Great, so thanks everybody for joining us here at day one annual Piper Sandler healthcare conference. I'm Joe Catanzaro, one of the Biotech Analysts here at Piper. It's my pleasure to welcome Gilead and their CFO, Andy Dickinson. Andy, thanks so much.
Thank you.
For joining us. Maybe before we jump into Q&A, I could just sort of give you a minute or two and you could sort of level set, let everybody know what you guys have been up to and what we have.
Sure.
To look forward to.
Yeah. No, first of all, thank you for having us. Appreciate everyone joining us today. As many of you know, Gilead is one of the largest biotech companies in the world, known for, you know, changing, HIV treatment and viral hepatitis treatment over the last many decades. You know, we have significant revenues on around $28 billion a year and three different franchises. I'd say that the most important update and the key takeaway is that Gilead that I joined eight years ago, versus the Gilead today, we now have all three of our franchises growing and growing substantially, and we have no major patent cliffs, you know, through 2033, unlike many of our peers.
So, we've substantially invested in our pipeline both internally and externally. We have a number of either recent approvals or expected near-term approvals that will drive additional growth and diversification of the business. Whether you look at our HIV business, our liver disease business, or our oncology business, all of them are growing and expected to grow for the foreseeable future. It's a pretty exciting time for the company.
Great. So with that, maybe we could start with the HIV business. Lenacapavir got data from both PURPOSE 1, PURPOSE 2, I think just recently published in New England Journal of Medicine. Maybe just sort of speak to what we learned about lenacapavir's profile and what it's gonna offer to patients relative to current offerings in the PrEP market.
Sure. Yeah. So again, for those of you that don't follow us as closely, lenacapavir is a first-in-class HIV capsid inhibitor, an incredibly potent molecule that has already been formulated and approved as a once-every-six-month subcutaneous injection, for treatment. It's currently used in the hardest-to-treat HIV patients that many of them have developed resistance to other existing therapies. The PURPOSE 1 and PURPOSE 2 studies are in HIV prevention, which is a significant area of growth. Gilead had pioneered the HIV prevention market. We have two daily oral pills that have been approved for HIV prevention over the last 10 years. But the HIV prevention market is still in its early stages, formative stages, and we expect substantial growth over the next 10 and 20 years in HIV prevention.
What we showed in the PURPOSE 1 and 2 studies, these are like 9,000 patients that were tested, both men and women, globally, is in the first PURPOSE 1 study, which was predominantly in women, 100% prevention of HIV acquisition in patients that you would expect to in a background population in sub-Saharan Africa where you would expect to see 10% or more infection rate on any given year, and then in the PURPOSE 2 study, which was predominantly in men, and in five large countries, including the United States, 99.9% of the patients did not acquire HIV. So incredible data. To put it in context, the pills that we developed for prevention are also incredibly effective. The challenge is that people that don't yet have HIV don't take daily pills on a regular basis. They will miss doses.
Even though the pill, pills theoretically could show very substantial efficacy, you don't see it in the real world. This is a real game changer in terms of having an every six-month injection that, you know, with long-acting coverage that shows that type of efficacy. The other thing I should mention is the safety profile of lenacapavir continues to look really, really good. The molecule has a very high barrier to genetic resistance. It's really a special molecule and an exciting time for us as we now approach the launch of lenacapavir in prevention.
Yeah. So maybe thinking about that launch and maybe help contextualize how we should think about the dynamic for lenacapavir as it goes into sort of maybe patients who are already on oral daily PrEP.
Yeah.
Those populations who aren't on PrEP and sort of what plays out early and what takes a little bit more time to materialize.
Sure. So the PrEP launch is unique in that, even though the market is nascent, there are about 400,000 to 450,000 people, almost all in the United States, that are currently using HIV prevention today, mostly our oral pills or generic versions of Truvada, which was a Gilead pill. The vast majority, when you look at the clinical data from PURPOSE 1 and PURPOSE 2 , our belief, and I think almost all the KOLs in the space believe that these people would benefit from moving to a long-acting injection. Not only does it sync up every six months with the visits that they should make to their healthcare provider in any event, you see the far better efficacy over time 'cause of the guaranteed adherence.
