Welcome, everybody, to our third session this morning at the Goldman Sachs Healthcare Conference. My name is Chris Shibutani, along with the team, especially the team that's based in London, Salim Syed, James Hobson. Thank you very much. We're very pleased that GlaxoSmithKline, GSK, can join us today. Today, we have Tony Wood, who is the Chief Scientific Officer. The focus of our conversation, there's so much that we can always talk about with GSK in terms of portfolio strategy, et cetera, but I always like to make sure that we focus the relatively short time that we have here, a 30-minute discussion, to being able to go a little bit more into depth.
There's a lot of critical areas from the clinical development standpoint and the pipeline, that is really sort of your power alley, and then we're also gonna beg you to ask and comment on some things that are clearly relevant from that pipeline standpoint on the HIV side. To begin with, just to familiarize the room a little bit about, who we're talking to, tell us about you, your professional journey.
Oh, thanks. Okay, first of all, hi, everyone. Pleased to be here. Sorry, we're just a few minutes late. Yeah, my professional journey, I'm now more than 30 years in the industry. I guess I'd describe myself as a drug hunter and a technologist. Last, 6 now of those years at GSK. Before that, 25 years at Pfizer. I grew up, initially as a medicinal chemist, then led technology groups. History in HIV, I discovered in HIV medicine in my early career. Through that career at Pfizer, increasingly was involved not just with technology and therapeutic area focus, but also later-stage development, large-scale development platforms, and led their immunology group for a little while.
Six years ago, moved to GSK. What I saw there was an opportunity to lead a broader technology platform with an organization that had a good track record of applying technologies. I joined just about the same time as Hal did, and so he and I were sort of part of that last five-year journey of really turning R&D productivity around at GSK, focusing on decision-making. For example, my role at that point in time was to broaden out the modality base. I arrived at an organization that was essentially a small molecule inhaled organization. We built in biologics. We built in functional genomics, AI, ML, things like that. I'll pause there because it's too easy for me to go on a long time on that.
Yeah, no, actually, you're giving us plenty of raw material to go on into, and then particularly with your vast industry experience and your purview and whatnot. Maybe we'll begin with a discussion in terms of strategy from the R&D standpoint and the portfolio there. There's been an identification by GSK of a therapeutic focus, right? On infectious diseases, HIV, immunology, respiratory, and on oncology. You had mentioned actually the word modality, when you pick these therapeutic areas of focus, talk to us a little bit about the modalities and how you feel about what you're currently equipped with, and what we might be able to see, you consider building further upon as you strengthen the portfolio and fortify it, even possibly through either partnerships or acquisitions.
Talk to us about sort of the modality basis within these identified therapeutic areas.
Sure. Why don't I bookend that first by starting with the therapeutic focus, very much in vaccines and specialty?
Uh-huh.
When you look across those two areas, I'll divide the modalities in that way.
Great.
Look, I think we're in a strong position as far as vaccines is concerned. I, actually, you know, we have obviously a well-established track record in protein subunit vaccines and in particularly.
Mm-hmm
... in adjuvants, and that's an area that we'll continue to develop, both in terms of the application of structure-based vaccinology in the subunit design, and also in terms of us continuing to invest in understanding adjuvant technology to work on the reactogenicity versus immunogenicity proposition. Behind that, of course, very excited about the deal, the acquisition of Affinivax, which brings in, I think, a unique capability in platform technology to get access to the pneumococcal market, one that we didn't play in, and of course, is the second largest vaccines market after COVID. I could double-click on the Affinivax technology, but perhaps we'll wait if you want to do that later.
Very pleased with the way our collaboration with CureVac is going with regards to mRNA, the nice initial data that they've described in the context of monotherapy settings for reactogenicity versus immunogenicity in both flu and COVID. Again, really a focus there for me for the high-dose flu, probably high-dose flu plus COVID is an area that we don't play in. Vaccines has a very strong technological basis. We've built out AI, ML capabilities there in terms of design. Actually, for nanoparticles, we hold some of the original IP in lipid nanoparticles.
Mm-hmm
... from the Novartis organization. We'll continue to look for technologies in vaccines that are really familiar about the broadening applicability of mRNA. Bearing in mind that, I think we're still on a little bit of a tipping point with regards to reactogenicity and immunogenicity, if you want to get into...
