Started. 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.
Yeah, thanks for having us. Pleasure to be here.
A lot to cover. I'll kick it off and maybe just start with Trodelvy because I know we're gonna 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 TROP2 ADC in frontline? How are you thinking about the competitive landscape overall here? Really just what should we be looking for?
Trodelvy is obviously our TROP2 ADC, where we had positive data recently in first-line triple-negative breast cancer. That's the ASCENT-0 3 and ASCENT-4 study, that's where we're looking forward also to hopefully get an approval later this year for that setting. EVOKE-03, 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.
Yeah.
You add Trodelvy to that, right? What we want to see in this setting, this is an early analysis, so yes, PFS is gonna be mature, OS is gonna be earlier, but what we really want to see is a significant PFS benefit, right? Of course, we will follow the study longer for OS as well. 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. Also when you think about it, these people are currently treated, depending on how quickly the tumor grows, either with pembro or also with the addition of chemotherapy.
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? That would be a meaningful addition obviously to what we can do with Trodelvy. We also have ongoing studies, you know, in endometrial cancer, for example, and, you know, a variety of other studies in different tumor types. From a competitive perspective.
Yeah.
Yes, there are other molecules targeting TROP2.
Seems like more and more companies are following in your guys' footsteps.
Yeah. TROP2 as a target is just one good target for ADCs. With Trodelvy, we have the biggest data set, right? 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. The 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? That's really testament to yes, there's good use, there's increasing use and that's where the EVOKE-03 will add to what we can do with Trodelvy.
Got it. Maybe kind of staying on the solid tumor front. You recently acquired a private company, Tubulis, and I know we're gonna see some updated data at ASCO. What excited you most about that asset? 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?
Yeah. We've been I mean, obviously, we just spoke about Trodelvy, so we have a lot of experience in ADCs.
Yeah.
We've been.
Yeah.
The planet pretty much for what's your next level innovation in ADCs. What we saw in Tubulis is, you know, both a really interesting frontrunner molecule, but also really interesting and differentiated platform. The platform is a completely different linker and payload technology.
Yeah.
They call this the P5 platform which is really more, you know, how is the antibody connected to the linker. There's the Alco5 platform, which is really more how is the linker connected to the payload.
Yeah.
Right? 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 really stable linkage, which means you don't get the systemic toxicities, 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 Tubulis. We really like the platform, and we knew a lot about the platform because we worked with Tubulis on novel molecules since two years. We had an ongoing project with them, we understood the platform really well. On top of that, their front-runner molecule is TUB-040, 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.
They had like a 50%-60% objective response rate. They had 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%-30% objective response rate. We saw a real benefit, and that benefit together with a really positive tolerability profile.
Going back to the really stable linking.
[inaudible]
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 tox or something. This was all really tolerable. That benefit, that combination was really important to us on top of the platform.
Okay. Great. Then maybe, I guess speaking of companies that you've acquired, you recently gained full rights to anito-cel. 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? 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?
Yeah.
I guess it'll be quite as prominent.
Yeah. Yeah. No, the anito-cel is obviously the BCMA CAR T, where we already had rights to and really acquired.
Yeah.
You know, the entire, company, the entire Arcellx, both anito-cel, but then also the platform, the D-D omain binders.
Yeah.
Were really important, these smaller binders.
Yeah, yeah.
That I think really make a difference and allow us to also go into our in vivo CAR T and apply them differently in different areas.
That's it.
That was part of the decision. Having, you know, full ownership of the commercialization and also full ownership of the future development was really important to us, right? You're asking about how confident we are with regards to, you know, the differentiation. I have to say I'm very confident in that regard, and that's based on, you know, the early efficacy data that we see, which is really more, you know, myeloma responses. Of course, we don't have the long-term tail. You're talking about the long-term, you know, PFS and OS tail. What we do have is an early indicator, which is measurable residual disease or MRD. How deep is the response, and how much do you really reduce the myeloma load in those patients?
MRD is a really good predictive parameter, and the MRD data for anito-cel are just, you know, better than anything that's out there. I'm actually I'm a hematologist, right?
I'm really looking at, these data are really attractive and I think, you know, are a positive signal regarding really good long-term outcomes. 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 neurotoxicities, no Parkinsonism, no Guillain-Barré, none of the enterocolitis effects also that you see with some of the CAR T approaches in myeloma. We feel there's really good differentiation with anito-cel from both an efficacy and a safety perspective. Obviously, you know, iMMagine-1, 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.
