I am very happy to have up here with us, Chief Medical Officer of Gilead, Merdad Parsey. It's great to have you, with us, fresh off of four or five days of ASCO.
Yeah.
So lots to talk about. Maybe just opening up for Gilead, I'd love to just have your view of the world about where Gilead's sort of R&D pipeline is today, because I would say, to be fair, and not only my reports, but others, there's been a lot of commentary around the development in oncology, and some of the other acquisitions, oncology or not. And so people are wondering whether Gilead is on the right track on the R&D pipeline. Maybe just describe maybe the two or three key points that you see about it to be excited, that maybe the Street has not seen, and to address some of that sort of criticism.
Great. Thanks, thanks, for having me. Great question.
Yeah.
Thanks for opening that way, 'cause I think that is very helpful. I do think that there's been a lot of a lot of chatter, and I think, you know, from our perspective, people are kind of missing, I think, the broader story, right?
Okay.
And for me, and the way I think about it, and the way I would encourage others to think about it, we are, you know, we are building a company, right? We're building a company, and we're... The core of our business remains our HIV business. Has been and will continue to be for the foreseeable future, and I think our HIV pipeline, our current assets in our pipeline, are best in the industry-
Yes.
I think we're hitting on all cylinders there, and I'm very excited about that.
Definitely no criticism on HIV.
Yeah.
Yep.
And I think people, that's, to me, I think, a huge part of the bigger picture. I and then what I would add is then in oncology, we're growing. We're building. We're growing. Cell therapy aside, I think we're building a portfolio, and I and, as you, when you do so, you have, you know, some wins and losses, but overall, I think we're I'm very happy with the direction we're headed, and we can talk about that more in a second. And then in inflammation, we just added seladelpar, and I think that's another, addition to our portfolio. Our goal has been to diversify-
Mm-hmm.
Right? To be HIV plus, and by adding inflammation assets, adding oncology, it's a very challenging and difficult thing to do. Many have tried, and it's a difficult thing. We're about 3.5 years into our oncology journey. We're a very young oncology company with what I would describe as a very early pipeline, but I'm really proud of how much we've diversified and where our agents are. I think if you look across our oncology pipeline, I think with Trodelvy, look, we had a hazard ratio of 0.51 in triple-negative. That's meaningful, and I think that's been really impactful. We are adding to the story for Trodelvy. The story's not over. We have a lot of data that we're generating and coming up, and so I think that's really great, and we have a number of things in the pipeline behind that.
Okay.
I'm really happy with where we are-
Okay
... and where we're headed.
Let's kind of break down some of those oncology areas, since we did come away from ASCO.
Yeah.
Just first, obviously the most important, I'd say, a driver outside of cell therapy-
Mm-hmm
... Trodelvy. And so Trodelvy is growing, obviously, in its approved indications as well, ramping in HR-positive breast cancer.
Mm-hmm.
But there were two slipups. One was in lung cancer, which we'll talk briefly about, and then bladder cancer. I don't want to spend too much time on that, but also in breast cancer, you have some data coming, but there's also competition.
Mm-hmm.
So, talk about how you see Trodelvy growing over the next five years, because Wall Street sees either that lung cancer was a slipup-
Mm-hmm
... came down, and I think-
Sure
... there's a write-down on that. Then in breast cancer, there are competitors coming, Daiichi Sankyo, et cetera, et cetera.
Mm-hmm.
How do you grow over the next few years in that? Because people see competition.
Yeah. Thanks. Yeah, so I'd start by saying, you know, we are still the only Trop-2 ADC that's approved, and people are, you know, fortunately, competition is always good and are gonna drive us, but I'm really glad we have that.
It's actually true. It's not 100% that Daiichi will be approved later this year. So -
No comment.
Yeah.
Yeah.
Sure.
