Good morning. I'm Brian Abrahams, one of the senior biotech analysts, here at RBC Capital Markets. Welcome again. Our next presenting company is Gilead Sciences. Really pleased to have with us their Chief Medical Officer, Merdad Parsey. Merdad, thank you again.
Thanks. Thanks for having me. Excited to be here.
A lot to cover. I wanna kick it off, maybe starting with the oncology portfolio and Trodelvy. You know, you recently got approval for Trodelvy, based on the positive TROPiCS-02 data. I guess I was wondering if you could tell us a little bit more about what you're seeing since the approval in terms of how Trodelvy is being incorporated into clinical practice. Maybe both, you know, what you're seeing in terms of the more mature, triple negative area, as well as the HR-positive indications and maybe the lines of therapy that it's been moving into.
I guess along those lines, would also love to learn how you guys are thinking about strategizing to pull it forward even more and into earlier lines in HR-positive patients, given what you're seeing on the ground.
Yeah, thanks. You know, as I think as we've said all along, we think the potential of Trodelvy for this idea of pipelining a product is really playing out nicely. You know, with Trodelvy now being on the market with several approvals now, including the ones you referenced, and also the accelerated approval in bladder, we think we've got a great foothold in the Trop-2 ADC area. So far the acceptance has been really good. We've had really positive uptake, great feedback, as we talk to our advisors and our KOLs out there. It's early days, so I think it's, you know, we just launched recently, so it's still early days, but so far things are going really well.
The way we see it playing out, is getting, you know, both as you alluded to, into earlier lines of therapy into the places where we've already been approved, and also expanding the footprint of Trodelvy. I think what we are looking forward to is, one, converting hopefully the accelerated approval for bladder into a full approval. Those data, should be reading out, as well as moving now into earlier lines in the HR-positive, HER2-negative field. Then, we have our ongoing lung cancer programs, all the EVOKE trials that are ongoing. Those data, should also be, you know, reading out. As we've said, I think, 2024 is gonna be a very big year for us in across tumor types.
We've got a number of those, phase II and phase III studies now, ongoing, enrolling really well, and I'm looking forward to seeing those data and sharing them with you guys as we go. I do think we'll be able to go. Maybe the last thing I'll add before going on is, you know, those are, those are I would call our anchor indications there, and we should be able to start sharing some data from other tumor types that we're exploring in earlier trials to see if we can see the signal for Trop-2 in other places, and we're really optimistic about that as well.
Great. Maybe expanding a little bit more on lung cancer, can you talk about your expectations for Trodelvy in that indication? Obviously a large indication, but there are other ADCs, you know, going after lung cancer. Where do you see the most differentiation for Trodelvy? Any read-throughs that you're gonna be looking for from upcoming data we might see from other Trop-2 ADCs in later stage development?
Yeah. I think that the read-through for me is really this further validation of the role of Trop-2 ADCs in non-small cell lung cancer. We're very optimistic. We're, as I said, we'll have our own data as well. Our expectation is that Trodelvy will really bring a meaningful improvement across a variety of non-small cell lung cancer populations, whether we're talking about frontline PDL1 high, we're gonna be looking at other populations as well. Second line, in the EVOKE-01 study, we'll be looking at PDL1 lower patients. I think the read-through is really gonna be the validation of Trop-2 in these tumor types.
The main point of differentiation as we go forward, look at, I think while these are, there are a number of now Trop-2-directed ADCs, the other things that differ are the linker and the payload. What we're seeing play out, in the data we're seeing from competition as well as ours, is that our adverse event profile and our efficacy profile have become pretty well established. We're seeing great efficacy across the board, and the adverse event profile has been really consistent along the way. We see neutropenia, we see diarrhea, and those are adverse events that our practitioners seem to be comfortable managing. The competition is seeing ILD, and we've seen that across tumor types, for their agent.
I think that will be one of the areas where we'll be looking very closely to compare their ILD rates, what the outcomes are with the profile that we're generating. We haven't really seen much ILD so far, knock wood. I think in lung cancer and breast cancer where you have, You know, you have radiation to the chest, you have lobectomies, I think ILD can be problematic. I think that'll be a big point of differentiation as the data evolve and emerge.
Great. Maybe just before we move on, any particular tumor types beyond the core breast, lung, bladder, that are most advanced that you guys are most excited about or we should be keeping an eye on?
