With that said, insofar as expectations, we do not know, our guidance has been that we expect median PFS to be mature in the second half of next year. So we’ll just have to see, obviously that’s event driven. We had a large, as you saw, a large number of patients remain on the study, so we’ll see how that plays out as the year goes along.
Jonathan Miller: But do you have a presentation at ASCO in the summer as well?
Terry Rosen: Oh yes, absolutely.
Pia Eaves: Okay, thanks. Hi everyone, this is Pia. If you could please keep it to one question as much as possible, we’d like to get to everybody.
Terry Rosen: Pia, I was liking the multiple questions. It’s a bonding experience.
Pia Eaves: So you can call the next person.
Operator: Thank you, our next question is from Peter Lawson at Barclays, please go ahead.
Peter Lawson: Great, thank you. Thanks for taking my question. I’ll try and make it a multi-part of you. Just on your HIF-2 alpha, the data we’re going to see early 2024, do you think that differentiation starts emerging, whether it’s in ORR, or do you think it kind of has to, we have to wait to see that emerging in PFS?
Terry Rosen: Yeah, I don’t, go ahead, Jim.
Jennifer Jarrett: Yeah, I think, so first of all, Terry started to talk about this, but maybe just again to tell you exactly what that data set is going to be. So the dose escalation is going to be 12 patients, approximately half of those patients, so approximately six of those patients do have RCC. All of those RCC patients were treated at a pharmacologically active dose. As far as will the ORR be differentiated relative to the 20 to 24% you see in cells, I think the problem is the sub-dominators are still going to be really small. So whether it’s really high ORR, really low ORR, I think the denominator’s too small to really tell you much, which is why Terry was saying we wouldn’t rely on the ORR for the dose escalation. So I think for the dose escalation, what’s going to be most interesting to see is, one, just what does the waterfall clot look like, and then RCC patients, are you seeing activity?
Two, are there any signs that maybe the responses are happening a little bit faster, because as we know it’s called Zutophan, for a lot of patients it can take six months or more to get a response. And then once we get to the expansion cohort, so that’ll be sometime in 2024, that will be a higher N in the denominator, and so the ORR will start to be more meaningful.
Operator: Our next question is from Robin Karnauskas from Truist. Please go ahead.
Robin Karnauskas: Great, I have 10 questions. I hope you can do them all in a very short period of time.
Terry Rosen: Robin, you can have 100 questions.
Robin Karnauskas: All right, I just was noticing, given the curves, like Bill and I were talking about, like how patients who experienced tumor reductions were PD-L1 negative, and that’s so unusual in the waterfall clot, so how do we think about that? How do we put that in perspective for PD-L1 high, and can you help us with the median 21 months of follow-up in pancreatic cancer, and put that into context? Like those are three, I’m sorry I got three, but like I’m just putting them out there. You can cut one off and give it to another person. But I thought the waterfall clots were very interesting.
Terry Rosen: So one thing to keep in mind with PD-L1 levels is that once you introduce chemo into the mix, you sort of have a dynamic situation, and that’s an important aspect of this therapy. So it’s not surprising if you heard one of the discussants talk about immunogenic chemotherapy and what that does. And so if you get an immune response, now having immunotherapy, you can generate what might be surprisingly good response. And I think it’s something we talk about, since we work on a number of immunotherapies, and we talk about this a lot in the context of QMLE, you can have a patient who might not even have that much of a tumor reduction, but from a survival standpoint can really benefit, because if they can amount to T cell response, you can enhance it.
So we just feel that that’s certainly amongst the rationales for when you start bringing in chemo together with immunotherapy, that the PD-L1 levels don’t tell 100% of the story. What was your second question, Robin?
Robin Karnauskas: So if you, for the pancreatic trial, like with the median follow-up of 21 months, how do we put that into context? Is that a long time? That seems like a long time for pancreatic cancer?
Terry Rosen: Yeah, yeah, it’s a long time. And to be clear, when we think about what the median OS readout is, that tends to range somewhere between like nine to 11 months on the high end. If you talk to clinicians, given this is so devastating, even something that was two to three months longer than that would be meaningful. So we think we’re going to have something that really looks like it’s moving the needle.
Robin Karnauskas: All right, I’ll put my another eight questions back in the queue, enjoy.
Terry Rosen: We can always talk later.
Operator: Our next question is from Kaveri Polman at BTIG. Please go ahead.
Kaveri Polman: Yeah, good evening and congrats on the EdgeCastric trial results. For PD-L1 expression, can you provide any color on your rationale for using TAP assessment and how different it is from the CPS score that was used for the 649 trial? Also, if you could tell us about your rationale for using cutoff of five versus one or can like some other trials have used?
Terry Rosen: Dimitry, you’ll take that.
Dimitry Nuyten: Yeah, so rationale to use TAP, there’s a couple of different things, right? So there’s the scoring method, which is TAP or CPS, and then there’s the different essays. And we need a combination of those for regulatory purposes. And we need to have the work done as companion diagnostic to use it as stratification factor in a trial. That work cannot be done on every single essay. That’s why we work with SB263. When it comes to TAP and CPS, my simplest way of answering the question is, as the discussant said, the TAP is kind of a visual scoring method. She didn’t use those words, but it’s easier for pathologists to do. CPS has a strong scientific rationale, but if you look at BMS’s initiated trial that was published, looking at 13 pathologists who have been in practice for 20 plus years and got training, the concordance of the inter-observer availability for the CPS essays is not great, wit in the 50 to 60% range.
So I think CPS is somewhat challenging in implementation in a larger setting, and TAP has the benefit that it’s easier to implement. The 5% threshold is a reasonable threshold extrapolated from the data for CPS in the public domain. We think it’s a good threshold. And then lastly, there was one more sub-part of the question. No, that was it? Okay.
Terry Rosen: Can we get everything to burn?
Dimitry Nuyten: No, sorry, no, and I wanted to make the point, we showed the concordance, right? So TAP is easier. I think that that makes it easier to implement it on a larger scale, also beyond clinical trials. But we have provided, let’s say, the CPS data on our own data set in the corporate deck as well, to provide confidence that the number of patients captured by both essays is not widely different. There’s a high concordance between these two methods.
Kaveri Polman: Got it. And if I can just squeeze one more. For ARC8 trial, the comment you made about sharing data from externally generated synthetic control with GenAbraxane, can you give us some color around that?
