Gilead Sciences, Inc. (GILD) Presents at RBC Capital Markets Global Healthcare Conference (Transcript)
Gilead Sciences, Inc. (NASDAQ:GILD) RBC Capital Markets Global Healthcare Conference May 16, 2023 11:00 AM ET
Merdad Parsey – Chief Medical Officer
Conference Call Participants
Brian Abrahams – RBC Capital Markets
Good morning. I’m Brian Abrahams, one of the senior biotech analysts here at RBC Capital Markets, and welcome again. Our next presenting company is Gilead. Really pleased to have with us their Chief Medical Officer, Merdad Parsey. Merdad, thank you again.
Thanks. Thanks for having me.
Q – Brian Abrahams
So a lot to cover. So I want to kick it off. Maybe starting with the oncology portfolio and Trodelvy. You recently got approval for Trodelvy based on the TROPiCS — the positive TROPiCS-02 data. And 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 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?
And then, I guess, along those lines, I 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?
Yes, thanks. I think as we’ve said all along, we think the potential of Trodelvy for this idea of a pipeline and a product is really playing out nicely, 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 advisers and our KOLs out there. It’s early days. So I think it’s — we just launched recently, so it’s still early days. But so far, things are going really well. And the way we see it playing out is getting 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. And 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.
And then we have our ongoing lung cancer programs, all the EVOQUE trials that are ongoing. And those data should also be reading out as we’ve said, I think ’24 is going to be a very big year for us 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.
So I do think we’ll be able to go — and then maybe the last thing I’ll add before going on is 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 that as well.
Great. And maybe expanding a little bit more on lung cancer. Can you talk about your expectations for Trodelvy in that indication? Obviously, a large indication. There are other ADCs going after lung cancer. Where do you see the most differentiation for Trodelvy and any read-throughs that you’re going to be looking for from upcoming data we might see from other Trop-2 ADCs in later-stage development?
Yes. I think that the read-through for me is really this validation — further validation of the role of Trop-2 ADCs in lung cancer. We’re very optimistic. We’re — as I said, we’ll have our own data as well. And 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 to frontline PD-L1 high, we’re going to be looking at other populations as well, second-line in the EVOKE-01 study, we’ll be looking at PD-L1 lower patients. So, I think the read-through is really going to be the validation of Trop-2 in these tumor types.
The main point of differentiation as we go forward, look, 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. And 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 has 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. And 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, not one. And I think in lung cancer and breast cancer, where you have — you have radiation to the chest, you have lobectomies, I think ILD can be problematic. So I think that will be a big point of differentiation as the data evolve and emerge.
Great. Any — 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 trial. So as those data evolve, we’ll start to share those data as they become available. So yes, at ASCO, you should see some more data.
Great. Looking forward to that. Maybe just diverting away from oncology for a moment. I would love to hear more about 5245, the COVID — the oral COVID drug. Obviously, COVID numbers are falling rapidly. So I’m curious your latest thinking in terms of enrollment time lines for this drug? How you’re thinking about 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 around?
Yes. 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, it’s become more quiescence. And it’s apparent that people are still getting symptomatic disease in a variety of settings. So our trials are continuing. We’ll update everyone on how — when we expect those trials to be over. But those are — 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. And the interaction has 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. And 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. And so I do think there’s going to be a place for both therapeutics and vaccinations in the long run.
Yes, 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. And so maybe going back to oncology, 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 in patient numbers? And I guess we’ve been curious what sort of response, depth and durability that you think might be necessary to convincingly show that Zim plus Dom may be more active than the current standard of care PD-L1s?
Yes. So to your point, as we’ve discussed, I think, with our partners at Argus, the data we showed in December at the ASCO plenary was for the first 133 subjects that have been enrolled in the study. And the update will have about 150 subjects now. So the full enrollment that was done back in August. And so 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 meaningful endpoints are going to be the approval endpoint OS, the meaningful endpoint in an early trial is going to be PFS. And so we are tracking that the most closely, and we’ll be looking for consistently improved PFS in patients who are getting treated with Dom compared to single-agent PD-1 inhibitors.
I think that’s the bar in many ways, and that should be — gives us the guidepost 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.
But 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 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. And 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?
Yes. We’re — 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 has 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 readouts. They’ve continued to start Phase III trials. I think we should — our confidence has been really, really steadfast.
