Judith Klimovsky: Yes. So as we all know, checkpoint inhibitors moving to the first line, a single agent, if patients have PD-L1 above 50% or in combination with chemo for patients with lower expression of PD-L1. There is a huge unmet medical need for patients that failing pembro checkpoint inhibitors and chemo where the standard of care, unfortunately is paxo [ph] that drive an overall let’s say benchmark bar but from 12% to 17%, 18%, 20% at the most and with very prognosis and this segment is growing. As you know, more and more patients received first-line combinatory treatment or even sequential. And it is in this very setting where we conducted the randomized 04 study assessing two different schedules and even 1046 single agent, which gives us a strong foundation for a potential Phase III in this very setting.
So we are encouraged about the methodical follow of the science and this is where we are engaging with health authorities in coming weeks to define better and we will share more as we define better those plans.
Jan van de Winkel: Thanks, Judith. So more to come in the coming weeks and months Jonathan for sure.
Jonathan Chang: Understood. Thank you.
Jan van de Winkel: Thank you.
Operator: Thank you. We will now take the next question from the line of Michael Schmidt from Guggenheim Partners. Please go ahead.
Paul Jeng: Hi. This is Paul on for Michael. Thanks for taking our question. First one is on the pivotal data for EFCO in follicular lymphoma at ASH. How are you thinking about the opportunity and differentiation from [indiscernible] based on the emerging clinical profile and your conversations with physicians? How much do you think that the evolving duration of response will possibly factor into how the two drugs are positioned? And then my second question is sort of building off the prior one on GEN1046. Can you sort of just talk a little bit about your decision to initiate that Phase II study for endometrial cancer, whether that was driven by emerging data in Phase I or perhaps the non-small cell lung cancer combo trial? Thank you.
Jan van de Winkel: Thanks, Paul. The first question I think can be handled by Tahi. And then the second one maybe Judith, you can talk a bit about endometrial on the start of that trial and why we are so excited there. Tahi?
Tahi Ahmadi: Yes. Thank you for the question. So, as it relates to the data in follicular lymphoma, there’s obviously some public release of our data top lines, but you will see more data. And I think here the most important part will be to pay attention to the optimized schedule that will be presented at ASH and then the safety profile of EPCORE in the optimized setting which will I think very clearly show that EPCORE then has a profile both on efficacy, but also from a safety profile that is extremely competitive with best-in-class safety and best-in-class efficacy even in follicular lymphoma. Duration of response is a tricky one. To some degree, it’s a question of follow-up. Obviously mosunetuzumab has significantly longer follow-up and EPCORE because they started about three years before us.
And so that is also reflected in the duration of response. And then there’s other parts that are kind of like compounders to some degree. The only point base certainly played that. But even with that I think there will be some data in the future and continuously showing that patients who are and that’s basically the truism about this mechanism. Patients who achieved a deep response particularly CR are staying very, very long in their in their CR. And in some cases, we will see if that is actually reflection of a big word in cancer about to cure, because we have patients now who are approximating five years in CR. So broadly speaking on EPCORE, I would say pay attention to the disclosure of data where we share at ASH and also the updated data and the optimization data set.
Jan van de Winkel: Thanks, Tahi. Let’s move to GEN1046, Judith and maybe talk a bit about rationale for endometrial cancel, why did we start of that study et cetera? : Thank you, so much. So, we started studying endometrial because it’s a tumor type where 4-1BB is constitutively over-expressed and is it setting to test an hypothesis different from what we have done in 04, which I already alluded to. So this is the reason total endometrial cancer. Now we understand that endometrial cancer is not a single disease. You have the MSI high and MSI low. We are gathering data as we speak. And based on the data, we plan to daggle these different subtypes and go from there. And so it’s very preliminary to say what is the path forward, because we are gathering data in this Phase 2 program to understand the data and where there could be a path forward.
As another point to flag is endometrial cancer in the Phase 1, we saw long durable responses with 46 as a single agent, which again prone us to investigate more. So again we expect to have this data in coming months to allow us to make decisions.
Jan van de Winkel: Excellent Judith. Thank you very much. Thanks Paul for your questions.
Operator: Thank you. We will now take the next question from the line of Etzer Darout from BMO. Please go ahead.
Etzer Darout: Great. Thanks for taking the question. The first one on sort of GEN1046 again, you have data next year at a medical meeting. Just how are you thinking about the target relative to other IO agents that we’ve seen now being combined with PD-1, like, what we’re seeing from the TIGIT class just how you see the PD-L1 4-1BB mechanism relative to that? And then maybe quickly on HexaBody-CD38. Just if you could remind us the opt-in rights for J&J with respect to that program, just so we could think a little bit about more or less when that could be triggered potentially by J&J? Thank you.
Jan van de Winkel: Thanks Etzer for the questions. The first one I will hand over to Judith to talk a bit about 4-1BB targeting versus other immune checkpoint targets. And I can take the HexaBody-CD38 question myself. Judith why don’t you go ahead?
Judith Klimovsky: Yeah. So I first tried to say that there is no precedent of IO as a single agent provided responses in patients that failed checkpoint inhibition PD1 inhibitors. So if you think about the array of diseases or other targets, the response rate in patients that failed checkpoint inhibitor is zero, or in a handful. So we — for PD-L1 4-1BB, we showed in the first cohort that there were responses. And there was 17% and we enrolled all comers. Then we presented in Q3 2021, when we segmented this population based on the PD-L1 presence, the response rate was higher albeit durable. However, we had this preclinical day that showed this synergy additivity with pembro, and this is what prone us to do the offer. So to reinforce the fact that high single-agent activity post IR it’s almost unheard of but we saw it with 1046 to overcome the durability and strengthened signal the right next step to combine with pembro was the next step and this is what we have done, which results are emerging and we will share.
So there is no precedent of IO, IO in a post-IO that PG are all going to first line in PD-L1 high. This is where the data show that there is a stronger activity. So even in the hypothetical case that DGD go to the first line it won’t change the huge unmet medical need in a post-IO for non-small cell lung cancer in particular.
