GSK plc (NYSE:GSK) 5th Annual Evercore ISI HealthCONx Conference 2022 November 30, 2022 8:00 AM ET
Company Participants
Deborah Waterhouse – Chief Executive Officer, ViiV Healthcare
Kimberly Smith – Head of Research & Development
Conference Call Participants
Umer Raffat – Evercore ISI .
Jessica Hui – Evercore ISI
Umer Raffat
Well, thank you all for joining us on our day two of the conference. It’s a pleasure to have the management team from GSK ViiV business. And I always really enjoy having them and that’s been a tradition now since the first time we ever did this conference in Boston. So, really good to see you guys.
Deborah Waterhouse
Great to see you too. Thanks for inviting us.
Umer Raffat
Absolutely. There’s a lot of talk about, but I felt like it’s always a great idea to turn it over to you. I feel like you guys framed the discussion very well every time. So let me defer to you.
Deborah Waterhouse
Great. Thanks, Umer. So at our business investor update last year in November, we made some commitments in terms of our progress during the next decade, both commercially and from an R&D perspective. So we talked about mid-single-digit CAGR, between 21% and 26%.
We talked about Cabenuva and Apretude together, being at around £2 billion of value by 2026. And we talked about the excitement that we had about our early development pipeline, but we had a number of milestones, which we knew that during 2022, we needed to deliver, to build confidence in the future of the — beyond the loss of exclusivity of dolutegravir.
And, I would say, 2022 has been a great year, like beyond our expectations, I would say, both from a commercial performance perspective, from an R&D perspective. So we are currently guiding that we will grow high single digit this year.
And that’s really powered by the performance of our innovation brands, principally Dovato and Cabenuva, but also Apretude has been launched. Fosamprenavir is doing well. And obviously, Juluca continues to power forward for a very sort of a specific population. So that’s been great.
And then, Kim and I set ourselves 10 really key milestones that we needed to beat or meet to give us confidence that we had the early development pipeline that we dreamed of. And, actually, we’ve met and exceeded many of those milestones, and we can talk about that today. So, I think, you find this very positive, very upbeat, very confident and really delighted to have the chance to talk to you today, Umer.
Question-and-Answer Session
Q – Umer Raffat
Outstanding. Well, thank you for that. So, maybe, just to kick things off, I feel like an important theme, and I think you kind of reflected on it when you opened it up as well. It looks like there was something unique that happened from a macro perspective in the HIV market during COVID. And now we’re starting to come out on the other side of that.
And perhaps, can we start by thinking about that and speaking to that? Because for a while, there was starting to be this perception that perhaps the next-gen integrase inhibitors are starting to plateau?
Deborah Waterhouse
Yes. So, let’s talk about the two markets that we play in. You’ve got the PrEP market and you’ve got the treatment market. So the treatment market is today worth about $23 billion and the pet market is worth about $3 billion, so important to put them into context.
The treatment market is growing globally at about 2% to 3% and currently, the PrEP market is growing at about 20%, so a lot more of a growth trajectory in PrEP, even though it’s a smaller market.
So what we’ve seen, and I’ll talk about now Europe and the US, because they’re both really quite material markets from an HIV perspective. So, in Europe, we have seen the volume at a total level and the dynamic market, pretty much return to the pre-COVID levels. There’s a couple of countries where that hasn’t quite happened yet. But in the main, Europe is back to the dynamism and the size of pre-COVID from the volume perspective.
If we talk about the US, we saw a significant suppression of the dynamic market as people were asked not to come into the office to see their position. And if they needed to see a position, it was virtual. We saw less testing, and we saw the dynamism of the market come down.
There’s been a bounce back. So the TRx market is now exactly where it was pre-COVID. So that’s come back, and in fact, that’s grown beyond that level.
