Gilead Sciences, Inc. ($GILD)

Welcome back, everyone. I'm Brian Abrahams, Senior Biotech analyst here at RBC Capital Markets. We're really pleased to have our next featured company, Gilead Sciences, represented by their Chief Medical Officer, Dietmar Berger. Dietmar, thanks again for joining us.

Yes. Thanks for having us. It's pleasure to be here.

So a lot to cover. So I'll kick it off and maybe just start with Trodelvy because I know we're going to see a big data point this year on EVOKE-03, can you talk a little bit more about, I guess, what you're looking for out of those results. In particular, what specific efficacy thresholds on PFS or OS? Do you think this trial would need to show in order to justify the positioning of a Trop-2 ADC in frontline. How are you thinking about the competitive landscape overall here? And really, just what should we be looking for? .

Trodelvy our TROP2 ADC, where we had positive data recently in first-line triple-negative breast cancer, that's the ASCENT 304 study. And that's where we're looking forward also to hopefully get an approval later this year for that setting. And EVOKE-O3, the study that you're talking about is a study in first line PD-L1 high non-small cell lung cancer, very straightforward study design. You basically have pembro as the standard of care and you add Trodelvy to that, right? So what we want to see in this setting -- this is an early analysis. So yes, PFS is going to be mature. OS is going to be earlier. But what we really want to see is like a significant PFS benefit, right? And then, of course, we will follow the study longer for OS as well. This would be -- if the study is positive, this would be the first time that you really see meaningful benefit of a combination in this setting on top of pembrolizumab. But also when you think about it, these people are currently treated depending on how quickly the tumor grows either with Pendal or also with the addition of chemotherapy. So there is benefit in -- with chemotherapy for these people. And that's where an ADC, obviously, can maximize that benefit. Also with good tolerability, and that's what we're hoping to see, right? And that would be a meaningful addition, obviously, to what we can do with Trodelvy. We also have ongoing studies in endometrial cancer, for example, and a variety of other studies in different tumor types. From a competitive perspective, Yes, there are other molecules targeting...

Seems like more and more people are -- more and more companies are following in your guys as well. .

Yes. TROP2 as a target is just 1 good target for ADCs. With Trodelvy with the biggest data set, right? And people are really comfortable with Trodelvy. That's also what we see in breast cancer, both in hormone receptor positive and in triple-negative breast cancer. -- level of comfort that people have with the drug, the confidence with the efficacy is really there. That's why we've seen year-over-year, also an increase with Trodelvy 37%, right? And -- and that's really testament to. Yes, there's good use. There's increasing use and that's where the EvoCowill add to what we can do with Trodelvy. .

Got it. And then maybe kind of staying on the solid tumor front. You recently acquired a private company, tubulus. And I know we're going to see some updated data at ASCO. What excited you most about that asset? I mean, to what degree was it the data, the unmet need, the overall technology that they have? And what should we be looking for at ASCO.

Yes, we've been -- I mean, obviously, we just spoke about Trodelvy. So we have a lot of experience in ADCs, and we've been scouring the planet pretty much for what's your next level innovation in ADCs. And -- what we saw in tubules is both a really interesting front-runner molecule but also really interesting and differentiated platform. And the platform is a completely different linker and payload technology. They call this the P5 platform, which is really more how is the antibody connected to the linker. And then there's the Alco5 platform, which really more how is the linker connected to the payload, right? And both of these are really novel chemistry and allow for kind of features of molecules that we had not seen before. For example, the P5 platform allows for a really stable linkage, which means you don't get the systemic toxicity, whereas the Alco5 platform allows for really combinatorial activity with different payloads, so completely novel payloads that we can utilize that either come out of our medicinal chemistry or that come out of out of tubules. So we really like the platform, and we know a lot about the platform because we worked with tubules on novel molecules since 2 years. We had an ongoing project with them. So we understood the platform really well. And then on top of that, the front-runner molecule is top 40, which is a NaPi2b directed ADC, where at ESMO last year, ESMO 2025, they presented in our view, really convincing data in platinum-resistant ovarian cancer. So they had like a 50% to 60% objective response rate, like a 90% disease control rate. on the basis of roughly 50 patients, which we found really encouraging when you think about the current standard of care with Bev and chemo is roughly 25% to 30% objective response rate. So we saw a real benefit and that benefit together with a really positive tolerability profile, right? Again, going back to the really stable in which biologically it makes sense. -- to then see less side effects and good tolerability. And we didn't see any of the kind of the major side effects that you see with some of the other ADCs, whether it's neurotox or eye toxicity or intestinal toxic this was all really tolerable. So that benefit, that combination was really important to us on top of the platform.

