So we actually go across many cell types so that we actually cover 100% of the proteome. And the picture that you’ve seen in our slides is consistent. We only really degrade STAT6 and I would say, we only really bind to STAT6. And that’s true also for the TYK2 program and for the IRAK4 program and for the STAT3 program.
Kalpit Patel: Okay. Thank you.
Nello Mainolfi: Sorry, I can keep going. Yes, thanks, Kalpit.
Operator: Thank you. The next question comes from Andy Chen with Wolfe Research. Please go ahead.
Unidentified Analyst: Hi, this is Emma on for Andy. Thanks for taking our question. I guess just focusing on TYK2, we’re curious where you see weaknesses with current TYK2 inhibitors on the market and just how much headroom there is for improvement with a potential degrader entrant like KT-294 into the market. Thank you.
Nello Mainolfi: The weakness, sorry, I didn’t hear it well. I mean, as we said before, there are several layers of differentiation. So there is first that small molecule inhibitors, these are allosteric inhibitors that actually block also the kinase function and some of the scaffold function but not the full scaffolding function. And so the actual phenotype of small molecule, even allosteric inhibitor is closer to kinase inhibitor than to the loss of function profile. We have a slide in our deck that shows you with the pluses and shows where is the kinase versus loss of function versus wild-type and only a degrader matches – sorry, the loss of function profile, which basically means we block IL-23 as well Type 1 interferon and spare IL-10.
So the compounder is approved. The drug that is approved right now, which is an allosteric inhibitor that actually is not as selective. It actually impacts also JAK1 and so also impacts IL-10, which is a big detriment for GI indications. It’s also not very selective so they have to play around with the doses in order to hit the target at a reasonable target engagement. Other molecules in the clinic have more, I would say, maybe a higher selectivity profile, but they’re not able to block all the scaffolding function and match the loss of function profile. And we believe that by blocking the pathway fully, we should be able, again, as we’ve shown with STAT6, we’ve shown with IRAK4, once you find the mode of full pathway blockade, you should be able to match the upstream biologics so the IL-23 biologics, the Type 1 interferon biologics in a single oral molecule.
So what is that going to translate in the clinic? We don’t have a number, right. So if you look at biologics in psoriasis, they reach close to 90% of PASI 75, for example. Small molecules don’t get there. They get into the 60, 70s, maybe pushing into the mid-70s. So maybe that is a gap that we can fill. But I think that the actual extent of gap that we’re going to be filling with our degrader. We have a goal of biologics, but we actually don’t know. It might be even superior or maybe slightly inferior. I think that is a clinical experiment that we have to run. All we’re saying here is that biologically we have a differentiated profile, and we have confidence that that will clinically result in a meaningfully differentiated drug.
Unidentified Analyst: Thank you.
Operator: Thank you. This concludes our question-and-answer session. I would like to turn the conference back over to Justine Koenigsberg for any closing remarks.
Justine Koenigsberg: Thank you. And on behalf of the Kymera team, we’d like to thank everyone for joining us this morning and look forward to keeping you updated on our progress. In the meantime, please don’t hesitate to reach out if there are any additional questions following today’s call. Thank you.
Operator: Thank you. The conference has now concluded. Thank you for attending today’s presentation. You may now disconnect.
