# GSK plc GSK plc presents at Jefferies London Healthcare Conference 2024
Tuesday, November 19, 2024 5:30 AM
## Event Participants
Analysts 1 Peter Welford
Executives 1 Tony Wood
#### Peter Welford Analyst
Good morning. If everyone could take a seat, please. My name is Peter Welford. I'm one of the European Pharma and Biotech analysts at Je!eries in London. It's my great pleasure to be hosting the next company in this track for a "reside chat, which is GSK.
And here from GSK, it's our pleasure to have Tony Wood, the CSO. We will take -- if anyone has any questions in the audience, we're happy to take some questions. We love a bit of feedback. So if anyone would love to put their hand up and ask a question, by all means we're well. But let me kick o!, "rst of all.
#### Peter Welford Analyst
So Tony, obviously, since you've been in the job now for, what -- just over 2 years at this point, perhaps you can talk a little bit, "rst of all, about what the notable changes you've done to GSK since taking over. And I guess, particularly as well, if we just think about the therapeutic areas, can you also just talk a little bit about your attitude to Oncology? Because we do get a question a lot, is GSK still in Oncology? Is that still a key area for you?
#### Tony Wood Executive
Sure. All right. Remind me if I get in and don't comment on that particularly, Peter. So look, I'm pleased with the progress we've made over the past 2 years. There's always more to do.
But for me, it's been characterized by, if you like, a very clear de"nition of our areas of therapeutic focus, those being vaccines and infectious diseases, including HIV, Respiratory and Immunology and Oncology. And what we've done is sort of organized the R&D structure around that and driven better partnerships with Luke's commercial organization. And the consequence of all of that is whilst we've maintained the performance of our late-stage
clinical portfolio with regards to the number of launches and the cost per launch, what we've also done is shifted it towards medicines and vaccines of larger scale, so higher value.
So other bookends in terms of technology, but I'll just pause there and "nish up on oncology, if I may. We talked about it as an emerging area of our portfolio. Those of you who are at the Q3 results will see that it's growing very well. I'm in particular, pleased with the progress we've made with Ojjaara and indeed Jemperli as we see the approvals in endometrial cancer there. And you'll see more focus on what we might call carefully selected areas of development for Jemperli.
Obviously, next year is all about BLENREP. I'm sure you'll come back to that. So I won't embroider it right now, and the ADC portfolio in general. So overall, I'm pleased with the progress we've made, always more work to be done, but very happy with where I stand and the team of people I have around me.
## Peter Welford Analyst
Yes. So before we get dive into the individual therapeutic areas, can we just step back and just look a little bit about -- can you just say a few words about what it is you think that di!erentiates at this point, GSK versus other large-cap pharmas now in R&D?
#### Tony Wood Executive
Yes. And let me just pick at the high level, the therapeutic areas. I'm going to give you a bookending of our focus on the application of technology. And we talk about science and technologies being core to our R&D strategy. But picking each of the areas in general, I mean, we have a very strong vaccines business grounded in, a range of platform technologies, be those adjuvants characterized by the most recent performance of Arexvy for example, through to other platform capabilities, our emerging platforms in mRNA for #u and COVID and the MAPS platform.
And of course, behind all of that, adjuvanted subunit vaccines and Shingrix really is, if you like, the leading asset in that portfolio.
Long-acting technologies in HIV, long-acting technologies in respiratory with depemokimab and increasingly an application of oligonucleotides into our immunology business as well. And then for Oncology, in particular, again, an underpinning in really ADCs building on from the progress in IO. I'll pause there so we can get into some more detail.
# Peter Welford Analyst
So let's go through some of the therapeutic areas. We're going to start with vaccines. Now let's kick o! with Arexvy because that's obviously a topic of conversation. Now putting aside, I guess, for vaccines, RFK and whatever his views may or may not be a vaccines, we won't ask your opinions on that. But if you just think a minute about for Arexvy, the immunity data and the safety data that we have at the moment to hand, how would you sort of put in context for the audience, when we get full year immunity data, how a decision is going to be made on when a booster is needed for Arexvy and how you can sort of help the ACIP get comfortable with the risk bene"t to potentially enlarge the age group to at least include the 60 to 70
#### [Indiscernible]?
#### Tony Wood Executive
Yes. Let me -- before I answer that speci"cally, Peter, let me just frame sort of the ACIP arena for everyone. COVID created a little bit of a false impression about the speed of approval of vaccines. Typically, ACIP moves slowly, particularly with new vaccines and Arexvy is a new vaccine. We're just beginning to understand its bene"t risk pro"le.