Mm-hmm
... high-dose flu, plus COVID, plus other seasonal vaccines. That, that might be an example of what we're looking for in that area, but largely speaking, I think we're very well set in vaccines. If you now pivot over to specialty medicines, what we've built there, as I mentioned earlier, obviously strong capabilities in medicinal chemistry. We built out over the past four years, I think, competitive capability in protein engineering and monoclonals, both in discovery and in manufacturing. I might point to, you know, Nucala, Benlysta, and sotrovimab as examples of performance in that particular field. Then an emerging presence in the other end of RNA oligonucleotides.
Mm-hmm.
Where, if you like, we're now witnessing, I think, the fundamental addition of nature's third molecule to the armamentarium of drug discovery and development. We have in our chronic hepatitis B treatment, but they reverse an oligonucleotide that has a unique profile and functional cure in HBV. Behind that, in the clinical portfolio, a collaboration with Arrowhead on a enzyme target that is the PCSK9 equivalent for liver disease. Of course, a recent collaboration with Wave Life Sciences, who I think have a unique oligonucleotide technology. You can think about the build in terms of modalities, well set in vaccines, looking for what I need, if the reactogenicity, immunogenicity, question around seasonal vaccination becomes important in the pharma world.
Well-established in the 2 core modalities, building out oligos. obviously, we've had a presence in cell and gene therapy. We retained some of the basic capabilities there, and we'll continue to monitor that field as it develops.
In particular, on the vaccine front, thinking about sort of how much the landscape has been altered by the emergence, obviously, of the commercialization of the mRNA-based COVID vaccines, it does bring to bear this question of relative competitiveness. You've made reference to the reactogenicity, immunogenicity dynamic. With candor, share with us what you think, you know, GSK's current equipment from a capability standpoint will position you from a competitiveness standpoint, and what is your hypothesis in terms of the, you know, the ultimate view on what the immunogenicity and reactogenicity could play out like, with these multiple combination seasonal vaccines?
I think we're in a competitive position that's slightly behind from a timing standpoint with respect to high-dose flu and COVID. You know, the recent Moderna results, particularly when you look at strain B immunogenicity, put them back slightly. Our technology, judging as one can from or rather the Q-VAX technology in collaboration, judging as where one can from the phase 1 data that we see, I think, places us in a very similar position as far as that is concerned. We're moving quickly now into multi-valent flu studies with the objective that we can establish a presence in the high-dose flu market on a timescale, which is competitive.
When I look at the broader proposition, and it, if you allow me to just get into a little bit of numbers here. If you look at the total RNA load that you might need to do a four-valent or eight-valent flu to compensate for B strain differentiation, plus COVID, plus perhaps RSV, if you're considering adding that-
Mm-hmm.
You're looking at a total RNA load, which is, I think, exceeding the current therapeutic index possibilities for reactogenicity versus immunogenicity. Whilst that might have been acceptable in the COVID to have grade 3 reactions that you meant you were off work for a couple of days, I don't think that's going to hold in a regularly administered seasonal vaccine. I think we're going to need to see a bit of a shift, let's say about a 5-fold shift. The question to be asked, of course, is: Is it determined by total RNA load, or is it determined by sequence? All of that yet still to be worked through. If you were... Where do I see the greatest possibility for us? It's high-dose flu plus COVID.
I probably need additional technology to extend it beyond that. I would put that across the entire field at the moment.
Okay, great. From a timeline standpoint, front and center, RSV, tremendous opportunity, innovation, GSK, as well as Pfizer. A lot of regulatory hurdles have been passed, and we're literally this month going to see the ACIP. Can you update us whether or not there's going to be any incremental data, particularly in the older adult population, kind of 50+ or whatever? Gosh, is that older adult? I think that's just adult.
I was pleased you said that, actually.
Naturally, the Street is always trying to contemplate how we should think about the end game, what the market share could be like. It clearly starts with product profiles. It starts with, you know, data sets and how those are interpolated.
Yeah
-by the regulators, et cetera. Walk us through.