I think we'll show some at ASCO this year, we'll have some endometrial data that we'll be showing. We are exploring a number of other tumor types in some of our broader basket trials. As those data evolve, we'll start to share those data as they become available. Yeah, at ASCO, you should see some more data.
Great. Looking forward to that. Maybe just diverting away from oncology for a moment. Would love to hear more about GS-5245, the oral COVID drug.
Mm-hmm.
Obviously, COVID numbers are falling rapidly, so I'm curious your latest thinking on terms of enrollment timelines for this drug, how you're thinking about, you know, the peak potential here as we kind of enter the next stage of COVID's evolution, and whether or not you've sort of been able to get any clarity on the U.S. regulatory path for that program.
Sure. Yeah, the one thing I've learned is that I've been right all along, which is I can't predict where COVID is going. That's the one thing I'm sure of. In terms of how things are going for us, I think from a clinical trial standpoint, the trials are actually going fairly well, to your point, with the caveat that the numbers are falling globally and relatively, you know, it's become more quiescent. It's apparent that people are still getting symptomatic disease, in a variety of settings. Our trials are continuing. We'll update everyone on how, you know, when we expect those trials to be over. Those are, you know, we're moving along.
We continue to have ongoing dialogue with the regulators in the U.S. and outside the U.S. around the various indications. As you know, we're doing a standard risk as well as a high risk. The interactions have been very positive all along the way. I think most of us are grateful that we can do things like this, and the pandemic is allowing us to do things like this, and also very aware that we're one variant away, unfortunately, from things changing. I'm more optimistic in that I think with vaccination and with immunity evolving, that we are starting to settle into a new normal. You're still seeing numbers that are in excess of flu.
Maybe if I use influenza as a benchmark, if you will. We've had vaccines and therapeutics for influenza for decades now, and I think COVID will end up in some similar place where we still have higher numbers of hospitalizations from COVID now than we do from influenza. I do think there's gonna be a place for both therapeutics and vaccinations in the long run.
Yeah, that makes a lot of sense. Certainly good to be back in person after the past few years. This is our second year back in person. Maybe going back to oncology, you know, we're just a few weeks away from ASCO. On the TIGIT, can you talk a little bit more about what we might see with the latest cut of the TIGIT data at ASCO, just in terms of follow-up and patient numbers? I guess we've been curious what sort of response depth and durability that you think might be necessary to convincingly show that zimberelimab plus domvanalimab may be more active than the current standard of care PD-L1s.
Yeah. To your point, as we've discussed, I think with our partners at Arcus, the data we showed in December at the ASCO plenary was for the first 133 subjects that had been enrolled in the study. The update will have about 150 subjects now, so the full enrollment that was done back in August. You'll see both a higher number, but also then a longer follow-up, duration of follow-up. What we'll be looking for. Look, I think if you step back for a second, in non-small cell, as we were talking about earlier, the provable endpoint is OS. The meaningful endpoint in an early trial is gonna be PFS.
We are tracking that the most closely, and we'll be looking for a consistently improved PFS in patients who are getting treated with domvanalimab compared to single agent PD-1 inhibitors. I think that's the bar in many ways, and that gives us the guideposts for our phase III trials. We'll be using that as well as the external data that are coming in to make sure that our studies are designed and powered appropriately for what I believe will be the approval endpoint of OS in the long run. What we've seen so far certainly has really supported very well that we're seeing improved PFS, as we showed in December, and I, and I expect to be able to continue to demonstrate that.
Maybe one thing to add is, people should not expect OS data from a study of this size and duration at this point. It's far too early for us to be looking at OS. Those data will be very immature.
Got it. Then you sort of alluded to this, but just the read-throughs you might expect from other late-stage programs, beyond, I guess, in terms of shaping powering and what other sort of learnings you might take from those.
Yeah, I mean, we obviously remain very confident based on our own data and also the data we've seen from the competition. I know the pendulum's been swinging back and forth. For us, we've been very steady on this, based on both our data and our expectations of the data we'll see from Roche and others. My expectation is that we'll see those data read out. They've continued to start phase III trials. I think, you know, we should. Our confidence has been really steadfast.
Got it. What about magrolimab? What's the latest on how you're envisioning that drug fitting into Gilead's oncology portfolio? I guess with the interim MDS data potentially coming up in the back half of this year, I guess how should we be thinking about or how would you frame expectations there? You know, outside of hemonc, are you thinking, still thinking about solid tumors as an area of priority, or are you mostly focused on hemonc now?
