Okay, good morning and welcome to the Cantor Global Healthcare Conference. My name is Carter Gould. This is my first one of these, so I'm very pleased to be here and welcome Gilead Sciences to the stage. We are joined by Dietmar Berger, CMO of Gilead. Dietmar, welcome very much.
Thank you.
Thank you for joining us today. Maybe before we get started, Dietmar, I don't know if you wanted to make any opening comments, and then we can kind of jump into Q&A.
No, it's just good to be here, right? As you know, I'm with Gilead since nine months now. It's been great so far, and happy to talk about the portfolio and where we're going.
All right, so I think that's a good way to kind of jump in here. In that eight months, nine months since you joined, maybe talk about sort of your initial impressions, things that jumped out, maybe things that weren't obvious at the outset that you've been pleasantly surprised with at Gilead.
Yeah, no, it's always, right? When you start in a new role, in a new company, you never 100% know what you're getting yourself into. I have to say the first few months have been really good. What I've been, I did know many people in the team. I did, of course, do my diligence on the portfolio, but it was really good to see the depth of the science, the quality of the team, how we approach research, how we approach manufacturing at Gilead and Kite, right? To see that all of those elements are really in place there. Of course, heading development, the important piece is what do you think about the portfolio? And again, diving deeper into the portfolio has been important and has been really good. You've seen that we had some really positive readouts over the last few months, which was very reassuring.
We also have a very clear strategy moving forward with the three TAs thinking about virology, oncology, and inflammation. And we're in different spots in those portfolios. And that's another important realization where virology, obviously industry-leading capabilities, industry-leading portfolio, really strong data more recently, for example, with Sunlenca, we're currently going through the launch. But there's also a really important portfolio behind that. And we're looking forward to further data readouts. Also, we've communicated that later this year we're going to have the ARTISTRY-1 and ARTISTRY-2 studies with BIC/LEN, for example, which is something to look forward to. But also thinking about on the prevention side and on the therapeutic side, how do we bring more optionality? On the prevention side, for example, we've started our study with a once every 12 months lenacapavir, PURPOSE 365, which is an important step forward.
On the treatment side, really looking at daily, weekly, monthly options, et cetera. In oncology, we really had a strong boost more recently with the ASCENT-03 and ASCENT-04 data in breast cancer with Trodelvy, with our TROP2 ADC. And again, we have a plethora of studies coming after that, right? We have a study in hormone receptor-positive breast cancer. We have an adjuvant study in triple-negative. We have studies in non-small cell and small cell lung cancer, and also in endometrial cancer. And the data of ASCENT-03 and ASCENT-04, and we've presented the first data set at ASCO, and the second one will be at a conference later this year, right? Has really given us reassurance about Trodelvy in triple-negative breast cancer and the opportunity in the first-line setting. And then also about the study readouts that will be coming.
And then inflammation, immunology is the third TA. I've worked in inflammation for some time, so I'm really behind this triplet of TAs, and I think that's the right strategy for Gilead. In inflammation, it's an earlier portfolio, but there are some really interesting assets there as well. There's an oral alpha-4 beta-7, which is in phase II testing currently for IBD, which could be a cornerstone on the IBD treatment side and also a combination partner. But there's also an IRAK4 degrader, there's a STAT6 degrader, all of those really strong molecules that, of course, we will need to bring through clinical development, but there's a real opportunity there. At this point in time, we have 52 molecules in development, and that's one of the most diverse and richest portfolios that Gilead had. Quite a lot for me from a development perspective to focus on.
Okay, definitely want to come back to inflammation. We're going to touch on HIV to start. No surprise there. You teed up ARTISTRY -1 and 2 coming later this year, phase III studies for both. And I guess for those people, I guess a little bit less familiar with ARTISTRY -1 and 2, I'm sure you'll talk about this a little bit. But as you think about that BIC/LEN combo and what needs to be shown there to potentially move the market, how should we think about that, particularly with an endpoint that's going to be a non-inferiority endpoint?
Yeah, so ARTISTRY-1 and 2 are two phase III trials, two different phase III trials with Bictegravir, which is like the cornerstone integrase inhibitor, INSTI, plus then lenacapavir, our capsid inhibitor, right? And ARTISTRY-1 is a study that has been specifically designed for people with HIV who are currently on complex regimens. So there's about 6%-8% of people with HIV who had a long disease journey, who developed resistance to different types of therapies, and who are currently on multi-pill complex regimens. Many of them have to take several pills daily at different times during the day. And for them to have something that's really easy, daily oral pill with a cornerstone integrase inhibitor and a cornerstone capsid inhibitor will make their life so much easier, right? So that's what ARTISTRY-1 is.