Okay. Great. And then Maybe, I guess, speaking of companies that you acquired, you recently gained full rights to anito-cell. I guess how confident are you on the efficacy side that we're going to continue to see similar response rates and a PFS tail that looks comparable to other -- what other CAR-Ts have seen? And as you kind of move on the safety side, as you move into the earlier line population, including newly diagnosed myeloma, how do you expect the safety differentiation to evolve with -- in a patient population that maybe has cleaner baseline organ function and less prior treatment exposure?

So it will be quite as prominent. Yes. Yes. The anito cell is obviously the BCMA CAR-T where we already had rights to and really acquired the entire company, the entire Arcellx, both Aidocell, but then also the platform, the d-domain bins were really important. These small binders that I think really make a difference. -- and allow us to also go into in vivo CAR T and apply them differently in different areas -- so that was part of the decision. But having full ownership of the commercialization and also pool ownership of the future development was really important to us, right? So you talk -- you're asking about how confident we are with regards to the differentiation. I have to say I'm very confident in that regard. And that's based on the early efficacy data that we see, which is really more myeloma responses. Of course, we don't have the long-term tail. You're talking about the long-term PFS and OS tail -- but what we do have is an early indicator, which is measurable residual disease, or MRD. So how deep is the response? And how much do you really reduce the myeloma load in those patients? And MRD is a really good predictive parameter and the MRD data for Anetocell are just better than anything that's out there. So I'm actually -- I'm a hematologist, right? So I'm really looking at these data are really attractive. And I think are a positive signal regarding really good long-term outcomes. Now on top of that, efficacy, what you also see with anito-cel is, I think, unprecedented safety in myeloma. We're not getting any of the kind of the longer-term severe neurotoxicity is no Parkinsonism, [indiscernible], none of the enterocolitis effect also that you see with some of the CAR-T approaches in myeloma. So we feel there's really good differentiation with anito-cel from both an efficacy and a safety perspective. Obviously, imagine, one, that's the study in fourth line plus that we're currently discussing with regulatory authorities with potentially an approval towards the end of this year. That's the initial indication. Then we imagine 3 is a study that takes us into second fourth line. That study is ongoing, really looking forward to seeing those data -- and then we're currently in planning for even earlier lines, so thinking newly diagnosed myeloma, both transplant eligible and transplant ineligible patient population, right? So really taking this also into earlier lines because we are more and more in myeloma speaking about long-term outcomes, even speaking about, is there a possibility to even have like cures in a sense for these patients. And that's what you reach in earlier lines, right .

So do you want to see it of Imagine 3? Or is there some degree of follow-up data that would inform the decision to go into first line? No, I think we're confident enough about the drug that really we are in planning stages for first line at this point, right? .

And imagine 3 will give us I think, really meaningful data in the second to fourth line setting. So really working late line, fourth line plus second to fourth and then early lines, but we're very committed to the overall anito-cell program.

Okay. Maybe shifting gears to I&I. On the earnings call, you mentioned that the alpha-4-beta-7 inhibitor 14.27 that we're going to see some data in the near term there. I guess what excites you most about this asset? What do you -- what would you want to demonstrate at this -- in this early to mid-stage point in its development to move it forward? And what do you think are the key differentiating elements versus the other oral alpha-4-beta-7, which have maybe shown some signals, but maybe you were a little bit more mixed.

Yes. The -- let me step back first and really say when you think about how the Gilead portfolio is shaping up, -- we've said for some time that we're focused on virology, oncology and inflammation/Immuno.

It's finally return now.