A great question. For us, I really do think of hematology and solid tumors as slightly different, but with potential overlap. When I talk about hematology, it's really cell therapy and Magro are the two primary players in hematology for us right now. For magrolimab, as you mentioned, we have three trials ongoing, MDS and two AML trials that are ongoing. We do have another interim analysis coming up for the MDS trial this year.
Very much actually like the discussion we were just having on the non-small cell study. That study is powered for the final analysis, which I think we've been guided to being sometime next year. Our expectation, our base case expectation is that when the interim happens, that we will get an all clear to continue to go. And we'll proceed to the final analysis. There's always the upside, potentially, that we would get, you know, positive signal before that, before the final analysis, but that's not our base case assumption. And then for Magro and solid tumors, we have a number of trials, phase II studies that are ongoing in a variety of tumor types, looking for signals in solid tumors.
As those data evolve, we'll obviously share them and make some decisions as to whether there is the opportunity to expand Magro moving from the hematology into the solid tumor realm.
Okay. Maybe shifting gears from oncology back to infectious disease. Can you talk on lenacapavir, can you talk a little bit about the latest progress with regards to long-acting partners as you pursue HIV treatment? I guess what mechanisms you're most excited about? What treatment interval do you think would be, I guess, which is most realistic but also most transformative for patients?
Sure. Yeah. In, in treatment it, first of all, I think, we're really excited about the highly treatment experienced patient population. It's always the first approval that you need to get, and we're really glad that we were able to demonstrate the efficacy of lenacapavir in that setting. Importantly, I think that also validates our every six-month dosing regimen, right? That's the approval is for every six months SubQ. That's gonna be really important for us going forward, and it also gives us this time to really learn about that long-acting approach with practitioners to get them comfortable with lenacapavir in the long run. As you mentioned, we have a number of different combinations that are brewing, ranging from the broadly neutralizing antibodies to a variety of other molecules.
We have a number of mechanisms. I think the one that we continue to believe is probably the most exciting for us is the INSTIs. We have a number of candidates there. I think of it in two different realms. The first is for oral treatment, and the other is for parenteral. For the oral, we have, I believe there's three candidates right now that we're targeting weekly oral dosing in combination with lenacapavir, potentially longer. Then we have three or four, depending on whether you include the bNAb for the parenteral. I'm really excited about the INSTIs. We have a number of shots on goal there. The molecules look really great.
The key thing about that's different in a sense from what we're talking about in oncology is often you have mechanistic questions about whether a mechanism's gonna work in inflammation or in oncology. Here we know INSTIs and NUCs work, right? The key for us is really in early development, figuring out whether the PK is compatible and whether the tolerability is there, especially for an injectable drug to move forward. We should be able to learn that. I've said really basically over the next 12-18 months, we should start to see data from those, and that'll allow us to make some selections on what to combine with lenacapavir, both orally and parenterally.
Got it. What about lenacapavir for PrEP? You're studying the drug in several phase 3 studies in PrEP right now. Can you talk about how the studies are going? It sounded like there may have been an acceleration in enrollments. Might we see those data even before 2025? I guess what shapes your confidence here from a mechanistic standpoint, given your experience in animal models, but I guess balanced by the fact that you haven't necessarily directly tested for lena except for PrEP in humans.
Yeah. I think, yeah, first point is the one you made, which is, you know, the preclinical non-human primate data have been really predictive for every PrEP treatment there is out there, and that's really been rock solid for lenacapavir. We've been able to show prevention of transmission in all of those models. I think the treatment data also gives us a lot of confidence. This is the first capsid inhibitor that's been approved, right? It's a, it's a completely novel MOA, and I think that really complements the other existing MOAs that we're talking about in that sense. As you noted, I think our phase III trials for prevention are ongoing. We did have an acceleration of enrollment.
You know, these are very hard to predict, and I would caution that one study is 5,000 patients, the other is 3,500 patients. They are going to I think I would not change our expectations for the timelines at this point based on one quarter. We have to see how things go. We're really encouraged by what we're seeing in terms of the enrollment and the acceleration there.
How much do you think this could expand the PrEP market?
