Brian DeSchuytner: What I think is important is we are still in dose escalation, not established an MTV. One of the reasons we mentioned that we were seeing objective responses, we did want to make it clear that we are in clinically relevant dose ranges. And so, now it’s a matter of getting that dose in schedule right, and I think that is the focus. We do have a better understanding of our PK than we had previously. I’ll give all the data. And as the other thing we kind of highlighted is there’s this concept of understanding exposure over time is important. And if you kind of put those two together, how do you get that just right. And that’s really our focus over the next cohorts that we’re studying to prepare, so that when we come out with the data set, we have a high degree of confidence in not only the dose but also the schedule.
Operator: The next question comes from Michael Schmidt of Guggenheim. Please go ahead.
Michael Schmidt: Hey, guys. Thanks for taking my questions. Just a follow-up on 1660. I guess, is their PK different from what you had expected? And are you surprised that you’re not yet seeing MTDs. I think last time you said you were in dose level 7. You’re obviously far into the active dosing range at this point. But I’m just curious if there’s anything unique going on or if this is just part of the regular Project Optimus, workflow that has to be done?
Martin Huber: I don’t think there’s so much anything unique. I think one of the things was we had gotten with 1592, our NaPi2b Dolasynthen. We have hit dose-limiting ILD at 56 milligrams per meter squared. As we’ve told — as we stated last time, we’re over that now. So, we’re at dose ranges that we haven’t been before, and that always you always want to be careful when you’re into new dose ranges on a platform. And I think the other thing is we’ve always been confident in our PK, as we’ve stated before on our previous molecules, we haven’t provided data on 1660, but we do see antibody-like half-life for our molecules. And I think when you take that into account, trying to understand what is the optimal schedule to get the right exposure, it’s some fine-tuning.
And your final point on Project Optimus, that is a factor because I think historically, we would have been very comfortable just get a dose you’re comfortable with, go straight into expansion. And if you have to change the dose, you did. I think in this current environment, we want to have a higher degree of confidence in the recommended Phase 2 dose that we take into expansion. So, I think it is just a little bit — and this has been a — for a lack of better work, a personal growth for myself, is appreciating the more time and energy on dose optimization than historically we did.
Michael Schmidt: Yes. No, I think that makes sense. And I think other companies have also looked at multiple different schedules before selecting an NaPi2b. Can you comment — is it every two weeks, I think, in the Phase 1? And what are you looking at as alternatives
Martin Huber: What we previously disclosed is every three weeks or every four weeks, but the protocol has given us the flexibility to look at alternatives, which we are currently doing.
Michael Schmidt: And then — yes, when we look at the Pfizer data that was recently presented at their R&D Day, they obviously saw some very nice enrichment of activity in biomarker-positive patients in triple-negative breast cancer. I think it was almost twice the response rate in positive patients and so, I’m just curious what your approaches might look like for biomarker development. Would you look at a similar, I think they used an IHC-based assay, or are there any other things that you could consider to enrich for biomarker expression?
Martin Huber: Yeah. Maybe I can take that. That’s a great question. We’re currently working on our biomarker strategy, and we’ve not made any final decisions about it at this stage. We’re enrolling patients’ regard with the biomarker status to ensure we fully understand the relationship between B7H4 expression and the probability of response. So in other words, we’re retrospectively running an IHC test to establish B7H4 expression levels. But we think this will be an important part of the development program to be re-nailed at.
Michael Schmidt: Awesome. Great. Thanks for taking my questions.
Operator: Our next question comes from Asthika Goonewardene of Truist. Please go ahead.
Asthika Goonewardene: Hi. Good morning, guys, and thanks for taking my questions. So previously what Michael just asked about as well, about dose level 7 or 59 mg per meter squared, that was, you guys were on there in Q1 this year. So let me be direct and just ask, how many dose levels above that have you reached right now today in patients? And then, Marty, you said that you’ve seen confirmed responses. Have you seen this in more than one dose cohort?
Martin Huber: We’re not getting into the details of either dose levels or the response data. I think it is responses. We did make sure we emphasized that. But I do think when you start looking at dose and schedule, focusing purely on an exact dose number becomes a little less relevant, because what you’re looking at is the total dose intensity of the regimen. And there’s ways you can dial that, both from not only the actual dose you administer, but the frequency with which you administer it. So I think what’s important is we are looking at more dose-intense approaches to the dose and schedule. But we’re not getting into the details of exactly what those are. And part of that is, this is something that is fairly competitive space, and understanding ADC dose and schedule is a competitive issue.
Asthika Goonewardene: Got it. Okay. And so should I read that since you’ve already tried Q3W, Q4W, you might be looking at some of the other more creative approaches, like Q2W or two-on, one-off. Is that how we should be thinking about it, without getting into specifics?
Brian DeSchuytner: Yeah. We’re really not getting into more specifics, Michael. Asthika, I’m sorry. So yeah, we’re just not going there at this stage.
Asthika Goonewardene: Okay. Great. Thank you. Appreciate the update.
Operator: [Operator Instructions] Our next question comes from Ashiq Mubarack of Citi. Please go ahead.
Ashiq Mubarack: Hi, guys. Thanks for taking my questions. I think you already addressed my first one, which is just to confirm that the biomarker you’re looking at is a B7-H4 biomarker based on IC. I’m assuming that’s correct versus maybe something else assuming that’s correct, I mean, where are you in the development of an assay? Is that something that’s been established or is that something you’re building from the ground up and how robust do you think that assay might be. Thanks.
