Great. Good morning, everyone. Thank you so much for joining us. I'm Salveen Richter, a biotechnology analyst at Goldman Sachs, and really pleased to be joined by Daniel O'Day, Chairman and CEO of Gilead. To start here, Dan, this has been a really, I guess, after a period of resetting the foundations and looking at various growth levers, you've really put yourself in a position here where you're executing across your core franchises, which are HIV and oncology. As you sit here, where do you see the growth playing out on the forward? Walk us through key priorities and then just overall strategy.
Yeah, sure. Thanks for hosting us here. Delighted to be with all of you too. It's a particularly important time at Gilead right now, after five, six years of kind of developing this strategy that we had around not only making sure that we could continue to lead in virology, and I know we'll talk about that, but also diversifying to other therapeutic areas, oncology and inflammation. I'm pleased to say that right now we have three growing franchises, obviously virology and HIV, but also oncology with some of the recent data that we just presented at ASCO on both Trodelvy and cell therapy. I think that even provides us with more growth opportunities ahead. Inflammation with Livdelzi, but also the earlier program. I would say that, look, I think we're in a very good position. We've got a strong balance sheet.
We have robust cash flows. We're now in a position where we're really looking at managing our operating expenses at a higher level that we built up over the past five or six years. Uniquely, we're one of the few companies that has very little patent exposure. Our next patent exposure is not until the end of 2033. We have a whole host of HIV long-acting programs that will help diversify that concentration risk before 2033. I would say that we're really in a good position to continue to grow and develop that portfolio over time, invest appropriately. I think we're in a very good position right now at Gilead.
Maybe starting here on lenacapavir and the outlook for the launch in HIV PrEP, given changes at the HHS and the FDA and CDC, is there any follow-through that could play out here on the HIV front as you look to this launch?
We have not seen anything so far that would have an impact on our exciting lenacapavir for PrEP launch that is really literally days away. The PDUFA date is June 19th. I would just point out that everything with the FDA has been going as you would expect for a priority review product. We have had very good discussions and are in the final stretch now waiting for their approval. Relative to the programs that support HIV services in this country, we have not seen a significant change that would impact necessarily the lenacapavir for PrEP uptake. What does that mean? That means that we have obviously been advocating with the government to make sure that core services related to surveillance of the disease, diagnosis, PrEP, linkage to care, that those are funded. At least the conversations we have had with the government, we have gotten good affirmation of that.
Of course, they are looking for efficiencies, but we pointed out the necessity of funding those programs at both a federal and a state level. As you know, within the HIV community, we support a lot of that funding, as do other philanthropic organizations. Given the incredible data around lenacapavir for PrEP, that it is 100% effective at preventing people from obtaining HIV, the community, the awareness of this amongst prescribers and amongst the community is very, very high. We are poised now to kind of bring this advancement to more and more people, those that may be on PrEP today and those that have not considered PrEP before for a variety of reasons. We believe we can really grow that population.
Importantly, I think this is potentially the best tool yet in bending the incidence in the arc of the HIV pandemic in this country and globally.
Maybe speak to the commercial strategy in that context, because there's a long-term outlook of how you can really grow this opportunity. In the near term, there's a compliance and adherence, a durability impact that could play out as well. Walk us through the initial targets here and then the cannibalization efforts that could also play out and how these various factors work.
Yeah. I think we think of it in three different phases. One is those individuals that are on PrEP today. The second one is getting to new people that could benefit from PrEP that have not been necessarily well served by a one pill, once a day regimen in this country. The third piece of it is expanding globally. PrEP is largely a U.S. phenomenon today for a variety of reasons that we can speak about. Given the incredible data on lenacapavir for PrEP, health authorities in other countries are looking at this differently than they did on a daily pill. Let's go back to the first set of individuals. Today, in a somewhat narrow, CDC defines that there are about 1.2 million people in this country that could benefit from PrEP. I think that number will expand over time given the nature of lenacapavir.
Of that 1.2 million, there's about 400,000-450,000 users of PrEP today. Those are largely one community, men that have sex with men in large urban areas. The reality is these people are not, they don't have a disease. They're not very compliant in their therapy. On average, and of course, this varies by different groups, there's about a 50% compliance rate on the oral pills. The way we think about it and the way the community has told us they think about it is the ability to be obviously more compliant, to not have to think about taking a daily pill, but going in a routine that corresponds with when you would get STI testing to your physician, get a subcutaneous injection, and then forget about it for six months.