ARTISTRY-2 is for those people who are currently on Biktarvy, which is obviously our state-of-the-art therapy for HIV. Those people are virologically suppressed. Biktarvy is a three-drug combination, right? There are specific markets, specific people where there's a preference also for two-drug regimens. And that's what BIC/LEN brings, right? It brings that optionality for people. If people prefer a two-drug regimen, they could theoretically switch, for example, or they could choose BIC/LEN. To say that very clearly, Biktarvy is standard of care. It has no resistance. It's a therapy. Somebody comes in with a newly diagnosed HIV case can leave the practice with drug in hand, basically, at that point. It's really well tolerated. So that's our mainstay standard of care. But it's really about optionality, right? For people on complex regimens or for people who are looking for something to switch.
Okay, I think that's clear. As we move on across the treatment portfolio, did have an update on the WONDERS program earlier this year. I guess first off, still on clinical hold, any updates there? And then I guess more broadly, as we think about that, what that hold really then potentially implies around the future development for 3107? And I guess put differently, does the experience in WONDERS in any way shift how you think about the appropriate INSTI partner?
Yeah, so the WONDERS -1 and 2 studies were studies that were done with what we call 1720 and 4182. So these are, one is an INSTI, the other one is a capsid prodrug, right? A lenacapavir prodrug. And in that combination, we did see some decreases in T cells, which led to the clinical hold. The clinical hold is still there. What we're currently doing is we're trying to understand what is the culprit, right? Which of these drugs? Is it the INSTI? Is it the lenacapavir prodrug? What's really important here to understand is we have a plethora of molecules behind that. So we have different other integrase inhibitors. We have different other lenacapavir prodrugs. So we will identify, and that's what we're currently doing in preclinical studies, which of the two is the culprit.
And then we will exchange that drug in the combination and we'll move forward with another combination for the weekly oral therapy, right? So we're currently in that phase of preclinical testing. We think it will take us somewhere between three and six quarters to really replace the GS-1720, GS-4182 with another combination for weekly. I also want to point out that we have a combination in clinical development in phase III, which is islatravir plus lenacapavir in collaboration with Merck, which is in that same spot, in that weekly oral spot. So we will bring something to patients much earlier, but we are obviously working on a wholly owned combination of an integrase inhibitor and a capsid inhibitor, right? Because we believe in that combination of those two principles.
Okay, and I guess one of the questions I've always kind of banged our head against is, as you think about those potential combos with the capsid, is there anything inherently, I guess, biased that you think is inherently better around an INSTI versus an NRTTI in this setting? Or is it really just going to, as you pointed out earlier, more around optionality for the patient population?
No, if you compare the different principles, I think it's important to go to those that have the highest efficacy and best tolerability, and that's where we believe an integrase inhibitor and a capsid inhibitor really has a benefit over a non-nucleoside inhibitor, over an NRTI.
Okay, maybe moving to the PrEP side, you sort of teed up PURPOSE 365. And I guess on the back of the data we've already seen with lenacapavir and PrEP, just outstanding data, is there, I guess, how much tolerance is there for a diminution of efficacy as we think about moving from every six months to every 12 months? Or should we just think that the bar is now 99.9%, 100% for anything coming to market?
Yeah, we believe it's really important to stick to those bars, right? When you look at the treatment side, we think the bar is Biktarvy with no resistance, right? When you think about the prevention side, 99%, 100% really should be the bar, right? Because we want the best prevention possible for people out there, for the community. Important to note that PURPOSE 365 is actually an interesting study that really looks at pharmacokinetics, right? So it's a smaller study. And what it's intended to show is that when we give lenacapavir on an annual basis, sorry, intramuscularly, that we achieve levels of the drug pharmacologically that are basically the same or above the levels we reach with once every six-month injection. So we want to have the same coverage, which then should lead to the same level of protection.
Okay, great. Maybe moving on to some other data that's going to come later this year, anito-cel, and we're going to get an update on iMMagine-1, maybe help frame expectations on that side of things for folks. We've obviously seen a couple of updates already. We're going to have more data. But how should investors expect that to play out and kind of how you're helping frame that for folks?
