Johoon Kim: Hi.. This is Joe on for Brian. Thanks for taking the question and congrats on all the progress. So I guess a similar question to what was just asked. So yes, we saw from the ASH abstract, I guess, there might have been some low yield issues. So just wondering what led to this issue and if there’s something that you were able to resolve. Thank you.
Paul Stoffels: Can you take this one?
Jeevan Shetty: Yeah. Thank you for your question. The issue — what we’ve observed with regard to the low yield is, as Paul just mentioned, this is a very patient-driven component, characteristics. Even in the few patients that didn’t achieve the dose level as intensified protocol, what we actually observed were the patients actually continue to have a very good response. And we also saw good expansion and good — a very positive phenotype of the cells in actual fact. So therefore, the — whilst the [indiscernible] might be the disease itself, it doesn’t appear to have an impact on the outcome and it may — and efficacy. And so therefore, this worked. We’re doing a very deep analysis with a very robust transformational plan and program that’s running in parallel to the program.
Johoon Kim: Got it. Thanks so much.
Paul Stoffels: Thank you.
Operator: Thank you. We will now take the next question from the line of Jason Gerberry from Bank of America. Please go ahead.
Jason Gerberry: Hey, guys. Just two for me. As you advance your CAR-T programs in ’24, I’m just wondering about the scope of R&D and CMC investments and how that sort of fits with kind of the outlay of operating spend this year. I imagine there’s some cost shifting post the Jyseleca update, just maybe it’s a shift in the composition of your operating spend more towards R&D. So just maybe if you can just talk about how the cost of the CAR-T program starts to scale directionally in the next few years. And then can you just remind us, so Gilead will have standard opt-in right here on the CAR-T program, I assume, up through the readout of the pivotal Phase II, if you get there. So Gilead obviously has more advanced marketed products and partnerships in these respective spaces. So how do you ensure, with that kind of dynamic, best efforts if Gilead were to opt-in towards your programs? Thanks.
Thad Huston: Thanks for the question. It’s clear that with the transfer of Jyseleca to Alfasigma, it does significantly improve our cash burn and allows us more flexibility to invest in broadening our portfolio. Part of the guidance that we gave about saving roughly $150 million to $200 million is assuming that we’re also increasing our investments in oncology, particularly in the CAR-T expansion. We’re adding resources to the 100 positions that Paul mentioned largely in those areas to help us build out regulatory CMC clinical capabilities to help us broaden our CAR-T network in the U.S. and in Europe. So we’ve been actively doing that and continuing to add. And roughly, that 100 heads will be over the next one year, 1.5 years roughly increasing our spend.
But on the Gilead side, I mean it’s clear that Gilead has been a great partner. We see they have opt-in rights to any of our programs after pivotal. And so, yes, they ultimately could choose to partner with us on that. We need to establish the clinical network and get to that point and then we’ll ultimately see whether Gilead opts in at that time.
Jason Gerberry: Yes. Sorry, how would that ensure that your program gets prioritized versus sort of maybe minimizing the competitive threat to the existing businesses that they’re in?
Paul Stoffels: Let me answer this one. The first one, Richter’s transformation and CLL — resistant CLL — double refractory CLL, Gilead doesn’t have the indication at this moment in their portfolio. So that’s complementary. At the same time, setting up a decentralized network for CAR-T provides more access not just in the U.S., but it could also bring it to much wider in the world. And again, there could be a significant complementarity with what Gilead is doing. And for us, being able to build on the Gilead expertise both in marketing and sales, but also especially in the reimbursement and dealing with this type of products in the U.S. could accelerate for us the roll-out. And as long as we can make sure that we can produce all CAR-Ts locally in the network, mostly close to the hospitals, we — absolutely, we welcome how we can work together with Gilead to accelerate access to patients and accelerate the reimbursement that we can get access.
Jason Gerberry: Perfect.
Operator: Thank you. We will now take the next question from Sebastiaan van der Schoot from Van Lanschot Kempen. Please go ahead.
Sebastiaan van der Schoot: Hi, guys. Congrats on the progress. Thank you for taking my question. The first one is on the dose level. You are now moving to the dose level 3. I am assuming that you use the same production process for each of the different dose cohorts and then insert the predefined dose. Can you maybe elaborate in what percentage of patients you get to that dose level 3 in the non-Hodgkin lymphoma? And I was wondering also with the data that you have generated so far in CLL, whether you can expand on how many different clinical sites have patients been treated at?
Paul Stoffels: At dose level 3, we are still preparing to introduce that based on the outcome of the first two dose levels, and that’s a discussion with the investigators. So the commitment is there to do that. I can’t give yet a percentage on how much we can — in how many patients we can achieve that dose level 3. And I don’t have the production — the detailed production data on the others to derive it from that. And on the CLL, at the moment, it’s done in one big center where a lot of patients are flowing in from different other centers.
Sebastiaan van der Schoot: Okay. Thank you. And then on the non-Hodgkin lymphoma data set, is that generated in different hospitals?
Paul Stoffels: Yeah. There’s been five different hospitals in five different sites in Europe.
Sebastiaan van der Schoot: And then those three patients that did not have a high-enough dose, were those at different centers or was that one single center?
Paul Stoffels: I can’t answer that on the spot.
Jeevan Shetty: Those patients were on different centers. We just want to point out that those patients, to the point that we made earlier on, were able to actually deliver good efficacy as well because the in vivo expansion itself I got is still being good at a dose that wasn’t achieved. So we are interrogating that data in more detail. It will be available in coming conferences.
Paul Stoffels: Let me add to it. As I discussed in previous meetings, what we see in our clinical trials is that because of the short life expectancy of the very aggressive late-stage NHL patients, that is the patients are in very high — highly pretreated, but at the same time in very bad condition. And so that made the incoming material very variable. And that’s probably why it’s across centers, but that’s probably why it’s difficult to reach the higher dose levels.