But the, sort of, NBRx part of the market is not in the same place as it was pre-COVID and I’m not sure it’s going to return. So if you remember going into COVID, I think, it was about 6,000 new – or 6,000 NBRx scripts per week. It’s dropped back to a fairly steady state now of about 4,500, 4,600. So you’ve got a little bit less dynamism in the US still. I’m not sure that’s going to bounce back all the way to where it was pre-COVID, and often, it’s new product launches that stimulate that to a certain extent anyway. So we’re a little bit less dynamism in the US. Europe back to where we were, but at the TRx level in the US and Europe back to pre-COVID level.
Umer Raffat
Got it. So back to pre-COVID levels. And, I guess, how do you think about the interplay between these — between the categories? It looks like the — at least on a TRx basis, it doesn’t look like the dolutegravir, bictegravir, that whole category is anywhere close to any sort of plateau?
Deborah Waterhouse
It isn’t. No. So I think we’ve talked in the past, Umer about the fact that integrase inhibitors are absolutely at the core of HIV treatment. And, I think, if you look at the dynamic NBRx, as an indicator, more than 70% of NBRx are integrase-based regimens, and we’re not at that level yet from a TRx perspective. So the market has still got a way to go in terms of adoption towards integrase inhibitor-based regimens. And particularly those single tablet ones such as Dovato, Triumeq or Biktarvy, that is still on the up and up. So there’s still a way to go and we’re excited about that given that we’ve launched, obviously, highly innovative two-drug regimen and in the form of Juluca and most importantly for us, Dovato.
Umer Raffat
Got it. And would you guys consider at any point having a triplet as well? When I say triplet, I’m talking about a slightly different triplet than the one like the Triumeq that you have?
Deborah Waterhouse
We’ve thought really hard about this over many years, and we know that from patient insight, they would like a couple of things. They want to suppress that virus with the least amount of medication possible. Because if you’re diagnosed with HIV, your 20s, which is sort of the most common time that it happened. You now live the same length of life as somebody who’s not living with HIV. So you’re going to basically be taking medication for 40 years to 50 years, and there is a real desire to minimize the amount of drug that you put in your body. The second thing people want is longer intervals between administration, which is how we can launch our long-acting injectables. But we’ve managed to bring a product with dolutegravir call it that suppresses the virus with two drugs, and we have in our pipeline only two drug regimens. So we would not go back to a three-drug regimen, mainly because every single drug brings with it some side effects of some sort. And if you don’t need — if you don’t need three drugs, why would you take them when you could have two? I mean, you are so connected still to the community and people living with HIV, what you hear?
Kimberly Smith
No, that — you’ve said it exactly right, Deborah. I mean, Umer, you know, that we basically pushed the envelope when we developed Juluca and then ultimately, Dovato. And Juluca we were a little more careful in that we focus that on individuals that were already suppressed or suppressed which or with Dovato, we went all the way there to naïve patients and have demonstrated with I think out of doubt now that two drug regimens that are based on dolutegravir or based on a potent integrase inhibitor are as effective as three drug regimens.
And so — and I think, you can see that our competition has followed us down that path. Our competition is not developing any three-drug regimens anymore with the exception of what they might be doing with regard to NASH were they are multiple in there. But every other regimen is being developed by either, I mean, pretty much is just Gilead and Merck that are out there now developing new regimens, everyone is pursuing a two-drug regimen. Now mind you, whether or not they will be as successful as our two-drug regimen is still to be determined, because we do believe that integrase at the core is critical, and we are the ones that have an integrase at the core of our two-drug regimens is a daily or long-acting.
Umer Raffat
Got it. I mean, I think perhaps at some level, one of the questions I always think about is — and this is more a high level, and there’s a lot of specific pipeline programs I want to get into today because it’s actually a very interesting stuff coming up. But one of the things I always look at is GSK size, so at the heart of it, the core offering is the next-gen integrase and you guys were the first ones to come up with that molecule and there was also some litigation on the chemical structure similarities with bictegravir.
