Well, good afternoon and welcome once again. We're delighted to have GSK here at the 44th Annual Cowen Healthcare Conference. Representing the company is Luke Miels, who is the Chief Commercial Officer. Lots to talk about today, lots of exciting dynamics at GSK, so we're just going to dive right in. We'll start with a product that's been a huge success over the last few years. That's Shingrix. I think that the latest guidance from the company is that peak sales would be GBP 4 billion plus, but the product is on a trajectory to do that this year. So how should we think about that guidance? Why isn't a better guidance GBP 6 billion, GBP 8 billion, and why are those numbers not realistic?
Sure. Yeah, I mean, I think you've got to break it into three buckets. So you've got the U.S., where we're picking up at about 1% every quarter in terms of penetration into the labeled population. But the deeper you go, of course, the less motivated those individuals are to achieve vaccination. So we're having to evolve our targeting strategy, and we still think there's room there within the U.S. And then you've got Europe, which with each year of incremental efficacy, we get a stronger position. We've been very disciplined on pricing, but we've had a lot of success in Germany, where we moved early and starting to now get contracts and government reimbursement in markets across Europe. And then you've got emerging markets, where the bulk of it is out of pocket. And again, we've been disciplined on pricing, and that's just getting started.
We've got about a 3% penetration in those markets. China's the biggest swing factor there. We have a deal with Zhifei. You probably know Zhifei through the success that they've had with Gardasil. And yeah, I mean, we've got a limit on the doses that we can ship to China this year because of the process that we need to be compliant with Chinese regulations. But in 2025, we're uncapped. 2026, we're uncapped, but we have minimum purchases. So yeah, I think the business in the US still has a good trajectory, but it'll be more and more an ex-US story over the next few years, hence why we're saying around GBP 4 billion. Of course, I'd love it to be much higher than that. And then the other things we're doing on a lifecycle point of view, at some point we will see breakthrough events with Shingrix.
We're not seeing that yet. We've got our 13-year data coming up, but there will be a point at which we can go back and rechallenge the U.S. population with our working assumption, is a singular dose. Then the other thing that we're exploring, which is very intriguing, there's been a couple of studies, population-based retrospective studies looking at the relationship between shingles vaccination and dementia. So now we're starting to look at that. We've got another publication coming, and we're starting to think about what's the appropriate next steps in terms of exploring that prospectively.
What could be the potential impact of that dementia data? Would it just be faster uptake? Would it be a broader population?
I think it could be transformational because you'd have a dual effect. So you would see individuals who are younger. I mean, the label's 50+, but the bulk of the uptake is in the 65+ population because actually they're at higher risk. So I think you could see individuals electing to be vaccinated earlier. And then, yeah, the ultimate penetration in the population would be significantly higher, and healthcare systems would, depending on what signal you saw, let's assume we had a positive study, there'd be heavy pressure for people to be dosed. And I think individuals would self-select to be dosed. But we have to go and we have to agree on a study design. We have to agree on that with regulators and then launch that study. Yeah.
Tell us about this another publication that's coming?
It's work that we did in a U.S. database looking at historical usage of Shingrix and, yeah, and the relationship well, it's not a relationship. It's correlation between that and observed dementia. So there's a huge amount of work that needs to be done, but it's intriguing. And there's also an interesting paper which was done with Zostavax that was published in the BMJ last year looking at U.K. subjects vaccinated with Zostavax. And again, it's another indication. Signal is probably the best way to describe it. Again, there are flaws to it because it's retrospective. So the question is, yeah, should we go and do a prospective study, and how do you design that?
Okay. And do you have the revaccination data in-house yet for Shingrix?
For Shingrix, no. No. So we keep tracking the original cohort. We're not saying in the 12-year data, we didn't see breakthrough events yet. At some point, you will see. Our working assumption is at some point you will see breakthrough events in individuals. And then it's a case of establishing with the regulator what type of label would a booster shot have. I mean, there is a scenario where you never need it, but I think that's unlikely because these are older individuals at high risk of getting shingles with declining immune systems. So there will be a point in time. It could be 20 years. It could be 15. It could be 13. We don't know. But at some point, we can go back and rechallenge those individuals.