We think it's really going to benefit these 400,000 people today that have been less compliant, make them more compliant, reduce the incidence of disease in that community. It obviously has an impact upon our business to be able to have that assurance of compliance around that somewhat 400,000 folks today. Moving to the next group of individuals that could benefit from PrEP, this is a variety of other communities. We have a good understanding of where those outbreaks are. There's more than 50% rural south of the United States. It's different populations of individuals. It's Black and Latino men. It's Black women. It's a larger population of underserved folks that for a variety of reasons, largely around stigma, discrimination, access to healthcare, we haven't been very effective at penetrating in the past.
We have new programs that will roll out at the time of launch, but it will take a while for those communities to kind of be able to have awareness and then seek potential appropriate prevention therapy. We really have to remember, HIV in this country is increasing. There are more than 700 new cases a week, and 100 people a week die from HIV in this country alone. There is a medical need out there. We will have both of those programs running from the launch, current users, those that have not been served well in the past, and eventually getting to countries outside the United States, where from a global public health perspective, this presents a real option for countries to think about ending the HIV epidemic in their country.
What that means is talking at the health minister level about programs where we could really work with their targeted populations, reduce the risk, and reduce their overall, obviously better for public health, but also better for their economics in their systems as well. Because in this country, for every HIV disease that you prevent, you save about $1.1 million in eventual lifetime healthcare costs, not to mention, of course, the benefit for the patient. These are strong arguments and I think good economic thesis to go and expand outside the United States. I'll just say one other thing.
Of course, we have a program for low and middle-income countries too, an astonishing program where we'll be able to license this on a royalty-free basis to more than five generic manufacturers and supplying lenacapavir in the interim period before they're ramped up at no cost to us to get it to more than 2 million people in the first few years of launch. Because if we don't stop this virus everywhere, we don't stop it.
Speak to the reimbursement aspect with regard to what you discussed and what maybe needs to be achieved here on the pricing side and the access side, but then also how you see this trajectory playing out over maybe the first 12 months or so.
Yeah. I mean, HIV is a unique disease in this country. If you stop taking medicine, you die from the disease, and of course, you spread it further. It has always been treated a bit differently than other categories of medicines in this country. What does that mean for PrEP today? For PrEP, because of the importance of preventing disease, Descovy, our current branded PrEP medicine, is covered on more than 90% of insurance payers, with zero copay. For those that are eligible for copay assistance, we do support it, but it is really not needed today with PrEP medicines and with Descovy. We believe that will continue because of the nature of the guidelines on to lent for PrEP. We expect high coverage over time. Having said that, anytime you launch a product, it takes a little while to get that coverage.
What we said is in the first six months, we expect to have around 70%-75% of coverage by payers. If you go out to one year, we expect that number to go up to 90% or similar to what we have for Descovy today. We expect high coverage. There is a tremendous demand for this. We expect the demand to be there as well. More broadly, there are several support systems for folks with HIV in this country. In addition to government support or commercial payer support for HIV, there are also special programs like the Ryan White ADAP program as well. What we have seen is that people with HIV, regardless of PrEP or treatment, have options to support them.
Of course, we always provide the backstop option for those folks that are either underinsured or eligible for copay assistance. It is a very well-covered class. We expect this to continue and even more importantly now with advancements like lenacapavir for PrEP.
Before we head out to the broader HIV pipeline, perhaps you could touch on the news announcement this morning about a clinical.
Oh, yeah. Yeah. Part of our treatment long-acting program has been, and I should say our general long-acting HIV program has been to have as many options as we can for patients either with HIV or for prevention. On the prevention side, it includes lenacapavir for PrEP. It also includes the data that we presented at CROI, where we believe we may be able to get to a once-a-year injection for HIV prevention. That study will start later this year and could be available to people as early as 2028. That is the prevention side. On the treatment side, we have more than seven programs between now and Biktarvy patent loss of 2033 that we plan to launch in different times and different phases.
The clinical hold this morning related to a specific program of those nine that is a novel integrase inhibitor and a novel capsid inhibitor in a once-weekly format that was in a phase two program. What we saw in this early phase two program is for a subset of patients, we saw some impact on CD4 cell counts, reduction CD4 cell counts, and absolute lymphocyte counts. In agreement with the FDA, we put this on hold and we'll be interrogating what that means for this particular treatment regimen. I would remind you that we actually have a more advanced once-weekly treatment program in phase three, and that then is lenacapavir. This was an alternative once-weekly that was intended to launch around 2030-2031, something along those lines. We'll take the coming quarters to look at what's happening with this particular trial.