Yeah, anito-cel is obviously our core T-cell therapy for multiple myeloma. iMMagine-1 is in the fourth-line setting, right? There's still clearly an unmet medical need in that setting. We have presented data at the EHA meeting earlier this year of, I think it was somewhere around 120 patients, 12 months of follow-up. What we've seen is very competitive efficacy, right? With the PFS and OS rates, for example, OS at 90% rate basically after a year. But then also very good tolerability, and that's important. What we want to see in an update later this year, it's an ongoing study, right? What we want to see in an update is clearly that same efficacy, but also the tolerability without major neurotoxicity or without colitis or any other of these events.
So far, what we've seen and what we've presented at EHA has been very encouraging, both on the efficacy and the tolerability side. So we believe that's a very differentiated product. We believe in that fourth-line setting will make a difference for patients. We've communicated that we're looking forward to bringing it to patients in 2026. Obviously, behind that, then we're looking at earlier lines of myeloma therapy.
Right, so I guess a couple of follow-ups on that upcoming data. So we should expect around 18 months of follow-up, just sort of another six months beyond what we saw at EHA. Is that a sort of fair assumption and same sort of patient numbers?
Yeah, I mean, that's when you look at the time that has passed, that's a fair assumption.
Okay, and at one point, do you think you can definitively say you're sort of in the clear on the neurotox side? Is it after 12 months, after 18 months?
There's two components. One is a number of patients treated, right? And at EHA, it was those roughly 120 patients already. So that already gives us a good level of reassurance. And then, as you said, it's really the duration of follow-up. 12-month follow-up for the neurotoxicity is already pretty good follow-up. But of course, we will need to see the data.
Okay, there's also been some reports of using GPRC5D antibodies approaches here as a bridging therapy before CAR-T to potentially reduce. I guess I'd love to hear your view on that approach. And does that reduce a potential source of differentiation on safety for anito-cel?
Yeah, the concept of a bridging therapy before a transplant or a CAR-T therapy in myeloma has been around for some time, right? Because when you look at larger data sets, for example, from EBMT or CIBMTR of the last large transplant regimens, when you go into a transplant or a CAR-T cell with a lower tumor load, a lower myeloma load, the outcomes of the transplant or the CAR-T cell therapy are better, right? So you're trying to bridge before the transplant. You can use different things for bridging. Classically, people have used chemotherapy for bridging. So now to use another type of therapy for bridging, for example, GPRC5D-based, is a very reasonable approach. It will not impact the transplant, right? For the transplant, you still want the most effective and most tolerable approach, right?
If anything, going in with another kind of biologic or ADC or any type of therapy like that means that the focus on safety in your transplant will be even higher, right? So I don't think it's taking away anything. I think if it will help to improve the long-term outcomes after CAR-T, then I think it's a good thing.
Okay, and how should we think about sort of gating steps to seeing the broader development plan for anito-cel? Obviously, you teed up iMMagine-2 already, but in terms of really kind of maximizing the opportunity for anito-cel, is it getting past the filing, et cetera, before we kind of see the plan to move up into earlier lines?
It's obviously a stepwise approach, right? Let's get to the data for iMMagine-1 first. You know that we're looking at earlier lines, right? For example, at second, third line, then eventually we'll also look at first line. But the exact timelines and approach for that, we will communicate once we have done the first step.
Okay, and on the market in 2026, but still no color on when you're going to file.
No.
Okay, great. All right, maybe as you think then about the broader oncology portfolio, you kind of teed up already some of an update coming on Trodelvy and I kind of thought about this year as a little bit more of an execution year for Trodelvy. Some of the prior years have been a little bit more data-rich. So I guess where should investors focus on the Trodelvy side this year? Should it be more on things like ASCENT-07, where we've been interested, but maybe you haven't talked about as much? Or is it really then more about novel combos coming down the pipe?
No, we will have, you're right, a lot of the kind of phase III opportunities for Trodelvy are currently set up. It will be important to see the data around those. So there is an execution component to that, but there's also a component of how does, based on data for Trodelvy, how will the market size shape up, right? Obviously, really happy about ASCENT-03 and ASCENT-04 because that takes us firmly into the first line setting. Obviously, we need to get the filings and approvals done, but there's a real potential in the first line setting to make a difference for patients, but also to really grow the market, obviously, because many patients don't make it from first line to second line. Having that first line opportunity will increase the addressable patient population and will also increase duration of therapy.