So I think, I think that's, that's key. Yeah, look, and I think, what I would say has been consistent across Trodelvy is that in every study we've done, there's activity. We've, we've seen good activity. Second-line lung is a really difficult space. You look at our data, hazard ratio of 0.83, it's, it, while it didn't hit what we were hoping to hit, there's clear benefit in a lot of patients, and the tolerability profile there looks, you know, and you look down the AE tables, and we have fewer AEs on the, on, the Trodelvy arm than, than in docetaxel.
If I look at the aggregate data for lung and where we're headed for lung, the frontline study, which is our EVOKE-03 study, I think we feel a lot of, you know, wind behind our sails in some ways because the EVOKE-01 data-
Yep
... clear activity.
Yep.
EVOKE-02 data-
Yep
... which we showed, you know, last year when we showed the ORR data at World Lung, the caution we gave is, you know, you combine chemo with pembro, you're gonna get high ORRs. We're excited about them, but we need to see it translated into PFS and OS. And with the caveat that it's a small data set, the PFS data we showed at ASCO Monday-
Yeah
... really give us a lot of, you know, optimism in that we showed a PFS of over 13 months.
And what would you expect for PD-1 alone or chemo combo? Do you know what I mean?
Yeah, that's a great question. I think, the PD-1 alone in the-
Yeah
... in this area, and PD-1 with chemo combo, the PFSs are in the eight, nine month-
Okay
- kind of range.
You're what, what number you're at?
We're 13+.
Thirteen, okay.
Right? We're a bit over 13 months. And I think this issue about chemo combos-
Yes
in front-line lung is-
Yes
An interesting one, in that, it is part of the practice pattern to use either pembro monotherapy or pembro plus chemo. Appropriately, I think a lot of folks use that. And what you see is, when you add chemo to pembro in the front line, you do get better response rates early, but you don't seem to get much of a PFS or OS benefit.
That is, that is fair. That is fair.
Right.
So, number one is, you believe that the opportunity for Trodelvy in lung cancer is greater than expected because you will work Trodelvy plus PD-1, and you should beat PD-1 alone in the EVOKE-03 study.
I'm not sure greater than expected, because I don't know what your expectations are. We-
Well, expectations on Wall Street are very modest-
But we are, yeah-
You clearly are confident that that's going to work.
But we are, we think we're on the right track-
Yeah
... right? Is what I'm-
Based on the EVOKE-02 data at ASCO.
That's right.
Showed 60-something% response rates.
That's right. 60, about 67%.
Higher than chemo combo.
Exactly, about-
PFS, 13 months, higher than chemo combo.
Chemo combo, exactly.
Actually, your point was that the response rates are higher than chemo combo already, but theirs, their response rates are higher than monotherapy.
Mm-hmm.
But that did not lead to a PFS benefit, despite the fact that doctors insist on using chemo combo, which is my view.
Yeah.
I know you guys sort of-
Yeah
... say, "No, people do use monotherapy.
It's a mix. It's in the-
You know-
It's a mix, but-
Your point is, you think you're better than chemo combo anyway, so.
I think if we can show... What I hope we can show is an improvement in PFS and OS.
Yeah.
That's the bar. I think that has a lot of potential for us in the long run.
Okay. When would that data EVOKE-03, first-line lung cancer readout?
Yeah, the study's enrolling really well. We've pointed to 2025+.
Okay, plus, okay.
... for that. It'll probably be a little bit later than 2025, but it all-
Okay
... depends on enrollment. It's going very well. Remember, that's-
It's PFS endpoint?
OS endpoint.
OS endpoint.
and that is a study-
Mm
... we're doing together with Merck in combination with pembro. They're actually running the study, and so and they're doing an amazing job executing it.
I'm gonna ask
Great, great partner.
The only wild card there, then, is what I would see is that PFS and OS in lung cancer don't always perfectly translate from ORR.
That's correct.
Certainly in breast cancer as well. We learn-
Yeah
... we know that. And so despite the fact that you have higher ORR, and you just pointed to me that-
Yes
... chemo combo did not show higher PFS or OS than just monotherapy, and so the same thing would apply to you, unless there's some magic science that-
I don't believe in magic science. It's faith-based science.
