Great. Good morning, everybody, and thank you for joining us for this next session with Gilead. On behalf of SVB Securities, I'm very pleased to host Merdad Parsey from the company to discuss the company's pipeline prospects. Merdad, it would be great for you to maybe just comment at a, you know, very briefly at a high level about the position you see Gilead in today versus, you know, obviously where it was even just nine- 12 months ago.
Sure. Sure. Thanks, David, and thanks for, thanks for the invitation. Happy to. Look, maybe I'll go back a little bit farther than nine-12 months ago. You know, when I joined, it's been just over three years now, we set out on a course of really adapting our pipeline and really building Gilead into a company that was going to be sustainable for the long run. Really building on the strength of our HIV and virology pipeline and portfolio, but really growing into oncology in particular, as well as building out our inflammation pipeline. Over that time, I think we've moved very aggressively to build our pipeline out. As you know, with acquisitions, in addition to our internal work.
That spans everything from remdesivir in virology to TRODELVY in oncology. We're really happy with where we are right now, with a lot of potential for additional growth over the near term or the near to mid-term. I would say, you know, we do continue to have a goal to try to build the pipeline out to be a truly sustainable pipeline for the long term. I'd say we're midway through that journey, and hope to keep building the portfolio out over time. Yeah.
That's great.
We can dive into whatever part of that you wanna talk through.
Great. Well, let's just pivot to specific products. It would be great to try to cover a lot of ground. It'd be helpful for you to talk about what you see as being underappreciated about TRODELVY, including the event path ahead that could bring Wall Street views closer to Gilead's views of its prospects.
Sure. Look, I think TRODELVY, we're really excited about where we are with TRODELVY over the past couple of years now. you know, we've built on the initial approvals in triple-negative and the accelerated approval in bladder, which I think is underappreciated with now the HR+, HER2-negative approval that we have. It really speaks to where we believe we're gonna go. First of all, I think the value or by value, I mean the benefit it brings to patients really is emphasized by the NCCN guideline update that we just got recently, where we're now Category one. I think that really speaks to the importance of TRODELVY in the treatment paradigm for people with breast cancer. I think that's a very important piece of it.
The other part I think that's underappreciated is our underlying strategy from the get-go, which was very much two key things. One is to expand the number of indications we're in, and the second is to go into earlier lines of the indications we already have approvals. Both of those things are underway. As we move into studies to look at earlier lines in triple-negative and HR+, HER2-negative and bladder cancer, those are all moving along. We are also expanding into non-small cell lung cancer, probably the most important part of our expansion for TRODELVY.
I think someplace where we feel very confident around where we're headed, given the validation of Trop-2, I believe in lung cancer as well as what I hope will be a differentiated profile for TRODELVY in this space. Then we are exploring additional indications. You know, I think probably the biggest thing is when you work with a molecule that has this sort of breadth of activity, it's clearly an active molecule that works across a number of tumor types. Our obligation is to identify the broad potential for a molecule like this and really to look for additional indications. So we have a number of exploratory earlier studies ongoing to identify additional areas where we can expand TRODELVY.
You know, the trajectory from a revenue standpoint in 2022 is, we're really excited about. I mean, clearly the uptake is going well, we really think there's only upside at this point.
Excellent. Let's talk about non-small cell lung cancer. If you could compare and contrast TRODELVY with AstraZeneca's Trop-2, that would be helpful. Also, compare and contrast EVOKE-01 versus AstraZeneca's TROPION-Lung01 trials.
Sure. Well, I think it's a great point where, I think it's very important to talk about the similarity in the sense of, you know, look, ADCs in the treatment of oncology have struggled outside of the initial first few ADCs. We've all worked on ADCs for a long time, I think the AZ molecule and ours, I think we're really seeing a new emphasis on the potential for ADCs. They are different, right? They are different in that there are three pieces to each ADC. There's the antibody, over time, we've all gotten used to talking about the differences between, say, PD1 inhibitors or antibodies directed against TNFs and the subtle differences between them.
Here now you have to add the complexity of the linker and the payload. The linker is different between ours and the competition. We have a hydrolyzable linker, and theirs is more of a protease-dependent linker. We believe that the effect of the hydrolyzable linker and having the payload available is part of what gives us that sort of zonal effect of tumor killing. I think that might be important in the long run. Our payload is what I would describe as a more moderately toxic payload. It's an irinotecan derivative as opposed to an exatecan derivative which can be more potent.
I would expect that we will see as you see in other therapeutics, a bit of difference in terms of our overall efficacy and safety profile over time. Where we think, where we're excited, as I mentioned earlier about the lung approach, we are excited in that in lung, our data so far, we have not seen, for example, on the safety side, a lot of ILD, any ILD at this point. I think that could become important, especially in patients with lung cancer who may have irradiation to the chest. They've had lobectomies. That could be one of those differences in the constructs of the antibody-drug conjugates that could play out in the long run in terms of nuanced differences.
