Conference Transcript - ACLX 2025-12-03

Speaker 2

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's the transition been, and how are things going on the West Coast?

Dietmar, Other

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 influenza. So it's been a really good year.

Speaker 2

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 Jackie would join us, but Jackie's staying there.

Dietmar, Other

But maybe, so I'll stick to the R&D topics, but because everyone cares so much on use2go, 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? yeah the the so so just stepping back for a second right the the nodules that you see have not been a problem at all on the on the clinical side right the the when you look at the the purpose one and purpose two study um people have been you know really content with a with a therapy, we have basically 96% of people who were on the study who said, I want to stay on Yes2Go. 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 to basically a vaccine-like approach. We're always saying it's not a vaccine, really important in the...

Speaker 2

I heard.

Dietmar, Other

These days, it's very important. 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.

Speaker 2

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

Dietmar, Other

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

Speaker 2

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 six months?

Dietmar, Other

So the intramuscular could be applied to different timing. So it could also be applied to the ones every six months.

Speaker 2

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 the early experience on um um nodules and the 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 you know i can live through it so we did not hear that at all and and the the important piece is obviously we're this is a complex launch obviously right we're in a 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

Dietmar, Other

a paradigm shift but the injectable has real benefits you know for example from a compliance perspective because the shot is in once every six months and people are protected for that six month period right and there's no question of taking daily pill no question of you know keeping the medications with you compliance is better with that and and that's that's one of the key benefits but we are really supporting that launch with you know a lot of information that we provide to people and one important piece is how do you inject right right for example when you when you cool the injection site right then then the pain is is not a big issue the nodules form in the

Speaker 2

beginning but then they go down over time for example and we have not heard any major issues around that hmm so you're okay so it's it's manageable is what it's going well yeah 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 about the durability we're seeing on patients staying on because you know there's always a concern they take up one or two shots and they're done how are you thinking about that from a compliance perspective so the there's two aspects right one is

Dietmar, Other

comparing the auras or the less frequent sure versus the every six months and they're clearly you know compliance with a with a once every six month is not an issue right because it's it's once and done I mean more like duration but you're talking more about people coming back right and then getting the treatment and 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 Yes2Go because I do see that benefit of the once every six 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 the next therapy. So we'll get more experience with that over time. But I think, you know, that everything that we've seen so far indicates, you know, real positive feedback with the therapy.

Speaker 2

Okay, great, excellent. So maybe we can start to move on. I want to start with a drug in your phase one, 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 big tarvi replacement if i may um am i over uh indexing on gs32 42 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 gs32 42 as you say right is an integrate inhibitor um with a longer half-life and and we had several of those We have several of those in our portfolio.

Dietmar, Other

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 Biktarvi. Biktarvi, 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, you know, how this plays out and how this is segmented, you know, we'll have to talk about that. And 3242 in itself is an integrase inhibitor, right? So you need a combination as well, you know, for these types of therapies.

Speaker 2

Sure. So I guess there's several follow-ups to that. First is you had two weekly integrases. It was 3242 and there was a 1219.

Dietmar, Other

The 1219 was terminated i think clin trial says only four patients were recruited could you remind us what happened there yeah no we we always said we have different molecules you know that we're exploring multiple shots on goal and then we will look at early parameters uh in order to to select the one that that we feel is is the best one and that's in this early stage is based on pk based on early tolerability data also based on pre-clinical data um and that's where we saw some benefits for 32 42 to over 1219, so it's really a portfolio prioritization.

Speaker 2

It was not like there was some CD4 drop problem or anything like that. Oh, no, not at all, not at all. No safety problem. The other one was, I think back in June, you guys had a clinical hold on a, I believe that was a long-acting capsid is where the hold was, is that right?

Dietmar, Other

So that was a combination therapy, that was the WONDAS-1 and WONDAS-2 study, which is a combination, again, of a long-acting, it was actually the wholly owned once weekly option, and it was an integrase inhibitor, an INSTi, and a lenacapavir prodrug, right? And we did see that drop in CD4-positive T cells. We're currently in the phase where we try and understand the data around that. When you look at the two classes, is the integrase inhibitors and the capsid inhibitors, lanacapavir and the broader class of the INSTEs. This is not a finding that's broadly linked to these drug classes, right? 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 lanacapavir, right? We did not see anything with the original INSTE, the 1720.

