GSK plc (GSK) Earnings Call Transcript & Summary

Very good afternoon. Delighted that you could join the GSK ViiV session. My name is Andrew Baum. I'm delighted to be joined by Dr. Kimberly Smith, the Head of R&D at ViiV. Thank you so much for joining us today. We've also got Frannie DeFranco from GSK's IR on the call with us. So look, we've got about 45 minutes to talk to what is really a critical part of GSK's business, not just in the fact it's serving an important unmet need but from a contribution economically. Because of the very high contribution margin, it punches well above the weight of the just near revenue contribution. So it's one that merits a lot of focus.

Now perhaps to kick off, if I was to set out a devil's advocate view of the landscape that this is a field where previous dominant franchises have been eclipsed by competitors and have ceded control of the space, and Merck will be an example of that historically, which participated in the development of first-in-class of many molecules only to be eclipsed by second, faster followers until they've more recently found their way again towards the light. So a devil's advocate view of ViiV may say, "Look, your capsid inhibitor, which is one of the more exciting innovative mechanisms, is well behind the market leader. Your NNRTI, your translocation inhibitor, again, is well behind the market leader, which is leading out this year. You have a strategy of long-acting cabo, which is important and I wouldn't want to undermine that. But just given the potential of less frequently dose regimens, oral depots, how confident are you in the ability of your cabo platform plus further out some of the very early products you have in the clinic to be able to withstand that competitive pressure? So discuss.

Right. Well, hello, Andrew. It's nice of you to have me give me a chance to talk about what we're doing because we're really excited about what we're doing and a competitive environment actually just stimulates the juices, just makes you eke more and be more creative. And so we're super confident in what we're doing. So let me just start by saying ViiV really was sort of created around dolutegravir, if you think about it. I mean you started out with that really important integrase inhibitor, but it certainly wasn't the first in class, right? It was late in comparison. Raltegravir was the first in class. So I mean it's a perfect example of the fact that first-in-class doesn't necessarily mean best-in-class and that you can sometimes improve on some of the earlier -- early agents in a particular -- the focus on a particular target. And so what we did with dolutegravir, we started out with a really potent, really effective single entity and then grew that out into a whole platform of products with a 3-drug fixed dose tablet and then 2-drug fixed dose tablets that have -- that are having a huge impact on field, really, I think, shifting the paradigm from always being a 3-drug paradigm to now really people asking, do I need to use 3 drugs or can I use 2? And so dolutegravir has changed the game. Cabotegravir is also extremely potent integrase inhibitor that has, as you know, long acting -- it's a long-acting drug. And so we're changing the game again and bringing out long-acting products. Our intention for the future is to do the same thing we did with dolutegravir with cabotegravir, and that means building out basically an entire platform around cabotegravir. And so yes, our competitors are following us down that path. They followed us down the path towards 2-drug regimens after they initially were really hesitant and didn't believe that it was possible to be successful in keeping virus controlled and getting virus control with 2-drug regimens. They followed us down that path, and now they're following us down a path for long-acting. So I think I love what we've got with cabotegravir as a foundation and then we just need to build on that by adding these novel mechanisms of action to cabotegravir. And why that's so important is that, as you know well, the second-generation integrase inhibitors led by dolutegravir absolutely changed the game for HIV and the expectation that your studies needed to be 90% effective or they weren't going to be -- they weren't going to have much value. We've changed this game with dolutegravir. And so it's established now that integrase inhibitors are the treatment of choice. Every guideline around the world has integrase inhibitors as the preferred option. And so providers are very much bought into the potency, the efficacy, the high barrier to resistance and the long-term tolerability of entities. And so we're building on that. So what our competitors are doing is really, they don't have that entity to build on. And so they're combining novel mechanisms of action with the hope that they work well together. But I think our competitors have acknowledged that they would prefer to combine their novel agents with an integrase inhibitor, they just don't have one this long acting that fits the bill to be able to create a long-acting regimen.