However, when I look at the actual reported sales, considering it’s the integrase driving the sales, there is a pretty large discrepancy in where the Gilead business tracks versus the ViiV business track. And I’m curious as you guys think about planning out in your long-term aspirations, doubled, like a $10 billion-plus HIV business. Is that something that a scenario that you guys contemplated not necessarily looking for any type of guidance, but is that something you guys aspire towards or something along those lines? Because it’s very much something that has happened off of dolutegravir, almost, I would argue.
Deborah Waterhouse
I, mean I do not said, I can answer and then I think I’ll hand it to you. So I guess the way we think about it is we look at our pipeline and we have target medicine profiles that we design our medicines to meet those target medicine profiles have value attached to them. And we believe that our third-generation integrase inhibitor plus a partner that could go every six months as a full treatment regimen will be — would be a game changer to take us to that next level.
And that’s — if you say what are we excited about in our pipeline, there’s actually an awful lot, but that’s third generation integrase plus the opportunity of pairing it either with a capsid inhibitor or BINA [ph] that starts to create a future vision in the realms of what you’ve described. I mean $10 million, $5 billion, $7 billion. I wouldn’t put a number on it. But if you ask me what I’m most excited about and how I see the evolution of ViiV and why are we confident about the evolution of ViiV beyond the loss of exclusivity of dolutegravir, that is why I’m really excited.
I mean, Kim, you’re the one to validate the drug, so what do you think?
Kimberly Smith
You’re exactly right. I mean, again, we said our foundation of our current regimens and future regimens is an integrase inhibitor. We have the next generation beyond dolutegravir, cabotegravir and bictegravir with our third-generation integrase inhibitor. And as we’ve said, it is — our expectation is that it’s going to give us more options for longer acting and that it’s going to cover mutations that may have been generated by previous generation integrase inhibitors.
And so we expect it to have a very, very high barrier to resistance. And so that that’s how you change the game further is to be able to cover everything, get to a longer interval and have integrase inhibitor at the foundation, and that’s our intent.
Deborah Waterhouse
I knew this — I mean, the work that Kim has been doing with the team have actually accelerated the development of that medicine. That’s one of the big wins in the year. So we are looking at the first time in human in the relatively in a near future.
Kimberly Smith
Very near future. The original plan was that we were going to get that done next year in 2023. We expect to have it done by the end of this year. So we’re accelerating that asset as quickly as possible, just because we think that it really can bring something unique and special.
And I think the point around integrase at the core is critical, and we know that our competitors would love to be able to say they have integrase at the core. That is part of the challenge, I think, that they — our competitors are experiencing is that the agents that they’re trying to build a new regimen on, have challenges that don’t make them the most ideal foundation.
Umer Raffat
Got it. But this will also be integrase plus one new kind of development path?
Kimberly Smith
Yes. One agent.
Umer Raffat
One agent, okay.
Kimberly Smith
Not necessarily. So it will be, yes, integrase plus one additional agent.
Umer Raffat
Got it. And if I may, and this is a loaded question. Has there been a lot of thought and discussion internally among between the two of you and also with your broader team around an IP mode, which is stronger than the last experience? Like, does this scaffold out there on the patent website somewhere? Like is there any development effort on related scaffold? I got to believe this is probably high on the agenda this time around.
Deborah Waterhouse
I would say that we have been very diligent and very focused on the IP coverage for our new medicines. I wouldn’t go any further than that. But obviously, it’s at the heart of any pharmaceutical company. And yes, I would say, high level of discussion and diligence has been applied to that area.
Umer Raffat
Okay. But the past experience was sort of fresh in everybody’s minds that would argue.
Deborah Waterhouse
Yes. I mean we believe we had a patent on the chemical structure of dolutegravir. And obviously, it would seem that we found a settlement with Gilead based upon maybe the IP that we had there.
Umer Raffat
Got it. Make sense. Can you speak to — and so this is sort of starting to think about the third gen integrase. Can you speak to any key resistance mutations that are being observed on dolutegravir and bictegravir, because the extent of use that’s happening, it’s only inevitable that they start to pop-up and Kim, I know you’re always very close to the patient community? So, like what are you hearing about? Is there a certain type of thing that’s starting to happen more profoundly?