From a side effect profile, that's another place where you see a bit of a difference. Ours, I mentioned the ILD, and then ours are really neutropenia and diarrhea. Those are better, you know, more typical adverse events that oncologists are pretty used to managing. They're fairly predictable and manageable with things like dose reductions or things like that. Whereas ILD can be a bit more challenging given the sporadic nature of the ILD, and it's something that folks aren't really used to tracking. I think those are potential differences that we'll have to watch over time as our data evolve in multiple tumor types and especially in lung cancer. I think you asked just to follow up on that, the differences in our trials.
There are a lot of similarities in our trials. Both of our trials We're roughly the same size in terms of sample size. They are, excuse me, essentially, very comparable patient populations. We do have some differences in terms of the patient population, in terms of how we think about it. Similarities, we both are looking at comparisons with docetaxel in the second line plus population, and we are looking at people who have had platinum and PD-1 inhibitors in the past. Those are some similarities. In terms of differences, we are looking at stage four only, and theirs are looking at 3L/4L patients.
The other I would say difference is that they're excluding patients with a history of ILD and pneumonitis, and we don't exclude those. Both trials are ongoing. You know, we'll just have to see how the data play out. I think we're on the right track there.
Got it. Okay. That's very helpful context. Great. Pivoting to TIGIT. There's obviously a lot of debate in the market about TIGIT, given questions about how much efficacy it can really add and how helpful it can be in combination. Could you just comment on that and just highlight your combo development plans and next cards to turn over?
Sure. Yeah, look, we're really excited. The data we presented at the ASCO plenary, and we're looking forward to updating at ASCO in May, ASCO 2023 in May, I think really answer the key question that we asked in the design of that trial, which is does TIGIT add to a PD-1 inhibitor in patients with non-small cell lung cancer?
You know, what we see there is that, you know, the PFS improvement with a hazard ratio of 0.55-0.6, depending on which cohort you're looking at, as well as the absolute PFS itself of 10-12 months PFS in an ongoing data set where we expect those numbers to mature over time, really, I think answer the question that TIGIT does really add to a PD-1 inhibitor. That's consistent with the public data so far. It's also the biggest data set that's been made public by anyone to date.
We have a lot of confidence based on our own data and watching these data mature over time and about the ability of TIGIT to really be an important next next generation immuno-oncology agent. Obviously, there are other data pieces that have to come together. You know, there's going to be additional readouts. I do think that people have paid attention to the Roche announcements in a way that I think, from my perspective, probably a bit of an overreaction to their not stopping the study or not announcing their data. As with most phase III trials, we all build in interim analyses in our studies for two reasons.
For safety, but also to see if you have a much larger effect on your treatment effect than you had initially planned for. You really only power the study for the endpoint at the final analysis, the overall survival at the end of the analysis. That's how our study is gonna be designed, and that's how we design all of our studies, and that's how Roche designs their studies. It would have taken an outsized impact for them to be able to stop the study and announce positive data. They're not gonna spend a lot of alpha on an interim analysis, nor should they, nor will we, nor should we.
We power to make the study as large enough to get to a statistically significant outcome at the end of the trial, and no bigger because we wanna go as fast as we can. Those interim analyses can be helpful, but I don't read too much into them when the studies continue.
Excellent. That's very helpful. Turning to the pipeline for cell therapy, could you talk about the steps you're taking to retain your leadership position, particularly as, you know, new technologies will be entering, such as Galapagos's program?
Sure. You know, I think, I like where you started. You know, we really feel that Kite has really demonstrated that it's the leader in cell therapy. The ability to provide treatment to patients 96% of the time, the ability to manufacture reliably, and the durable responses that have been shown time and again now over five years after treatment, I think really establish that primary position if you will, in terms of where we are as an organization with cell therapy.
You know, I remember a year or two ago, I think the question was always, "Well, what are you gonna do about Allo?" Unfortunately for patients, I think, we've not seen that area develop the way people initially thought. I think it's going to be harder than people thought. I think providing the treatment approach that we have now with the CAR T technology that Kite has, and really working to optimize the delivery time, both in terms of reliability and in terms of being able to get the cells back to patients as quickly as possible, reduce the need if you will, of off the shelf.
If you can turn around and, you know, apheresis and then treat a patient quickly, with what I'll call standard CAR T therapies right now, the value of being able to get to allogeneic is reduced, not eliminated, but reduced. Now, of course, we are really focused on what's going to come in cell therapy, and we believe that given our position, a lot of people seek out and work with us, and we have a lot of partnerships, and we keep a very close eye on where things are headed in cell therapy. We are constantly looking at that next generation of work. As you know, as you mentioned, a good example is Galapagos. Galapagos remains a partner of ours.