Yep. Okay, let me just sort of step back and describe things as I see them currently. Obviously, we're delighted with the overall profile of our vaccine and the VRBPAC vote, which I think really substantiated that. As you point out, ACIP coming out, we have second season data in-house that we'll present at ACIP. I think as we stand right now, I'm more focused on the 60 to... Is it 60 or is it 65 plus? Obviously, there's a question of the GBS matter, which needs to be considered. We have, I think, stronger data there, small numbers. Then, Flucoad and the broader strength of our package.
In fact, if you look at the labels, we have secondary data in our label. We have Fluarix in our data in our label. Pfizer doesn't. Another important thing to consider is presentation. From the human factors standpoint, our vaccine is a four-stage presentation. Pfizer's is a nine-stage presentation. We'll continue to build out the dataset, where we are running studies now, looking at the 50 to 59 population, and this will just be part of an ongoing program. Obviously, seasonality is going to take longer to play out as well.
Is there anything that you can just make memorable, the key differentiating factors in your view of GSK versus Pfizer and versus the Moderna product?
Yeah, I would say it's back to the point that I made earlier, that, you know, we have-... It's probably actually, before I get there, if you don't mind, I just wanna underscore a few things about the phase III program that underpin all of this, because without it, I wouldn't be able to say what I'm about to. That is, you-- we were very careful to use epidemiological modeling when we started the study in 2019, recognizing that COVID would disrupt the normal status for RSV epidemiology. What that meant was that we were able, on a study that is about the same size as Pfizer's, to really target a mixed and severe population, which gave us the strength of the data that you see.
We also called the interim, I think, at just the right point, too. We end up with 94% vaccine efficacy in the at-risk population. They really are... If you remember, the CDC has published on this. These are the folks who end up hospitalized and from RSV infection. We have a strong data package, A versus B. We have a strong data package for the subgroups and secondary endpoints beneath that. As I mentioned earlier, that's reflected in the label that you see. We also have a strong data package in the context of flu coag. We'll be adding adjuvanted and high dose to that, and we will continue to explore the efficacy of the vaccine in the younger population, starting from 50 to 59.
I very much see that as the, if you like, the scientific differentiators, and then there's the presentation point that I made earlier of a four-step versus nine-step vaccination.
Okay, terrific. Maybe a little bit on the commercialization preparation launch timelines. I think, Pfizer has talked about being able to, consider, posting some revenues in the fourth quarter. How do you feel in terms of what's the house view, in terms of communicating timelines for potential revenue?
Yeah, very much, Bill. I mean, this was all done with the intention of being ready for the 2023 season, so very much prepared for that. Probably another thing to stress in terms of platform approaches, we applied it. We have a digital twin model for manufacturing, and that means we're unconstrained for vaccine supply.
You made reference to this a little bit earlier about expanding the potential opportunity set across different age group subpopulations here. Remind us, in terms of whether or not you're considering exploring anything in the sort of the 2 years to 18 years population group? Historically, I think there had been a maternal vaccine candidate, pregnant individuals, to address the risk of infection amongst infants. There had been a prior pause owing to safety considerations. Does the team contemplate considering, you know, continuing to renavigate the development of that?
Yeah. No, look, in terms of that expansion, as I mentioned earlier, very much at the moment, the target for us is the 50-59 population.
Mm-hmm.
We don't see the maternal market as being a substantial component of it, so not with the current construct. I don't expect us to go back into maternal.
Okay, great. Finally, on RSV combination vaccines, how do you see these impacting the space? I mean, we talked about some of the scientific risk considerations that you think are important to be aware of. What would be the impact of having these combinations out there? There certainly seems to be this simple notion of convenience instead of combining these things, what's your view?
Yeah, I mean, look, I think it boils down to really how do you trade vaccine efficacy, particularly for the at-risk population, versus convenience? As I mentioned earlier, we really don't know the proposition with regards to let's call it multipathogen seasonal vaccination with regards to reactogenicity or vaccine efficacy. Right now, I think, you know, as I mentioned, the real differentiating feature of our vaccine is its 94% vaccine efficacy in those who are at most risk of hospitalization and mortality as a consequence of infection. Right now, I think that plays out against an as-yet-to-be-determined convenience proposition. Although, obviously, we're evaluating the seasonal vaccination market in terms of looking at the optionality for multiple presentation in seasonal vaccines.
Mm-hmm. Okay, great. Let's transition over to HIV.
Sure.