What you saw in ACIP decisions this year was essentially that and an underscoring of the bene"t risk pro"le in the current 2 populations of adults for whom we have both approvals and recommendations. And you should expect to see that, that picture will continue as more data is brought to bear. The most signi"cant data, I sort of think about it in 3 di!erent components. There will be the ongoing vaccine e!ectiveness data that will come out of the CDC and FDA-based systems that, if you like, is a retrospective look and answers questions associated with the protection of at-risk individuals, for example, from hospitalization. That will continue and will weigh into the decisions that they make.
It's worthwhile emphasizing that now we have 3 years protection for Arexvy, of course, ACIP will not make a decision on revaccination probably until 2026. And that's why we've not included any revaccination in next year's forecast. And what we will bring in addition to that, and I'm going to do this kind of in order of where I think data will impact is the continued accrual of immunogenicity data in adults at risk, particularly we published our own 18-plus data recently. I expect that to be adjudicated in the near future. We will add more to that and in particular, in populations who constitute those who are the larger proportion of hospitalized adults.
I'm not going to go into the details associated with that.
For immunogenicity, we'll continue to assess boosting immunogenicity. You'll see season 3 boost data on immunogenicity background at the beginning of next year. Remember that what we know, and this is typical for vaccines is the time between prime and boost usually results in greater boost. And that's all we are seeing with Arexvy. I expect revaccination will be required on 3-, 4- or 5-year schedules.
The reason I'm somewhat uncertain about that is, I'm sure those of you who have been plotting graphs on the decline in vaccine e\$cacy can see that in the second and third years. It's plateauing to some extent. That, I think, has more to do with the nature of the individual seasons and therefore, the con"dence intervals on the data than it does about the pro"le of the vaccine.
It's very unlikely that for a mucosal infection, we will not need revaccination. This is not chickenpox. You get it repeatedly through life, not a single event. So con"dent at some point in time, revaccination will be required. We will bring more immunogenicity data.
But what I want to give you, Peter, is a sense that it will be a range of data that ACIP will collect in order to make that decision.
#### Peter Welford Analyst
And then moving on to Shingrix. Can you just talk a little bit about there, the life cycle management strategies that you have for Shingrix? You mentioned vaccines that last a long time. I mean Shingrix is a good example now. We've got data that shows it lasts more than 10 years, if not more.
Can you talk a little bit about that? And I guess, particular as well, how you're also leveraging the dementia data for that.
## Tony Wood Executive
Yes. Well, I won't comment in detail on the sort of geographical expansion associated with Shingrix. That's a topic for Luke. But as you say, the vaccine continues to show long-lasting e\$cacy. I think we're actually at 12 years now and counting.
The interesting data, of course, is the relationship discovered through real-world evidence studies between vaccination and mild cognitive impairment, perhaps dementia. This is an area for which there is very little science. We are taking our own data that we published in September, was a careful real-world evidence analysis. And for those of you who don't spend time thinking about epidemiological real-world evidence analysis, let me just describe some of the characteristics that we were careful about.
The main factor you often have to deal with in these types of analyses is something called healthy vaccinee bias. People who get vaccinated tend to look after their health more e!ectively. So we were careful to remove that from a very large U.S. database. We actually removed nearly 400 confounding factors, things that would introduce bias into the analysis.
And from that, we found that after 3 years that Shingrix outperforms or delays the onset of cognitive impairment relative to either a competitive -- sorry, a competitor shingles vaccination or PCV vaccination, again, the importance of that being removing healthy vaccinee bias, extending on the order of, I think, 27 months on a 3-year analysis.
So we have this tantalizing view that with the best we can possibly do with real-world evidence, it seems to be having an impact on the onset of dementia. Starting a prospective study requires careful design and consideration of feasibility. That is work that we're conducting at the moment, and I expect to be able to say more on that before the end of the year.
