clinic.