Gilead Sciences, Inc. (GILD) Earnings Call Transcript & Summary

Thank you guys for joining. Super excited to have Dietmar join us from Gilead. I know we spent time at your prior company as well. So how has the transition been? And how are things going on the West Coast?

Transition has -- first of all, thanks for having me. Transition has been great. I'm with Gilead since a year. I've always been excited about the science and the people and the impact that Gilead has. And what I found is exactly in line with that. I'm really excited -- it has been going well. We've had good data during the year. Obviously, we have different launches going on. We have the portfolio focus on virology, oncology and inflam. So it's been a really good year.

Fantastic. We're going to focus this conversation today more so on R&D. I know we had Andy with us earlier as well. I was hoping Jacquie would join us, but Jacquie is staying there. But maybe -- so I'll stick to the R&D topics, but because everyone cares so much on Yeztugo, I guess my only question to you from an R&D perspective is, how have you looked at some of the -- when you got in and you saw some of the nodule data and perhaps even like in talking to clinicians at some of these conferences, how have those conversations been? And how important was it that you moved to IM?

Yes. The -- so just stepping back for a second, right, the nodules that you see have not been a problem at all on the clinical side, right? When you look at the PURPOSE 1 and PURPOSE 2 study, people have been really content with the therapy. We have basically 96% of people who are on the study who said, I want to stay on Yeztugo. So this has not been clinically any issue. And you have to see that the nodules are really part of the mechanism of action. You basically get a depot, a subcutaneous depot. The move to intramuscular is another option that gives us another option for longer duration therapies. It also gives us an option to then go to once every year therapy. That's the ongoing study that we have, which we call PURPOSE-365, which will get us to a prevention option for HIV with a once every year intramuscular injection. And that's important for, first of all, further extending the intervals, right, to basically a vaccine-like approach. We're always saying it's not a vaccine, really important in the...

I heard. It's very important.

These days it's really important in the environment, but having a once per year option is really important for us. And the intramuscular helps with that basically, smaller volume intramuscular.

Got it. So the one thing I always think about is the nodule still happens just deeper or no?

The -- you cannot feel a nodule with the intramuscular, right, because you are deeper, but there still is a depot, right?

Okay. Got it. Got it. So there still is a depot. It's just not as big. Okay. Got it. Also, would you remind us, the intramuscular is only being studied for your annual shot or also for every 6 months?

So the intramuscular could be applied to different timing. So it could also be applied to the once every 6 months.

Okay. Is that being pursued right now? Or is that sort of -- you'll think about it depending on how the data comes in?

We'll think about it depending on how the data comes in.

Okay. Got it. And from a patient feedback perspective, maybe clinician feedback perspective, like the early experience on nodules and there's an aesthetic side to it and some pain side to it. Like what has that been? Is it like rate limiting? Like people are getting their first shots right now. Are they like, oh, I don't want to do that again? Or is it sort of like I can live through it?

So we did not hear that at all. And the important piece is, obviously, we -- this is a complex launch, obviously, right? We're in a situation where a lot of the prevention is also oral. So now you're talking about an injectable, right, which is a bit of a paradigm shift. But the injectable has real benefits, for example, from a compliance perspective because the shot is in once every 6 months and people are protected for that 6-month period, right? And there's no question of taking daily pill, no question of keeping the medications with you. Compliance is better with that, and that's one of the key benefits. But we are really supporting that launch with a lot of information that we provide to people. And one important piece is how do you inject, right? For example, when you cool the injection site, right, then the pain is not a big issue. The nodules form in the beginning, but then they go down over time, for example, and we have not heard any major issues around that.

So -- okay. So it's manageable is what it sounds like.

It's going well. Yes, manageable.

Okay. The other one is, Dietmar, as you think about from a compliance perspective, based on your conversations with clinicians, how are you feeling? We had GSK management earlier this morning, and I was asking their broader experience on long-acting on treatment. And they said, you know what, we're surprised by the durability we're seeing on patients staying on, because there's always a concern they take 1 or 2 shots and they're done. How are you thinking about that from a compliance perspective?

So there's 2 aspects, right? One is comparing the orals or the less frequent versus every 6 months. And they are clearly compliance with the once every 6 months is not an issue, right? Because it's once and done.

I mean more like duration of their treatment.