That Trodelvy-
Yeah
... will add a PFS benefit.
Yeah, we're. So I think, let me tease that apart a little bit.
Yeah.
I think you're absolutely right in breast cancer, that,
Yeah
... PFS ends up being the endpoint precisely because it's difficult to translate into OS. Because in breast cancer, the survival times tend to be longer-
Mm
... and there's a lot more crossover post-study.
Okay, many different drug options.
In many-
Okay, yeah.
What you see in general, in early-line lung, breast cancers in particular, is a focus on PFS as an endpoint. PFS does not always predict OS, usually because there's more noise in the OS signal.
Okay.
By contrast, in lung cancer, the PFS does-
Okay
... predict the OS much better, and so there is a little bit of a dichotomy there in terms of those two endpoints.
Okay. And so we will lean on a better durability of the response, higher responses, better durability, and the PFS data you have shown and will continue to follow.
Yeah.
Uh, yeah.
We think all those things support our phase III trial.
And to be clear for those, because this is the same debate with TIGIT, that-
Yeah
... the magnitude of the result will also be better cross-trial comparison than KEYNOTE-189, because everyone just says, "Everybody uses chemo combo, Merdad." So even though-
Yeah
... you're saying you're beating PD-1 and chemo combo is not the control arm, you're gonna be better than that cross-trial.
We recognize that we need to demonstrate-
Okay
... a better PFS and a better OS.
For commercial uptake in those settings.
Well, for patients, right? I think we need to make sure we're-
Okay
... we're bringing something for patients.
So that's one, is lung cancer. Other competitors are going there, too, but you are-
Mm-hmm
... you are, you're running that study, and that's... What about in breast cancer? One of the things that has come up is that in HR-positive breast cancer, you see Trodelvy growing, but Daiichi says, "Hey, we have ultra-low HER2 now-
Mm-hmm
... coming out of ASCO this weekend. And that's, I saw their slide, expanding more across all. They had one of the discussers like, "Why do we even need to test for HER2? Just use it in everybody.
Yeah.
I would be interested in your response there, because that would be impinging on your market. And then too, is that Daiichi Astra are also running a Trop-2 first-line triple-negative.
Mm-hmm.
Your results coming. We actually got a lot of questions from clients, this week about when that data's coming-
Mm-hmm
... because they're also reporting. So HR-positive, where-
Yeah
... they're coming in on ultra-low and also triple-negative.
Let's separate the two.
Yeah.
So for HR-positive, look, I think Enhertu is a great drug. It's bringing a tremendous value to women with breast cancer, men and women with breast cancer, and it's showing something great. And I think it's important to recognize that we're different targets, right? We're going after Trop-2, they're going after HER2. And while there is overlap between those populations, there is also, there are also places where there is no overlap. And I think in triple-negative in particular-
Yeah
... where we talked about, I think those patients are going to benefit from Trodelvy, and that's where we believe we're bringing a huge amount of benefit. And in HR-positive, it's difficult to suggest that patients wouldn't be better served by getting Trodelvy when they're HR, you know, when they're HER2 diagnosis-
Zero.
Is a 0.
Certainly a 0, yeah.
It certainly seems that that's the case, and I think it's challenging for us to know how to translate the ultra low into practice today. I think you heard that from the discussant as well. And so, look, at the end of the day, these both are gonna bring benefit to patients, and I think in the HR low population, I certainly have more confidence that Trodelvy will bring that back.
I would say that, and certainly again, reflective of what is, there's already represented in the stock and the valuation-
Mm
... that Enhertu-
Mm
Will be a, a commonly used drug in that setting. Yes, it may or may not be used in front of Trodelvy, but it's a different target. It's not the same target, so go ahead and use Enhertu. Trodelvy could be your next option. Anyways, one of the questions come up is whether there is going to be, and I'm sure someone's looking at this, evidence to look at whether there is impact on Trop-2 use and efficacy, both not only with yours, but also with, Daiichi's. And I can't remember if the mechanism is exact same, but people have talked about cross resistance-
Mm
... off of Enhertu. So because of the chemo that's on or the toxin off Enhertu, does following that then with, Trop-2-
Mm
... because of the toxin, have some overlap in terms of the mechanism as it relates to the way this... You've heard about this?