Yeah.
iMMagine-3 is a study that takes us into second to fourth line.
Okay.
That study is ongoing. Really looking forward to seeing those data. Then we're currently in planning for even earlier lines, so thinking newly diagnosed myeloma, both the transplant eligible and transplant ineligible patient population, right?
Yeah.
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.
Yeah.
For these patients. That's what you reach in earlier lines, right?
Is that what you want to see out of iMMagine-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.
Okay.
About the drug that really we are in planning stages for first line at this point, right?
Okay.
iMMagine-3 will give us, I think, really meaningful data in the second to fourth-line setting. Really working late-line, fourth-line plus second to fourth, and then early-lines. We're very committed to the overall anito-cel program.
Okay. Good. Maybe shifting gears to I& I. On the earnings call, you mentioned that the alpha-4 beta-7 inhibitor GS-1427, that we're going to see some data in the near term there. I guess what excites you most about this asset? What would you want to demonstrate at this, you know, in this early to mid-stage point in its development to move it forward? What do you think are the key differentiating elements versus the other oral alpha-4 beta-7s, which have maybe shown some signals, but maybe were a little bit more mixed?
Yeah. 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, you know, we're focused on virology.
Yeah.
Oncology and inflammation slash immunology, right?
It's finally really maturing now.
Yes, I look at this as one signal, and I think a strong signal that, you know, the inflammation portfolio is also coming together, right? 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 Tubulis and now also about the cell therapy portfolio. In inflammation, there is really an emerging portfolio for Gilead. We currently have more than 10 molecules in the inflammation portfolio, and three of them are in phase II. 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 α4β7, which I'll talk about in a second, you know, for IBD, which I think is a really interesting molecule. There's an IRAK4 inhibitor. edecesertib, which is also in phase II. There's a TYK2 also for IBD. There is an emerging portfolio that I think is really interesting, also addressing really important targets in immunology. Getting to α4β7, that's a validated target, right?
Yeah.
ENTYVIO is out there.
Yeah.
As, you know, one 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? As we're moving also more and more to orals in IBD therapy, you've got the IL-23s.
Yeah.
You've got the , you've got other molecules that are going oral. It's really interesting to think about what can an oral α4β7 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?
Okay.
That's why I think we have a real opportunity, and let us show you the data first, and then we can talk about, you know, what can we do with this, with this type of molecule. I'm really encouraged about, you know.
Yeah.
What I see in the inflammation portfolio and how they're coming together, and α4β7 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?
Yeah, and I wanna stay in the hypothetical, right?
Yeah.
Because we haven't communicated the data yet. In principle, everything is possible, right? α4β7 ENTYVIO is there as a monotherapy. There are obviously also combination approaches, and what we currently see in IBD, in inflammatory bowel diseases, is most people, you know, start with some type of monotherapy. Of course, you know, they have to go through different steps before they go to the biologics.
Yeah.
There are patients where we have an efficacy ceiling with the monotherapies, where you really have to think about combinations.
Okay.
It's really those patients that it's not that I would believe everybody would go on combination.
Yeah.
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.
Okay.
A lot is possible. Let's show you the data first.
Okay. Looking forward to that. Speaking of data in the relatively near future, you guys are looking, you know, you've had a successful launch with YEZTUGO so far, and it's only early days, but you're already looking at next generation versions. I know you have a once yearly study lenacapavir study ongoing that's intramuscular. Tell us a little bit about, I guess, how you selected the right formulation to move into the phase, this phase III study.
Just what has the FDA said will be the bar for bioequivalence that you think you need to hit to be sure that you are comparable to YEZTUGO, 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?
Yeah. It's really important to realize what we're talking about here is prevention.
Yeah.
You're not thinking about, hey, there's a virus.
Right.
That can develop resistance over time. This is more like you prevent an infection.
Yeah.
A person is exposed to a virus. Your typical resistance discussion in that point is very different.
Right.
for the prevention setting, right? 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.
Yeah.
Right?
Yeah.
Get that prevention efficacy.
Yeah. I know I think as a public comment, yeah.
Exactly, we have those PK data, 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?
Yeah.