So -- okay. So there's a lot of places we can go within those comments. But maybe starting with the proximal data readout, which is a head-to-head for Merck, doravirine/islatravir combination versus Biktarvy. And the Biktarvy combination contains TAF and it also contains an integrase inhibitor, both of which are associated with weight gain and unfavorable dyslipidemic profiles, now granted you don't have TAF, but you still have integrase, which is associated with both those things. So we were expecting, and you tell me if you disagree, that at least in 1 of the 2 Phase III trials that's reporting out later this year, there's going to be materially low weight gain, particularly within the 52-week period of the trial in the doravirine/islatravir arm compared to the Biktarvy arm. Is that -- and again, I know you're not the sponsor of Biktarvy, but just thinking about the beginning of the erosion, which is obviously the comparator attempt of integrase inhibitors to supplant it with an alternative, be it a capsid or be it a NNRTI. So what's your -- is that your expectation that the narrative will start to change, focusing on weight? Or you think that, frankly, people will say, "Look, it's 52 weeks when you initiate therapy. And after that, you really don't see much more than that." How important is weight and lipid profile?

Yes. So I think the weight gain story has been -- has evolved pretty dramatically over the past few years. There's no question that really all the integrase inhibitors have been associated with some weight gain. But how much has varied depending on the study and what it's combined with. As you mentioned, when you combine an integrase inhibitor with TAF, you're going to see more weight gain. It also depends on sort of what type of study you're talking about. So in a naive study, you're seeing weight gain. But how much of that is return to health versus some added -- some "toxicity" from medication. So that's been debated. And what we know is that drugs like efavirenz, for example, people aren't gaining weight. And that in itself is actually probably not a good thing. And so I think what providers are now recognizing that some of the weight gain is a natural return to health. Some of it is people start to gain weight just like the non-HIV-infected population gained weight. And -- but there's some added impact of the INSTI inhibitor. And so I think providers now have gotten their heads around what they can expect. There may be some situations where they see people that have excessive amount of weight gain, that may influence them to look for alternative medications, maybe not an INSTI, but those situations are rare. And so I think I wouldn't want to hang my head on weight gain as being the differentiator given the long track record that integrase inhibitors have. I think it's going to be hard to get HCPs to really move away from integrase inhibitors on the basis of something like weight gain. What they're going to want to see from any new regimen is what's the efficacy, what's the barrier to resistance, what's the overall tolerability and they're going to want to see it in the long term. Because I think from our own example with Dovato, we started out the gate with non-inferior efficacy, but it's taken long-term data and multiple studies to really move the needle where practitioners now are saying, "You know what, I believe in that 2-drug regimen because we are seeing -- now we have 3 years, 4 years of data and multiple studies showing non-inferiority and multiple studies with virologic failure being extremely rare and confirming our high barrier to resistance. It's taken that to move folks from 3-drug regimens, INSTI-based 3-drug regimens, to believing in INSTI-based 2-drug regimen. So when you come with a 2-drug regimen that's novel mechanisms of action, people are going to be waiting on the other shoe to drop, Andrew. What else is there to find out about these products. And so I just don't see the field shifting overnight from, again, really established products like integrase inhibitors to novel mechanisms of action.

Going back just a little bit to Dovato and the barriers to uptake. I know initially there was some concern about the need to screen it for M184V lamivudine-resistence mutations. Is that still standard practice? Or are physicians initiating therapy without having those data to hand in treatment-naive patients? What's going on, what is required?