Yeah.
Yeah, so.
Yeah, it's a hypothetical. I think it's difficult to know. I don't think there are any data, clinical data, and certainly we've seen that because SN-38 is a different payload than what either Daiichi brings or in-
Yeah
... in either case-
Yeah
... I think we feel comfortable. And we're seeing a lot of sequential use, and we're studying.
Yeah.
You know, so I think it's right now I'm not sure there's a... It's something to think about, but I don't think there's any data to worry about that. Should we talk about-
So, I wanna talk about triple negative.
I was gonna-
Triple negative-
I was gonna answer triple-negative.
... phase III, first-line data coming possibly later this year.
That's right.
Apparently, in the recent last earnings call, you said you could file it or whatever, but talk about when first-line triple-negative data is coming. And do you expect to be better, or how do I compare and contrast that? Because AstraZeneca will also have phase III data, same setting.
Yeah. So look, I think, yes, to your point, ASCENT-03 is our-
ASCENT-03, yep
... first-line. We have two first-line studies going on. One is in the PD-L1 low population, and that's ASCENT-03.
Mm.
ASCENT-04 is in the PD-L1 high population. ASCENT-03 will be done, we think, late this year, maybe early next year, but late this year, early next year. Again, it all depends-
Or this is in combo with PD-1.
PD-1
... PD-1 high.
That, yes.
Yes.
This is the PD-L1 low population-
Yep
... is ASCENT-03, and then ASCENT-04 is our PD-L1 high population that, that'll be coming later.
Yep.
That's gonna take a little bit longer-
Yep
... partly because, remember, the PFS we were just talking, the PFSs are longer.
Right
... so it will take longer for the PD-L1-
Okay
... study to read out.
But in ASCENT-03,
ASCENT-03, PD-L1 high. So as we've said, that, we expect late this year, you know, maybe, maybe into next year-
Yep
... but we think this year.
Sure.
And then it's hard to predict, you know, head-to-head, what... I can't predict. What I can do is say, based on what we've seen so far-
Okay
... I like that our tolerability profile in breast cancer has been strong.
Okay.
We see diarrhea and neutropenia. Those are well managed. We do not see grade three stomatitis. We do not see ILD at that extent, at the extent that others have seen.
Okay.
We think that if we can bring something that brings the efficacy that we're anticipating and is tolerated-
A better tolerability.
... and is tolerated well.
Don't really have stomatitis, right?
We do not-
Okay
... see the
All right
... extent, neither the severity nor the frequency.
Okay.
So I think those are... Again, we'll have to let the data read out, and once we both have data, it'll be, you know, we can, we can do-
Okay
... more of a compare and contrast.
Okay.
But we like our chances there.
Should I pivot anywhere else on Trodelvy, or should I move to a different program? Those are the two big ones I-
Yeah, I think, yeah.
EVOKE-03, lung cancer next year. If that's positive, that would move you into a first-line setting. You said later in 2022?
2025 +.
2025 + .
2025 + .
Okay, 2025 +
We need to fully enroll and then-
And then first-line triple-negative.
Yeah
... end of this year or early-
Early next
You could file on that data?
We believe so, yeah.
Okay.
Phase III.
Okay.
Registration trial.
Okay. And then, secondarily, maybe what would you point me to? I'd pivot to TIGIT, but then, you know, I think it's, like, the same thing, and people would say, "Well," you know-
In oncology-
In oncology.
Sure, in oncology-
Because this is supposed to be your most important growth driver, so TIGIT was one of those-
Oncology
... ones. Yeah, oncology.
Yeah, yeah. So, so in oncology, and, so just to move then to TIGIT-
Yeah
... that is the next, I would say, most mature program we have-
Yes
... coming through.
phase III, yep.