We continue to have options on the programs that come out of Galapagos. We will stay close to the Galapagos team, and as that evolves, if that becomes something that we believe will bring value to patients, it'll definitely be something that we will bring into our armamentarium to help with cell therapy. In the meantime, with the deals you've seen Kite make more recently with the BCMA agent, as well as the armored CARs, I think all of those things are evidence, I think that we continue to work to innovate in the space and look for new opportunities to bring our expertise, our manufacturing prowess and expertise to the evolving landscape in cell therapy. We're really excited about where we're headed there.
Excellent. Thank you for all of that color. Let me just glance at the time here. I wanna make sure we cover as much ground as possible. Why don't I just ask you to touch on magrolimab quickly? I mean, obviously the data at ASCO last year was encouraging in terms of efficacy, obviously, you know, the toxicity needs to continue to be managed carefully. Could you just discuss how you see magrolimab with respect to its opportunity, news flow ahead, and then how you see it potentially being positioned longer term versus next generation CD47 bispecifics?
Sure. Yeah, look, I think magro remains one of those areas where it's one of those pipeline products that we acquired in the past few years and are looking for its maturation and hopefully contribution. I always think of CD47 in two buckets, solid tumors and Heme. Heme is obviously we're far out ahead, those phase III trials are ongoing. We'll look forward to the readouts of those studies as they mature over time. As you know, we have another interim coming up this year that, as we were talking about earlier, you know, we'd have to see a big signal into to unblind, we are on pace to get to our event-driven outcome next year.
I think the potential in MDS and in AML remain sort of the cornerstone. We're, you know, we're far out in front there. I think we are leading the pack. You know, in this business, I think co-competition is the name of the game. The days of being, you know, the only player are far behind us. We're really happy with where we are from a timing standpoint in terms of the maturation of those studies and our ability to get to that answer before anyone else. In terms of solid tumors, we have four ongoing phase II trials that are fairly far along.
They're, you know, I think, as you mentioned, there are a number of folks who are dabbling in the in the solid tumor space as well with CD47. I think we're all looking to see proof of concept there, us included. We're really happy with how far ahead we are in the breadth of our programs, there to really suss out things like which combinations could potentially be the best, and which tumor types we expect to see that efficacy most likely. You know, I think we are far ahead. It's too soon, honestly, with other agents, especially the bispecifics to really see how they're going to play out. We certainly think we're very far ahead.
Then in terms of safety, I think it's a great point to hit on and remember that we actually, the company 47 actually patented the dosing approach that we take. We believe that the anemia that you get with the CD47 really has to do with those senescent red blood cells, and it's a on target effect. So we have our dosing paradigm built in a way to minimize that adverse event with an initial low dose, and then we're able to escalate our doses over time to get to, you know, better tolerability.
I think that's gonna be key to finding the right therapeutic index, if you will, the right window of treatment to mitigate the effect, the on target effect for the red blood cells while getting to maximum efficacy. We're really excited about where we are.
Excellent. Okay, great. Let's do a little bit more of a, sort of rapid fire on some of your other key programs. With respect to your oral COVID, treatment, you know, Pfizer's claimed that no other company will be able to compete with PAXLOVID's label because they were able to show high efficacy during, you know, the peak pandemic period. Could you discuss, your strategy to demonstrate compelling efficacy and comment on Pfizer's statement?
Yeah. Look, I think it is true that the pandemic has changed dramatically. Certainly it's difficult for me. From the outset with remdesivir, we tried not to predict where the pandemic was gonna go, and I certainly wouldn't try to do that today. It is certainly more difficult. I completely agree that it's much more difficult to conduct trials today than it was during the height of the pandemic when there were no other alternatives. What we've done is we've initiated the two trials that we're moving on with. We have a lot of confidence in the ability of 5245 to demonstrate activity in that, it is based on similar MOA as remdesivir, highly validated.
We know it's effective, and so we expect it to be highly efficacious. The challenge will be finding in the two trials, high-risk patients and what are called standard risk patients. I would be the first to acknowledge there's gonna be a challenge there, both in terms of recruiting those patients and then the severity of illness that we've seen with the newer variants. I think a couple of things are also true. One, that the pandemic will continue to evolve. PAXLOVID does have limitations in terms of the patient population that we know, right? It has a booster. There are patients with drug-drug interactions who can't take PAXLOVID.
Of course, as with any viral infection and any treatment for viral infection, resistance is, you know, over time is a possibility. We believe that having another mechanism of action available for patients should the pandemic shift over time, is going to be important from a public health standpoint, if nothing else. We will do our best to move that program forward for both standard risk and high-risk patients, as quickly as possible. The vagaries of the pandemic will be something we'll have to manage over time.