Normally, questions that would be probably addressed to the R&D head of ViiV, but you're being a good sport, so let's talk about the dynamics here. On the competitive front, obviously there's, like, well-established franchises with you guys, as with Gilead. We see them entering the long-acting space with approval of lenacapavir for multi-drug-resistant HIV, allows for six-month dosing. How do you see this potentially impacting cabotegravir for both treatment and for PrEP in the future?
Yeah, I mean, let me just sort of step back, if you like, and give you a sense of how I see the, the ViiV strategy. I promise I'll get.
Okay
... to answering your question. you know, our strategy at the moment is very much about having led innovation in the area, going from 3 to 2-drug regimens. Our strategy is very much then about the next wave of innovation, moving over to long-acting regimens, be they at-home treatments, be they treatments which are phased with physician visits or extension of PrEP. I think what's important to consider in all of that is, what is the foundational medicine that is part of your 2-drug treatment?
Mm-hmm.
You, what we have in cabotegravir, and ultimately, potentially in the third generation integrase, is a mechanism which is solidly proven to have very, very substantial characteristics in terms of robustness with respect to resistance. I think if you look at the proportion of individuals living with HIV who are currently treated, more than 70% of those have dolutegravir as a background regimen. I think the credentials of integrase inhibitors as the foundation of a long-acting regimen, which is robust with regards to resistance are extremely strong.
Mm-hmm.
Capsid, of course, is interesting, but doesn't have anywhere near that level of supporting evidence. Of course, we have a capsid and a maturation inhibitor in our portfolios.
Mm-hmm.
as well. What we've said is that we will make decisions on the components of longer-acting regimens in the middle of next year.
Mm-hmm.
Before I finish on that, I should also stress the, you know, the interesting, emerging, I think, quite exciting data for the broadly neutralizing antibody that we disclosed at Glasgow last year. This is the first example of a single antibody that gives substantial coverage, and one that gives efficacy at a dose, which is in a sort of realm that you could imagine would be effective for a longer-acting treatment. In headline, although we haven't yet decided on exactly what those various regimens would look like, we have a number of different studies and ongoing evaluation of the pharmaceutical properties as the one or the pharmaceutical proposition that one requires for a long-acting agent.
The details of all of that, Deborah and Kim haven't disclosed, it will all come together, as I said, in the middle of the next year, with the choice on what is the right regimen. As far as lenacapavir is concerned, it's gonna need another medicine on top of it in order to be a robust regimen, and we'll wait to see what that is.
A year from now, when GSK is on the stage being grilled by the Goldman team, we'll hopefully have more insight.
Exactly
into what the next go forward is gonna be.
Exactly.
That's helpful. Within HIV PrEP, obviously, a fascinating market. Gilead had mentioned in their first quarter earnings call, that of patients who are eligible for PrEP in the US, actually only 25% are receiving treatment. Just curious to know what you're seeing from a market perspective, and how you think perhaps there's an opportunity to enhance the penetration here, in particular, looking at how original expectations have been framed, and how the reality of the commercial market has played out?
Yeah, I would say. Look, I mean, obviously a question that I'm sure Deborah could answer in greater detail. The way I think about this in terms of that, is it's both a matter of reshaping and if you'll let me go back to the treatment market for a minute...
Mm-hmm
... you know, in the US, still something like 37,000 new infections every year, less than 50% of people living with HIV are fully suppressed. There's an opportunity, not only in reshaping the, let's call it, the components of the market between oral and long-acting...
Mm-hmm
... seeing greater penetration to ensure, a shifting of that proposition to one that is more like, the European one, where I think it's 95% of individuals, are suppressed. Obviously, all of that work sits alongside establishing the credentials of a long-acting PrEP agent, which again, plays to another segment of patient choice or, and indeed of, medical need that we see. As regards to strategies for expanding the market, I'm not entirely sure what Deborah has described, so perhaps you'll allow me to leave that answer at that point.
Okay. A little bit more on the vaccine front and the infectious disease, Shingrix, complications obviously addressing of a legacy infectious situation here, tremendous franchise for GSK. There's some other sort of presentations that are coming up. Pfizer-BioNTech have an mRNA-based candidate, phase I, II. How do you view the outlook for potential different modality entrants competitively impacting the Shingrix franchise?