Sure. So obviously, in treatment-naive patients, everybody gets a resistance test, that's the standard. And so you have that information to hand. But for individuals that are switching, you don't have that information to hand. And so now that we have the TANGO study that we've shown now data out to 144 weeks with no virologic failures. And obviously, those folks didn't have -- we didn't screen those individuals with deep sequencing to look for 184V. They just didn't have past failure. Now we have the SALSA study that we shared new data actually at the international meeting. It's now the second switch study where we are a year out with no failures. Again, those individuals didn't have resistance tests in their hands to know sort of if they had 184V or not and still no virologic failures. And so I think that those 2 studies have convinced providers that if you select the patients that had -- that are -- that Dovato is indicated for, which is individuals who have -- don't have past failure and don't have suspected history of 184V, that you can successfully treat those patients without individuals breaking through. And so I think that confidence around being able to switch a large proportion of individuals that are in the clinic that haven't had failure, that are on even older drugs, which is what the SALSA study showed, that confidence is there. In SALSA, the individuals in that study had a range of past antiretroviral therapy of up to 250 months. So you have some individuals, came into that study, had been on antiretroviral therapy for 20 years, switch to Dovato and nobody failed. And so that kind of data gives folks tremendous confidence that they can use this in a big fraction of their populations.

So maybe just switching to [ PrEP setting ] and congratulations on the 2 positive trials that you delivered. But unsurprisingly, again, competition is coming and in the form of a once-monthly tablet and the trials are on the way, and Merck has seemingly expedited the clinical development for the MSM patient population, but this is a very innovative trial design that I'm assuming the FDA has signed off upon. So the question I've got for you is, if they deliver the same level of efficacy in the sort of the matched historic control they're effectively doing in that trial, to what extent do you think that the absence of having outcome data in terms of our control arm, or placebo control effectively, is going to hinder their adoption? Or whether because of the approval in the -- likely approval in the therapeutic setting in combination with doravirine and the fact that it's an easy once oral -- once monthly oral, that actually it's not going to be a barrier that basically they'll be a ready market for it because it [indiscernible].

Yes. I mean, one, let's let the studies play out and see what they show because we've set a super high bar with the 083 and 084 studies. 083 showed that cabotegravir dosed every 8 weeks was more than 3x more effective at avoiding HIV acquisition compared to oral Truvada. And the 084, it was 9x more effective. And so that's a super high bar to have 2 really strong superiority studies that are, I think you could argue, sort of the gold standard as far as design. These are double-blind, double-dummy studies that were huge and were endpoint-driven. And so they were basically the design everyone would dream to have their products deliver in a design like this. The newer study designs are going to be more complicated for people to understand. It's going to be difficult to demonstrate superiority. If you just demonstrate noninferiority to tenofovir FTC or TAF FTC, you haven't demonstrated superiority in the way that we have. And so I think we set the bar pretty high. The patient-reported outcomes we've gotten generally from our long-acting CAB treatment program and some of the newer information that's starting to come out around PrEP is that people really are happy about their experience. They love the fact that they don't have to think about it. And they don't have anything in their house that identifies them with HIV. And so will a monthly tablet give them that same satisfaction, that's what we'll have to find out. And then what -- the issue around adherence to PrEP is really the biggest challenge. As you know, with daily oral PrEP, people do well in the beginning and after roughly 6 months or so, their adherence tails off and they become vulnerable again. Monthly still requires an individual to act and take their medication on their own. And what -- one of the benefits of the injectable PrEP is that it is -- it's directly observed therapy. They come into the clinic, they get their shot and they'll keep moving, and they don't have to do anything in the interim. And so it provides the patients and the providers with the assurance that they've gotten the drug.

And if we talk to some of the commercial challenges, both at the physician level because, obviously, it's time taking just to make sure administer an IM injection as well as to the patient and the inconvenience of having to go and get a shot. Could you talk to some of the things that you're exploring in terms of self-administration, subcu and so on and so forth and the time lines to that? And what can be done in the interim to mitigate both those 2 dynamics, both at the physician level as well as at the individual level?