Okay. By the way, anyone has a question anywhere along the line, just raise your hand, and we'll call upon you. Let's move to another successful launch for GSK, and that's Arexvy. It is quite impressive how you've done so well in this market. Pfizer is not a weak company yet. You've done really well competitively. To what do you attribute that, and how do you look at that going forward?
I mean, it's all going to get reset again as we start the contracting discussion. So we're sort of starting from zero again. Look, our working hypothesis was that this would be a retail vaccine, and the positioning of the vaccine was in high-risk individuals because we thought they would be the most motivated to present for vaccination. And so we aggressively targeted the retail chains. We were very disciplined on pricing and will continue to be disciplined on pricing because, again, we see this as a 30-40-year vaccine here. And yeah, our concentration was on those high-risk individuals. Things like a number of steps of dosing were very, very secondary, tertiary even. And then we had a very targeted approach at the primary care level to explain the vaccine and the benefit of the vaccine. And that's why we have two-thirds of physicians preferring Arexvy over that.
So ideally, they instruct their patients when they go to the pharmacy to ask for Arexvy. And yeah, now we'll see what happens at this ACIP. I don't think we're going to see discussions around when to boost yet. It's probably too early. I think ACIP will sit back and wait until February next year or June next year until we've got our third season. But there may be some discussion about expanding use or making it a general recommendation. We'll see where they land. But yeah, we're going to take our 50-59 dataset to ACIP in June. That's also a variable. So yeah, lots to happen, I'm sure. Everyone, Pfizer, we have huge respect for Pfizer. I'm sure they've gone and had a very good think, and they're going to come out very strong in the next round.
How are you thinking about market penetration in this coming season? I think you hit 16% penetration of the population. Do you think it'll accelerate? Do you think it'll kind of maintain that rate?
Yeah, I mean, it's interesting. So Shingrix was 4%, 11% in the first two years. So it did better than we were expecting. I thought it'd be a bit more of a cautious uptake. Yeah, I mean, I think the trajectory we're on is fair. The question then becomes, what share do you get? Are there two players? Are there three? We'll know that in June.
Questions from the audience? We could always come back to the vaccines. Let's go on to some other products at GSK, and we'll talk about Ojjaara. So Q4 was a very big quarter. Is that a new run rate, or is there something unusual about Q4? How should we think about that?
I mean, I think it's us getting traction. The market research we've got is very encouraging for this product. Again, the logic behind the acquisition is we could see from our market research that we knew that a lot of patients present a diagnosis with anemia and that physicians were very loyal to ruxolitinib as a general concept but recognized its limitation in individuals with anemia. And really, they had one of two alternatives, which is to de-titrate, back-titrate, or stop therapy. And we were really excited with the concept of the off-target effect of momelotinib and ACVR1 and just the elegance of positioning it solely for patients with anemia. And it tested really well, and the FDA recognized that with the first-line label. So yeah, it's really exciting. I mean, if you look at the trajectory at launch, it's several orders of magnitude better than fedratinib and pacritinib.
Yeah, we're seeing really good penetration. We've got about 15% of first-line patients with anemia, which works out to about 10% of the population overall. That's the Q1 . We'll have an update. Again, it's got better since then. But these are the most robust figures I have at this point and around a 25% penetration of the second-line anemic population, which yeah, it's a bit more of those are anemic. So yeah, exciting, high awareness, high intention to prescribe. And yeah, we'll see where we go over the next few months. But our intent is to take Incyte head-on and really challenge them for the anemic population.
This could probably be calculated from the numbers you just provided, but I can't do it in my head. So of the patients on Ojjaara now, what percent are first-line versus second-line?
In terms of the revenue split at the last quarter that we disclosed, it was about two-thirds were second-line and a third were first-line, but that has changed because a lot of those second-line were warehouse, so they have a relatively short duration of treatment. The first-line, we typically model 3 years of treatment based on the phase 3 program. So that's shifting quite dramatically. And in some clinics, we are really challenging ruxolitinib. Again, we don't want to displace, we don't expect to displace ruxolitinib more broadly. But if a patient has anemia, our challenge is they should be given momelotinib in first-line. Full stop. And there's a very clear clinical consequence of ultimately needing transfusions correlated with life expectancy. So physicians know there's also the challenge of having to do EPO, having to do transfusions. So it's a really simple story that resonates with them.