In terms of the design of those studies, how large are they?
They're, you know, both fairly big. I'm just gonna look up real quick the sample size. For our high-risk study, it's about 2,300, and for our standard risk study, it's about 1,900 subjects that are gonna be enrolled. Those are all both based on assumptions that we've made around the event rates that are gonna occur, right? In the high-risk patient population, we're looking for hospitalization, mortality, the usual, very similar in a sense to that high-risk population that's been studied in the past. In the standard risk, we're looking to alleviation of symptoms, the time to alleviation of symptoms.
Because we've had to make a number of assumptions about the event rates there based on, again, where the pandemic's going, we will, over time, have interim analyses that will check to see if the event rates are where we thought they'd be, higher than what we thought they'd be, or lower than we thought they'd be. We can adapt the trials, the sample size, based on what we see in terms of event rates. We've tried to both move very aggressively forward because we think it's critical to be there. You can't predict when you're gonna need it.
We've established sites globally to be able to capture, if there are new outbreaks, so we can capture patients, should they appear, and to adapt the studies, based on what's actually happening on the ground.
Okay. If, and if I might push back, I don't understand why the company isn't spending triple and enrolling 5x the number of patients you just described, given the fact that it would be, if successful, at least a $5 billion product annually. Meaning it seems like a no-brainer to me, given Gilead's expertise in virology, given Gilead's presence globally, that the company should be spending dramatically more money given the revenue opportunity. I mean, we can see it in PAXLOVID. Now, granted, PAXLOVID is collapsing, but could you just help me understand that better?
Yeah.
Why we're going so small with those counts? I'm surprised that, you know, you mentioned 2,300 for high risk and 1,900 for standard risk.
Yeah. The answer is we will if we need to. I think those sample sizes are based, as I said, on an assumption of what the, what the event rate's going to be and how much of a treatment effect we're going to have. If the event rate is lower or we think we have a good idea what the, what the treatment effect size will be, if we need to expand those studies, we will. That has to be balanced with trying to get it done as quickly as possible. You know, we're gonna do the study that will get us to approval as quickly as possible in the appropriate sample size. If we need to go bigger, we'll go bigger.
Okay. Thank you.
Yeah.
Why don't we pivot to the lenacapavir combo development. It would be helpful, and I know that you have many, many molecules in development, but it'd be helpful for you to educate us on how close you are to a drug with islatravir-like efficacy, and dosing frequency.
Yeah. We have 10 different molecules, both in the oral space as well as in the parenteral space, the injectable space. We will be seeing data starting to roll out as early as this year. We'll be presenting data at CROI coming up, gosh, I think it's next week, on our bNAb combinations, the broadly neutralizing antibody combinations with lenacapavir. That's one of our efforts. I would say that's the one we felt we could go most quickly with. We then have all the small molecule approaches that we have. What will happen, what you'll see evolve over time, is we will be looking at the PK of those molecules and the tolerability of those molecules.
As we get that information, we can move very quickly then into the appropriate trials in combination with those. We should see those data rolling out really fairly soon. I think over the next year to two, we'll see a lot of data. Our goal is to provide, I think, a meaningfully an important durability of those treatments. We believe that getting to three months, if not six months of parenteral treatment is really critical to being bringing something to patients, people living with HIV that will matter and make a difference, and that it's tolerable. That's our objective. Looking at the characteristics of those molecules, both in terms of durability and tolerability, is gonna be critical in choosing the right molecule.
We hope to have a lot to choose from. We'll choose the ones with the best characteristics to move forward with.
Got it. Excellent. Okay. One final question. Gilead has a number of inflammation programs that are progressing. Could you just frame those for us and what, you know, the key candidates are to watch over the next year or two?
Yeah. I think as we've said for a long time, you know, with our inflammation group is young but mighty, and we're really looking to build that portfolio out over time. It is an early portfolio, but we really are excited about things like we have an oral α4β7 program. We have an IRAK4 program. We have a TYK2 program. All of those are in early days and will be moving into phase II studies here in the next year or two. Those studies will, as we design them and share them with folks, we'll be you'll see the timing of rolling those out. We'll be looking at a broad array of indications, obviously from IBD to other inflammatory indications.
We're really excited about our portfolio. We're really looking to bring, you know, first and best in class, differentiate molecules there, in the long run. Obviously they're also potentially looking at combinations as we get to trying to move the needle on improved efficacy and tolerability for those molecules. Early, but very exciting portfolio. We'll update you as those studies get underway and we expect to see data.
Wonderful. That's great. You saw me typing away. We covered a lot of ground.
Yeah.
It's been super helpful. Really appreciate you taking the time out of your schedule to be with us.
Absolutely. My pleasure. Thanks a lot, David.
All right. Have a great rest of the week.
You too. Bye.