Well, what I think is most important is for us to get to longer intervals. So I'd really like to have intervals that are 3 months, 4 months or more so that people can get their directly observed therapy but need to come into the clinic less frequently. And so that we are laser focused on delivering that. And we have a vision to deliver that. And that was a big part of -- the Halozyme deal that we announced is part of helping us to get there, gives us more shots on goal to get there. With cabotegravir, again, still as a foundation, but adding in those novel agents. And so just it gives us way more options. I think that's the most important thing, is getting to longer intervals. Now the self-administered part, I think that there are some individuals that are interested in self administration. And so we're looking for opportunities to be able to deliver that as well. But the self-administered part is kind of a double-edged sword. The thing that we have heard from participants in our clinical trials is that they love not having to think about it. They don't want to have it in their house. They don't want to have it in their refrigerator. They don't want the chance that someone comes across their medications. And so the idea that self-administered means you bring it back into the house and most likely have it in the refrigerator or have it stored somewhere and somebody can still stumble on it is concerning for some individuals. But there are other individuals, and I think this is a smaller fraction of individuals, but there are some individuals who are very much out with their HIV status. They're not worried about somebody finding out about their medications, and they want control of their medications and want to be able to give it to themselves. And so we're working on ways to be able to offer that to individuals as well. So -- and then you asked a question about time frames. So what we believe is that between -- by 2027, we think we can have a self-administered option for treatment that is, again, CAB-based combined with one of these novel mechanisms of action. And then in the time frame after that is when I really see us coming with the ultra-long acting. So the CAB plus, again, all these novel mechanisms of action, but dosed every 3 months, maybe every 4 months, ideally every 6 months, but a full regimen that people can, again, come into the doctor's office, get it be done, not think about it again until many months later.

And so it's a nice segue to the Halozyme relationship, which you announced. And obviously, I'm familiar with hyaluronidase in terms of its utility for the Roche Biologics that facilitates subcu usage. I'm unaware that it's been used successfully, but I haven't hunted, to be honest, the data demonstrating the utility with small molecules as opposed to biologics. So what data -- and from a neutralizing antibody point of view, I get it because it's the same thing as where Roche has gotten, so I -- it's less of a jump, right, because you have proof of concept. But what data have you got? And I presume that you have some preclinical data with small molecule-based mechanisms that it can actually change the PK in a safe, predictable way as it seems to with biologics.

So I think that it's important to really think about what does a Halozyme product deliver. It basically is a facilitator of drug delivery, and that's how they're using it in oncology, that's how they're using it with biologics. They're basically just opening up a space to be able to allow you to give the dose subcutaneous that you couldn't give otherwise. You have to give it IV because the volume limitation is that a subcutaneous injection, you're limited to max 2 milliliters. Most people would even say 1, 1.5, but you could probably push 2. And so it basically -- you can't give a biologic with that small of a volume. And so what the Halozyme product does is basically clears out a space in the subcutaneous region, where you can give a larger volume. And so the -- how it impacts the PK is really that it allows you to have a wider surface area in order to be able to absorb the drug. So it doesn't modify the drug in any kind of way. And so there's no reason to believe it wouldn't work with small molecules. And actually -- in the literature, there's actually quite a bit of data about the use of recombinant human hyaluronidase, that's a mouthful, and with small molecules. One example has been used with ceftriaxone, for example. And so the...

The antibiotic?

Yes, the antibiotic. And it's also been used with morphine. And so it basically is a facilitator of drug delivery. And so there's nothing that makes us believe that it wouldn't work with small molecules in the same way it works with biologics. I think we're basically being innovative in taking that, the use there and saying, well, you know what, we -- one of our limitations in delivering our long-acting products is the volume issue. So take cabotegravir, for example. When we're giving cabotegravir intramuscularly, once a month it's 2 milliliters; every 2 months it's 3 milliliters. The maximum IM dose is basically 3 milliliters. So we're maxed out with how much CAB we can give to a person intramuscular. And then again, subcutaneously, you can only give up to 2 milliliters as well. So if I can open up a space where I can give 5, 10. And actually with Halozyme, you can give up to 20 as an injection. Now I can give a bigger dose with my current formulations or any future formulations and not be limited by volume. And so that's what it gives us. And so we don't have any reason to think that it wouldn't work to give us that sort of facilitation of bigger doses.