Speaker 2

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

Dietmar, Other

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

Speaker 2

I remember when Lenacapavir got approved and prepped, 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 Pro drug, if you want to do a monotherapy trial on that, that's doable?

Dietmar, Other

So we have several Len Pro drugs in our portfolio, right? Oh, I see. So what we're talking about is a very specific combination of one insti and one lanacapavir prodrag. We have other instis in our portfolio and we have other lan prodrags 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.

Speaker 2

Okay, got it. Got it. 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.

Dietmar, Other

Yeah, 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-Lanacapavir combination that we're doing together with Merck. Those are ongoing phase three studies that we'll read out during the coming year. So we have already a combination that we're moving forward with these phase three trials in the once-weekly setting. Or treatment 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, 41, 82, we've always said that will lead to a three to six quarter delay for our wholly owned. But we are continuing to work on a wholly owned combination as well.

Speaker 2

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. Yeah. And then you also had a weekly all oral of your own, which went into clinical hold. So that's three to six quarters behind. We'll see when that comes back. But for market positioning, you'll 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 nukes. How dangerous is that in terms of resistance profile?

Dietmar, Other

Yeah, the resistance is a really important question. When you look at the different drug classes in HIV, you had the protease inhibitors, which is an old class. Then you've got the reverse transcriptase inhibitors, which is where the nukes are, the NRTI or NNRTIs. Now you've got the capsid inhibitors, like lenacapivir. What we do with Big Len is we combine two of the most active drug classes. We have an integrase strand transfer inhibitor and INSTE plus then a capsid inhibitor. Both of those individually show basically very limited resistance formation. We did publish on, you know, resistance data for Bigtegravir, which is the component in Big Len, and Lenacapivir at the EACS meeting in Paris earlier this year, right? And when you look at the resistance formation with the INSTE, 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 with by what we've seen in the clinical trials we've not seen any resistance formation obviously you know we're gonna watch that as we go to a larger patient population but we don't think at this point that there's you know any reason to believe that there would be a resistance formation.

Speaker 2

Because we've seen one experience with your competitor. They tried a two-drug regimen. They dropped one nuke, only kept one nuke and one integrase. That integrase is nearly identical to Bictagravir. 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...

Dietmar, Other

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 lanacapivir, right? And lanacapivir as a new mechanism, capsid inhibitor, there's really no cross resistance between the two. There's no cross resistance formation as well. So we have not seen any concerning data at this point.

Speaker 2

So I was going through the phase two data and I noticed there was a N74T pop-up and that conferred resistance in phase two, and I was like, oh, so this could happen in phase three, or is that not a common enough mutation that you wouldn't see necessarily?

Dietmar, Other

That was a single case in the phase two, right? And we also had the phase three studies. We didn't see that again. That N74T is, you know, when the capsid forms, it's actually a capsid polymorphism. It's a really weak resistance that emerges with N74T. There's no circulating N74-2 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 ARTIST-3 studies. So again, Big Len, this combination, is in two Phase III studies at this point. ARTIST-3-1 and ARTIST-3-2. ARTIST-3-1 has read out, as you said, right? And ARTIST-3-1 is a study in people who are currently on complex regimens. that is about six to eight percent of the 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 one study more than 80 percent of patients in artistry one had a 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 big len so so that's another argument that basically shows you even in people who have pre-existing resistance big len is a highly active regimen that's that's effectively treating those people right and that is a is a i think a real benefit people on complex regimens are on regimens with you know up to 11 or more drugs at 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 one pill a day very simple um is a real advantage for them as long as we really cover those resistance mutations as well which we do uh according on to the study data so the artistry 2 trial is that a naive setting The artistry two-tile is in the switch setting. It's in the switch setting. So we're basically taking people who are switching from effective therapies, one to go on to another therapy. But they're not switching from, like, the highly complex regimens. They could actually switch from any type of regimen. Can they switch from BICTARVI? They can also switch from BICTARVI.

Speaker 2

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

Dietmar, Other

Anything, exactly. And the second trial is reading out in the near future. and once we have these these two studies then we can take big 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 big tarby market yeah we we could theoretically do that but when you look at the strategy that we have big tarby 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 big tarvi is going to remain standard of care in the naive in the naive population and another daily oral doesn't really provide a major benefit versus big tarvi 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, integrase plus LEN like drug on a weekly basis oral for naive setting, that will be the big replacement yeah that that would be i i still believe that you know victory because it's so easy right and 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 you know really satisfying the needs that they have and you see that for example we also developing a once every six month injectable regimen for therapy, right? So people want different types of therapies, and that's where these options come in.