We also publish data that shows if you switch off ruxolitinib, you can reverse anemia, address anemia, but not disrupt spleen size. So that's also landed well. Yes?
There are a number of agents going through the myelofibrosis phase, and there's T1. What are you most worried about in the next sort of three to five years?
Let me just say the question is about additional agents in the myo.
Molecular process?
Yes.
Yes. Yeah. I mean, what's attractive about the strategy is those programs tend to target upregulating efficacy in that first-line setting. If they do get traction there and look, there's been a high failure rate and yet most recently as well, arguably, at least based on historical FDA's decision-making, we can then if they've got anemia or diagnosis, those programs typically exclude those patients, so we get those anyway. And if the physician does elect to use those combinations, typically, the patient's either through the trajectory of the disease or the underlying treatment with RUX is going to generate an anemic profile anyway. So we win either way there. We did a lot of due diligence before the deal, and that's why we're stuck to our lane in terms of anemia. We're not trying to displace RUX in that non-anemic phenotype.
Other questions? So not only did Ojjaara have a big Q4, but Jemperli did too. Is that a new run rate for this product? And what indications are the biggest drivers right now?
Yep. Yep. So endometrial is the driver. I mean, Pembro still gets two patients for every one patient we get. So that was partly the fact that they're on formulary everywhere, of course. And I think we were about the 800th PD-1, so people didn't have us on formulary. We're now getting traction there in formulary. So every month, we're signing up new accounts, which obviously drives volume. But critically, the beauty of the RUBY study, the first-line endometrial study, is it's powered for overall survival. And GY018 Merck's program, that was a cooperative study, our understanding is that's not powered for survival. So second half of this year, we'll see if we can achieve survival. And our initial label is the MMRd population, which is about a quarter of patients, but they're obviously a much more durable response.
The other upside is if we can get broader approval in the MMRp. So shorter duration, but obviously a bigger number of patients. But that's the primary driver. We've also got experience in. We've had an excellent study result, exploratory study that was best of ASCO last year or one of the two best of ASCO and locally advanced rectal cancer. So we're trying to replicate that study. And then we've also got programs in colorectal. I mean, it's basically a high-dose Pembro. That's what this product is. And we've got another study as well in lung called COSTAR, which we'll read out in the second half of this year looking at Pembro failures. And that's either with Jemperli by itself on a background of chemo or with a TIM-3 cobolimab on top of that. So that's another swing factor that we've got there.
But yeah, it's really endometrial and outstanding data there and a lot of excitement around that.
Okay. Questions from the audience? Moving on to another product, we'll move to Nucala. Now, unlike the other products that we just discussed, which have a lot of momentum, Nucala would seem to have a lot of other products targeting it, trying to chip away at its sales base and so forth. So what is the future for Nucala in your eyes?
It's a population that is going to be transferred to depemokimab as quickly as we can. But there's still growth for Nucala. I mean, you have relatively low penetration in the U.S. We've done some work around characterizing this concept of remission where using an antibody early enough in the disease, you can start to change the nature of the disease, the underlying pathophysiology of asthma. I think that's quite exciting, and we need to do more to understand that. But that could be what we need to try and get antibody usage earlier. And then there's nasal polyps, which we've been very encouraged by the speed of adoption by ENT surgeons. They seem to be much more. Pulmonologists are relatively conservative in terms of the adoption of antibodies, a bit like rheumatologists were 15, 20 years ago.
Now, the rheumatologists coming through, graduating now, they've used antibodies from day one. So I think that's only going to increase. But we have a program in depemokimab called NIMBLE, which is patients who are on benralizumab. So for Fasenra, AstraZeneca's product, and mepolizumab, Nucala our product. And then they're switched, double-blind, double placebo, switched across to depemokimab. And if remission becomes more and more in the minds of physicians, that's going to mean earlier initiation. Then long-acting antibodies are really going to become very, very compelling, better outcomes, better adherence in first line treatment via IV, etc. So a lot of things that are in favor of it.
