Bill Sandborn: Now related to the NLRP3 inhibitors. If you recall the translational medicine Phase 1 data that we shared at R&D Day with the 2735 NLRP3 inhibitors. So the peripheral compound during the multiple ascending dose portion of the trial, we did a whole blood ex vivo stimulation assay at day 10, where you give LPS/ATP and then look at the ability to block the IL-1β production. And that the higher doses €“ in the higher doses in MAD were 100mg and then 200mg, we were really able to completely aggregate 1β production, and what we’re looking for is read-throughs, the clinical efficacy where you have clinical diseases that are €“ you have an alteration in NLRP3 that leads to an excess in IL-1β and where you can see effects of monochrome antibodies against our IL-1β treating that excess and resulting in disease improvement.
So as I mentioned earlier, we are for instance treating the NLRP3, gain of function mutation CAPS with this. We know that’s characterized by very high levels of IL-1β and currently treated with antibodies, and we will need to aggregate the IL-1β production to see those patients get better. And what we, the point of that trial is to show that the complete abrogation that we saw with those higher doses in MAD and Phase 1 translates into the clinic. Having shown that, then you could have some confidence that you could think of a variety of other diseases where randomized controlled trials have shown that IL-1β data antibodies are effective. This would be things like recurrent pericarditis, juvenile arthritis, Adult-onset Still’s disease, there were definitely studies that showed that acute got to achieved that.
You’ve seen it for secondary prevention of MACE events and patients with the prior history of MI. We know that there’s translational medicine studies have shown high rates of expression of IL-1β in biopsies of patients with Hidradenitis suppurativa. So there’s a variety of places that one could logically go once you’ve shown that your small molecule NLRP3 inhibitor treats an IL-1β driven disease.
Unidentified Analyst : Got it. Thanks so much.
Operator: Thank you. Our next question will come from Emily Bodnar with H.C. Wainwright & Co. Your line is open.
Emily Bodnar: Hi there! Thanks for taking the questions. I guess going back to safety for VTX958, without the NIMBUS molecule there is some signals of acne and viral infections. Could you maybe talk about if you expect to see this in your Phase 2 study? I know you didn’t really see it in Phase 1, but it was as well, so to hear your thoughts there. And then maybe if you could just give your perspective on the oral psoriasis market in general now that we’re getting a lot of new mechanisms showing positive data, like the recent IL-23 agent and also an oral IL-17, so curious how you think the two sets. Thanks.
Raju Mohan: Yeah, a number of great questions Emily. So let’s just take them one by one and I’ll have Bill jump in if needed here. So first, on the dermatologic side effect that you’ve seen now with the NIMBUS compound, and it’s been seen with the , so €“ and we made this very categorically clear that we do not believe these are on target. So there is no reason mechanistically that TYK2 should manifest or IL-23 pathway that TYK2 is targeting. It should manifest these dermatological effects, the acne and the proliferates and other effects. So, as you pointed out, this kind of magnitude of effects, and we ran trials in a similar timeframe that folks have done before, the sort of 14 day Phase 1 study where these effects were elicited very early in these trials.