Kimberly Smith
They’re rare, actually. So — and individuals who start with dolutegravir, bictegravir as naïve, the likelihood of failing with integrase resistance is still very rare. Occasionally, you’ll have somebody fail 263 or a 118 mutation, but they are rare. The most resistance is seen in individuals who had first generation integrase inhibitors and fail those and dolutegravir has basically been able to suppress most of those, but not all. And so when you get to multiple integrase mutations, you could even get to a point where dolutegravir is vulnerable. We believe that the third generation — third generation integrase will cover even those multi INSTI mutation viruses.
Umer Raffat
Got it, got it. And because it covers that, presumably, its data strength might be stronger than what Dovato put up, being a doublet. Am I following the logic path right?
Kimberly Smith
Well, I mean I think Devoto has shown itself to be extremely strong. And when I say that failure with resistance is extremely rare, that includes Devoto. And so, failure of Devoto is not associated with integrase resistance. It has literally this case report when it happens, it’s so rare. And so we expect to step that up even further. But the — so the benefit from that third-generation integrase inhibitor is, yes, a broader coverage of INSTI mutations. But it’s the longer half-life it actually is probably the most exciting, because stability to get to longer intervals longer than what we can get with cabotegravir.
Umer Raffat
I see. So weekly dosing, that kind of thing as well as a six month of the injectable?
Kimberly Smith
Well, oral weekly is something that we’re discussing, but we haven’t made a decision to make a commitment in that area, but we really want to get to six months, and that’s what we see that third generation integrates giving us.
Umer Raffat
Got it. And Kim, I remember the very first time, I spoke to you about this broader topic you were telling me that was one of the motivations for you to lead clinical practice being able to be in a setting where patients could just – it’s kind of like a vaccine of sort for these HIV patients, and they don’t have to show the disease and the pills to anyone else. How has that evolved since in terms of penetration for the long-acting and – it looks like it’s on a certain path and it’s continuing to evolve, but I’d be curious what you’re hearing and seeing over the course of the last five years of takeaways?
Kimberly Smith
So, Cabenuva or Vocabria/Rekambys as it is in Europe, has delivered exactly what we expected from a patient perspective. That’s what we hear, and that’s what providers come back to us and say is that, the patients come back and say it’s changed their lives, because they no longer have to worry about remember to take their pill, they may no longer have to worry about disclosure of their status when we’re carrying that bills around all of those things that we saw in the clinical trials, when we did questionnaires for patients, all those things that we saw on the clinical trials are playing out in real life. And so it is changing their lives. And that’s why we see the future and everybody else sees the feature of HIV being long-acting.
Umer Raffat
Got it. What’s the penetration right now for the long-acting’s across the overall HIV prescription?
Deborah Waterhouse
So, about 10% of switches are going to Cabenuva and the penetration at a TRx is probably around the 2%. So it’s still quite low. But we’re in the – really one year into kind of the – the launch of that medicine. Last year, obviously, we haven’t got – we’ve still got COVID hangover and we haven’t got the license that we wanted. This year, we delivered every eight-week license. The oral lesion is optional, and we’ve seen quite a significant uptake. And actually, every quarter, we’ve delivered, I think, ahead of consensus on Cabenuva. So that product is really, really growing – when….
Umer Raffat
You know, what’s interesting is about the – about the data point you just shared is I remember in antipsychotics, which was – there was a lot of parallels there for particularly….
Deborah Waterhouse
Yeah, we use it as a comparator. I mean, we’re developing our models. I think we talked about that before.
Umer Raffat
Right. And I know in the US, they’re mid to high single-digit penetration and growing and ex-US surprisingly in the teens in Europe. So it will be interesting to track this. One last thing….