And there's no crystallization or local effects within that compartment you've created that's been seen? I mean just as a function of local reactogenicity or that hasn't been seen?

So what the work with the Halozyme products up until now has shown is that pretty much Halozyme is relatively -- I have to say, relatively benign in not impacting the immune response or injection site reactions that exist with the drug. And so whatever you're going to get with the drug is -- without it is pretty much what you were getting with it. And so that's been the experience that's described up until now. And so for us, at this point, yes, we do have some preclinical data that gives us confidence that we can move forward here, but -- and we haven't put all of that out in the public domain yet. But clearly, we have lots of confidence here. Otherwise, we wouldn't have went forward with this deal.

And this is mice or nonhuman primates?

I'm not going to go into too much detail because we haven't put that out in the public domain yet, but we will be putting it out in the public domain. And so I'll share it with you as soon as we're sharing it with the world.

And the first-in-human dosing with hyaluronidase and cabo, I guess, will be your first biologic to be tested. When will that take place?

So that study is literally in development now. Our goal is to get it kicked off before the end of the year.

Okay. Fine. Neutralizing antibodies, broadly neutralizing antibodies where GSK has been one of the pioneers, but they're expensive. They're expensive to manufacture compared to small molecules. I understand that by going down a subcu delivery system, you may be able to mitigate some of that as well as some of the compliance issues associated with IV administration, which is, I would imagine, a nonstarter. So could you talk to where you see broadly neutralizing antibodies within the future for ViiV's treatment offerings? Is it for the many? Is it for the few? Is it with one on a potential functional cure based regimen? Where does it fit in? Where does it fit in for you?

So I'm not a manufacturing expert. So I won't speak to sort of the complexity of the manufacturing process. But what I will tell you, I'm told by our people is that actually, there have been a tremendous amount of efficiencies that have come out of NAb, the fact that there are so many antibodies, mostly monoclonals, that it's not nearly as expensive as it used to be. One of the big attractions of broadly neutralizing antibodies is their -- the likelihood that they're well tolerated, that's essentially what we've seen so far, and that they're long acting. And so we're excited about the idea of being able to combine a small molecule like CAB with a broadly neutralizing antibody. I would be concerned about costs if I had to create a regimen that had multiple broadly neutralizing antibodies because that might get to be cost prohibitive. But if we're talking about one combined with a small molecule, we think that that's feasible to do. And I think it's exciting for the field. You brought up the fact that is there a potential benefit from a broadly neutralizing antibody beyond its antiviral effect. So does it have some effects on the reservoir? Is it doing something else? We -- those are one of the -- some of the other things that could be exciting and another part of what we want to understand as we're looking to take this into the clinic.

And then on your NRTTI, which I think is just about to enter the clinic or maybe it's already entered the clinic. So my understanding is, it's a prodrug of Merck's islatravir. And the immediate thing I thought of when I learnt of this is Merck has assiduously built out the IP that came with the drug when they licensed it back in 2012. And looking at other molecules or prodrugs, there's a pretty strong track record of the sponsor of the prodrug running into legal issues with patent infringement. Now I'm assuming your desire to take the drug forward suggests you feel pretty confident that that's not going to apply to this drug. But perhaps you could provide some additional color? And just confirm it definitely is a prodrug, it is metabolized to islatravir in vivo, correct?

It is a prodrug. But let me say that I'm not going to talk about IP because that's not my expertise. But what I will say is that our discovery scientists are always trying to basically innovate and deliver something that's unique with any particular molecule. And so for example, can we deliver an NRTTI that is -- has a formulation that's injectable, that can provide long-acting and even ultra-long acting. Same thing for the capsid inhibitor class and every other class because that's our strategy to focus on long-acting. And again, as I said, we're keyed in on that ultra-long acting. And so I -- we are just trying to deliver some innovative medicines for patients living with HIV and folks at risk. And so we basically build on the information that's out. And again, we have some great discovery scientists that are pretty miraculous in what they come up with.

