But I would say that there, while there are several TYK2 small molecule inhibitors, we’ve seen also recently data from an IL-23 peptide from Protagonist/J&J. There is still room to match IL-23 type 1 interferon biologics, especially in a single oral molecule that is well tolerated and active. And so I think that is the gap that we’re going to fill with our programs. So just patience on the design, but they will come as we get into the Phase 1 study.
Operator: Thank you. The next question comes from Thomas Smith from Leerink. Please go ahead.
Unidentified Analyst: Hi. This is Will on for Thomas. Thanks for taking our questions. A couple on the ZEN and ADVANTA trials. If you could give us a sense of how enrollment is progressing thus far and any color on what the patient enthusiasm and willingness to enroll has looked like? And when enrollment is complete for those trials, are you planning to share that information or just wait until the data release. And then I have a follow-up.
Jared Gollob: Great. Thanks for the question. As you know, Sanofi is running both of those Phase 2 trials. If you look on clintrials.gov, you can see the publicly stated timelines for estimated primary completion for both of those studies, which is in the first half of next year. And to our knowledge, both studies are still on track to meet those timelines. That’s pretty much all we can really say right now with regard to how those are staying on track. Our understanding is that there is significant enthusiasm on behalf of the various sites who are being engaged. These are both sort of global studies. And so I think that’s been very encouraging in terms of what we’ve heard from Sanofi in terms of site engagement. And so I think, again, we’re still expecting that both of those studies would readout on the publicly stated timelines.
In terms of sharing data, I think that will be something that Sanofi and Kymera will need to sort of work out in terms of exactly how that will look next year – in the first half of next year when those readouts are expected to occur.
Unidentified Analyst: Okay, that’s helpful and that answers the follow-up as well.
Operator: The next question comes from Kelly Shi from Jefferies. Please go ahead.
Unidentified Analyst: Hi, good morning. This is Yun for Kelly. Thanks very much for taking the questions. Are you able to share the status of dose escalation in STAT3 and also the MDM2 program? And also are you able to disclose have you reached the targeted 90% degradation that you thought could be required for clinical efficacy. And also for I&I indications, is there a specific threshold like the 90% in oncology indication that you think you will have to achieve? And based on your experience with oncology indications, how confident are you that the preclinical degradation data will translate into human data? Thank you.
Nello Mainolfi: I think three questions. I even lost back track of them. So let’s start with the oncology program. So we generally do not provide updates in these quarterly calls on how recruitment is going. We provide updates when we disclose data, obviously, and we try to target medical meetings. So you should just look out for meetings later in the year where a full update on each of those two programs will be provided. We love to share our plans, but because as you know, there is abstract emission and we need to hear from the conferences, we’re not able to now confidently say exactly where, but just know that there is a plan in place and we believe this will be both presented at high impact medical meetings within 2024.
If you look at what we’ve disclosed so far, obviously we have reached for STAT3 the targeted degradation. And really here, we continue dose escalation because we’re getting through – we’re targeting to reach an MTD, which as we’ve seen pre-clinically seems to be above our targeted degradation. And that’s really a testament to the design of the molecule, the design of the study that the translation has happened in a very predictable and positive manner. For MDM2, really I think it’s hard for us to comment based on three, four patients worth of data that we shared in November. So just stay tuned for our next update where it’ll be clearer where we are with regards to target engagement. I think if you look at all our programs, if you look at our R&D data or actually on our corporate deck today, you will see that each one of our programs, whether in oncology or immunology, we have reached targeted degradation in the clinic with a good safety profile.
With IRAK4, we reached complete degradation in blood. With STAT3, we’ve reached more than 90% – around 90% or more, depending on patients in both blood and tumors. With even 413, we reached that targeted degradation. So we know really well how to design our molecule and translate those profiles in the clinic. So we expect that for STAT6 and TYK2, that should happen just the same way. That is one thing that we’re not concerned about here at Kymera. With regards to what is the profile in immunology? The profile in immunology is what you’ve seen in our preclinical data. You’ve seen that if you degrade, for example, STAT6, anywhere between 80% and 90%, you can match dupilumab activity in those preclinical, for example, asthma models or even AD models.