But you're talking more about people coming back, right, and then getting the treatment. And the main experience that we have at this point is from the clinical trials where more than 95% or 96% to be exact of people decided, I want to stay on the Yeztugo because I do see that benefit of the once every 6 months, and I want to do that for a longer period of time. Obviously, we are just getting into that phase where we get the retreatment, right? The launch was starting in June. So we're now getting into the phase where those people come back and then ask for their next therapy. So we'll get more experience with that over time. But I think that everything that we've seen so far indicates a real positive feedback with the therapy.

Okay. Great. Excellent. So maybe we can start to move on. I want to start with a drug in your Phase I, which I don't know how many questions you get on, but I'm just particularly focused on it because I sometimes wonder if this could form the basis of sort of like a Biktarvy replacement, if I may. Am I over-indexing on GS-3242, the new integrase and if that could be the basis for a new life cycle management for the franchise as well?

So we've just communicated GS-3242, as you say, right, is an integrase inhibitor with a longer half-life. And we had several of those. We have several of those in our portfolio. We've just communicated that we've prioritized 3242 versus another very similar molecule, 1219, which shows you the depth of the portfolio. 3242 is a basis for some longer-acting treatment. So we're not thinking about this in terms of Biktarvy. Biktarvy at this point in time is a really important molecule for us. is a daily oral for therapy is the standard of care that people, for example, with newly diagnosed disease get. They can get it at the first time immediately when they come into the physician's practice. We've got really good efficacy. We've got absolutely no safety issues. So that's our standard of care. Over the longer term, if you get with, for example, a molecule like 3242 into longer treatment intervals, how this plays out and how this is segmented, we'll have to talk about that. And 3242 in itself is an integrase inhibitor, right? So you need a combination as well for these types of therapies.

Sure. So I guess there are several follow-ups to that. First is you had 2 weekly integrase. It was 3242 and there was a 1219. The 1219 was terminated. I think clin trial says only 4 patients were recruited. Could you remind us what happened there?

Yes. We always said we have different molecules that we're exploring multiple shots on goal. And then we will look at early parameters in order to select the one that we feel is the best one. And that's in the early stages based on PK, based on early tolerability data, also based on preclinical data. And that's where we saw some benefits for 3242 over 1219. So it's really a portfolio prioritization.

It was not like there was some CD4 drop problem or anything.

No, no, not at all.

No safety problem. The other one was, I think back in June, you guys had a clinical hold on -- I believe that was a long-acting capsid is where the hold was. Is that right?

So that was a combination therapy. That was the WONDERS-1 and WONDERS-2 study, which is a combination again of a long-acting -- it was actually the wholly-owned once-weekly option and was an integrase inhibitor, an INSTI and a lenacapavir prodrug, right? And we did see that drop in CD4 positive T cells. We are currently in the phase where we try and understand the data around that. When you look at the 2 classes, the integrase inhibitors and the capsid inhibitors, lenacapavir and the broader class of the INSTIs, this is not a finding that's broadly linked to these drug classes, right? We -- at this point in time, our main hypothesis is with these prodrugs, you do get metabolites, right? And we think it's most likely linked to one of the metabolites that you get when the prodrug is cleaved right? And the metabolite per se is circulating and that it's a metabolite-associated effect. We did not see anything like that with the original lenacapavir, right? We did not see anything with the original INSTI, the 1720.

Right. Makes sense. So both the molecules are on clinical hold then?

So the combination is on clinical hold. And then as long as we need to really understand which molecule is linked and what exactly is the mechanism until we have that, we're not moving these molecules forward.

I remember when lenacapavir got approved in PrEP, one of the things I was very focused on was did this hold show up in some shape or form in the FDA review documents and it totally didn't. So is the len prodrug, if you want to do a monotherapy trial on that, that's doable?

So we have several len prodrugs in our portfolio, right? So what we're talking about is a very specific combination of 1 INSTI and 1 lenacapavir prodrug. We have other INSTIs in our portfolio, and we have other len prodrugs in our portfolio. So at this point in time, we're taking these other molecules forward while we try to understand what happened in that specific combination.

Okay. Got it. Got it. And okay. And maybe just remind me, that INSTI that was in this trial that was on hold 1720, that was also weekly integrase just like 3242, which is also weekly integrase.