## Peter Welford Analyst
That's great. And so I guess moving on then to the other part of your business, #u vaccines. But I guess more speci"cally, the future of #u vaccines for GSK. Can you talk a little bit about that, what you're doing with the CureVac collaboration for mRNA? But I guess more broadly, how you see -- what is your development strategy for the future of your respiratory vaccine franchise?
# Tony Wood Executive
Yes. Well, I think in answering that, obviously, I have to underscore what I mentioned earlier that we will continue to generate data to support life cycle innovation and label expansion and harmonization ultimately for Arexvy, that will be an important part of our ongoing endeavors.
Then if you look at our adult vaccination portfolio in general, there are 2 areas for which we currently don't have competitive vaccines and yet they represent signi"cant opportunities. One of those being high-dose #u, and we put that in the context of #u/COVID combinations and the other being pneumococcal disease. In terms of high-dose #u, we've made good progress in developing our own mRNA platform.
I'm sure you'll appreciate that the key factor for high-dose #u and indeed #u COVID is the overall mRNA load and managing that versus reactogenicity.
What we know from the platform is its "rst generation and what we have here is sequence optimization from CureVax work plus base modi"cation. So what we get is immunogenicity now across both A and B strains. We ran recently a Phase IIb study that we announced that supports that proposition and with reactogenicity that is at least equivalent, if not moderately better to that of Moderna. I expect to be reversioning that platform as we go on. But in the "rst instance, the major milestones are a #u COVID Phase II proof-of-concept readout next year and starting a Northern Hemisphere #u study in the winter season of next year.
# Peter Welford Analyst
Makes sense. So let's move now on to the other bit of the infectious disease portfolio. And perhaps you can just frame for us a little bit GSK in antibiotics, an area a lot of pharma has stepped away from. But you actually have a Phase III -- positive Phase III data for gepo. Perhaps you can just talk a little bit about that and how we should position that and more broadly, how you're looking at this space.
## Tony Wood Executive
Yes. I mean we've talked about the antibiotic portfolio really as a constellation of 3 assets, of which gepo is one. And I think earlier in the year, we commented on an expectation across that portfolio of peak year sales of around about \$2 billion. Gepo is doing really very well. First new antibiotic in uncomplicated urinary tract infections actually for more than 20 years.
It targets a particular enzyme, actually 2 DNA gyrases, which are uniquely important to E. coli. So what it provides for urinary tract infection is an interesting proposition that although it is broad spectrum, it's broad spectrum only against the pathogens that cause E. coli and therefore doesn't constitute the resistance risk of, for example, the #uoroquinolones. And just to give you a sense on that.
And we expect, by the way, gepo approval next year. Just to give you a sense on -- in terms of that, our estimates are, if we can displace about 25% of second-line use of #uoroquinolones, which is at 25% despite resistance and black box warnings. So that underpins the \$2 billion. I would say it's a portfolio that you should consider in that context and not something that I would point to as a major allocation of capital across the R&D landscape.
## Peter Welford Analyst
And then going on to another infectious disease asset, which gets very little airtime, but is in Phase III as well, bepirovirsen for chronic hep B. Can you just talk a little bit about your strategy there, when we can get data and how we should think about that?
## Tony Wood Executive
Yes. I mean it's had very little airtime this year just because it's been quietly exceeding recruitment rates and accelerating through the B Well Phase III studies. For those of you who don't follow the area, chronic hepatitis B is a signi"cant killer, 300 million individuals infected worldwide.
Actually, that's probably a pretty signi"cant underestimate. There are no e!ective cures for chronic hepatitis B at the moment. The community looks at something called functional cure, which is an expression of the surface antigen from the virus, which you can measure in a blood test and the DNA, which indicates that you have ongoing viral replication. You need both of those factors to be below level of quanti"cation to count for functional cure, and that needs to be observed for a period of time, which exceeds the coverage of the medicine that you're using from a pharmacokinetic standpoint. Bepi is the only molecule to achieve that.
You get some tiny amount of it with interferon of around about 5% to 7%, but interferon therapy in that context is intolerable. We have on the order of -- depending on whether you're looking at low -- very low or medium, surface antigen cover anything from 15% upwards, clinically signi"cant is 15%. We're running now 2 Phase III studies looking at patients cut by di!erent levels of surface antigen. They're the B Well studies that I referred to. They recruited very quickly.