Speaker 2

Got it. I realize this is a bit more of a commercial question, so it may not be fair, but just to frame it for you, I think a lot of times investors are saying there's a big Tarby business that's very large. A portion of that is 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 BICTARVY? Would you know, or you wouldn't know that?

Dietmar, Other

Oh, I wouldn't. I don't know the exact percentages there, but you're absolutely right that we want the initial therapy, the naive setting, absolutely, with BICTARVY we have that. And we also want to provide options for SWITCH. Some people want to go from a three-drug regimen, which BICTARVY is, for example, to a two-drug regimen. That's where BICLEN comes in. 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.

Speaker 2

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 where these programs are heading. oral glip first of all can you remind us what type of scaffold is that is it awful or is it the Pfizer scaffold or the Lilly scaffold we have not communicated that right it's it's coming out of our of our chemistry but we've not and we've not talked about the scaffold yet got it is this like if it shows what you wanted to remind me how big is the trial what's the trial when does it do?

Dietmar, Other

So it's currently in phase one. 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 is interesting um we will evaluate the kind of the phase one study it's in dose escalation we are also getting from the phase one study data on metabolism right obviously phase one 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 um i guess if it shows what you want it to show on 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

Speaker 2

the core gilead let's see the data first we have the possibility you know obviously to take it forward on our own but but you're absolutely right this is something where a partnership would also be helpful okay got it um okay got it and then um okay so so we will sort of revisit of that the other one that's also intriguing is the oral um antivio if i may the oral alpha 4 beta 7 there's a phase 2 ongoing um 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 that fits into the core strategy right when you when you we've communicated for some time we have these three areas we're

Dietmar, Other

focusing on virology we're absolutely industry leading oncology and then inflammation immunology The oral alpha-4-beta-7 is part of that inflame strategy, right, where the only marketed molecule in our inflame portfolio at this point is lymphdelti, right, in primary biliary cholangitis, and then we have an earlier portfolio. Currently, we have three molecules in inflame in phase two. One of them is the oral alpha-4-beta-7, and then there's a broader portfolio in phase one 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, you know, antivio 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 antivio-like activity, then an oral can have real advantages, and you can also think about taking it into different segments of that IBD market.

Speaker 2

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 antivio necessarily for it to be a drug that moves forward?

Dietmar, Other

I mean, I don't have a clear threshold in mind. And as you know, the antivio 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 antivio-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 antivio-like or maybe not entirely the same activity, you could still take it as a prebiologic 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 Antivio so we have not spoken about that in detail but but obviously what you see is a more steady are you have you has the exposure response considered limitations of Antivio are those like loud and clear to the Gilead team as you were thinking through doses well we we have not really not spoken about that level of detail so let's wait for the data the clinical data is gonna trump everything and then you're gonna see

Speaker 2

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 as for the glib right we have the possibility to take it forward on our own if we want to just from an investment perspective, obviously.

Dietmar, Other

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 really attractive. You said TIC2? TPL2, 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 could. Okay, so you look to maximize the value. Exactly, we look at maximizing the value. Okay, fantastic, okay. Any questions on anything we discussed so far?

Speaker 2

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?

Dietmar, Other

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

Speaker 2

Okay, got it. Okay, fantastic. Maybe transitioning quickly then to the cell therapy side. I want to come back to our sellics in fair amount of detail, but just ahead of that. At Ash, you're showing some data on a CD19, CD20 card T. I don't think it's clear to folks, to clear investors whether this is your follow-on to YesCarda and maybe even transition a little franchise over or is this more a sort of expand the use of, like how do you position that first of all?

Dietmar, Other

So that's a next generation approach, right? YesCarda, 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, 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. Those are some of the attributes that we would like to generate. So this is what we call a bisystronic, 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 Yascarda and Tecardus 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.

Speaker 2

But price point would be so different, no, for that immunology? I mean, you can't develop it for both.

Dietmar, Other

Yeah, 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, who 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.

Speaker 2

Do you anticipate better safety on this as well?

Dietmar, Other

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 actually the kinetics of the cells over time? So we feel there's a real potential for a better safety as well.

Speaker 2

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

Dietmar, Other

Yeah, 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. I'm usually saying efficacy is 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.