And yes, I look at this as 1 signal and I think a strong signal that the inflammation portfolio is also coming together. -- right? So we have HIV with long-acting. We've got other virology assets that's the underlying virology strategy also in different types of hepatitis, et cetera. You've got the oncology strategy we talked about Trodelvy, we talked about tubules and now also about the cell therapy portfolio. And then in inflammation, there is a billion emerging portfolio for Gilead. We currently have more than 10 molecules in the inflammation portfolio and 3 of them in Phase II. So granted somewhat earlier -- but when you think about those molecules that are currently in Phase II stages, we're really looking forward then also to data readouts, there's the oral alpha 4 beta 7 which I'll talk about in a second for IBD, which I think is a really interesting molecule. There's an IRAK-4 inhibitor. It is acertib, which is also in Phase II -- and then there's a type 2 also for IBD. So there is an emerging portfolio that I think is really interesting also addressing really important targets in immunology. Getting to alpha-4-beta-7 that's a validated target, right? And Teo is out there as 1 of the backbone therapies in inflammatory bowel disease in Crohn's and colitis. -- what people really like about ENTYVIO is the balance of efficacy and safety. It's an efficacious approach that shows really good safety as well, right? It's an injectable, right? And as we're moving also more and more to orals in IBD therapy. You've got the IL-23s, you've got the -- you've got other molecules that are going it's really interesting to think about what can an oral alpha 4 beta 7 actually do. And obviously, what we are hoping to see, right, we have the Phase II study in-house, and we'll communicate the data later this year at a medical conference. What we're really hoping to show is, obviously, differentiated efficacy and safety with the added convenience of the oral, right? And that's why I think we have a real opportunity and let us show you the data first, and then we can talk about what can we do with this type of molecule. But I'm really encouraged about what I see in the inflammation portfolio and how is it coming together and alpha-4-beta-7 is one component of that.

Okay. Do you think about that as a potential monotherapy -- or is that potentially combinable with some of your other assets? .

Yes. And I want to stay in the hypothetical because we haven't communicated the data yet. But in principle, everything is possible, right, alpha-4-beta-7 ENTYVIO is there as a monotherapy and there are obviously also combination approaches. And what we currently see in IBD in inflammatory bowel diseases as most people start with some type of monotherapy. And of course, they have to go through different steps before they go to the biologics -- but there are patients where we have an efficacy ceiling with the monotherapies, where you really have to think about combinations. And it's really those patients that it's not that I would believe everybody would go in combination, and that's where it's important to have data, especially if you think about developing a backbone therapy where you have data with different iterations, right, monotherapy and combination A lot is possible let's show you the data.

Looking forward to that. And then speaking of data in the relatively near future, you guys are looking -- you've had a successful launch with S2G so far -- it's only early days, but you're already looking at next-generation versions. And I know you have a once-yearly study lenacapavir study ongoing that's intramuscular. Tell us a little bit about, I guess, you selected the right formulation to move into the phase this Phase III study? And then just what has the FDA said will be the bar for bioequivalents that you think you need to hit to be sure that you are comparable to go whose efficacy is really unprecedented. -- and that there aren't any sort of outlier patients at week 50 or 51 that might drop below the necessary exposure?

Yes. So it's really important to realize what we're talking about here is prevention. So we're not thinking about, hey, there's a virus that can develop resistance over time. This is more like you prevent an infection as a person is exposed to a virus. So your typical resistance discussion in that point is very different for the prevention setting, right? And that's where really the understanding that we have developed with lenacapavir with the Yeztugo is very important. We can absolutely model what type of level like serum level eventually of lenacapavir we need in order to protect, right, in order to get that prevention [indiscernible]. Exactly, we have those PK data -- and what we can do is we can model if you wanted to have that level of coverage over a year, what type of starting dose would you need, right? Because you form a depot. And then over time, obviously, you get lower and lower levels, right? And we need to have those 52 weeks full coverage at the levels that we've seen with the Stuge once every 6 months. And we've modeled that, and we are very confident that with the once every year injection that we use in purpose 365, which is the Phase III study, where we've already completed recruitment that the levels we need that we will actually have those throughout the full year. Actually, what we know at this point is we think even after -- at the end of the 52-week period, the levels we will still see are higher than the levels that we see with subcutaneous once every 6 months, right? And we were able to get to a slight change of the formulation, which then is used in the intramuscular injection that we use in the once every 12 months. application. And that's where the FDA then has also agreed to a PK-based study. So the purpose study has endpoints around PK and around safety, and we basically need to demonstrate these levels over time, and we need to demonstrate safety. And we believe that we can do that. .

