Richard Miller: Okay, so in our — Mara, in our experience so far, now we’ve got a lot of late line patients. Our experience so far, about 70% of patients are greater than 900. I think as we move earlier, if we were to move earlier, you would get that number would probably go up.
Mara Goldstein: Okay. And okay. Perfect. And then I also wanted to ask just on the meeting with the FDA a about starting a registration program, you mentioned later this year. Are there gating factors for you to request the meeting? Like things that you need to do ahead of the meeting at this point, because it certainly does accelerate and change your clinical plan.
Richard Miller: Well, we have to prepare a package. It summarizes our safety and efficacy data and a few other things. So that’s a gating item, but we should be able to do that. That’s straightforward. We have the experience and the team that can do that.
Mara Goldstein: Okay. So is it reasonable that you might be requesting the meeting kind of around either sort of end of second quarter, early third quarter, that kind of timing?
Richard Miller: Yes. I think we could be meeting with them in the next few months.
Mara Goldstein: Okay. Thanks. I really appreciate it.
Operator: Our next question comes from Roger Song with Jefferies. Please go ahead.
Roger Song: Great. Thanks for the update. And thanks for taking the question. Maybe just homing this potential Phase III redesign, Rich, I understand you have been seeing this biomarker see the difference, huge difference between treatment and so just above and below 900. So just curious how confident you about this cut-off and how much data you need actually need — how much more data you actually need to make sure that’s the cut-off you will propose to the FDA, or you’re waiting for — you have seven patients still ongoing and they’re all selected for the ALC and how likely you will need to change the cut-off. Similarly, for the dose selection, seems 200 milligram is the dose you’ll move forward. And how likely you need to do additional dose ranging or optimization before you can start the pivotal. Thanks.
Richard Miller: Okay. Regarding the 900 ALC cut-off the date is in the press release and I mentioned it eight out of eight disease control four out of eight objective response versus zero in the other group, 28 month PFS versus two month. There’s a very substantial difference between 900 and above 900 and below. Could we use 1,900, a 1,000? Yes. That — that’s almost within experimental error of the test. Normal, is a 1,000 — lower than a 1,000 is lymphopenia. A 1,000 has been used in other settings. It’s a prognostic. It was, for example, a very important prognostic feature in hospitalized COVID patients. If they were under a 1,000, they did very poorly. In head and neck cancer, it’s a prognostic feature and there are other cancers as well where it’s been a prognostic feature that is using lymphopenia or not, a 1,000.
We find that 900 is a really good cut-off, and we wanted to give ourself a little bit more room. But so, I think that cut-off makes sense from looking at our data. It makes sense from mechanism of action. And, I don’t have any reason to think we would want to change it. Now with regard to the dose, we have a lot of information now on dosing. I don’t think we’re going to have to explore other doses. Number one, we know that 200 milligram dose, first of all, as you know, we even looked at a 100, 200, 400, 600 milligrams, BID. We know that 200 gives you near complete receptor occupancy. We’ve done very careful studies on that. So 600 is not better than 200 in terms of occupying your receptor, your ITK target, number one. Number two, we see more efficacy at 200, not only in our lymphoma patients.