And I guess I'm sort of reserving judgments on ViiV's discovery just because of the legacy of cabotegravir, dolutegravir, maturation inhibitor, they're all licensed products. So the -- as far as I know, this prodrug is one of the first ViiV internally developed, discovered compounds together with your capsid, correct?

Well, so remember that much of our discovery science team came from the BMS discovery scientists. And so fostemsavir is a product that was developed by those discovery scientists. The maturation inhibitors were developed by those discovery scientists who are now ViiV folks. And so it's not that all of our products are in-licensed. And importantly, folks that are part of GSK played a big role in development of dolutegravir and cabotegravir along with Shionogi scientists. So our scientists have absolutely contributed greatly to the portfolio that we have. It's not all in-license.

Yes. No, I'm just focusing on discovery elements. I mean clearly, you've been absolutely pivotal on the development side. Then just moving forward to the broader issue of the PrEP market, where we have managed a bridge between Truvada, Descovy and then cabo and there is the potential to grow that further, but there's still some material issues where PrEP is not being used in many parts of the world. And I'm not talking about the less-developed countries, I'm talking about the fact some of the most developed countries like the U.S. So there are a whole series of barriers, education access and so on and so forth. So what realistically can be done and at what speed to lift those barriers? I know under the former administration, there was some effort to eradicate HIV and a big part of that was PrEP. We're now, I would imagine, in perhaps more favorable world, although with additional cost pressures because of the pandemic. But how quickly can those areas be opened up and some of the issues which are precluding PrEP access addressed in order to build the commercial potential of the segment?

So we're really excited to launch long-acting PrEP because we think it's going to make a big difference because the daily oral PrEP has started to make a dent, but has not had nearly the impact that I think people hoped because of, again, the long-term adherence challenge. So what we think with long-acting PrEP is that because it is a directly observed therapy, because you can actually find ways to get to people, give them a dose and not have to see them again for 2 months and have them be protected, that you have opportunities to work with communities that may have been challenged before. And when we designed the 083 study, for example, which is the men who have sex with men and transgender women study, we made a point of enrolling, we said that 50% of the folks who enrolled in the U.S. needed to be black men who have sex with men, who are the population that are the most rapidly growing population in the U.S. We mandated that because we wanted to have a study that answered the question about does this PrEP agent work for that population? And so it did. And so when we -- even when we look at the subset of just the black MSM population within 083, it shows the same thing as the overall study, superiority versus oral Truvada. So we get to go to the community with that data that is from those communities, which has never happened before. As you know well, the previous PrEP studies really did not include young men, and it didn't include men of color for the most part. We got that in 083, men of color and young men. So we came -- we're coming with data from those populations to share with them and say, "Here's what this can do to transform the risk of HIV acquisition in our communities." And so we're excited to be able to launch this and really expand PrEP beyond sort of what has been the limited group that has received it so far to really the highest risk groups in the U.S. and in other developed parts of the world. Developing world, obviously, 084 looked at women in South Africa and demonstrated incredible results. And we -- that has stimulated a lot of excitement in the country, from the women, but also from health ministries, just because they see the potential for what this product can do to transform the epidemic in their countries. And so we're really excited to be able to hopefully get our first approvals soon, and then we'll move -- really march around the world to get more approvals. I do think this can have an impact on ending the epidemic. The U.S. has focused on sort of the end the epidemic sort of strategy. I believe that long-acting PrEP is going to be a big part of that strategy as to how do you roll this out? How do you get this into more communities? And we're working with the U.S. government to try to talk about ways that we can do that.

And how much of the barrier is the lack of data in the high STD group, so men of color, MSM patient populations that there wasn't historically data on and now there is? And how much is it that by its nature, PrEP therapy is a function of relationships? As people cycle in and out of relationships, they'll just stop using PrEP and then you got to restart it and maybe they do, maybe they don't. And I'm just trying to gauge how successfully -- to what extent is the missing data in a similar patient population addressing it? Or are they other exogenous factors such as the relationships...