So the low-hanging fruit and the focus of the launch is gonna be converting the patients that are currently utilizing PrEP, again, most of them are in the United States, to this better, longer-acting version. The next step of the launch is broadening the people that could benefit from PrEP. So even by the CDC standards in the United States, which is a very narrow definition of people that could benefit from HIV prevention, the market is only about a third of the way penetrated. We believe that the people that could benefit from prevention are far greater than the CDC definition, which really focuses on men having sex with men and IV drug users.
If you look at the United States, the number of people that are diagnosed in any calendar year with a sexually transmitted disease is roughly 10 times greater than the CDC definition of people that would benefit from PrEP. So over time, Joe, to your question, you know, it's building out these concentric circles. The focus of the launch out of the gate is converting the existing users. If all of those users were on a branded medicine today, we would estimate that the sales would be between $3 billion-$3.5 billion.
Again, only half of them are on branded medicines today, half are on generic. We believe all of those people should move to the long-acting over time. And then the market should grow substantially from there as you expand the population of people either by the CDC definition, the broader definition, and then finally into other countries outside of the United States. There's a significant growth opportunity in Europe and Asia, etc.
So on that sort of second leg of expanding, excuse me, the PrEP market, what are the big gating factors there? Is it education, awareness, or is it just the convenience over a once-daily pill?
I think it's all of those things. There's very high awareness today. Now, after 10 years of HIV prevention medicines being available, very high awareness in small segments of the population. So in large urban centers in the LGBTQ+ community, you see reasonably high awareness. But there's low awareness in smaller cities, more rural areas. Many of those are the areas where you see the highest incidence of HIV infection in the United States today, and in Europe, because these therapies haven't been broadly available, there's lower awareness, so a lot of this is going to be, as we move out in the concentric circles, raising awareness through direct-to-consumer advertising.
The good news is that there are a number of clinics that treat people at risk of getting HIV that have built businesses around treating HIV patients and people that are at risk of getting HIV and raising awareness. So we're not doing this on our own. I mean, there are a number of groups out there in the United States and in Europe and other countries that will also be working to raise awareness of this important new treatment opportunity.
Great. Maybe with that, we could shift to, stay with HIV but shift to the sort of treatment market. It seems like with now some visibility into lenacapavir and PrEP, maybe there's some growing questions on sort of the treatment market and your efforts there.
Sure.
How we should think about Biktarvy and its loss of exclusivity in 2033. So maybe just start with sort of all the work you're doing on the treatment side and some of the offerings you'll have.
Sure.
There.
Yeah. Again, just to put the treatment market in context, you know, we have about $18 billion a year of sales in HIV. The vast majority of those today are in HIV treatment. The treatment market is still growing in all major markets 2%-3% year- over- year, despite the availability of HIV prevention and greater awareness. Biktarvy, which is the gold standard once-daily pill that Gilead developed and launched roughly eight years ago, which is a $12 billion+ product now, has 50% market share roughly in the United States, very substantial market share outside of the United States. All of our medicines still have 72%+ market share in the U.S. And there's still a very substantial opportunity.
The easiest way to think about it, and then I'll talk about what we're doing over, you know, that we have in programs in the clinic. 42% of patients with HIV in the United States are not virally suppressed today, which is shocking. That means that they're either not taking an HIV medicine or the medicines that they're not taking are not effective or they're not taking them every day. 42% of people are not virally suppressed. Even the people that are virally suppressed, the vast majority of them say, "I would rather not take a pill every day. I'd rather have a weekly pill, a monthly pill, or an injection every three or six months." And that's exactly what we're working on.
So to Joe, to your question, as you know, lenacapavir is not only the background or a backbone for HIV prevention. It will also be a backbone for all of our next-generation HIV treatment therapies. In HIV treatment, you need more than one drug to suppress the virus and prevent viral breakthrough. So we have a number of partner agents that we're developing to pair with lenacapavir in all these different treatment regimens. The vast majority of them are integrase inhibitors, which is the other kind of important HIV backbone. It's the backbone of Biktarvy, for instance. We're formulating once-weekly pills. We do have another once-daily pill that could be an important launch here in the coming years, with lenacapavir and bictegravir, which we think will become a best-in-class two-drug combination for the patients that want that.