In phase III for both lung and, as we showed our esophagogastric data at ASCO, we're encouraged by the data that we're seeing there-
Mm-hmm
... in combination in gastric CA, and that's also in phase III. That study is enrolling incredibly well.
Okay.
So, we think that study will be the potential for that one, if it reads out the way we hope it will, we'll be ahead of the competition in terms of being able to file. So we should be first in class if gastric works out.
Okay.
The other thing I'd say about TIGIT is what we're seeing evolve is part of our hypothesis for why we took an Fc-null molecule into the clinic, was that we believed we would get better tolerability. And I think as you see the data come out, we are really happy with what the tolerability profile looks to be with TIGIT. Our hypothesis has always been that, excuse me, that in order to get TIGIT approved, not only do you need the efficacy, you need the tolerability. And the tolerability critically for us within for combinations within the portfolio-
Yeah
... is really critical. If you have a drug that's well-tolerated when added onto a PD-1, it gives you flexibility to think-
Is there a TIGIT Trodelvy?
We are—there are some early studies that we're doing to look at that combination-
Okay
... to see if we can get even better activity.
Okay. One last question, if I may, 'cause it was reminded to me that, on your Trodelvy lung cancer study, just one last question on Trodelvy.
Yeah, yeah.
That obviously you presented the data, and you highlight this big subgroup of prior-
Mm-hmm
... non-responders to PD-1, which is two-thirds of the study.
Mm-hmm.
Most people don't get a great response from PD-1. And that you kinda leave it open that you're discussing with FDA. Is that, like, a legitimate, we would like to try and file that or what?
We would definitely like to try to file that.
Okay.
I think it's, as I think is true for all of us, when you take a study where the primary endpoint wasn't met, it raises the bar.
Right.
It's, you know, while this was a predefined subgroup, because of the primary endpoint, it makes it more challenging. This is a patient population with a huge unmet need. They don't really have great options. We're showing, you know, in particular in that subset, evidence of efficacy and good tolerability. We think it's worthy of having a discussion, to see if we can do something for patients.
When could we hear an update on whether that's yes or no?
I think it'll be sometime this year, later this year.
Sometime this year.
Yeah.
Okay. All right. Let me pivot to two other things. One is I would like to talk about HIV because there are two important drivers. One is the fact that you have phase III PrEP data coming.
Mm-hmm.
And the other is the fact that I believe that if you could tell Wall Street you did have a long-acting regimen for the treatment of HIV, like once every six months-
Mm-hmm
... I think everybody would agree that that would be a very great option for people, and that would extend your HIV business further.
Yes.
People believe you can do this-
Yeah
... because you guys crush it in HIV, so.
We believe we can as well.
Okay.
So, and, and-
So tell me when, six-month-type data, where are you with six-month injections?
Yeah. So I'll, I'll remind that we will have phase II data for our every six month lenacapavir plus bNAb.
lenacapavir plus bNAb, okay
... which is an every six-month regimen, and that'll be this year.
Okay.
So, it'll be... It's early. Yeah, I wanna always caution-
phase II you call it?
It's early phase II data, yeah.
Okay.
I think that will be very directionally important for us. So that's our, I think that's a starting point for us.
For the treatment of HIV?
For the treatment of HIV.
Now, just to remind everybody, in the treatment of HIV with just bNAbs-
Mm-hmm
... it was basically positive.
Yeah, we had
Okay.
It was lenacapavir plus bNAbs.
Oh, it was lenacapavir plus bNAb?
Lenacapavir-
Yeah, okay
... plus bNAbs in the treatment study.
Okay.
We saw 18-20 patients who did.
That was, like, a monthly thing?
No, every six months.
That was every six months?
Yeah, yeah.
Okay, so-
Because the bNAbs are there for six months-
Yeah
... right? And the lenacapavir we already know is gonna be there for six months. So we're very encouraged by that. We need to build more data. I think there's a lot more work to be done, so I wanna make sure we're, you know, covered.
What would we learn in this data coming up?