Yeah, I mean, you know, 10 years protection and counting out to 12, I think that is gonna be a high hurdle to beat. From our standpoint, you know, what we're very much interested in Shingrix, is beginning to ask the questions about, again, is there, are there other populations that could be eligible, for example? Luke is building out in broader terms, but I would say that the 10-year projection gives us a substantial benefit over new entrants.
Another dynamic, which is very exciting, but once again, a situation where some of the stalwarts in the space are potentially going to be competing here. Meningococcal ABCWY here. We have a regulatory decision coming up for Pfizer in the second half of this year, anticipated launch next year. Comment about relative comparative profiles and how you see that shaping up.
Yeah, I mean, I think just to start with meningococcal disease, I think the first thing to do is to stress that between Bexsero and Nimenrix, we have two great vaccines, greater than 80% vaccine efficacy. In the case of Bexsero, of course, a 0-2 schedule, which is critically important for the adolescent population. Bearing in mind that most of the burden of invasive disease in the U.S., I believe, is in the 15 to 23-year-olds. Having said that, as we look at the convenience, let's say, and perhaps therefore increased penetration, because I think we're still only about 30% of penetration there, the convenience of a pentavalent proposition, obviously very important.
If I take you back to the comment that I made earlier around vaccine efficacy. This is another infectious disease in which the invasive disease has significant consequences, and therefore, vaccine efficacy, and in particular, strain coverage, I think is very, very important. What we're focusing on in our pentavalent vaccine is demonstrating improved strain coverage. We recently described the headline data. We were delighted with hit all 11 endpoints, and we're working across a B strain proposition that covers more than 100 strains, in contrast to Pfizer's, which looked at four.
We're very much focused there, on, you know, building on the basis of what we already have with Menveo and Bexsero, and delivering a next generation, broader agent, which is not only more convenient, but has a very strong proposition in terms of strain coverage, given the invasive disease consequences.
Okay. Another category, pneumococcal. A very well-established presence out there, of course, obviously with Pfizer's Prevnar, Merck has Capvaxive as well. I think, you guys are in position to commence the phase 3 trials for adults.
Correct
next year. Any updates on the infant trial in terms of status and how on track you are with that?
Yeah, let me just sort of step back. First of all, just remind everyone quickly about the platform. you know, this to me is a unique platform with regards to, if I do it very quickly, to 2 or 3 components. First of all, it's chemical complexation, not chemical conjugation. What that means is getting beyond 20 to 30 is a much easier proposition than it is with chemical conjugation. It also means that because of the way the antigens are presented, we see improved immunogenicity, and you see that. Our data compared to Prevnar 13 and Prevnar 20 immunogenic responses, which are anchored in being better than Prevnar 13. I would remind everyone that based on what I've just said, Prevnar 20 is less immunogenic.
We have advantageous immunogenicity. We also have advantageous strain three coverage. There, what the pneumococcal strain three does is cuts the glycoprotein. Unless you have a vaccine which is aimed at protein components, you won't see efficacy in strain three. The Affinivax platform brings us this. In terms of the manufacturing scale-up to get to the 24-valent proposition, we're making great progress there. I'm very happy with the acceleration we've seen. You'll note that we paused the infant program and the 24-valent.
That was simply because of a need to ensure that we moved from a fill-finish operation that was anchored in a phase I, phase II clinical setting, into a fill-finish operation that would allow us to move into a larger scale and ultimately commercial setting. I'm not concerned about that. I see it more as the sort of ins and outs of taking an early program and then accelerating it to ensure that we end up with something that will reach the market as soon as possible, and everything I've stressed about the immunogenicity profile of the vaccine, I remain confident in.
Okay, terrific. I mean, infectious disease and HIV really constitutes two-third, roughly speaking, in terms of the portfolio. The last dimension of that is in antibiotics, boy, is there a tremendous challenge. It seems academically recognized, Burroughs Wellcome Fund talks about, you know, bacteria don't care, that the drugs that we have, that they're becoming resistant to. You know, the statistics are actually quite horrifying from a humanity standpoint in terms of somebody dying every five minutes, I think, from a serious bacterial infection, for which we do not have an effective agent. Yet the dynamics of the business of antibiotics is just a tar pit in terms of just so many nettlesome difficulties. Just the business proposition is improbable and paradoxical, very difficult, and yet you guys persist.