And do you anticipate that the market will shift from every 6-month subcu years to go to annually -- annual I am?

What we've learned about the prevention market is that people really like optionality, right? And that's also what we see now. We see really good adoption of Descovy, right, which is a daily order. We also see, as you all know, really good adoption of yes to go which is the 1 every 6 month injectable, right? And we've just updated our predictions for this year where we Yeztugo to be a blockbuster by the end of the year. What we do get back from people in the community is they're really excited about the once every year option, and they liken it to -- this is simply, I get my 1 shot once a year, like a vaccine and then I'm protected. And then we're always saying yes. But be aware, it's not a vaccine, right? It's actually better than a vaccine because you get much better protection able. So there's a lot of excitement around it. it would be hard for me to predict now whether how the market will develop. But I do believe it's going to be a really important option for people with on prevention, right? And I think one of the big positives around this type of prevention is you really don't have to think about forgiveness or gaps in prevention or anything like with an oral. The key benefit is really you're done 1 short once a year and you protect it for the entire year. And that's what people see.

Let's shift gears from HIV prevention to HIV treatment. You have a number of next-generation is completely proprietary as well as partnered assets that are continuing to emerge. So maybe just starting on the selective lenacapavir once-weekly oral I guess, what were you looking for out of those data to dictate the regimen's potential role?

Yes. The -- obviously, we'll have data from our Island 1 and 2 studies, which is a weekly treatment. -- later this quarter. So really looking forward to that. These are studies in already virologically suppressed people. So these are people who are, for example, on Biktarvy, which is currently absolutely the standard of care, who then switched to islatravir plus lenacapavir to once weekly oral treatment option. Biktarvy, basically, everybody is biologically suppressed. So we want to see that same level of suppression, right? We do not want to compromise on efficacy. And we do want to see that same level, obviously, with good tolerability. That's also then positioning is Latrobe land clearly into the switch market, right? About 20% of people. On Biktarvy, for example, per year, want to switch to something else. That's where is [indiscernible] would be a really important option right? And that's how we're looking forward to the data.

Got it. And then for your own potential wholly owned weekly oral, I guess, what characteristics are you going to be prioritizing versus lenacapavir for a potential capsid in that regimen and so some of the PK properties time lines that you envision for that to move forward? .

Yes. We do want to develop a wholly owned combination. We believe an integrase inhibitor plus a capsid inhibitor is a really strong option for that .

By resistance exactly high.

Exactly, barrier of resistance. So -- we're currently in the process of -- from our large portfolio of integrase inhibitors and capsid inhibitors and capsid inhibitor prodrugs, we're currently selecting the 2 combination partners -- and then we're looking forward to bring those into the clinic. And we'll obviously communicate around those plans as soon as we finalize them.

Got it. Then speaking of long-acting is even longer acting, I know you guys are looking at the potential for an every 6-month injectable on the treatment side. And you've had some encouraging early data, I think it was at Core for 3242 I know historically, it's been tough to get integrated dose high enough in a subcu to have multi-month durability without running into tolerability issues like injection site reactions. But it seems like so far, so good with $32.42. I guess, where do you stand with the ongoing dose escalation work and what gives you confidence that the higher doses will have the durability to get to your goal of every 6 months and you won't run into any safety compromises.?

Yes. SP29289590 So again, optionality is really important. That's how we're looking also at the treatment space, and then we're talking about these different options. For the once every 6 months, we also have an injectable option, right, with lenacapavir and 2 broadly neutralizing antibodies, where we're planning to start the Phase III later this year. For the integrase inhibitor based option with 32 42, as you said, we have the PK data that we presented some of that at CO -- and this is a dose escalation study. So what we know for sure right now is once everybody [indiscernible], right. And the even higher dosing cohorts are still ongoing. From a modeling perspective, from what we've seen from a safety perspective so far, we're confident that we can get to the ones every 6 months, which -- but of course, again, we need to see the data eventually. And you're right, it hasn't been easy to get to that once every 6 months. integrated inhibitor offering, but we're confident that 30242 will potentially provide a path forward.

Excellent. Well, unfortunately, we're out of time, but Dietmar, thank you so much for being here. Thanks, everyone.

Thanks a lot.