So there's a real opportunity around that with some cannibalization, obviously, in second line once you go into first. But then beyond that, as you said, there's ASCENT-07, which takes us into the first line hormone receptor-positive, HER2-negative setting, which is a larger patient population, but also with more competition. So it will be really important at one point to see the data. We have not communicated the exact timelines for that because these are event-driven studies, but they have been ongoing for some time. So really focusing on bringing that to a close and then thinking about how does that stack up versus competition, obviously, in that area. And then we have ASCENT-05, which is currently still recruiting, which is in the adjuvant setting. So that will take us even earlier.
Trodelvy, at this point in time, triple-negative breast cancer has been a real mainstay and a real focus area for the drug. That's an important piece. Beyond that, you have non-small cell lung cancer, EVOKE-03, which is ongoing, and also small cell lung cancer, which is currently recruiting. In small cell lung cancer, we also have breakthrough therapy designation. These are additional opportunities. We also got the endometrial study ongoing. There is an overall package, which we're also supporting with additional cooperative group studies, et cetera. There will be really good news flow around Trodelvy for years to come.
Okay, and should we expect that development program to continue to enlarge, or do you feel like it's sort of settled business now in terms of how broad you're thinking about it?
I think we're set up for the key opportunities, but Trodelvy has quite a few years before LOE. So we're really trying to maximize the opportunity, and some of it will be data-driven, what we see in those ongoing studies.
Okay, maybe circle back. I guess since we came up with the questions, you did have another deal in the CAR-T space that got announced. You acquired Interius and in vivo CAR-T platform. Can you talk a little bit about how you see that fitting in within the portfolio? I think obviously Kite had such a strong track record of success kind of out of the gates. And I think there's been a lot of questions around what's next for the CAR-T platform. To what extent does Interius kind of address that? Or maybe just put that in the context of the other kind of innovation efforts within the CAR-T portfolio?
Yeah, it's a great question because I feel at Kite, there has been a lot happening, but you really need to put the different pieces together to really understand where the journey is going. We've spoken for some time about headwinds, obviously, with the current product portfolio. And we're working intensively to address that, right? We're working to open up opportunities in the outpatient setting, for example, with a current portfolio. And then we've already spoken about anito-cel as an addition to the portfolio that really will put us firmly, we hope, on a growth trajectory. Beyond that, we have a refocused effort on research and bringing new products forward at Kite.
We have spoken at ASCO, for example, and also about EHA, about next-generation CAR-T approaches, for example, bispecific, bicistronic, CD19, CD20 CAR-Ts, which would be a next generation for the current indications in leukemia and lymphoma, but also be a next generation based on efficacy and tolerability that we're thinking about for inflammatory conditions, right? Say lupus, for example, or also for neuroinflammatory conditions, right? Those are early efforts at this point in time, but what we're seeing in early data, and we've communicated some of that, is really encouraging. We also have spoken about taking CAR-T cells into the solid tumor setting. We presented some data, for example, in glioblastoma that are early, together with the University of Pennsylvania, the group there, but that are directionally really interesting.
And then on top of that, we're investing now in vivo CAR-Ts, really to make sure that that's an area we also focus on, we also understand, and we can also lead in, right? Because that could be a disruptive move. The in vivo CAR-T progression could be disruptive for the current autologous CAR-T approaches. And with the Interius acquisition and also with different other acquisitions around, for example, technology and IP, we are in a leadership position for that and want to be in a leadership position for that development as well. Again, it's about covering different avenues and developing a more consistent vision that consists in how can we really focus on the current portfolio and bring that forward and optimize? How can we add to the portfolio with anito-cel and CD19, CD20, and grow into different areas like inflammation?
And then how can we cover our bases and really lead also on the in vivo CAR-T side?
Maybe the last question on oncology. I think we just kind of hit the two major thrusts. I think when people think about Gilead Oncology, what else are people missing? What else is there going on that maybe we haven't talked about, you haven't touched on yet?