We're expecting to see readouts towards the second half of next year. That's because we have to wait for this period of time that I mentioned.
And we also -- just to remind people, we signed a deal at the end of last year with an siRNA that also targets the bepirovirsen replicating machinery, if you like, does it orthogonally to bepi. And we expect that together, those 2 medicines will produce a broader and deeper impact than we see with bepi alone. But even considering the proportion of individuals with surface antigen of less than 3,000 we're looking at based on our analysis of epidemiology, about 40% of the chronically infected population. So just expect to hear more. It's been quiet because it's been progressing.
### Peter Welford Analyst
That makes sense. Let's go to Respiratory then. So depemokimab, the long-acting IL-5, basically long-acting Nucala, I guess we could call it. Could you just talk a little bit about, I guess, from an R&D perspective rather than commercial perspective, how you're developing depemokimab and how we should think about that relative to Nucala?
#### Tony Wood Executive
Yes. Well, the "rst thing to say, we're expecting simultaneous "les for depemokimab in both severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps. What we did relative to Nucala was quite an accelerated phase -- clinical development program. We knew enough about depemokimab at the end of Phase I to be able to predict e!ective dose, and we went straight from that into Phase III. We also know enough about the role of hyper eosinophilia in the diseases that I mentioned and others that we are con"dent to run parallel development programs.
So this will be all done for depemokimab in something like 4 years, whereas for Nucala, it took 7. The initial indications, as I say, are severe eosinophilic asthma and chronic rhinosinusitis.
Just to give you a headline on the eosinophilic asthma indication, there what we're doing is moving treatment focus, if you like, the history of -- you start with the bronchodilators in the 1960s onwards. That was about improving lung function through acute intervention. Then we've led the "eld in recognizing that exacerbations are the next wave of treatment in lung disease, particularly in COPD. I'll come on to that in a minute. So what we have for depemokimab in the 2 SWIFT1 and SWIFT-2 studies, nearly 70% of the individuals on depemokimab in those studies experienced no exacerbations at all.
And this is for patients who had exacerbated at least once in the previous year before recruitment into the study.
So it is going to be a very important medicine when you consider that 2 doses a year protect you to that extent and reduce exacerbations across the broader population by more than 50%. We also have headline data from Nucala in COPD. There, the important feature to focus on is the breadth of coverage of di!erent patient types. And what you'll see if you join us for the management event in December is the next wave of our investments in COPD with obviously depi, given the data that I've just described there, IL-33 and TSLP in all in longacting formats.
# Peter Welford Analyst
And you mentioned Nucala, you sort of stole the question, but I guess you didn't really address what I was going to ask, which is you said breadth of coverage. So importantly, we've all seen, obviously, Dupixent is approved for COPD now, and you're, therefore, potentially the second [Indiscernible] to market here. So can you just talk a bit about what you mean by breadth of coverage? Why is the Nucala, MATINEE and the other study [Indiscernible] di!erent to the Dupixent data that we've seen?
## Tony Wood Executive
Yes. So important to recognize the Dupixent data is in patients with high eosinophil counts, that's greater than 300, but also carefully selected patients who have a bronchitic phenotype. This is associated with airway reactivity and a phenotype that we know responds well to IL-5. We were careful to include all of the potential patients for COPD. This is the third largest killer in the world.
It's a signi"cant consumer of emergency room resources.
It's a disease which if you exacerbate, you do not return to your original level. You're iller than when you started. And actually, about 10% of people who go into ERs with COPD don't come out. So we were very keen on focusing across the entire population, including 30% of the COPD population who have emphysema. This is structural changes in the airway.
And so what you'll see for Nucala is data which covers both emphysemic and bronchitic patients with high eos. We were, by the way, the "rst to show that eos play a signi"cant role in exacerbating outcomes for COPD. And you'll also see a breadth of coverage across the
currently accepted di!erent forms of COPD, and these are usually determined by do you have a high eo count, have you been a smoker. What we have is breadth of coverage across all of those, and that's what's exciting the KOL community.