This has nothing to do, by the way, with lenacapavir. It's a completely separate novel agent. And because of the nature of Gilead's kind of continual innovation, we actually have alternative integrase once-weekly inhibitors and alternative capsid inhibitors in a phase one or late preclinical right now. If needed, if we need to shift out either that integrase or the capsid inhibitor in this combination approach for once-weekly, Gilead wholly owned, we have the ability to do that over the coming quarters as well. We believe this is probably somewhere between a three-quarter and a six-quarter delay on our Gilead once-weekly that has no impact upon the other nine options that we have for patients. When you push the limits of science, I think we're going to see some of these unexpected scientific readings. We have to take them seriously.
It is part of a very comprehensive program for HIV long-acting.
Could you also just touch on the late-stage pipeline and where it stands and particularly your thoughts around diversification away from Biktarvy?
Yeah, absolutely. The three most advanced HIV long-acting programs or alternatives to Biktarvy, I should say, are the BICLEN program that's in a phase three right now that could be launched as early as 2027. It's an alternative daily regimen for patients. The second one is the weekly oral, which is the one I just referred to, the lenacapavir, again, in a phase three program potentially launching as early as 2027. Then a novel once-every-six-month approach, which is lenacapavir plus so-called bNAbs. That's a once-every-six-month injection infusion program that could launch in the 2029 timeframe, 2029- 2030, I think, timeframe. Those are the most advanced programs. Behind that on HIV, we've got once-monthly programs oral, once-every-three-month subcutaneous injection, and once-every-six-month subcutaneous injections. Those are all either in late research phase one programs that we expect could launch before 2033.
It's a very comprehensive program. The reason we're doing this is because we've heard from patients from a person-centered innovation standpoint that different people want different options. Some people will want to take that daily pill. Some people want it every six months and forgetting about it. I think what we want, because today, still in this country, about 40% of people that have HIV are not virologically suppressed. That is despite the fact that Biktarvy is the gold standard of care. If you take it, you're virologically suppressed and you die from other things other than HIV. There's obviously 40% of people at least that need different types of options. Of course, those people on daily oral options would like options as well.
That's the whole nature of this program and why we are so convicted when we say that our HIV business is not only secure and growing until the late 2030s with this robust portfolio.
Transitioning over to oncology, as you noted, there was data at ASCO and we saw the full phase three data for Trodelvy in first-line PD-L1 positive metastatic triple-negative breast cancer. Among other updates, maybe help us understand how you think about this data set with regard to positioning these drugs in the marketplace and where you can have dominant positions.
Look, this is really important news for women with breast cancer. The data that was presented at ASCO covered the ASCENT-04 trial, which is one of two trials in the first-line triple-negative breast cancer setting. The other trial is called ASCENT-03. The way they differentiate is ASCENT-04 is for PD-L1 positive patients in combination with Keytruda in this case or a PD-1 inhibitor. ASCENT-03, which also read out positive, we've announced that in a top-line press release, is for the PD-L1 negative patients, right? They split roughly, things split roughly 50-50 in terms of PD-L1 presence in first-line triple-negative breast cancer. We'll be presenting that ASCENT-03 data a little bit later this year at a conference. We've already said it's clinically meaningful, highly statistically significant, which is what we said about the ASCENT-04 trial.
The reason this is so important is because triple-negative breast cancer, which represents 10%-12% of breast cancer cases in this country, is such an aggressive form of breast cancer that more than half of the patients with this disease actually never go on to a second line or beyond therapy because of the aggressive nature of the disease. Another way to think about that is if you move a therapy from second line and beyond up into first line, you more than double the number of women that you can impact accordingly. This is important for women with triple-negative breast cancer. It's also beyond the Keytruda approval. It's the first time we see a potentially new regimen in the first-line triple-negative breast cancer in more than 20 years. All we've had really is common chemo in that setting for more than 20 years. It is critically important.
Both the presenter and the discussant at ASCO were using words like this is clearly the next standard of care in first-line triple-negative breast cancer. Big patient impact, most importantly. Secondly, I think it bodes well as the only company with a TROP2 ADC in breast cancer that has two clinical trial readouts in overall survival. It is now the fourth positive study for breast cancer in Trodelvy. It bodes well for the other work we are doing in breast cancer with Trodelvy, including earlier line HR positive HER2 negative, that is the ASCENT-07 trial, and the adjuvant trial in triple-negative breast cancer, that is the ASCENT-05 trial. Both of those are still ongoing trials and will read out in the near-term future.