Do you philosophically have a sense that continued clinical development of antibiotics can ultimately yield a valid business proposition?
Yeah, and look, a couple of ways to answer that one. Let me just start, first of all, anchored in the reality of what we have been doing. The bolt-on acquisition of teicoplanin in complicated urinary tract infection, juxtaposed with gepotidacin in uncomplicated urinary tract infection, our deal with Brexafemme for candidiasis. These are all examples of actually where we can make the economics work, if you look at it from a sort of a bundling standpoint from Luke's world. We'll continue to, if you like, make those or look for those tuck-in opportunities where we can build that presence and have the economics make sense.
As far as the broader proposition is concerned, you know, the fact that I hang on to is I think antibiotics have saved 200 million lives.
Mm-hmm
... in their
Mm-hmm
... in their total presence of existence. As you point out, there is increasing resistance. At some point in time, I think that has to pivot, and then the question is, how well-placed are you to be able to respond to it?
Right.
Our bolt, these tuck-ins and the presence of our capabilities, I think, places us well in that regard. It's sort of positioning ourselves with deals that do make sense from a financial standpoint, ready to be able to respond when a pivot takes place.
Yeah, no, I would argue that one of the few global houses that would be well equipped to remain dedicated to having the lights on across-
Yeah
... the spectrum of research and commercialization. wish you well in that resilience. How's tenure oncology? There seems to be less of a focus here, you know, beyond momelotinib. Should we expect more to come with oncology? Is that TDD? Where does oncology fit?
Yeah, I mean, let me just sort of, because it's not so much less of a focus as you'll just hear me talking less about it, because I'm gonna talk about things in proportion to where we're seeing capital allocation.
Sure
In the portfolio. Look, we still see oncology as an emerging area, and, you know, despite the headwinds, when you look at the amount of investment that's gone into that area, it will still create opportunity. I think we've got to be realistic about our abilities to compete relative to the larger players. For me, that boils down to, if I very quickly sort of give you three tranches, you mentioned momelotinib. For niraparib, it's very much focused on getting OS data in Primus so that we have a setting which supports the outcome as label for that molecule. In the IO field, the credentials of gemcitabine continuing to build those credentials in a setting where gemcitabine efficacy is going to deliver, let's call them transformational results.
You see that in the rectal cancer data. You see it potentially in the, in the first line, endometrial cancer in the dMMR population. You know, PERLA, for example, although it wasn't designed to show superiority, I think that's gemcitabine very much in a, in a favorable light. We'll continue to be very thoughtful about where to invest in gemcitabine, bearing in mind it has a much longer runway on loss of exclusivity, but we need to see efficacy that would justify its use. Largely driven from biomarkers, we're monitoring the CD226 axis very, very closely. We have our own internal platform studies, and interims from those will dictate the path we decide to take towards the end of the year, when we also see competitive data emerge.
Early in oncology, that will be very much focused on, smaller scale deals, which are, identifying agents which give demonstrable efficacy in Phase Ib. That pretty much boils down to tumor targeting the CD3, detuned CD3 bispecific deal that we signed with Hansoh and other related areas.
Got it. For a final question, the most recent captive brought into the portfolio, Bellus, and recurrent chronic cough. The MOA here, thinking about the P2X3s, tolerability is something that has to be navigated, and we're seeing it through clinical development, et cetera. As a chief scientific officer, what's your perspective about being able to come up with a maybe more preferred, because kind of demographically, the numbers are extraordinary?
Yeah
... how do you thread that needle, coming up with a therapeutic that will be broadly adopted, and is that scientifically possible based on the mechanism?
Yeah, look, I mean, I think there's a really strong foundation to believe that, and it's borne out in phase II data. If I just do it quickly, the selectivity profile for camlipixant, so P2X3 versus P2X2, is orders of magnitude greater than gefapixant. You actually see it in reported dysgeusia in the phase II studies, which is around about 6% for camlipixant, and it's as high as 60% for gefapixant. It's a very, for me, straightforward proposition and something that I really like, because then I can anchor clinical results and what I know about the preclinical profile of the molecule.
Terrific. Well, we're out of time. We appreciate your overview. Tremendous focus. Headlines will be coming in terms of RSV. Wish you and the GSK team well. Thank you for joining us.
Thanks.