It's absolutely both, Andrew. I mean there's no question that some of the social determinants of health are some of the -- they impact the fact that it's primarily black MSM that are at the highest risk in the U.S. Those challenges aren't going to go away because we have 1 study. However, having a study and a product that you can deliver in a different kind of way with directly observed therapy, where you can -- as long as you can connect the individuals and get them into a clinic or get a clinic to them, can you dose people from mobile vans and that sort of thing, finding ways to get medication to them in a way that is acceptable to them and doesn't require them to take a pill every day, we think that can make a big dent. And so I think you have to change the paradigm and then be aggressive at how -- figure out how to roll it out to the communities that need it.

When we talk about women, which is a significant contribution to new infections, which because of the medical -- or going to family planning clinics, it may be possible to intervene with greater success than perhaps in the male population. So could you talk to women PrEP both with the IM, but also where you think depot formulations fit in? Because obviously, they exist within a contraceptive framework. Family planning centers are set up. And obviously, Merck is exploring that with -- presuming they're going to do a PK/PD trial once they get approval for the once weekly oral. So how successful do you think a depot is going to be, particularly in the women? And so I guess I'm asking 2 things at the same time, which is, one, the ability to capture women with somewhat greater use than men? And then respective market shares of IM versus a capsule-based, a depot-based formulation?

I think one of the challenges with not enough women on PrEP is that not enough providers are informing them and offering them PrEP. And so I think if we -- we do need to train providers to stop assuming who they think might be at risk for HIV and really start doing what the CDC and other sort of public health organizations are advising, which is talk to everybody about HIV risk and talk to everyone about the potential benefit of PrEP. So I do think that the idea that you can talk to a woman who's in a family planning clinic about contraception and about how she can stay HIV negative with long-acting contraception and long-acting PrEP, I think, is actually -- it is a good match, and it's something that we definitely think is a wave of the future in resource-rich and research -- resource for environment.

So then segue into the therapeutic side. [ Till ], today, the massively dominant patient population on triple therapy, although the patient may only be aware they're on a single tablet, but it is triple therapy. I know parts of your early arguments of moving to doublet therapy was reduced drug-drug interactions, particularly in the aging population, which is growing as a function of improved outcome in these patients. So to what extent is that message resonating? And do you have data to support that in order to drive switches, particularly from the more mature segments of older regimens? Because I know that you've stated it often, and there is some evidence of drug-drug, but I've never seen the hard data set, if I was a clinician, for someone to show, look, this is a preferred option in terms of reduced events. Do you have that? Are you using that? And how big is that opportunity to switch, just in the very near term with Dovato?

Sure. So the benefits of 2 drugs over 3 drugs are, taking away a drug -- every drug has side effects. And so if you can take away 1 drug, you're reducing -- you're just, by definition, reducing side effects. That's kind of a no-brainer. And providers absolutely accept that idea. Even they recognize how tough it is with some of the newer regimens that you don't necessarily see huge numbers of individuals having to stop due to side effects in the short term. But over the long term, the reality is that all medicines have side effects, and so you want to be able to avoid those. And then the drug-drug interactions is the other part that you mentioned. So in our clinical trials, we were able to show fewer drug-related adverse events with the 2-drug regimen in comparison to 3-drug regimens. We don't really compare for drug-drug interactions in the clinical trials, as you know, because they're just by definition, the clinical trials, you're avoiding the medications that potentially cause drug interactions. So you don't necessarily get it out of that. But what we're seeing, so how do we know that it's resonating? Well, we actually do talk to HCPs about sort of their attitudes, their intent to prescribe and we see the prescription patterns. And we see the uptake of Dovato and Juluca. And it has absolutely been a very positive trend. You're seeing more and more providers using the 2-drug regimens. And then once providers prescribe it for one individual, they start prescribing it for more and more because their experience is positive. And so we see that trajectory going in a very excellent way. We're actually seeing more switches to Dovato, both in the U.S. and in Europe. And we think that trajectory is going to continue. Because I think what's happened is that, again, as I mentioned, that data that we've shown is now long term and it's multiple studies. And so people needed to be confident in the 2-drug regimen. They've got the concept that, yes, 2 drugs is better than 3 in the long term. But am I giving anything up. And that's what we've needed to demonstrate, is that long-term, continued efficacy, continued benefit, not breaking through, high barrier to resistance, because we've shown them that, we're seeing providers with more confidence in Dovato. And that's what they're telling us, and we're seeing it in that update.