That's also why we did the TSLP deal at the end of last year because I think it was that Astra and Amgen will go and de-risk the target, and then we'll just follow behind them and target wherever they've got activity with a higher probability or high probability of succeeding like they did. And then we have a very simple proposition for physicians, which is stratify based on eosinophil profile, eosinophilic phenotype. So 85% of people are 150 and above EOS. So use depemokimab there. And for T2 low or low EOS, then you should be using long-acting TSLP. Very simple argument. And yeah, again, that's the theory. We've got to make it work in practice.
Remind me where depemokimab stands. When will we see the phase 3 data, and how soon could it be on the market?
Yep. So you'll start to see phase 3 data second half of this year. So we've got SWIFT 1 and SWIFT 2. These are the primary registrational studies. And then NIMBLE 1 is quarter one next year. That's the switch study. And then we've got EGPA, HES, nasal polyps. These are all loaded and started. So nasal polyps we'll get in the second half of this year. The only program we're waiting on is COPD. And the second that we see the readout from Nucala, if it's positive, we'll engage and start the COPD study with depemokimab. And just to contrast, so if you look at first indication for Nucala and nasal polyps, that's an 8-year journey. We are going to get all of those, excluding COPD, within 2 years of launch on depemokimab. So a very different approach to lifecycle management with this portfolio.
Okay. Questions from the audience? A product that's kind of nearing the end of its journey, and it's been a long journey, is Benlysta. So as we approach the LOEs in the U.S. in 2025 and EU in 2026, what's going to happen? Is there biosimilars ready to launch? Is there going to be some adherence to the brand because of for whatever reason? What is this going to look like?
Yep. Yep. So we have different numbers to the IP, but the key thing is for Benlysta, the key thing is there's no biosimilar in development that we know of at this point. So if someone started today or one became visible, typically, you have an 8-year timeframe to do that. The challenge is establishing efficacy in SLE is really difficult. And you've got active drugs that have failed phase three programs. And so it's not a risk-free proposition for a biosimilar to develop. CAR-Ts looked interesting, but are probably unlikely to be even if they did make it to market, I think there's going to be a reluctance to employ them. You're looking at young females here. So using CAR-T interventions, unless in really refractory cases, is probably difficult. And then yeah, BAFF/APRIL is intriguing so far, but you haven't really seen knockout data yet.
So I think Benlysta's going to be around for a long time. And we keep accumulating really good organ damage data. Lupus nephritis is going very well. So it's a very durable product. We've got a new formulation, which lowers the cost of goods outside the U.S., which has been an impediment for us ex-U.S. So we're starting to see some traction there. So yeah, I mean, it's a product we relaunched in 2017. All the spend had been taken off. All the resourcing had been taken off. And we just made a decision that this was a product that needed yeah, it needed a different way of being explained to physicians and a different approach, and that's paid off.
Okay. So just kind of summing up what you said, it should grow for the next 8 years, basically?
It should keep going. Yeah. Yeah. I mean, penetration is relatively low. And that's historically been because there wasn't end organ damage data available. And also, to see efficacy, it typically takes a six-month process. So physicians, we're not sure getting patients to persist with there. And of course, Astra is now there with their product, so there's more share of voice. But again, we've got really good traction in that first-line setting. And there's just more comfort with antibodies over time. But we are very active in the BD space. So we're not sitting around thinking we've got this solved. Actually, quite the opposite. I operate with a high level of paranoia. So we are very busy looking at what could disrupt Benlysta or what could be used in combination. And yeah, we spend a lot of time looking at that.
Questions in the audience? Let's move to a product in late phase development, and that is camlipixant. So I know GSK has big expectations, and maybe you can remind us of what those are. But we do have one example on the market now. Of course, that's the Merck product in Japan, and they don't even report the sales, so they must be pretty low. So what has Merck done wrong that you're going to get right?