And then we have once-weekly options. One is wholly owned. One is a partnership with Merck. We have once-monthly treatment options, pills that we're developing, and then the injectable treatment options, which are three months and six months and maybe eventually once yearly. So when you kind of wrap it all up, you know, in the interim between now and 2030, we expect to have at least four launches of new treatment options for patients. And then between 2030 and 2033, we'll have additional treatment launches. We have an HIV Day next week, Joe. Hopefully you will attend, or be able to listen to. It's open to analysts and shareholders. And we're gonna spend a lot of time talking about both what we expect for the HIV prevention launch as well as where we're going in HIV treatment with all these different programs.
Perfect. Yeah. I was gonna ask about the HIV Analyst Day and what we could expect, but I think you maybe covered it there. So maybe we could move to the cell therapy business. And I wanna sort of take this in sort of two parts. One first, a little bit more granular, and that's the upcoming data update for anito-cel at ASH, the BCMA CAR that you're partnered with Arcelix. Maybe you could just speak to maybe the what we might learn next week about the program and its profile, and how you think about where it fits in relative to the other BCMA CAR offerings that are out there on the market.
Sure. Yeah. Again, just background, we acquired a company called Kite seven years ago. Kite is the world's largest cell therapy company. So this is, you know, in patients today and hematology indications, taking their white blood cells out, re-engineering them to recognize the cancer, growing up those cells, re-infusing them. And you're seeing cures today in 40%-50% of the patients, depending on the indication or what look like cures, depending on the indication and the line of therapy. Really remarkable, incredible clinical data and real-world data. It's about a $2 billion business for us and growing. The next really big growth driver for us is a cell therapy called anito-cel that's partnered with Arcelix. This is a BCMA-directed cell therapy that will be used in multiple myeloma. We had one small study that Arcelix did.
They reported some additional data at ASH, and then the phase two study, which is registrational and fourth line plus, there will be an updated data set at ASH. So far, and this is about 140 patients that have been treated with anito-cel in multiple myeloma so far. It appears, and that's a large data set for cell therapy, that this is a best-in-class therapy, both in terms of efficacy and in terms of safety, and in efficacy, a lot of the patients that were treated early on were very advanced patients with lots of extramedullary disease, and you see really remarkable responses and durability of response in those very difficult-to-treat patients. Just as importantly, on the safety side, the competitor therapies that are approved, there's two cell therapies directed against BCMA that are approved for multiple myeloma.
They both show a high incidence of neurotoxicity, and specifically Parkinsonism or similar, you know, side effects, which are quite severe in patients. And we don't see any of that. We in Arcelix don't see any of that. So in terms of the update that's coming at ASH, well, you saw in the abstract that we put out a couple weeks ago, the updated data set, we will have another cut of the data with more patients and more longer duration of data that will be presented at ASH next week. And what we've said is we're really excited to share the data. But as of our third quarter call on the side effect, we said clearly we don't see any signs of these CNS side effects that you see with the existing therapies.
How much value do you think there is in bringing Kite's expertise in manufacturing to that program that will be for commercial launch? I think.
Yeah.
Every KOL I speak to says, Kite has sort of set the standard on cell therapy logistics and manufacturing. Sort of conversely, I think the BCMA CAR space has maybe faced a little bit of its challenges. How important do you think that's gonna be in the future?
Yeah. I think it's critical. I mean, to put it in context, I was in London a couple weeks ago and had a chance to visit one of the largest CAR T centers. And the physician that runs the center said, you know, there's nothing worse than having a patient where we order a CAR T therapy and we wait 40 or 50 days, and it either doesn't come or it comes out of spec or it comes late. You know, we have a 96%-97% manufacturing reliability. Our turnaround time from when we take a patient's cells and redeliver them is now 14-15 days on average, which is really remarkable. A lot of these patients, especially in DLBCL, but also in multiple myeloma, can have more explosive disease, and every day really matters.