And presumably the switch market, you would imagine, would begin to reaccelerate as hopefully COVID comes under control. And you see it in the data, and you start the switching that's slow during the pandemic.

Absolutely. It's been slow to recover. But I mean we've been slow to get out of the pandemic, right? I mean every time we think we're making good progress, we keep having sort of a little bit of slippage back in the wrong direction. But it's definite. Switch market has definitely been suppressed. And not just the switch market, but actually, HIV diagnoses have also been suppressed. There's new recent data that's just come out that I think I saw that in the U.S., in 2020, there were something like 700,000 less HIV tests done, somewhere in that ballpark. And that means that people are not getting diagnosed. So a lot of the sort of, where emergency rooms were doing routine HIV testing for everybody that came through the door, whether or not they had any reason to test them for HIV or not, and where you had all sorts of HIV tests being done in different public health settings, all that attention got shifted towards COVID. And so HIV has been tremendously downplayed. So you're not diagnosing new patients and then the switch market is suppressed. So I do think after we get past this pandemic, hopefully sometime soon, I think we're going to see -- we'll be able to understand what's happened over the past couple of years. And we'll be able to get caught up again and start seeing more patients in the clinic, docs will have the opportunity to offer them switch options and then hopefully individuals that are HIV-infected and not being diagnosed in this period where not enough testing is happening, those folks will get diagnosed and get started on treatment as soon as possible.

So my final question, as we're pushing up against time, is, ViiV has been historically laser-focused and very successfully focused on HIV. But of course, infectious disease doctors who treat HIV, there are a lot of comorbidities which come with HIV, hepatitis B, opportunistic infections and so on and so forth. To what extent has ViiV opened broadening its R&D efforts beyond PrEP and therapeutic HIV approaches? Or does it remain business model as before, we have enough to execute and do within these segments and we can always work with GSK hep B efforts or whatever it is, we don't need to go broader into antivirus, antibacterials, whatever.

It's the latter, yes. I mean we believe our focus is a major strength of our organization, that many of the people that are part of ViiV have been doing HIV work, research and clinical work for their entire careers. They have a passion around it and they -- that focus is really where a lot of that energy comes from. I mean that's -- I can just say that some of the most passionate people I've ever dealt with in research are in ViiV, focused on HIV and have been for their whole careers. And so I do think we're happy with the business model as it is. There are opportunities to partner with GSK and other companies to look at HIV plus hepatitis or HIV plus TB, but HIV is our focus, and that's the case for the time being.

And then I lied, there is one final question, which is on your capsid inhibitor because I've been having conversations probably going back to 3 years with Deborah, where it was about to go into the clinic. And I think now it's finally going to the clinic. And I'm assuming that the lead candidate has dropped, and this is -- there's been backups or whatever. So am I correct in that assumption? Has the lead candidate changed during that period and if so, for what reason? Or has it just been resource prioritization in terms of the broader portfolio?

The lead candidate has not fallen over, and it will get into the clinic next year. And there have been some delays in progressing some products, more of it formulation related than anything else. And -- but we continue to march down this path and are confident we're going to get into the clinic. Most likely, it will be early next year for the capsid inhibitor.

Got it. Well, look, I think we've taken up all the time. Thank you so much, Kim, for joining us today. And look forward to seeing, hopefully, in person before too long.

I hope you're feeling better, and I wish you a full recovery of brain fog and everything else. And thank you for having me.

Thank you very much.