Speaker 2

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

Dietmar, Other

I mean, as you know, we have the Imagine One study going on. As you think about myeloma therapy, initially we are taking this into fourth line plus. That's the Imagine One study. that's the next data that you're gonna see we also have studies on a study ongoing in the second to fourth line setting and then we are also working on you know 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 gonna see at ASH which is from the imagine one 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 more.

Speaker 2

And you remain comfortable that there is no neurotoxin on this molecule across trials? Yes, absolutely. And Dietmar, this is a question I've sort of discussed with Meridat in the past as well. There's ICANs on this, but there's not Neurotox. Those are separate things. Could there be any overlap between those two?

Dietmar, Other

Yeah, that's a bit of an open question, right, that people are debating. Obviously, Neurotox is a much broader category than just ICANs, right? and ICANNs is the more severe described outcome. But at this point in time, we see really good tolerability.

Speaker 2

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

Dietmar, Other

We don't see that. Okay, there is no ICANN. There is very limited in the single percentage, right? Got it.

Speaker 2

ICANNs in single digit percentage. And would the risk of neurotoxic or ICANNs be higher or not into an earlier line trial?

Dietmar, Other

I think the line of therapy doesn't make a big difference for this, right?

Speaker 2

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 if it's grade one CRS, you allow steroid administration. So there's a lot of steroid usage up front, which prevents sort of like uncontrolled cell expansion. So is that a theme across the trials that grade one CRS and you can get steroid?

Dietmar, Other

Yeah, 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.

Speaker 2

Okay, got it. So imagine one, we get some updated data at ASH. I guess when do we see imagine three, which is earlier line? When would that readout be?

Dietmar, Other

That would 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? I don't think so. No, not a 26. But we've not communicated that exactly.

Speaker 2

Okay, so I guess, and this is my last question, just as we start to wrap it up then. One thing I've been confused about is, if one of the BCMA CAR T's hits in the first line setting versus transplant, don't they effectively become the standard care then at the transplant level? So then the ability to do another BCMA CAR T just changes completely when that happens, no?

Dietmar, Other

So first of all, the outcomes for the CAR T's are, in my mind, you know, 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 long-term... 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 that's a really important distinction so you're right if bcma car t's move earlier then i do think uh they will replace um autologous transplants right allogeneic transplant in younger patients is a is a different story right and and um again i feel the the oh i see so even within the trans you're saying first of all not everybody may get transplant yeah um so that that remains eligible for BCMA CAR T's.

Speaker 2

Within transplant, you're saying allotransplant will remain happening anyway, so BCMA remains eligible. 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.

Dietmar, Other

But then if somebody comes, as we take BCMA CAR T's 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.

Speaker 2

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

Dietmar, Other

We are preparing for a first-line trial. Yes, absolutely.

Speaker 2

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.

Dietmar, Other

So if in vivo is what's next, how's Gilead positioned on that? yeah we we have actually so we are getting into in vivo as well obviously we would as as car t is such an important business for for you know the the kite part of of you know our business uh it's really important that we also have a leadership uh position in in vivo right in vivo basically means uh you give a viral vector or a non-viral vector and 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?

Speaker 2

But everybody's made investments now as if it was over.

Dietmar, Other

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.

Speaker 2

But I thought there's all this data. I thought this ash is about in vivo CAR T, is it not?

Dietmar, Other

Well, it's an early, really interesting new technology but it doesn't take away from the fact that you know patients now need therapy now and and that's where the current car t's and and then also a needle cell in myeloma and other approaches come in um but there is real promise right we've seen some early you know anecdotal data with really good efficacy so so what you do you uh you give the viral vector non-viral is even a few more years out and we're working on both you know the the viral vector based and the non-viral so we're trying to to stay in the leadership position both of those areas with the kind of the viral approaches we have some anecdotal data that demonstrate yes car t's are formed and yes we see clinical responses right and we've communicated actually several acquisitions, right? More recently, the interiors acquisition, the pre-gene 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're also preparing for a leadership position in the individual space.

Speaker 2

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

Dietmar, Other

Yeah, that's what we currently need to demonstrate, right? How many...

Speaker 2

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

Dietmar, Other

Well, you know, 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 T's. 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 interiors approach that that's the licensing deal that we did um we feel quite encouraged by their early data got it okay fantastic fantastic um 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 yeah all right excellent we'll wrap it up right here Thank you so much, Damar. Thank you very much.