Got it. What about magrolimab? What’s the latest on how you’re envisioning that drug fitting into the Gilead’s oncology portfolio? I guess with the interim MBS data potentially coming up in the back half of this year, how should we be thinking about — how would you frame expectations there? And then outside of Heme/Onc, are you thinking — still thinking about solid tumors as an area of priority? Or are you mostly focused on Heme/Onc?
Great question. So for us, I really do think of hematology and solid tumor is slightly different, but with the 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 — we’ve guided to being sometime next year. Our expectation — our base case expectation is that when the interim happens, that we will get in to continue to go, and we’ll proceed to the final analysis. There’s always the upside potentially that we would get a positive signal before that — before the final analysis, but that’s not our base case assumption.
And then for magro in solid tumors, we have a number of trials, Phase II studies that are ongoing in a variety of tumor types looking for signals in small — sorry, in solid tumors. And 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. And then 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? And 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. Yes. In treatment, 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 month subcu. That’s going to 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. And we have a number of mechanisms. I think the one that we continue to believe is probably the most exciting for us is the
We have a number of candidates there. And 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 are three candidates right now that we’re targeting weekly oral dosing in combination with lenacapavir, potentially longer. And then we have three or four depending on whether you include the parenteral.
And I’m really excited about the — 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 is going to work in inflammation or in oncology.
Here, we know studies in nukes work, right? So the key for us is really in early development and figuring out whether the PK is compatible and whether the tolerability is there, especially for an injectable drug to move forward. So we should be able to learn that. I’ve said really basically over the next 12 to 18 months, we should start to see data from those. And that will allow us to make some selections on what combined with lenacapavir, both orally and parenterally.
Got it. And then what about lenacapavir for PrEP, you’re studying the drug in several Phase III studies in PrEP right now. Can you talk about how the studies are going? It sounded like there may be an acceleration in enrollments. 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 lenacapavir for humans.
Yes. So I think, yes, first point is the one you made, which is 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 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. These are very hard to predict. And I would caution that one study is 5,000 patients, the other is 3,500 patients. So they are going to — I think, I would not change our expectations for the time line at this point based on one quarter. We have to see how things go. But we’re really encouraged by what we’re seeing in terms of the enrollment of 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 — 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 eradicate the epidemic. And 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 twice a year, I mean it’s a game changer. And so we do believe that, that should increase the uptake in the PrEP market pretty dramatically from I would say, 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. So 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 the — and improving the infrastructure for delivery of CAR-T and really having leading manufacturing capabilities and then 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, bicistronic, 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?
Yes. 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 — have been out there and continue to be very successful in terms of bringing the therapy to patients. So the longest OS data will show more OS data this year at ASCO as well. So — and 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. And 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. And 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.
And I think there’s a real — with the OS data, we’re hoping and as people get more comfortable and experience with using cell therapy for their patients, I do think that there’s — that’s just making that work is going to be really important going from 20-ish percent of people getting it to a much higher rate, hopefully, will be very important for cell therapy broadly.
We do believe getting to earlier lines is going to be important. And 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. But 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, but we believe they’re in the offing.
Autoimmune, I think, is more challenging. It’s definitely something we think about a lot. 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. So — and I think it’s really exciting that 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. It suggests that there’s — it really shows that something is possible that I don’t think we knew was possible before. So I think that is — gives us incentive to keep trying.
Maybe in just the last minute, I’d love to hear kind of what’s next in terms of the earlier-stage programs? Where are people not focused, but that you guys — maybe the Street is 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
Yes. We remain focused on our three key areas, and I think we have excitement across all of those. I think in oncology, you saw the Zenthera deal and our interest in the PARP inhibitor there. We have a CCRA that excited about, moving that forward. I think in autoimmune, we did MiraBio earlier. To your point, I think we have a number of additional programs, our Alpha 4 beta 7, our program. Again, very early. And then in virology, we talked about our early-stage pipeline. I think all of those are 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 are going in work. We know how this business goes. But boy, some of the early data we’re seeing and some of the targets we’ve got, I’m really excited about it. I think we’re going to be able to be talking about Phase III trials for those next time I’m here, maybe not next time, maybe in a couple of years.
Great. Well, Merdad, thanks again. Really terrific to catch up.
Pleasure. Thanks a lot.