The reliability, I mean, and to put this in context, many of the competitors in cell therapy, their reliability until recently has hovered around 50% or 60%. They're getting better at it. We have three large global manufacturing facilities. We've already done the tech transfer for anito-cel to our manufacturing. We feel, and I think Arcelix feels, it's a huge competitive advantage for us.
There are no limitations out of the gate at launch in terms of how much we can manufacture, how quickly we can manufacture. We have plenty of capacity in our manufacturing facilities. You know, based on the clinical data, we think we have a best-in-class therapy. We think, you know, if that holds up, we're gonna have a very strong launch with no, you know, no limitations on our ability to satisfy the market, which has been a challenge over the last couple years for the competitors.
So, the second part of the sort of cell therapy discussion here I wanted to cover is maybe a little bit more holistic and specifically speaks to maybe the ongoing experience in the U.S.
Yeah.
Some of the in-class, out-of-class competition that you're seeing there and, you know, how long that persists. Maybe you could contextualize a little bit and maybe some of the efforts you are employing, to sort of get past that and return that business in the U.S. back to growth.
Sure. Yeah. So what Joe's alluding to is that the cell therapy business overall is growing. Today, though, most of the growth is coming from Europe and Asia. And the U.S. business for us is not growing. The market is growing slowly. But to put it in context, again, you're talking about a lifesaving therapy in 40%-50% directionally of the patients that get this. In the U.S., about 15%, this is in DLBCL, 15% of patients that should be getting this lifesaving therapy are getting it. If you contrast that to France, 40+% of patients in France, second line plus, are getting cell therapy. So the challenge for us is to break through the barriers in the United States to getting broader adoption of cell therapy.
The biggest barrier is that the vast majority of patients in the United States are treated by community oncology groups. Many of them are not set up or accredited to do cell therapy. And they don't, for various reasons, have an incentive or want to send the patients to academic centers. So of the 150+ centers that are doing cell therapy with our products today, the vast majority of those are large hospitals in large cities or academic centers. And the key is really gonna be moving cell therapy over time into the community. It's not easy. It will get done. And we're making progress. We've been working on it for a number of years. We're working with a lot of the large, community oncology groups. But it requires a lot of work and training on their side.
Some of them have to get this FACT accreditation in order to get reimbursement from payers. So it's gonna take a concerted effort of working with payers, with government officials, with the community oncology groups. We believe we'll get there. I mean, at the end of the day, it's incredibly rare in the biopharmaceutical industry to see this type of efficacy, as you know. I mean, this is game-changing for people. We'll get there. It's just, and it's, you know, it's disappointing to all of us that it's, it's so much more challenging to get there in the U.S. than in Europe. But the overall, the cell therapy market will return to growth. So in terms of the timeline, it's probably too early to say. In the U.S., we expect the, the headwinds that we're facing. And there is increased, in-class competition too.
I think the other thing I should mention is with all the cell therapies now either approved or in clinical studies with bispecifics, there are more options out there. And in the academic centers, there's more limited treatment beds. So there's a number of headwinds that we're working through. It's not just the referrals from the community physicians that we need to work through. This will all work itself out over time. And we believe every way that we look at the cell therapy business, this is a really substantial growth business for us. And in the United States, it's gonna take certainly into 2025, if not beyond, to kind of continue to see that growth.
The last thing I'll say to put it in context, with the 15% of patients being treated with our cell therapies today in DLBCL, it's a $2 billion business. If you just, you know, get it to 30%, which is still below most of the major European markets, you know, the business doubles or more, then you layer on anito-cel to that in multiple myeloma, which is twice as big of an opportunity. This is a big business opportunity and a large growth opportunity for us over time. It's just gonna take a lot of work to get there.
Great. So maybe in these last five minutes, we could sort of tick through a couple things, first starting with Trodelvy. As we look at Trodelvy and maybe sticking with its current labeled indications and maybe more broadly breast cancer, as you look at what you guys are doing there, where do you see the biggest opportunity to grow Trodelvy within, again, maybe we stick.
Breast cancer.