I think it really rounds out the important nature of Trodelvy as I think a unique TROP2 ADC, certainly in the breast cancer setting, both in terms of efficacy and its tolerability profile. In the meantime, we have a very comprehensive program at Trodelvy in other disease states like first-line non-small cell lung cancer, small cell lung cancer, where we have a priority review designation, and endometrial cancer, amongst others. Trodelvy, I think, is proving to be now in some of these trials a really important addition for oncologists to use in cancer. We'll see how broad that goes with the other disease states.
What is the longer-term outlook for Trodelvy at this standpoint? If you could venture a guess on the opportunity size here on a sales basis, that would be helpful, I think, to put this drug in context.
Yeah, as you'd expect, we're not giving necessarily sales guidance today. But today, our oncology business at Gilead is more than $3 billion on an annualized basis and growing double digits. $2 billion of that is cell therapy. A little over $1 billion on an annualized basis is Trodelvy. What this does is more than double the potential population going into the first-line setting of triple-negative breast cancer alone. I think you can imagine as we read out the different trials, studies, and lines, Trodelvy becomes, in our opinion, a sizable portion of our oncology franchise moving forward. That's complemented by our cell therapy business, which in addition to having the world-leading cell therapy business today in lymphoma and leukemia, and at ASCO, we presented kind of next-generation concepts for those diseases. We also presented data in solid tumors at ASCO and glioblastoma.
At EHA, which I think is this week, we will provide some extension data on our multiple myeloma and needle cell product, which we expect to launch next year in late-line multiple myeloma, which is a market that is roughly two times the size as the lymphoma and leukemia market. You start to see, back to your, you start to see this growing potential on the oncology side with both Trodelvy and in needle cell. We have other very interesting options, if you like, in compounds in earlier stage development, whether that's still having an FC silent digit in late-stage development or a really interesting CCR8 program in phase two, amongst others.
What is the longer-term strategy here for the cell therapy business, recognizing you have a needle cell, but also recognizing that there's significant development going on in the space with next-generation approaches or broadening beyond cancer?
Yeah, so we're participating in each one of those. As I said, going from lymphomas to multiple myeloma, going potentially into some types of solid tumors, but then also expanding out to autoimmune diseases. Our strategy is to potentially use kind of next-generation cell therapies. We call them bisystronics because they're targeting more than just CD19. We have CD19, CD20 bisystronics that we think can be effective in enhancing the number of people that can benefit from lymphoma and leukemias. Also, those constructs we will be taking into autoimmune diseases because they're the same targets for autoimmune diseases that we think we can have an impact outside of that. It is a completely different construct, by the way, for the solid tumors because you're dealing with different targets in those areas.
Being the world-leading company in cell therapy and having scientific expertise on both Gilead and Kite to be able to put to work towards novel targets is really, really important to us. It goes beyond just the scientific because of the nature of autologous cell therapy, having the world-leading manufacturing capability with turnaround time for these diseases is really important. We have our turnaround time now down to five or seven days with lymphoma and leukemia. That is the same turnaround time we will take into multiple myeloma where we know patients are waiting for those diseases. We can apply those to other disease states as well. We are constantly trying to iterate to make that time even shorter.
We always have our eye on what are the next disruptive therapies that could come into this space and how do we make sure we're participating in those as well.
Is there anything else you want to highlight from the pipeline overall?
I forgot what we've talked about.
Talked about Trodelvy.
I think we've covered it. The other thing I would say is that I mentioned a little bit about the early oncology pipeline. I would say that Dietmar Berger, our new Chief Medical Officer, came in about six months ago. He's an oncologist, but he has depth of experience in immunology inflammation development, which is important at both Sanofi and their work with Regeneron in the past. I think he shares our enthusiasm around some of the novel targets that some have come out of our research lab, some we've acquired. So things like Alpha4, Beta7, IRAK4, the Stat6 that we brought into our group from Leo Pharma at the end of last year. He's really interested, as are we, in saying how can we potentially be driving the next wave of breakthrough efficacy in autoimmune diseases.
As you know, we've kind of been, while we've improved in terms of methodologies of delivering autoimmune agents, making them less frequent, making them more tolerable, we haven't really broke through those efficacy barrels. We think we're going to get at that through novel targets and novel targets in combination. I would say when you think about Gilead, think about the here and now, which is clearly virology, HIV, oncology growing business. When you think about Gilead's portfolio, maybe 2030- 2040, start to think about novel inflammation targets complementing those other two therapeutic areas. Yeah, I think that's what I'd want to cover on the portfolio side.