Yes. That's a weekly. 3242, we need to see about the different approaches where we want to take it because the PK is longer for 3242. But again, it goes back to this fact that we have a variety of these molecules with different PK, different half-lives that we can take into different settings. 1720, 4182, that combination we're talking about was specifically our wholly-owned once-weekly combination. Remember, we have a once-weekly combination that is coming. That's the islatravir, lenacapavir combination that we're doing together with Merck. Those are ongoing Phase III studies that will read out during the coming year, right? So we have already a combination that we're moving forward with these Phase III trials in the once-weekly setting -- in the once-weekly treatment setting. But of course, we want our wholly owned combination. And that's where with the ongoing work on 1720, 4182, we've always said that will lead to a 3- to 6-quarter delay for our wholly-owned, but we are continuing to work on a wholly-owned combination as well.

Got it. Okay. That makes sense. So I just want to make sure for everyone listening in, you have ARTISTRY trials with integrase plus len daily treatment.

Exactly.

Then you have with Merck, the weekly treatment, also all oral. And then you also had a weekly all oral of your own, which went into clinical hold. So that's 3 to 6 quarters behind. We'll see when that comes back. But for market positioning, you have a daily fully owned and a weekly partially owned. That's sort of like the near term. But the commonality in both of those daily and weekly is you're dropping the nucs. How dangerous is that in terms of resistance profile?

Yes. The resistance is a really important question. When you look at the different drug classes, right, in HIV, you had the protease inhibitors, which are really -- is an old class. Then you got the reverse transcriptase inhibitors, which is where the nucs are, right, the NRTI or NNRTIs. Now you got the capsid inhibitors like lenacapavir. What we do with BIC/LEN is we combine 2 of the most active drug classes. We have an integrase strand transfer inhibitor in INSTI plus then a capsid inhibitor. Both of those individually show basically very limited resistance formation. We did publish on resistance data for bictegravir, which is the component in BIC/LEN, and lenacapavir at the EACS meeting in Paris earlier this year, right? And when you look at resistance formation with the INSTI, it's very low, right? And you don't see clinically meaningful resistance with that. With lenacapavir, again, you see very limited formation of resistance. There's also no cross resistance. So at this point in time, we're very encouraged by what we've seen in the clinical trials. We've not seen any resistance formation. Obviously, we're going to watch that as we go to a larger patient population. But we don't think at this point that there's any reason to believe that there would be resistance formation.

Because we've seen one experience with your competitor. They tried a 2-drug regimen. They dropped 1 nuc, only kept 1 nuc and 1 integrase. That integrase is nearly identical to bictegravir. And they did see -- so as much as the primary endpoint looks amazing, they did see resistance profile emerge over time. So I just wonder like...

So we'll watch that very closely. But at this point in time, we haven't seen anything, plus then what the competitor did, they did not have the combination with lenacapavir, right? And lenacapavir as a new mechanism capsid inhibitor, there's really no cross resistance between the 2. There's no cross-resistance formation as well. So we have not seen any concerning data at this point.

So I was going through the Phase II data, and I noticed there was an N74T pop-up and that conferred resistance in Phase II. And I was like, oh, so this could happen in Phase III? Or is that not a common enough mutation that you wouldn't see necessarily?

That's really -- that was a single case in the Phase II, right? And we also had the Phase III study. We didn't see that again. That N74T is -- when the capsid forms, it's actually a capsid polymorphism. It's a really weak resistance that emerges with N74T. There's no circulating N74T mutations or anything. So we've not seen that as a pattern. We've not seen other cases of that. It's really interesting when you look at the ARTISTRY study. So again, BIC/LEN, this combination is in 2 Phase III studies at this point, ARTISTRY-1 and ARTISTRY-2. ARTISTRY-1 has read out, as you said, right? And ARTISTRY-1 is a study in people who are currently on complex regimens. That is about 6% to 8% of the HIV population. These are people who've been on therapy for decades, right? So they've cycled through all these therapies, and they have actually accumulated resistance, right? In the ARTISTRY-1 study, more than 80% of patients in ARTISTRY-1 had a type of resistance, right, either to the NRTI or to any of the other drugs. And these people were very effectively treated with BIC/LEN. So that's another argument that basically shows you even in people who have pre-existing resistance, BIC/LEN is a highly active regimen that's effectively treating those people. And that is, I think, a real benefit. People on complex regimens are on regimens with up to 11 or more drugs at this point in time, right? And they have to take them at specific times of the day and some of them have to refrigerate it, others not. And for them, going on to this like 1 pill a day, very simple, is a real advantage for them as long as we really cover those resistance mutations as well, which we do according to the study data.

