Terry Rosen: We don’t just think that, we know that. The study is set up for exactly that it was designed to detect both. And that one, Demetri was talking about the co-primary endpoints. Both of those are opportunities for the way the trial is designed and both opportunities for approval. And we think it’s a very meaningful opportunity.
Operator: Thank you. Our next question is from Salveen Richter from Goldman Sachs. Please go ahead.
Unidentified Analyst: Hey, thanks, this is Matt on for Salveen. On the gastric TIGITdata, could you share anything on how median PFS is currently tracking? I know you’re going to share more next year. And what do you view as a meaningful improvement over the seven to eight months of standard of care? And then could you share anything on how current standard of care breaks down between Keytruda and Nevo combos? And are most patients actually treated with an IO combo? Thanks.
Dimitry Nuyten: That’s a lot of questions. So when it comes to are most patients treated with an IO combo, it depends on where you are, what the reimbursement structure is, and what the experience of investigators is. There are plenty of investigators, especially in the US, that give Nevo-based regimens to everyone because you don’t have to wait for the testing and there is a modest benefit for low expressing and there is, of course, significant benefit for high expressers and the toxicity profile is very manageable. There’s definitely markets where reimbursement would come to be an issue. And in that case, typically reimbursement focuses on 5% and higher. When your question about the median PFS, we can’t really say anything about it.
The median hasn’t been reached. We need more follow-up to reach a median that requires a number of events for Kepler-Meier to calculate that so that there’s nothing what we can say except that we emphasize the numbers we have right now look very, very promising. And obviously, they are significantly away from the medians that we think we should be reaching. When it comes to a meaningful improvement, that to me is actually a question about survival benefit in a phase three. If the PFS benefit would be in the same range, then let’s say in hazard ratio of 0.75 starts to get interesting. For survival, probably a little bit higher. That’s as much as I can say. When it comes to absolute differences in months, I think that’s very hard to state on a single arm trial.
I would be looking at the hazard ratios in the phase three setting. I think you had another question in there.
Jennifer Jarrett: One other question you had was I think the mix of NEVO versus PEMBRO maybe in gastric. And today, NEVO is the only PD-1 that’s approved. Mark has filed for approval with Ketruda for their study. Keynote 859 was conducted later. And I think their PDUFA dates in December. But our assumption is that NEVO will continue to have the vast majority of share in the PD-1 market for gastric. And that is the comparator for our phase three.
Terry Rosen: One other thing I just think is probably worth highlighting because it’s something that like questions that somehow sometimes evaporate like FC versus non-FC, which for a year or two was the continuous question and overnight, somewhat evaporated. I think another one that’s evaporating, but I’d like to address it is the ZIM-Ketruda comparison and I think this data set is another one that just the anti-PD-1 performance clearly looks good. It also was got another approval in China recently, but I think that’s another example of ZIM behaving as you would expect an anti-PD-1 to behave.
Operator: Our last question for today comes from Jason Zemanski from Bank of America. Please go ahead.
Jason Zemanski: Thanks. Hey guys, congrats on the progress this quarter and appreciate taking the question. So I have to ask during asthma, one of the big debates was obviously over how the treatment paradigm would evolve in gastric. And I think one of the big kind of takeaways here was that in any cloud and positive patient who was also CPS greater than or equal to one, the algorithm would likely move towards combining both agents to get that potential synergistic benefit. Now, obviously it’s still very early, but I’m curious, how are you working to position TIGIT as the conversation starts to evolve? I mean, if KOLs are already thinking about this type of combination, what do you need to do to enter the discussion in favor of a TIGIT PD-1 combo, particularly as cloud and is biomarker driven?
Jennifer Jarrett: Yeah, and I think, and we’ve spent a lot of time with KOLs talking about anti-clotting and we’re working with the same KOLs as the anti-clotting companies are. So the first thing that I’d say about anti-clotting, if you look at the prevalence of high clotting 18.2 in patients, I know there was a number cited today, 40%, which was the percentage that was seen in spotlight, but there’s literature out there that puts that number well below 20%. And my hunch is that if you go outside of Asia, the prevalence of high clotting 18.2 is lower. The other thing that’s interesting, if you look at literature, is there seems to be more of a prevalence of high clotting 18.2 in patients that are PD-L1 low for some reason. And we’ve heard statistics like only 10% of patients that are CPS high are also high clotting 18.2 expressors.
So even just looking at that piece, they may not be viewed as directly competitive. I’d say on top of that, when people look at anti- TIGITversus anti-clotting, we’re obviously much less toxic. So if you look particularly at the Estella’s antibody, which is the most advanced antibody in clinical development, there’s a lot of GI toxicity in the plenary presentation today. They obviously talked about some of the other toxicities that they’re seeing with the ADC, so that’s something else to keep in mind. And then the third piece is clotting 18.2 testing does not happen today. And as we’ve talked to the KOLs, they think it’s going to take up to five years or more for that to roll out. There’s a lot of sites that don’t even test for PD-L1 today, and because PD-L1s are relatively safe agents, they just feel like, you know, I’m not going to test, I want to put my patient right on treatment, and so I’m just going to give them PD-L1 antibody anyway.
So we do think the need to roll out testing is going to be another impediment to the uptake of anti-clotting. So we’re definitely keeping a very close eye on the class, but at least today, I think we feel very, very good about our chances to compete with anti-clotting, and maybe, you know, way down the road, there’s a potential to combine PD-L1, TIGIT, and anti-clotting as well, anti-clotting ADC.
Dimitry Nuyten: Yeah, I do want to add to that, right? So people typically talk about toxicity in grades, but I would encourage you to look up what it actually means. So the clotting antibodies, they have at least 10 or 15% grade three nausea and vomiting. If you hit that as a patient, that means you’re hospitalized, you’re on tube feeding, you get parental feeding. It’s a really, really big deal. We talk about grade one and two toxicities that are obviously a burden on patients, but grade three nausea and vomiting is a really, really big deal. So I think that’s another uphill battle for the clotting field. Obviously, the efficacy data is absolutely promising, but to the point that Jen made, I think it’s going to be a small subset of patients that’s funneled into the clotting high, PD-L1 high population and then honestly ask yourself the question, like, could you deal with grade three nausea and vomiting?
I think that is incredibly, incredibly bad toxicity for patients that are in grade three.
Operator: That concludes today’s conference call. Thank you everyone for joining, You may now disconnect.