How does the business development lever come in here as a tool to kind of enact that path to getting that portfolio you're looking to?
Yeah, I mean, look, the business development tool has been instrumental in getting us to where we are today. I would say that having said that, the way we use business development over the past five or six years will be different than how we use it moving forward. One thing that will be the same is that every year we spend around $1 billion plus or minus on late research, early development assets. And we've done that ever since I've come in. And we'll do it for many years to come because I think that's kind of a healthy, always comparing your science to outside science and bringing in new concepts. So that's, I think, important for the routine business. What will change is we had to put a lot of capital to work in the period of time where we doubled our overall portfolio.
Now we have a very healthy, competitive internal portfolio that both our internal things coming from our own research house have to compete with, but also outside innovation as well. I think you should think that, I mean, we have the portfolio we need today to drive our growth ambitions on both the top and bottom line in the years to come. We want to continue to make that stronger and stronger. Think mid-stage acquisitions every couple of years, something like a CymaBay acquisition that we think kind of mid-single digit billions to complement our portfolio. The bar is high. They should be later stage that allow us to kind of drive growth in the near term. I think that'll be a healthy rhythm we can get into over time. We are going to continue to be a strong cash-generating business.
We will look for ways beyond just investing in our own R&D portfolio or that type of EV to continue to return money to shareholders, including very intent upon our dividend policy of a healthy, growing dividend. We are doing more share buybacks than we have done in the past, given our confidence in the business moving forward. We can always look for different ways to return that cash to shareholders over time as well.
One last question here. President Trump's recent MFN executive order has clearly been an overhang on the sector. What are your latest thoughts here on the prospect for such a policy and the mechanism for an approach? Just for you, how you position Gilead through this period, not just maybe from an MFN, but we can go broadly to.
More broadly, the principles. Yeah, yeah. I mean, I would say before I answer your question, that in any scenario like this, no matter what country in the world is considering policy changes, I always think the best defense is a good offense. Everything I just said about our position on the balance sheet, cash flow, innovative products that are all being launched right about now, you always want that healthy business going into uncertainty, right? Control the things you can control. We will continue to focus on that. Now, having said that, I think there is still a lot of unknown in that question. I will just comment on a couple of things. I mean, the first thing is that we are engaging with the administration. We always believe in engaging, having a seat at the table.
MFN as a concept and application can be looked at many different ways. At the end of the day, it is about this kind of disparity between what the U.S. may pay for medicines and what ex-U.S. pays for medicines. Those are often really difficult apples-to-oranges comparisons because we are the only country in the world where 50 cents of every dollar goes to people that do not make the medicines. I mean, other countries do not have that phenomenon within their distribution system. What we say to the administration is, if you want to reduce that difference, the first thing we should do is focus on what we are doing here in the United States to reduce that difference. Do not import policies from other countries where many fewer medicines are available to patients in those countries.
On average, around 40% of novel medicines are available outside the U.S. versus around 80% here. Americans largely get their medicines quickly after launch outside the U.S., two to three years. Let's not bring America down to the rest of the world. Sure, let's try to encourage other countries to pay more and let's address some of the fundamental issues associated with our system that need to be addressed. That is the conversation. Where exactly we'll go on MFN, I don't know, but we're at the table and we're trying to dialogue to be productive on that side. The other aspect is on the tariffs. Just to say one thing on the tariffs where I think Gilead has maybe a bit of a differentiated approach. That is, we're an American company. We've been in America for around 37 years.
The vast majority of our IP is in this country. You can tell that by the tax rate that we pay, which is different than most of our peers. We pay a higher tax rate than most of our peers. During the first Trump administration, we actually repatriated even more of our IP. What does that mean? At the end of the day, it does not mean we will not be impacted by tariffs. What we have said about tariffs is the non-sector tariffs we can largely absorb or we will absorb within our guidance for this year. That is things like steel, chemical supplies, sector-specific tariffs that do not exist today, but if they do exist, we are less vulnerable than others because we import products in our global supply chain at a higher price than folks that have their IP offshore.
I think that's just something to keep in mind. We would much rather spend money on developing the next cure in our portfolio than spending them on tariffs. We'll work with the administration to try to get that point across. Our vulnerability, I think, is lower than the overall sector there is what I would just leave you with on that point. Let's keep dialoguing. There are ways to solve these problems in the U.S. without policies that harm an industry that is arguably the envy of the world in terms of what U.S. biopharma does.
Thank you so much, Dan.
Thank you.
Appreciate it.
Thank you, Sylvie. Appreciate it.