So the ARTISTRY-2 trial, is that in naive setting?

The ARTISTRY-2 trial is in the switch setting.

It's in the switch setting.

Basically taking people who are switching from effective therapies want to go on to another therapy. But they're not switching from like the highly complex regimens. They could actually switch from any type.

Can they switch from Biktarvy?

They can also switch from Biktarvy.

The first trial was from complex. And the second one is from anything.

Anything. Exactly. And the second trial is reading out in the near future. And once we have these 2 studies, then we can take BIC/LEN forward.

Got it. I guess why not run a trial in naive setting then if there's so much confidence in this? Why not just go after the Biktarvy market?

Yes. We could theoretically do that. But when you look at the strategy that we have, Biktarvy is such a strong standard of care at this point in time, right? Efficacy, safety, immediately usable as patients are newly diagnosed, no resistance formation, right? So we believe Biktarvy is going to remain standard of care in the naive population. And another daily oral doesn't really provide a major benefit versus Biktarvy. So what we've been focusing on in the naive population is longer duration intervals, right? That's where we're thinking about can we take a weekly regimen, a monthly regimen, other longer duration regimens into the naive population with our studies.

Okay. So I'm just putting your HIV strategy in perspective then. Integrase plus len daily being positioned for switch setting?

Being -- exactly...

Integrase plus len-like drug on a weekly basis oral for naive setting, that will be the Biktarvy replacement.

Yes, that would be -- I still believe that Biktarvy because it's so easy, right, and such a well-established standard of care will remain the standard of care, but we do want to provide more options, right? It's -- a lot of it is really about optionality, right, getting to people really satisfying the needs that they have. And you see that, for example, we are also developing a once every 6-month injectable regimen for therapy, right? So people want different types of therapies, and that's where these options come in.

Got it. I realize this is a bit more of a commercial question. So it may not be fair. But Dietmar, just to frame it for you, I think a lot of times, investors are saying there's a Biktarvy business that's very large. A portion of that is in naive, maybe it's a substantial portion. And then a smaller portion is switch. And people just want to see what are the new drugs that allow this franchise to just keep going. So in that switch setting, how meaningful is that of the total Biktarvy? Would you know? Or you wouldn't know that?

No, I wouldn't.

Okay. Fair enough.

I don't know the exact percentages there. But you're absolutely right that we want the initial therapy, right, the naive setting, absolutely with Biktarvy, we have that. And we also want to provide options for switch. Some people want to go from a 3-drug regimen, which Biktarvy is, for example, to a 2-drug regimen. That's where BIC/LEN comes in, right? For example, in Europe, for many people, that's a key question. And we want to provide that option. But we also want to make sure we have options for weekly, for monthly, for longer duration.

Great. Fantastic. I want to switch to -- I want to go to cell therapy, but last. I want to do a couple of parts of your pipeline, which perhaps there's curiosity around, but people don't really know if those are -- where these programs are heading. Oral GLP, first of all. Can you remind us what type of scaffold is that? Is it orfo or is it the Pfizer's scaffold or the Lilly scaffold?

We have not communicated that, right? It's coming out of our chemistry, but we've not talked about the scaffold yet.

Got it. Is this -- like if it shows what you want to -- remind me how big is the trial? What's the trial? When does it do?

So it's currently in Phase I. And just to remind everybody, this is not part of our main strategy at this point. This is coming out of really strong chemistry capabilities that we have at Gilead, where people came up with this molecule. And it's an oral, which we feel is interesting. We will evaluate the kind of the Phase I study. It's in dose escalation. We are also getting from the Phase I study data on metabolism, right? Obviously, Phase I study will not give us data on obesity, for example, just to be very clear. But we will get data and hopefully can communicate more around the plans for the molecule during the coming year.

Got it. I guess if it shows what you wanted to show and checks all the boxes, do you intend to find a partner for this? Like how -- what's the strategy going to be? Because it doesn't look like this fits into the core Gilead R&D strategy.

Let's see the data first. We have the possibility, obviously, to take it forward on our own, but you're absolutely right. This is something where a partnership would also be helpful.

Okay. Got it. Okay. Got it. And then -- okay. So we will sort of revisit that. The other one that's also intriguing is the oral ENTYVIO, if I may, the oral alpha-4-beta-7. There's a Phase II ongoing. Can you remind us when is that coming? And is that also something that fits into the core strategy? Or is that also open for partnership?