Kimberly Smith
I think Umer — one quick point about this. Every conference is dominated by discussions of cabotegravir, because what is happening is – the clinics took some time to figure out how they were going to implement cabotegravir. And they’ve come with their plans and now we’re seeing that dramatic uptick because they all have waiting list, I mean, literally every provider that I talked to says, I have a waiting list of people that I want to put on Cabenuva. We are doing – we’re going slow in order to manage our capacity. But we see tremendous excitement about Cabenuva and is only going to grow.
Umer Raffat
And it’s every couple of months, right?
Deborah Waterhouse
Every two months, yes.
Umer Raffat
Right. So the step-up on the third gen would be you effectively start to make it more like a long-acting PCSK9 in every six months?
Kimberly Smith
Every six months is our goal, yes.
Umer Raffat
Got it. Got it. Last thing, no data presented to date on the third gen integrates, correct?
Kimberly Smith
No data presented in the public yet to-date.
Umer Raffat
Got it. Okay. Excellent. Maybe that’s a nice segue into some of the other pipeline programs as well. I know the bispecific antibody looks very interesting. But I also know there’s been some attempts in the past, like Gilead over the years has shown some stuff, but it’s kind of gone nowhere. Could you maybe just remind us what’s been the history there? I know Jessica had some specific ones on your program?
Kimberly Smith
So we have a bispecific antibody that we have not presented any data in the public domain on that one yet. But we have presented on the N6LS broadly neutralizing antibody. And so that was the proof-of-concept data was posited at the Glasgow conference. And that everyone was excited about it, because of the potency, but also because it showed good activity even at low doses.
And so what that does is give us the optionality that we hope to have with this. The possibility they could be a candidate to partner with cab in a self-administered option or in an ultra long-acting option, because obviously, the neutralizing antibody. This is has the LS modification on it. It is already long-acting. And so we’re very confident it gets to easily three months, four months is likely and six months as possible.
So all of that will understand more of the over the course of next year, and we will share some more data on the N6LS broadly neutralizing antibody in basically the first quarter of next year, hopefully, at Crown.
Umer Raffat
Got it. Jessica, did you have a follow-up on this?
Jessica Hui
Yes, you basically answered my question. But I guess the question is, in prior monotherapy bNAb studies resistance emerge in nearly all treated patients, was N6LS resistance potential evaluated in the Glasgow study that was presented?
Kimberly Smith
So in the proof-of-concept study, they were just given one dose. So you’re giving one dose to see how much viral potency you got. And so we did not — it wasn’t continuous dosing to look for resistance. And so we have one individual in that study did not respond, which is we expect that there will be occasional individuals that aren’t sensitive to broadly neutralizing antibodies.
The nice thing for N6LS we expect it to be rare, because it should cover 96% to 97% of viruses. But that one individual is who you kind of almost want to have that so that you can understand what are the mutations that need to be present in order for people not to respond so you can have an appropriate test, just screen for who’s sensitive and who’s not.
Jessica Hui
Okay. And just to follow-up. So you think that the addition of cabotegravir in the Phase 2b study will deter resistance and dosing could be every three to six months, you said with this combination?
Kimberly Smith
Yes, yes.
Jessica Hui
Okay.
Kimberly Smith
So, yes, at least three and as far as we can go. So at least three. And yes, the combination of two drugs, we expect to reduce the likelihood of resistance occurring. I mean, any product that you give as monotherapy resistance is selected. That’s even given even with the second-generation integrase inhibitors and given a monotherapy, you see resistance occurring more frequently than when there as a part of at least a two-drug regimen, still not common, but it occurs. And so monotherapies a challenge in any circumstance. Here, our expectation is that combining with, again, a highly potent high barrier to resistance integrase inhibitors is going to reduce the likelihood of resistance occurring to N6LS.
Umer Raffat
Okay. Excellent. Between your maturation inhibitor, the capsid and the nuke. I guess, where would you like to spend more time first?
Kimberly Smith
So when you say the NUC, I think you’re referring to the NRTTI.