Yep. Yep. So if you go and ask pulmonologists—and we do this, of course, because we spend a lot of time talking to these people—what's your area of unmet need? And chronic cough always comes up. And we disclose these statistics before the market research. 3% of them are happy with current therapies today. So if you've got chronic cough, typically, the interventions are speech therapy, I wish there are not enough, or low-dose opioids, or things that make you drowsy and don't really work. Yet the burden is there. So typically, in the U.S., there's about 800,000 patients a year being managed by pulmonologists. Those patients have typically been coughing for multiple years and have gone through about 5 years of the journey to end up in a cough clinic. So high unmet need, typical late 50s female, healthy otherwise.
The problem with the disease, it's typically via exclusion. So do you have lung cancer? Do you have asthma? Do you have reflux? And eventually, you end up in a cough clinic. But typically, a lot of those patients then get sent back to their primary care doctor saying, "Can't do anything." So high unmet need. Now, as part of the due diligence of acquiring Bellus, and we've been following Bellus for a long time. This is where camlipixant came from. It's a little bit like momelotinib. We always want to start with the basic biology. So the good thing about gefapixant is it validated the target. The target is P2X3. It exists as a homotrimer in the lung, and that's the mechanism. Once it gets upregulated, you just keep coughing. And it's very different to shut this pathway down.
The problem with gefapixant is it's a promiscuous binder. So it binds to P2X3 in the lung. But the problem is there is a similar target called P2X2, which is present in the taste buds in a heterotrimer. So it's typically two P2X2s and one P2X3. Long story short, it's about a 3:8 ratio. So gefapixant does prefer P2X3, but it will happily go and bind to P2X2. Our ratio is 1200:1. So dramatically different. So that's the first thing. And that was validated a couple of ways. Firstly, through animal models. So they gave these guinea pigs quinine-laced water. The ones that had gefapixant were happy to drink the quinine water. The guinea pigs on camlipixant did not want to drink the quinine-laced water. And that's a good analog.
Then if you look at Gefapixant, they're losing big numbers of patients quite quickly within a couple of weeks. Then the other issues the FDA had was a cough counter. We've resolved that through discussion with the agency. There's a software question. That's done. The other challenge Merck had is they I think it was only about a 2-week placebo wash out. We have a 6-week placebo wash out. And then also, they included low cough rate, low cough frequency, which these patients are typically idiosyncratic. So we're looking at 45 coughs per hour and above in our population. So that's enriched for that. We will test it in a lower frequency, about 22 per hour. But the main thing is to preserve efficacy in this true P2X3 phenotype. So we knew all of that.
We knew everything about gefapixant that came up at the ad board before we acquired. We've designed a phase 3 program to address that. It's recruiting really well. It's 2025 launch. It's highly compatible with Trelegy. It fits our specialty portfolio of IL-5 TSLP. Yeah, a lot of interest on the part of physicians that manage this and decent-sized patient numbers. So I think it's a multi-blockbuster. We feel very confident about that based on the EPI we've seen and the efficacy we expect.
Yes. Yeah. So the target I mean, it was originally described in pain, but we're not going to go there. The receptors are present in the bladder as well. So urinary incontinence is one area that we're thinking about exploring. We just want to get the primary program underway. And then typically, you'll see there are other targets that we expect we can explore through interventional studies, through partnering with clinicians. And if we see the signal, then we can expand the program there.
Other questions? Let's move on. So you have a development program in pneumococcal vaccines, as do other companies. But when we poll even thought-leading vaccine experts, they seem to be narrowly focused on Pfizer offerings and not kind of receptive even to what might appear to be better vaccines. So how do you break that?
Yep. I mean, ultimately, it's going to be efficacy. What this entire market has been primed a bit like an iPhone. Everyone expects an upgrade every few years. I think there's very little I don't think anyone's going to care whether it's called Prevnar or Pneumovax or whatever. The question will be, "What's your serotype coverage? What's your efficacy?" And so if you look at the history of 7 and 13 and 20, I think we're about 60% efficacy for circulating strains at this point. If we're looking at our 24, we think we can get comfortably more than 80%. And our 30-plus and the emphasis is on the plus, then we're getting up into the 90s. And then you've got, obviously, competitive pressure on the circulating serotypes. That evolves over time. We've published this. We've got really good data on serotype 3.