That fits into the core strategy, right? When you -- we've communicated for some time, we have these 3 areas we're focusing on, virology, where absolutely industry-leading, oncology and then inflammation immunology. The oral alpha-4-beta-7 is part of that inflam strategy, right, where the only marketed molecule in our inflam portfolio at this point is Livdelzi, right, in primary biliary cholangitis. And then we have an earlier portfolio. Currently, we have 3 molecules in inflam in Phase II. One of them is the oral alpha-4-beta-7. And then there's a broader portfolio in Phase I and in research. So it's a real focus area for us, and it fits into our strategy. The alpha-4-beta-7, the oral alpha-4-beta-7 is in inflammatory bowel disease at this point in time in the SWIFT study. That study will give us data during the coming year. Obviously, ENTYVIO is a standard of care in inflammatory bowel disease. A lot of people have tried to come up with an oral. There have been issues both from an efficacy and safety perspective. We've been encouraged by the data that we've seen so far in both of these areas. And then, of course, we have different options as the data come, right? If we see ENTYVIO-like activity, then an oral can have real advantages, and you can also think about taking it into different segments of that IBD market.

Okay. Got it. And in terms of sort of an efficacy threshold that you have in mind, like do you want -- do you have a certain number in mind? Does it need to match ENTYVIO necessarily for it to be a drug that moves forward?

Yes. I mean I don't have a clear threshold in mind. And as you know, the ENTYVIO data in different types of settings have also been different, right? So it really depends on what the exact data is. In our study, we're looking after 12 weeks, which is another factor. So the data will not be entirely comparable, right? But thinking about this, there's different possible outcomes. With a daily oral, you do get different PK, you do get different target coverage. So there is a possibility that you can see ENTYVIO-like or even better efficacy. That would then position us, for example, as an additional pillar in monotherapy, right? Combinability, safety profile will be really important. Could you also go for a combination with one of the other oral molecules that are out there to further increase efficacy and really break the current efficacy ceiling there that you see in IBD? Or if you see ENTYVIO-like or maybe not entirely the same activity, you could still take it as a pre-biologic, right, and take it into earlier stages of the disease. So it really depends on the data, on the strength of the data, what are we doing with that molecule specifically. We have different options there.

Got it. Okay. Great. Do you know by any chance what the AUC looks like and how that compares versus the AUC delivered by ENTYVIO?

So we have not spoken about that in detail. But obviously, what you see is a more steady...

Are you -- has the exposure response limitations of ENTYVIO, are those like loud and clear to the Gilead team as you were thinking through doses?

Well, we have not really not spoken about that level of detail. So let's wait for the data. The clinical data is going to trump everything, and then you're going to see much more about that as well.

Okay. And if the data shows what you wanted to show, this could be a broader development program within Gilead? Or would you potentially look for the right combo partner for this because there's also a lot of combos in the works in the IBD space.

This is the same as for the GLP, right? We have the possibility to take it forward on our own if we want to, just from an investment perspective, obviously. But we'll think about that really carefully because as you know, in IBD, in inflammatory bowel disease, people are also thinking about combinations. We have different internal molecules that could be a combination partner, right? We've got the TPL2. We've got an FXR, but they're also...

Did you say TPL2?

TPL2.

And what's the second one you said?

And the second one is an FXR agonist. So those could be potential combination partners internally, but they're also really attractive external combination partners. So it's also an option that we...

It looked to maximize the value.

Exactly. We look at maximizing the value.

Okay. Fantastic. Okay. Any questions on anything we discussed so far? Okay. Great. So maybe we can perhaps keep rolling here and transition to cell therapy. A couple of things here, if I may. Actually, just before that, there's an RA trial, 0511, I have no idea what that is. That's not an oral TNF is it?

No, it's not an oral TNF. No, exactly. We actually have 2 RA trials ongoing. One is with a PD-1 agonist, right, which I think is the one that you're talking about.

Okay. Got it. Okay. Fantastic. Maybe transitioning quickly then to the cell therapy side. I want to come back to Arcellx in a fair amount of detail. But just ahead of that, at ASH, you're showing some data on a CD19/CD20 CAR T. I don't think it's clear to folks -- clear to investors whether this is a -- your follow on to Yescarta and maybe even transitional franchise over? Or is this more a sort of expand the -- like how do you position that first all?