Umer Raffat
Correct.
Kimberly Smith
Which we’ve paused because…
Umer Raffat
Oh, is that right? Okay.
Kimberly Smith
We’ve paused the development of that because of the ezlotivir lymphocyte toxicity. We have not — we’re not further developing that for the time being. I think that’s a significant problem. And I just think we’re in a world now where that level of toxicity, particularly lymphocyte toxicity is not something that most providers are going to be willing to accept given the options that are out there as alternatives. So we’re not developing that.
Umer Raffat
And that will require monitoring, right? The real world?
Kimberly Smith
Well, it’s actually — really to me in the longer term is the goal of HIV treatment is to have recovery and increases in CD4 cell counts, if you see them declining because of a drug toxicity, that’s not acceptable. And what is the long-term consequence to that for patients is the question. So that’s why we’ve made a decision not to pursue that particular because our drugs were pro drugs of ezlotivir. And so any challenge that came with ezlotivir was going to be present.
Umer Raffat
I see. I didn’t realize that. My thought, Kim, on this broader point was I thought Dovato perfectly reasonable and a very good drug. It was being forced in to being a weekly. So you’re going from like 0.5 milligram to a 1 milligram dose daily to having to do 20 milligrams just to get to the weekly or 60 milligrams to get to monthly. And it was at Cmax that was causing some of these lymphocyte problems. So as long as you stuck to a once-daily kind of regimen, it would have been just fine and you wouldn’t have run into the CD4 problems.
Kimberly Smith
Well, that’s possible, Umer. But remember that the decision that they’ve made now in pursuing even the daily dosing is they reduce their daily dosing from 0.75 milligrams down to 0.25 milligrams because they did see some of that lymphocyte change even with the 0.75 daily dose because it’s an accumulation of the product within the cell. And so they dropped quite substantially. So they’ve got to do those studies to show that the 0.25 milligram is going to give them the same kind of potency and varied resistance that they got with 0.75 and then whether or not they can actually get to a weekly dose is still to be determined.
Umer Raffat
Do you think it’s a metabolite that might be driving this, or is it active metabolite?
Kimberly Smith
All I can go by is what Merck has said, and they say it is apoptosis of lymphocytes.
Umer Raffat
Driven by the active metabolite, not necessarily a side metabolite, because presumably, you can get around that problem in your side metabolite?
Kimberly Smith
Yeah. Not — they haven’t gone in anything specific about whether or that is the parent or metabolite.
Umer Raffat
Got it. Okay. Perhaps if we could spend a quick second on your maturation inhibitor. I think this is being developed for the refractory HIV setting? And maybe just the high-level questions before we get into data. A lot of investors often ask what the commercial opportunity looks like for some of these. And I’d be curious how you would characterize that?
Kimberly Smith
So we haven’t defined exactly which population we will target MI254. We have a commit to Phase III decision that we’re going to take in the first quarter of next year. And so we’ll define the populations in more detail at that point.
Deborah Waterhouse
I think the way that we’ve been sort of talking about to Emma is that we’ve got in treatment to target medicine profiles that we’re focusing on. The one is about the ultra long acting. So getting to the longest gap between administration possible, and the other is a self-administered at home. And so what we’ve got is the number of shots on goal in our pipeline, and we can talk about each of the individual ones, because I think that could be interesting. But what we said is that, by 2024, in the first half of 2024, we’ll have enough scientific data to decide which bets we’re going to take in terms of our next generation of either a self-administered at home or a sort of a longer-acting than Cabenuva, Cabenuva plus almost option.
And then, the next stage is to get to the third-generation integrase inhibitor, and that ultra long-acting every six months kind of option. And so, for us, it’s about looking at each of the assets and we’ll make a decision in 2024, which ones will progress as ultra long-acting or at home. We were not — we don’t see ourselves launching all of the options in our pipeline just to clarify that.