It's 5 and 19F, remember, is what we're doing. But I think the way the market will evolve is if you can demonstrate activity in the strains which are causing people complications, then the market will shift to you quickly. But these are really tricky things to make. Our assumption is that Pfizer is saturated with their existing technology. So we're looking at Merck. We're looking at Vaxcyte. But this is going to be the bulk of this business is in pediatrics, and that is a portfolio play. You need a portfolio of assets to compete in that setting. And these are three things to match. So you need scale. You need critical mass. So yeah, we'll launch the 2024. That's a pathfinder way of entering the market. And then ultimately, our aim is to really disrupt this market with the 30-plus technology a couple of years later.
It's upside for us. I mean, we have a marginal presence there. We ourselves were disrupted many years ago by Pfizer. We had two strains, Synflorix PCV vaccine, and Pfizer come along with all of theirs. Every couple of years, the market has been taught to expect an upgrade. So I think people will be agnostic and rapidly shift to whatever's available and go back and revaccinate those patients who were vaccinated earlier in the adult sector.
Questions in the audience? So GSK has a hepatitis B program underway. So tell us where that stands and why should we be focused on it?
Yep. So it's a high unmet need, as you can imagine. And I mean, typically, when you talk about hep B, people think, "Okay, Southeast Asia, etc." But actually, there's about 4 million patients in the U.S., most of whom are medically infected. And yeah, we've shown good activity in the low S antigen population. And efficacy here is very marginal. It's sort of 2%-8%, depending on the regimen that you use. And the regimens are pretty tough on patients. It's 12 months, and you have flu-like symptoms, and you have lifelong treatment to maintain that. So yeah, we've seen good efficacy. I think if we can get to functional cure rates in the 20s or 30s, then we have a very exciting product. We did a deal with J&J to acquire their siRNA product. And the intent there is that suppresses surface antigen.
The hypothesis is that then puts us into the realm where you see activity of hep B virus. There's actually a larger population—it's about 5 million in Europe—that have hep B as well. So it's a really attractive product. It's oligonucleotide, so it's hard to make. But we think we've got a pathway to build that. But it means that you're not unlikely to have 800 competitors coming after you. Yeah, that's probably what I can say at this point. We did test a sequencing of hep B virus and integrated interferon. That didn't work. We were wrong there. But also, that then obviously increases the hurdle for competitors to come after us.
We are out of time, but allow me one last question. You know what investors think of GSK. You can read it in reports and so forth. You have far better knowledge about the company and its outlook. What is the one thing that we are missing that we will all see in 5 or 10 years?
I mean, the problem is, as you're sitting inside it, okay, now you're probably heavily biased too. But I've seen this movie before. I had the privilege of participating with Roche. And when I went to Roche I mean, I've said this before. Everyone says, "What the hell are you leaving Sanofi to go and join Roche for?" And that's when Roche had three Phase 3 failures and lost $150 million on a FX trade, which I think at that point, that group probably made more money in the pharma division. And then assets. You get the right assets in a row. And then when I joined Astra, people said, "Why the hell are you leaving Roche to join Astra?" It's products. And I think with GSK, we're now assembling. We've got the right people in place.
And these are people that have deep experience in the areas where we need to have experience. And it's a small group of people that you need to fix a company. It's not tens of thousands. You need a very small group of people that are empowered to act. So I think over time, it's following the same formula of those companies, which is focusing on a set of assets that are differentiated and being very objective about it, and then putting all your effort behind those assets and moving them through and developing them in a way that they show clinical difference. And get enough of those things right and a bit of luck, then you're in a different position. And I think internally, you can see the momentum. Not everything's going to work, but we're in a much better place than we were a few years ago.
If we can keep doing intelligent business development as well, yeah, I mean, I think we've got momentum. We've shown that if we do have an asset, we can compete against the best in the business and hold our own or more than hold our own commercially. Yeah, let's see.
Yeah. I think you've beaten consensus in the last 10 quarters. I think you do have momentum for sure. Thank you so much, Luke. It's always a pleasure. Thank you, everyone, for joining.
Thanks for coming.