The headline exacerbation data, I wouldn't compare directly. But to give you a sense, if you want to dig out numbers forward, look at the metrics and the [TRIO] endpoints from our earlier studies, and you'll get a proper sense. So it's not going to be the 34% that Dupi has as a headline, but it's going to give broader coverage, which in the population in question is important.
## Peter Welford Analyst
I guess let's move on to another asset in relative which is chronic cough. Now perhaps the only sort of late-stage chronic cough asset still in pipeline is Camlipixant. Can you talk a little bit about when we could see the Phase III data for this and how you would di!erentiate Camlipixant with some of the other prior attempts companies have made to get into this market?
### Tony Wood Executive
Yes. Let me start with the last question "rst, and then I'll put the Phase III readouts, which are going to be towards the end of next year into context. So when we acquired BELLUS Health, we were very careful to establish a couple of important things about the medicine itself. This is an area of research that's been going on for gosh -- I mean, I was looking at these molecules nearly 20 years ago. What was always a problem in the "eld, the P2 X2 and X3 receptors was selectivity over those 2 things.
If you don't achieve it, you have an extreme metallic taste. The previous molecule su!ered from that problem.
One, it means that you have a lot of discontinuation. And two, it means you can't run a blinded Phase III study because it's fairly obvious if you're on active. The other important thing about the studies themselves is you have to take account of the fact that this is a diagnosis by exception and then you have a range of di!erent coughing frequencies and a high placebo e!ect. So we've been very careful to do 3 things. First of all, choose a molecule that has fantastic selectivity propositions.
There's a very small dropout rate associated with Camlipixant relative to Gefapixant. Secondly, to make sure that we have placebo run-ins to the study that takes account of the variability that I just described.
And we've also worked very hard with the regulator to ensure that the cough counter and the analytical methodology associated with that is going to deal with the original objections they raised with the Merck complete response letter. What's also true about the population in general is that the higher cough frequency you have, and at the upper end, this is many hundreds, 500 to 800 coughs per hour. This is a level of coughing frequency that causes broken ribs, ruptured tissues. It's a signi"cant disease and a stigmatizing disease as well. So -- but what we wanted to do is make sure the design of the studies was such that we were properly re#ecting the severe end of the coughing frequency where you see the greater
#### e!ect.
So all of that is playing into the design of the KALM-1 and KALM-2 Phase III studies. As I say, I expect they will read out towards the end of next year, but I'm going to use time to make sure that the patient populations in those studies are optimally recruited so that we can properly show the credentials of the molecule.
#### Peter Welford Analyst
And then last few seconds, BLENREP, I wanted to make sure we touched on that. You said we should get approval next year. Can you just talk a little bit about how we should think about that? It's often, I still think, sort of overlooked here, given obviously how crowded the multiple myeloma marketplace is. But can you just frame for us the data you've seen and how we should think about that?
#### Tony Wood Executive
Yes. So just very brie#y, "rst of all, the headline is you'll hear about our [Indiscernible] OS data from DREAMM-7 at [NASH] at the beginning of December. That's atypical for myeloma as is 2 successful Phase III studies, which we have. The headline that we have published is it triples survival relative to Darzalex in the second-line setting. Darzalex is already a pretty good medicine.
What we are doing in terms of regulatory submissions, I was careful to time all of that so that we had a very clear e\$cacy proposition with DREAMM-7, DREAMM-8 and OS and DREAMM-7, so that we can move the conversation on to what exactly the label will look like, and we're busy educating key opinion leaders on managing of the safety e!ects, which are transient -- reversible, transient and entirely manageable with dose scheduling.
What would the initial impression of the molecule, which was formed by the DREAMM-3 studies, where we knew relatively little about its performance in the myeloma setting, and it was given a high hurdle in DREAMM-3 in the third line plus and in comparison to a [Indiscernible] relative to BLENREP alone, I think initially set an understanding and expectation, which is not accurate.
And so we've been working heavily to make sure that, that is properly understood by the key opinion leader community. And as I say, everything going well on the submission landscape at the moment and expecting approval under normal circumstances. I did something unusual, I don't usually talk about submissions until we've had acceptances for submissions, particularly in the U.S., but I felt given the interest in BLENREP at Q3, it was worthwhile mentioning to you that we had submitted the "le.
#### Peter Welford Analyst
That's great. We're over time. Thank you very much all for your attendance.