Yeah, there's obviously an earlier portfolio. We pruned some of that earlier portfolio more recently because we felt that we had done enough evaluation around those molecules. But we will bring more molecules into the oncology portfolio. For example, there's a CCR8 molecule that targets regulatory T cells. There's different other early portfolio molecules in phase I that we've currently developed. One of the questions around the oncology portfolio, and we're thinking about that also from an internal research perspective and from a business development perspective, is how do you make this really a sustainable portfolio over the long term, right? We have a really nice trajectory at this point between anito-cel and what we've seen with Trodelvy and the Trodelvy data, but we need more sustainable portfolio behind that. So we're working on the internal portfolio with different mechanisms.
A lot of it is early, but we're also looking actively from a business development perspective.
Maybe switching gears to immunology. I think from the outside looking in, I think immunology has been one of those TAs that's been listed for quite some time. I think from the outside looking in, it's been sometimes difficult to discern exactly what the Gilead strategy has been or to the extent that you guys might focus there in terms of BD. You highlighted some of the earlier stage assets there. What does it take to win in immunology, particularly if you're going to focus sort of organically?
Yeah, I'm fully behind the strategy of virology oncology inflammation, right? And as we're going through the portfolios, you understand that these different components are at very different stages, right? Industry-leading virology, I think really good trajectory for oncology, earlier portfolio in inflam. So your question is exactly right. What does it take to win? Currently, there is a portfolio of around 10 molecules in this early inflam portfolio, some of them in phase II, like the oral alpha-4 beta-7 or the IRAK4 inhibitor. We will, of course, focus on developing that early portfolio. And then there are some other early molecules, like, for example, the STAT6 degrader, the IRAK4 degrader, that have the potential to become real drivers for the portfolio. But again, it's early, right? We're talking about phase I stage molecules at this point in time.
It's really about how can we further build a sustainable portfolio in inflammation as well. Some of it may be development of the early molecules. We also have very active research efforts ongoing in inflammation, but it's also about how can we build a commercial portfolio. At this point in time, we have Livdelzi. We're grouping liver and inflammation together internally, which is on a good trajectory in PBC, and we're thinking about how can we further develop that. Some studies are also ongoing to increase the addressable patient population. Then we will actively look also and see are there other anchor assets that we can bring into the immunology portfolio.
Okay, and I guess as we then approach that alpha-4 beta-7 readout, I guess as you think about it, just you've obviously been in inflammation for a long time. As you think about sort of the trajectory of things like IBD, do you see that ultimately moving into a combination MOA kind of market, which it hasn't been historically? It feels like we've been talking about that for a decade, but haven't really moved the ball forward there. So would it be things like an oral alpha-4 beta-7 or other kind of mechanisms here? I guess trying to pick your brain a little bit in terms of how you see major markets like IBD that Gilead historically has focused on.
Yeah, I think there are two areas that I would like to focus on with that. One is, of course, there's a move to orals, right, in the IBD setting. And you see that also with competing mechanisms, right? You see oral IL-23, you see oral TL1A, you see oral JAKs, right? So that move to orals is very clear. There's no oral alpha-4 beta-7 at this point in time. So that's a really good addition to that, and we'll need to see the phase II data, obviously. But then combinations is an area that people are asking about, right? Because we have not been able, with the current monotherapy approach, to break the efficacy ceiling. And there's some early combination data that give us some hope that combinations could actually be necessary and could help to break that efficacy ceiling.
And then having an oral alpha-4 beta-7 could be a cornerstone of that combination strategy. And there are obvious combination partners. Some of them we have internal. So we currently have four molecules in the IBD space that we're evaluating, and some of those could be internal combinations. But we're also open to look at external combinations, right, with some of the very established mechanisms in the field.
Okay, maybe just we've got about a minute left here. And only because you guys haven't talked about it in a while, just sort of the latest updates on how you're thinking about your GLP-1 program. Obviously, there's been some competitor oral data, and if that in any way has kind of evolved your thinking around your own internal program?
Yeah, that molecule comes out of the really strong chemistry and research efforts at Gilead, and they came up with this molecule. It's currently in evaluation in phase I, right, and obviously, what we want to see is we need to identify the dose, obviously, and then we want to see what's the impact on obesity and diabetes, so that's currently ongoing. I don't have anything new to tell you at this point in time, but the molecule is in active early development.
Perfect. I'll have to leave it there. Plenty going on at Gilead beyond the Yeztugo launch, but great to talk to you, Dietmar. Thanks for the time.
Thanks very much.