Well, I think this would be sort of broadening and the number of patients in the trial, getting us more confidence. That was 20 patients. This will be a larger sample size.
Okay.
So, you know, getting us confidence, and then, and then, helping define patient populations that we would go into potentially for registrational trials-
Mm
... if we go down that path. And I just wanna... There's a big if there, so we wanna make sure-
What would be the if? The only caveat for Wall Street is that it's basically for half the population who have that antigen for the test-
To which the bNAb-
To which the bNAb binds. So, hey, 50%-
Yeah
... of the market is nice.
Yeah. So we'll-
Why would you not go for it?
Well, I wanna see the data first.
Oh, okay.
So once we see the data, we'll make that decision, so, but-
Okay. Now, do you... So that's one.
Yeah.
What, are there also others?
So that's one. So I think, I just wanna make sure I answered that six-month question directly.
six-month, six-month injection.
And to your point, I think very importantly, the lenacapavir every six-month PrEP studies, PURPOSE 1 and 2, will be reading out PURPOSE 1 later this year and PURPOSE 2 potentially this year, maybe early next year.
Okay.
Those are the two studies we need for registration for PrEP. They're both very large studies, just under 6,000 and just under 4,000 people in those two trials. We're, you know, we're very encouraged by those data, and I think it, you know, we believe it'll be a real sea change for PrEP, right? These are every six-month injections would be a far cry from daily pills.
What % of people do you think currently on Descovy would swap to this? And what % of people do you think out of 100 people would start this because they don't wanna take daily pills?
I think that's the exact right question, Mike. I would say-
I haven't done my survey yet.
Yeah, I think-
Okay
... I think, we believe that the availability of an every six-month injection not only allows those who would rather not take one every day or are non-compliant with taking-
Right
... one every day to go, but we also believe that it will expand the lens for people who Remember, again, it's healthy people, right? These are people without an infection. There will be a lot more people willing to take PrEP if they know that they're gonna be protected for six months, and, you know, come in, get an injection six months, for, and are covered for six months. So we do think there's both the transition of some people-
Yeah.
Um, uh-
Also growing the market.
And then growing the market. And I think that potential for the market growth, given what the, you know, recommendations are from-
Yes
... even the CDC for-
Yes
... for PrEP in people who have two sexual partners-
Yes
... or more, those sorts of things, it's, it's-
Well, even 10% of the market, 1 out of 10, of people who are not, but technically at risk-
It's vast
... I think is material, but we need to do some more survey work, and I was hoping you'd maybe share your survey work.
We think it's gonna make a
Okay
... an impact, and we're really looking forward to that. So I think that's, when you think about underappreciated, I think that may be one area where-
How about this: Can PrEP ever be reimbursed at a monetizable revenue situation outside the United States?
Well, I would definitely say that we believe there's a possibility that will happen, and we believe the reason for that is we will be able to... Part of what we're aiming to show is that the ability to cover someone for six months to have compliance guaranteed-
Yes
... for six months, will lead to better outcomes for people, right? And that should be something that is, brings more value to healthcare systems.
Someone who's taking pills and may not be on it, so they could get infected, and therefore, the value is not-
That's right
... obviously gotten.
We think there's. I mean, we believe that for public health, I mean, that the ability to really prevent infections in a much more impactful way is going to be-
Once you get the data, again, this is a longer-term thing, but you would like to launch that. 'Cause I understand GSK does have approval-
Yes
... for their PrEP long-acting monthly-
Yes
... monthly or-
Monthly
... monthly.
Yeah.
Yet they've told us it's still a struggle for them, although-
It is, it is challenging. I mean, I think that it, there's no argument that in Europe this is a more challenging,
Thank you very much. We've run out of time.
My pleasure.
So we could talk for-
Absolutely.
I know, I know. We didn't-
There's more to talk about.
But, thank you very much, Merdad. We'll be in touch with you, and thank you for your time today.
My pleasure. Thanks, Michael. Thanks for having me. I appreciate it.