Umer Raffat
I see. But the once-daily should be — but as a — okay, got it. So, I guess, what you’re saying really is that, there’s like this underlying momentum, which is towards where is the market and the patient treatment landscape going, which is towards longer acting. And those are the stuff — those are the regimens you’re prioritizing. Maturation could very well be a perfectly reasonable molecule, but this is still in the once-daily, perhaps more competitive in the HIV of 2000s, but perhaps not on the HIV 2030s.
Kimberly Smith
So we’re still determining whether or not there’s a possibility for maturation inhibitor to be long-acting, that’s still in the works.
Umer Raffat
Got it. But as a once-daily, looked like the data was better than the prior maturation inhibitors.
Kimberly Smith
Well, we’ve not put the Phase IIb data in the public domain yet. I think, you’re talking about the proof-of-concept.
Umer Raffat
Yes.
Kimberly Smith
The potency was quite good, and the barrier to resistance is, I believe, to be better than the first, what we call the first generation, well, I guess, the second generation, which was 795. And 795 also had GI toxicity. And so what we saw in some of the early studies with 795, while both GI toxicity and some resistance that occurred. And so, it didn’t have the barrier to resistance that we felt like needed to be in place for us to pursue that. That’s why we moved on to 254 and 937
Umer Raffat
Got it. Okay. So the Phase II — and I think this is the 160 patient trial. That’s the one that’s not out yet.
Kimberly Smith
So there are two Phase IIb studies. One of them is over 200. The other one is roughly 160-ish and one is a three-drug combination with the maturation inhibitor, and the other is a two-drug combination with dolutegravir and the maturation inhibitor.
Umer Raffat
Got it. Okay. Makes sense. And, okay, excellent. And one last thing, Kim, maybe just to clarify this, mostly, it’s my lack of understanding. What are subtype B and subtype C viruses?
Kimberly Smith
So, I mean, there are literally dozens of subtypes of the HIV virus, and there are regional differences where those particular subtypes exist. And so, in the US, it’s primarily subtype B virus, whereas in South Africa is primarily subtype C. And so — now, most of the time, that’s not a relevant question, because the drugs will cover all the different subtypes, but in some cases, you’ll find a particular class that might not have as good activity against one subtype or another.
And so, some of the unique — so, for example, fostemsavir doesn’t cover AE virus that is present in Southeast Asia, for example. And so, that’s the difference between — there is minor differences in the virus that are the various subtypes. And, again, it’s mostly that you see those subtypes based upon the region that the person comes from.
Umer Raffat
Got it. Okay. Excellent. I guess a question for both of you really is, as you think about sort of the next 10 to 20 years because that’s really where your pipeline is going to be playing and including your third-gen integrase inhibitor, what are some of the key competitor molecules that you’re looking at for that get your attention?
As both Mark and Gilead are hinting at some additional stuff coming up, but it’s never quite clear to me if they actually have a third-gen integrase or not, I know they both have an integrase, but I don’t know if any of that is third-gen?
Deborah Waterhouse
I don’t know any more than you do about their integrase inhibitors. It’s just word that they have some in their pipeline. I mean, I think …
Umer Raffat
Right.
Deborah Waterhouse
…I mean, as you know I mean, obviously, we’re developing a capsid inhibitor, so Gilead’s capsid inhibitor, I think, is certainly an interesting molecule. And any time there’s a new drug that is new mechanism of action that can help individuals who are highly treatment experienced that need a new drug, that’s a positive thing. So that’s — that would be my comment about the competitors’ products.
And I think over the way that we’re looking at it is, we’ve done a huge amount of work on patient insights and what they’re looking for from medication to treat their HIV or to prevent HIV in the future. And what comes back is, the least medicine I can possibly take, the longest interval between having to take my medication.
Although some people are happy with what its late day, but the kind of the duration between administration is a really important need. Obviously, safety and efficacy goes without saying to high barriers of resistance, minimal side effects.