Yes. So that's a next-generation approach, right? Yescarta, Tecartus, those are molecules that are focusing on CD19 as a target. And we've been, for some time, working on -- really think about if you target CD19 and CD20, right, can you improve efficacy, but also can you think about improving safety at the same time, improving benefit risk and potentially also taking this then to the outpatient setting, right? Those are some of the attributes that we would like to generate. So this is what we call a bicistronic CD19, CD20. So you've got different activating regions as well. And we can very carefully modulate that. So really to get to this better benefit risk equation. What that does, then it opens up a broader possibility, first of all, to, quite frankly, replace Yescarta and Tecartus with a next-generation treatment approach, but also to get into more broadly also inflammatory conditions, for example, classic immunologic disease or also neuroinflammatory conditions. So there are various opportunities...

But price point would be so different for that immunology. I mean, would you -- you can develop it for both?

Yes. We -- this is really early to talk about pricing, right? So I'm not going to do that. But you also need to think about what are the patient populations that you take it into. For example, when you think about SLE, where we have some positive data, right, systemic lupus, these are people who have exhausted all other options, right, to have a really large unmet medical need. So let's focus on the clinical benefit first, and then we'll talk about pricing. And I'm not the right person to talk about pricing anyways.

Do you anticipate better safety on this as well?

Yes. I think there's a possibility for that. And that's really based on the construct of the molecule, right, where we can -- with the bicistronic construct, we can really dial what is the activity on the CD19 side and on the CD20 side, right? So how is the -- actually the kinetics of the cells over time. So we think there's a real potential for a better safety as well.

Anything in particular we should look out for at ASH for this molecule?

Yes. I mean the early data, obviously, what we want to demonstrate is good efficacy. Efficacy is always because we see this really high efficacy with the current therapies, there's a ceiling effect. So I'm usually saying efficacy at least as good as what we see with the current molecules. Then obviously, we want really good safety. And then this is all supported by the manufacturing capabilities that we have moving this forward.

Okay. Great. So last question on the Arcellx development effort. I guess the first question is, what's the most important next data set coming up for this?

Yes. I mean the -- as you know, we have the iMMagine-1 study going on. As you think about myeloma therapy, initially, we are taking this into fourth line plus, that's the iMMagine-1 study. That's the next data that you're going to see. We also have studies on a study ongoing in the second to fourth-line setting. And then we are also working on getting this into the earlier line setting. These are discussions we currently have, so to really also get it into the first-line setting. The most important next data set is actually what you're going to see at ASH, which is from the iMMagine-1 study, which is more data in this fourth-line plus setting, which will tell you more about efficacy, tell you more about safety. I'm encouraging everybody to also look at the minimal -- the measurable residual disease, the MRD data, which are really strong for the CAR Ts. So I'm looking forward to the presentation at the ASH meeting where we're going to talk much about that.

And you remain comfortable that there is no neurotox on this molecule across trials?

Yes. Absolutely.

And Dietmar, this is a question I've sort of discussed with Merdad in the past as well. Have -- there's ICANS on this, but there's not neurotox. Those are separate things. Could there be any overlap between those 2?

Yes, that's a bit of an open question, right, that people are debating. The -- obviously, neurotox is a much broader category than just ICANS, right? And ICANS is the more severe described outcome. But at this point in time, we see really good tolerability.

Really good tolerability. Okay. Okay. Fantastic. And remind me again, what's the rate of ICANS on this molecule?

We don't see that.

There is no ICANS.

There is very limited in the single percentage, right?

Got it. ICANS in single-digit percentage. And would the risk of neurotox or ICANS be higher or not into an earlier line trial?

I think the line of therapy doesn't make a big difference for this.

Okay. Got it. Got it. And the extent of steroid usage continues to remain high? Because I think one of the big differences versus some of the early cell therapy work was even for a Grade 1 CRS, you allow steroid administration. So there's a lot of steroid usage upfront, which prevents sort of like uncontrolled cell expansion. So is that a theme across the trials that Grade 1 CRS and you can get steroid?

Yes, exactly. So steroid use, I don't have the exact data on steroid use across the different studies at this point in time, but no change to what we've demonstrated before.

Okay. Got it. So iMMagine-1, we get some updated data at ASH. I guess when do we see iMMagine-1, which is earlier line, when would that readout be?