Right? Because you form a depot, then over time, obviously you get lower and lower levels, right? We need to have those 52 weeks full coverage at the levels that we've seen with YEZTUGO once every six months. We've modeled that, and we're 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 at the end of the 52-week period. The levels we will still see are higher than the levels that we see with the YEZTUGO subcutaneous once every six months. Right. We were able to get to a, you know, a slight change of the formulation, which.
Right.
is used in the intramuscular injection that we use in the once every 12 month application. That's where the FDA then has also agreed to a PK-based study. The PURPOSE 365 study has endpoints around PK and around safety, and we basically need to demonstrate these levels over time, and we need to demonstrate safety. Right?
And.
We believe we can do that.
Do you anticipate that the market will shift from every six months subcu [inaudible] YEZTUGO to annual IM?
You know what we've learned about, the prevention market is that people really like optionality.
Yeah.
Right? That's also what we see now. We see really good adoption of Descovy.
Yeah.
Right? Which is a daily oral.
Yeah.
We also see, as you all know, really good adoption of YEZTUGO , which is the once every six month injectable, right? We've just updated our predictions for this year, where we expect 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, oh, this is simply I get my one shot once a year like a vaccine, and then I'm protected.
Yeah.
We're always saying, "Yeah, but be aware it's not a vaccine, right? It's actually better than a vaccine because you get much better protection levels.
Yeah.
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 who want prevention, right? I think one of the big positives around this type of prevention is you really don't have to think about, you know, forgiveness or gaps in prevention.
Right.
Or anything like with an oral. The key benefit is really you're done one shot.
Yeah.
Once a year, and you're protected.
Right.
For the entire year.
Right.
That's what people see.
Let's shift gears from HIV prevention to HIV treatment. You have a number of next generation, both completely proprietary as well as partnered assets that are continuing to emerge. Maybe just starting on the islatravir/lenacapavir once weekly oral, what were you looking for out of those data to dictate the regimen's potential role?
Yeah. Obviously we'll have data from our ISLEND- 1 and ISLEND-2 studies, which is a weekly treatment, later this quarter.
Really looking forward to that. These are studies in already virologically suppressed people.
Yeah.
These are people who are, for example, on Biktarvy, which is currently absolutely the standard of care, who then switch to islatravir plus lenacapavir to a once weekly.
oral treatment option. Biktarvy basically, you know, everybody's virologically suppressed.
Yeah.
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, you know, then positioning islatravir/len clearly into the switch market, right? About 20% of people, on BiktarvyI , for example, per year, you know, want to switch to something else. That's where islatravir/len would be, a really important option.
Right? That's how we're looking forward to the data.
Okay. Got it.
Yeah.
For your own potential wholly owned weekly oral, I guess what characteristics are you gonna be prioritizing versus lenacapavir for a potential capsid in that regimen, some of the PK properties, timelines that you envision for that to move forward?
Yeah. 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.
High barrier resistance.
Exactly. High barrier of resistance. We're currently in the process of, you know, from our large portfolio of integrase inhibitors and capsid inhibitors and capsid inhibitor prodrugs, we're currently selecting the two combination partners. We're looking forward to bring those into the clinic.
Right.
We'll obviously communicate around those plans, as soon as we finalize them.
Got it. Speaking of long-acting, I guess even longer acting, I know you guys are looking at the potential for an every six months injectable on the treatment side. You've had some encouraging early data. I think it was at CROI for GS-3242.
Yeah.
I know historically it's been tough to get integrases dosed high enough in a subcu to have multi-month durability without running into tolerability issues like injection site reactions. It seems like so far so good with GS-3242. 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 six months and you won't run into any safety compromises?
Yeah. Again, optionality is really important.
Yeah.
That's how we're looking also at the treatment space, and then we're talking about these different options. For the once every six month, we also have an injectable option, right, with lenacapavir and two broadly neutralizing antibodies, where we're planning to start the phase III later this year. For the integrase inhibitor-based option with GS-3242, as you said, we have the PK data that we presented some of that at CROI. And this is a dose escalation study.
Right.
What we know for sure right now is once every four months.
Three months. Four months. Yeah.
Right?
Yeah.
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 once every six month. Of course, again, we need to see the data eventually. You're right, you know, it hasn't been easy.
Yeah.
To get to that once every six month integrase inhibitor offering. We're confident that GS-3242 will potentially provide a path forward.
Excellent. Well, unfortunately we're out of time, but Dietmar, thank you so much.
Oh, thank you.
For being here, and thanks everyone.
Thanks a lot.