And we feel that, we’re leading the way from an innovation perspective, both in terms of oral two-drug regimens, but also treatment, we have a treatment, a long-acting treatment, in Cabenuva that is meeting to a certain extent that the needs of people who are living with HIV.
What we’re trying to do is to do a better-and-better job of meeting those needs. And that’s where our pipeline is. And I think we can see our competitors are following that route as well.
But at the moment, it looks like there’s going to be quite a long way between the next long-acting injectable from a competitor for treatment and what we’ve got in our hands today on the market, which patients are benefiting from.
So we’re just trying our very best to accelerate the molecules in our pipeline so that we can continue to serve people who are live with HIV or who would benefit from perhaps in the way that they’ve asked us to. I think that’s the way that we’re looking at it. And we think our competitors do a good of similar thing. And it’s great to have people innovating in HIV and fundamental, we are competitors.
But at a macro level, we’re all trying to solve a global problem, which is how to suppress the HIV virus, how to end the epidemic how to prevent people becoming HIV-positive and ultimately have to find a cure, and that is what makes us excited every day about the job that we get today. And I know that our competitors they do the same way too.
And if I could just make one quick build. You’ll probably remember, Umer, a few years ago, Gilead was saying Biktarvy was their last HIV medicine.
Umer Raffat
Yeah.
Deborah Waterhouse
And the innovation that we have brought is what has pushed them to continue to try to innovate. And so what that ultimately does, is makes better options for patients. We’re not accepting the idea that a single three-drug regimen is going to be the answer for all patients. We feel like we can do better. And that’s pushed the field. And we’re proud of that.
Umer Raffat
Makes sense. Maybe just in the last couple of minutes or so, could you remind us, and I think it’s always relevant, the LOE profile for your portfolio? And I know there’s been — this is probably the best time from an LOE perspective then because a lot of the major ones are behind us, but could you just remind us?
Deborah Waterhouse
Yes. So if we secure pediatric exclusivity in Europe and the US, which we have all the days to and are in the process of preparing the files as we speak, you will, in the US see, the loss of exclusivity of dolutegravir in Q2 2028. And you will see the loss of exclusivity of dolutegravir in Europe in the middle of 2029. So, it’s like a staggered. It’s a staggered approach to that lot of exclusivity.
And we believe that the pipeline that we have in our hand today, both in terms of the newly launched medicines that we have, particularly Cabenuva and Apretude, and then the follow-on products that we’ve been discussing over the last 10, 20 to 30 minutes, that is what will enable us to replace the revenue that will be lost when dolutegravir goes off patent. But we don’t expect it to be a cliff.
We think it will be applied, and we think we’ve really got a great opportunity to continue to have a very successful business past that loss of exclusivity, and as time has gone on, this year as the clinical data for the pipeline has come through, we get more and more and more confident, and obviously, you can see Dovato and Cabenuva are performing ahead of expectation. And again, that Cabenuva trajectory, the trajectory of Apretude that you’ll see next year and the year after and beyond, is really going to be the kind of the foundation for our future success.
Umer Raffat
Outstanding. And the third gen integrase should be — as long as things stay on track, should be sort of done on the market well before that 2Q 2028, correct?
Deborah Waterhouse
Do you want to talk about the date side, how was the [indiscernible] generation?
Kimberly Smith
Yes, around that time frame, towards the end of the decade is when we expect to be able to launch the third generation integrase inhibitor. But we both agree that cabotegravir is — has a loss of exclusivity out to 2031.
Umer Raffat
Got it. Make sense, excellent. Well, thank you again. This was extremely helpful and always really enjoy. I feel like I learned so much about HIV every time I sit down. So thank you again for your time.
Deborah Waterhouse
It’s a pleasure. Great to see you, Umer.
Kimberly Smith
Thank you.
Deborah Waterhouse
Thanks.
Umer Raffat
Likewise. Miami next year, sounds good, guys.
Kimberly Smith
Sounds good.
Umer Raffat
Thank you, guys.
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