We think it's going to be a substantial increase. We really, you know, right now when you look at the PrEP market, it's really a fairly small proportion of people who are offered PrEP and take PrEP and are compliant long term with PrEP. Our mission has been to, you know, eradicate the epidemic, I think getting to a PrEP regimen that can really be broadly used and really doesn't have those issues about, for example, compliance, is going to be really important. If you can go in and get an injection two times a year, I mean, it's a game changer. We do believe that that should increase the uptake in the PrEP market pretty dramatically from, you know.
I would say, you know, right now we're under 50% to at least we're thinking we should be able to get to at least 50% of the market over time. We do think that it will be a game changer in the PrEP market.
On the cell therapy front, you guys have obviously had a lot of recent success in terms of broadening out and improving the infrastructure for delivery of CAR T, and really having leading manufacturing capabilities and then, you know, promising early stage data and moving into earlier lines. What's next for CAR T? Is it just kind of continuing to broaden out Yescarta into earlier and earlier lines? Is it about novel targets, allogeneic, bispecific, solid tumors? What's next and where do you think we can, like, feasibly go in the next two to four years with the CAR T franchise?
Look, I think we consider ourselves really at the vanguard of cell therapy, in large part driven by both our experience. I mean, we are really have been out there and continue to be very successful in terms of bringing the therapy to patients. Some of the longest OS data, we'll show more OS data this year at ASCO as well. Our manufacturing, as you say, really from a reliability standpoint allow us to really deliver the cells to patients in a very predictable way and have them get their treatments. I think that's been a really critical differentiator for us. Leveraging that more broadly is certainly part of our plan, right? I think that investment, in many ways shouldn't end with Yescarta and Tecartus.
We have a long way to go there, I think that's probably the most important thing. It remains the fact that most people who are eligible for cell therapy are not getting it offered to them. I think there's a real, you know, with the OS data, we're hoping and as people get more comfortable and experienced with using cell therapy for their patients, I do think that's. Just making that work is gonna be really important. Going from 20-ish% of people getting it to, you know, a much higher rate hopefully will be very important for cell therapy broadly. We do believe getting to earlier lines is gonna be important. We are investing in a variety of earlier assets, looking at everything from solid tumors to allogeneic.
As you pointed out, we're really excited about the Arcellx partnership that we've put together, I think in expanding into multiple myeloma. I think that's a key area of expansion for us. I think all the areas you noted, we're taking, I would describe them as measured approaches in that looking for clarity and clear data. These are high bars that we have in terms of making progress there, and we are really looking for those transformative therapies. We believe they're in the offing.
Autoimmune?
Autoimmune I think is more challenging. It's definitely something we think about a lot. You know, to me for autoimmune it's about therapeutic index, as well as the breadth of the population. I think getting into a broader autoimmune population really will require a very well-tolerated regimen, to get beyond a select population. I think it's really exciting that, you know, despite the fact that we've been treating with B-cell antibodies for a long time, that we're seeing really game-changing efficacy now.
Yeah.
It suggests that there's a, you know, it really shows that something's possible that I don't think we knew was possible before. I think that is, gives us incentive to keep trying.
Maybe in just the last minute, would love to hear kind of what's next in terms of the earlier stage programs. Where are people not focused, but you guys, maybe the street's not focused, but you guys are particularly excited. I know you announced a collaboration this week to expand the partnership with Arcus. Is autoimmune and inflammation sort of the next wave for Gilead, and what programs are you most excited about that we should be?
Yeah.
-keeping an eye on?
You know, we remain focused on our three key areas. I think we have excitement across all of those, right? I think in oncology, you saw the XinThera deal and our interest in the PARP inhibitor there. We have a CCR8 that I'm excited about moving that forward. I think in autoimmune we did MiroBio earlier. To your point, I think we have a number of additional programs. Our alpha-4 beta-7, our TYK2 program, again, very early. Then in virology we talked about our early stage pipeline. I think all of those are, you know, irons in the fire and I'm really excited about the portfolio we've built. I think there's a lot of potential there, and we should start seeing some of those play out.
I'm not, I'll never say that they're all going to work. We know how this business goes. Boy, some of the early data we're seeing and some of the targets we've got, I'm really excited about. I think we're gonna be able to be talking about phase III trials for those next time I'm here. Maybe not next time, maybe in a couple years.
Great. Well, Merdad, thanks again. Really terrific to catch up.
Pleasure. Thanks a lot.
Okay.