That will be some time before you see those readouts. We don't have an exact date for you at this point.

But that's not a '26 event or...

I don't think so. We've not communicated that exactly.

Okay. So I guess -- and this is my last question, just as we start to wrap it up then, Dietmar. One thing I've been confused about is if one of the BCMA CAR Ts hits in the first-line setting versus transplant, don't they effectively become the standard of care then at the transplant level? So then the ability to do another BCMA CAR T just changes completely when that happens?

So first of all, the outcomes for the CAR Ts are, in my mind, better than the -- and you distinguish between the autologous and the allogeneic transplant, right? We've seen cures with allogeneic transplant. We've not seen that with autologous transplant. With CAR Ts, you do see...

Sorry, we see cures with?

We do see cures with allogeneic transplant. We don't see cures with autologous transplant. But we do see cures with autologous CAR Ts, right? That's a really important distinction. So you're right, if BCMA CAR Ts move earlier, then I do think they will replace autologous transplants, right? Allogeneic transplant in younger patients is a different story, right? And again, I feel the...

I see. So even within the -- you're saying, first of all, not everybody may get transplant. So that remains eligible for BCMA CAR Ts. Within transplant, you're saying allo transplant will remain happening anyway. So BCMA remain eligible patients. It's really in the autologous setting is where maybe BCMA becomes standard of care and we can think about the penetration. Okay. This is very important.

But then if somebody comes -- as we take BCMA CAR Ts forward in earlier lines of therapy, of course, once you have an established standard of care, then you always need to compare to that established standard of care.

Would you guys run a transplant trial or a first-line trial?

We are preparing for a first-line trial. Yes. Absolutely.

Okay. Got it. Last question on this. There's starting to be this perception that the Street is moving on to beyond these current CAR Ts to perhaps something more in vivo in nature and depending on the target. So if in vivo is what's next, how is Gilead positioned on that?

Yes. We have actually -- so we are getting into in vivo as well. Obviously, we would as CAR T is such an important business for the Kite part of our business. It's really important that we also have a leadership position in vivo, right? In vivo basically means you give a viral vector or a nonviral vector and you really stimulate the body to produce its own CAR T cells, right? So it becomes a very natural extension of what we're doing. To be very clear, this is years out, right? So...

But everybody has made investments now as if it was over.

You have to make investments now, right? Because you need to secure the IP, you need to be a player in that area, you need to be a leader in that area.

But there's all this data -- I thought this ASH is about in vivo CAR Ts, they're not?

Well, it's an early, really interesting new technology, but it doesn't take away from the fact that patients now need therapy now, and that's where the current CAR Ts and then also anito cel in myeloma and other approaches come in. But there is real promise, right? We've seen some early anecdotal data with really good efficacy. So what you do, you give the viral vector. Nonviral is even a few more years out, and we're working on both the viral vector based and the nonviral. So we're trying to stay in the leadership position in both of those areas. With the kind of the viral approaches, we have some anecdotal data that demonstrate, yes, CAR Ts are formed. And yes, we see clinical responses, right? And we've communicated actually several acquisitions, right, more recently, the Interius acquisition, the Pregene collaboration and some other acquisitions that basically position us well in this in vivo field also. But as I said, we're focusing right now on CAR Ts. They will play a role, and we are also preparing for a leadership position in the industry...

So Dietmar, what happens if a patient -- let's say, 10 patients take it, 7 of them develop CAR T, 3 of them not really. What happens to those guys?

Yes. That's what we currently need to demonstrate, right? How many...

And is this happening, by the way, that some patients just don't develop cell therapy?

When you look at the space more broadly, the data is very different, right? There are some approaches where you go -- where people do apply the kind of the viral vector and then not everybody develops the CAR Ts. If that is what people observe, then they need to go to different types of therapies...

But this has been happening a little bit, you're saying?

With some of the approaches, yes, right? With other approaches, you see the CAR T formation more reliably, right? So that is one characteristic where you have differentiation between the different approaches, right? And that's where we, for example, with the Interius approach, that's the licensing deal that we did, we feel quite encouraged by their early data.

Got it. Okay. Fantastic. Fantastic. Any questions from the audience? I know we went through a lot of different types of topics. From immunology to cell therapy to in vivo CAR T to HIV treatment, HIV prevention. All right. Excellent. We'll wrap it up right here then. Thank you so much, Dietmar.

Thank you very much.