Ahu Demir: Congrats on the progress. I have 2 questions. One of them, we heard you say the entity was not and also you don’t have observed the neutropenia and diarrhea. I am curious to hear if you could provide more color on the similarities or differences between narazaciclib with other CDK4/6 inhibitors. Do you observe similar safety profile? Or is it very differentiating? If you could provide some color on that, that would be helpful.
Steven Fruchtman: Mark?
Mark Gelder: Yes. So I think when I look at what really differentiates us, as you’re well aware, palbo and ribo are the 2 “purest” CDK4/6 inhibitors with ribo being the purest followed closely by palbo. Abemaciclib, like narazaciclib, is truly a multi-targeted kinase inhibitor. It hits several different kinases at low nanomolar concentration, but the kinases that abemaciclib hits are very different than the kinases that narazaciclib hits. All of them are very potent, very effective CDK4/6 inhibitors. What differentiates narazaciclib are the other kinases that it hits at low nanomolar concentration, particularly the ARK5 orn NUAK1 and the CSF1R. But there are others, the FLT3, the , et cetera. So there are actually several kinases that we hit that we think have the potential to be very important in terms of the overall efficacy as well as the safety of narazaciclib.
We — This is all preclinical data. We’re just getting into the clinic. We’ve now had in our Phase I dose escalation study. We’ve now had 21 patients total who have been exposed to the narazaciclib at escalating doses. And as I said, so far, the safety profile looks very, very good. Very similar to what we had anticipated based on all of our preclinical data. And we are very excited, as we’ve said, to be moving into the low-grade endometrioid endometrial cancer study because now rather than using a typical Phase I solid tumor population, we will be using a population where we expect — where we anticipate to start to see some really significant activity. So this is sort of where we are. I hope that answers your question, but it all has to do with the other kinases that we inhibit.
Steven Fruchtman: And actually, there will be more data that — Mark alluded to, there will be greater detail at the AACR meeting in Orlando.
Ahu Demir: That’s helpful. I have one more question on the letrozole combination trial. For the — since the both drugs are administered daily, I am curious if you have looked at the safety profile. Are there any overlapping toxicity? Are you expecting anything major in the combination trials?
Steven Fruchtman: Mark?
Mark Gelder: So when I look at letrozole and it’s got a very well-established AE profile. And when I look at what we’ve seen so far with narazaciclib and what we expected based on the other CDK4/6 inhibitors that are already approved, and based on our preclinical data, there really is very little, very little overlapping toxicities of the 2. The biggest one is really fatigue.
Steven Fruchtman: And if I can add to that and also add to the previous question because letrozole is an anti-estrogen, and as Mark just said, a very different safety profile and a very acceptable safety profile, a very different mechanism of action as an anti-estrogen. That’s why rather than waiting to — wait for the phase — the recommended Phase II dose of mono narazaciclib study to read out, we are comfortable combining narazaciclib with letrozole with a lower dose of narazaciclib to make sure . But this approach of already opening the combination trial and endometrial saves us 2 key factors, which are both very important, time and money. But we now will have, as we mentioned in this quarter, the first patient on this combination trial with endometrial cancer, studying the combination.
Operator: Our next question comes from Joe Pantginis from H.C. Wainwright.