Specifically within breast cancer.
Yeah. I mean, I think the biggest market is the hormone receptor-positive, HER2-negative market for us where, you know, we're currently approved in second line plus. There's more competition in that market. We do have some first line studies underway, in that market in both triple-negative and hormone receptor-positive. Trodelvy is the standard of care in later line triple-negative breast cancer. Incredible data. That's just a smaller population. We do have additional data coming, as I said, over the next two years in both triple-negative breast cancer and hormone receptor-positive breast cancer. I'd say the biggest opportunity, just given the size of the market, is hormone receptor-positive breast cancer, and we expect Trodelvy to grow as we move up in lines of treatment in both of those areas.
The other thing that we're seeing is there's a competitor antibody drug conjugate that was approved last year that has seen substantial uptake. And as patients cycle through that and need another therapy, many of those patients will likely be put on Trodelvy over time. So just in breast cancer alone, we see, you know, meaningful growth for Trodelvy. As an antibody drug conjugate like our cell therapies, it's hard to see biosimilars coming to market. So we think we'll have a long runway with Trodelvy to continue to build the market.
And then outside of breast cancer, of course, we have studies in first line lung cancer that we think are promising, especially in PD-L1 high, first line lung cancer in combination with a, Keytruda or another one, PD-1 inhibitor based on our phase two data. That's also; those studies are underway, and we'll have data in the next couple of years there. So there's substantial opportunities in non-small cell lung cancer, small cell lung cancer, and endometrial cancer in addition to breast cancer.
I wanna just ask maybe a quick follow-up on Trodelvy and lung and where you see, ADC plus Pembro, what it offers relative to other offerings in lung cancer, whether it's chemo Pembro or maybe some emerging potentially IO combos.
Yeah. I think that you've seen the incredible synergy over the last 10 years in chemo combos with PD-1 inhibitors, right? And I think that the Trodelvy just offers a better chemo option to pair with a PD-1 inhibitor, given that you have, you know, the side effect profile is, although it's still a chemotherapy at the end of the day, it's generally more tolerable than traditional old-world chemotherapy. So, I mean, again, we'll have the data and we'll be able to see kind of, but in PD-L1 high, non-small cell lung cancer today, the vast majority of the patients just get a PD-1 inhibitor. Only about a third of the patients get a chemo with it.
If you can then, you know, open the market and get greater efficacy as we saw in our early data where we showed a significantly greater response rate than the PD-1 studies, kind of the benchmark PD-1 studies and significant durability in those patients and it's tolerable, you could expand the number of patients that get a chemotherapy in combination with the PD-1 and get better outcomes. That's the vision. Obviously, we need to see the phase three data to get there.
Great. So, maybe we can move to Livdelzi and its early launch in PBC. Maybe you could just speak to sort of early insights you're gleaning from physicians, from patients, and what your expectations that it becomes a more meaningful contributor to the top line.
Yeah. I mean, maybe starting with the last piece of question, it should become a meaningful contributor in 2025 and beyond. So Livdelzi is a novel therapy that was just approved for PBC or primary biliary cholangitis. It's a perfect fit with our liver disease franchise. We have a number of viral hepatitis drugs across hepatitis B, hepatitis C, and hepatitis D delta. It's a lot of the same physicians that treat these patients. We launched the drug in the third quarter. We've always said you'll see relatively modest sales in the third quarter and the fourth quarter as we're getting both formulary access and getting patients on drug. For rare disease, this is a large orphan disease similar to pulmonary hypertension. It takes months to get patients on drug. The launch has gone as well as we could have expected.
In the third quarter, you know, we exceeded kind of our goals in terms of the number of patients on drug. The awareness of the drug is very high. The label that we have highlights a benefit of a major side effect, or a major issue with PBC, which is pruritus, this unrelenting itching that keeps people that drives people mad. It keeps them up at night. They can't focus. They have, you know, many people can't sleep. And this relieves the itching in addition to, like, resolving some of the issues in the liver in terms of the liver bile acids, and liver enzymes. So the label is great. The launch has gone as well as we could have expected. And I think the key takeaway is, we look forward.