GSK - GSK plc (GSK) Presents at 6th Annual Evercore ISI HealthCONx Conference (Transcript)
2023-11-29 12:33:02 ET
GSK plc (GSK)
6th Annual Evercore ISI HealthCONx Conference
November 29, 2023 07:30 AM ET
Company Participants
Jeff McLaughlin - Director, Investor Relations
Philip Dormitzer - SVP and Global Head, Vaccines R&D and Infectious Disease Research
Conference Call Participants
Umer Raffat - Evercore ISI
Jessica Hui - Evercore ISI
Presentation
Umer Raffat
Good morning, everyone. Thank you for joining us, our Day 2, and, I am really excited to kick the day off with our friends from GSK. There is a lot to talk about, in particular, because what makes this fireside chat exciting is, we are going to focus specifically on the vaccine business, and it is going to allow us to do a little more of a deep dive on this aspect of the broader GSK story.
But just before we do that, I realize GSK is not a vaccine-only company. So, Jeff, maybe I will turn it over to you, things off. I realize there is a bunch of other higher level GSK topics too. Maybe you can spend about five minutes on that on a couple of things and we will jump much more specifically to vaccines.
Jeff McLaughlin
Sure. I mean, vaccines is key, and we are happy to have Phil here, who leads our vaccines R&D efforts. GSK is big in HIV. And if you didn't see it, we had an HIV Management Meet event back at the end of September. So slides and transcript are available there if you want to thumb through that, but we have been pioneering long-acting injectables in HIV and two drug regimens for some time, and that has been key to our business. And then, tomorrow we are actually doing one on respiratory. So you can learn more about Nucala, mepolizumab, some of the assets in our respiratory health space, which has been a big legacy for GSK for some time.
Question-and-Answer Session
Q - Umer Raffat
Excellent. So over the last couple of years, Jeff, obviously, there has been a couple of legacy issues which have weighed in more heavily than the rest of the business including some of the litigation stuff. Could you just remind us and orient us where things stand on that front and where we are now?
Jeff McLaughlin
Yes. So, there has been ongoing Zantac litigation. The next event that I think people have their eyes on is in January of 2024, there will be a hearing in Delaware to consider, what is included, in the class action that's ongoing there. But the federal MDL case was effectively tossed back in December of last year. And a couple of the cases in California have been addressed through settlement, as we have moved through the course of this past year. So, it is not as hot of a topic in conversations with investors as it once was, but we're working through that litigation process.
Umer Raffat
Got it. But just to be clear, I remember, we really looked into this at length. We spoke to you at length about it. I recall much of the, like, the origin of the suit, some of the players involved in that suit origination, courts found and got to the bottom of a lot of that. And when that ruling came out, I think it was about a year ago in December, I thought this was all over. So, I was still puzzled to see some of these Delaware and some of these cases coming later on.
Jeff McLaughlin
Well, that was the federal case. So that was, that handled a number of different claims. But after that, there were state level cases. So, many emerged in Delaware overtime and that process kind of started off much later than federal one. So, that's why we're just kind of getting now to the point through the process where Delaware is having a hearing. And the judge will make a determination on timing for when to decide on that hearing, but that will come in due course throughout 2024.
Umer Raffat
So here's what we'll do. We'll jump right into the vaccines now and spend a fair amount of time. If we have about 5 minutes in the end, we can come back to a couple of GSK specific topics again.
Jeff McLaughlin
That's good.
Umer Raffat
Broader based dev strategy at financial, et cetera. So really looking forward to this, I know there's a ton to talk about. Maybe we can kick it off on your RSV launch, which has been tracking very well. I know there's a lot of broader interest, and I also know, it's quickly picked up a fair amount in sales. So could you maybe, can we start there and maybe turn it over to you and both of you perhaps?
Philip Dormitzer
Sure. So, we're obviously very pleased with the way this has started off. We've had a very effective rollout. The uptake is excellent. And we're now really working on making sure that we maintain this lead. We're looking at, for example, age expansion, so looking to, we have good data on 50- to 59-year olds. I wish we hope we'll maintain differentiation and then we're looking beyond that to, your potential accommodations in the future to make sure that we maintain the early lead.
Umer Raffat
So maybe let's start there. I was going through, in preparation for this, I was going through the ACIP recommendations, and they're specifically focused on 60 plus cohort. I know, I was speaking to my colleague Jessica about it, and she was sharing some of the data on 50- to 59-year olds. Was that reviewed in ACIP or not? And sort of what's the path to regulatory indication for that?
Philip Dormitzer
Yes. So, we're going to particularly focus on 50- to 59-year olds at increased risk. And we are on track to file, looking to get the expansion in this year. We can't guarantee what the regulatory outcome will be, but we're on track to…
Umer Raffat
This as in 2024?
Philip Dormitzer
2024. Yes, correct. 2024.
Umer Raffat
But the existing, the Study 1, Study 2, those were 60 plus only?
Philip Dormitzer
Yes. That's right there. They were 60 plus. We've done another study, at 50- to 59-year olds at increased risk. Another thing of course we're very interested in is continuing to accumulate data, hoping at some point to be able to move from a shared clinical decision-making to a straight recommendation. I think that's going to be includes -- some real world effectiveness studies and just building the case with the impact that the vaccine is having and that will take a careful moderate of what's going on out there.
Umer Raffat
Phil, I know vaccine was not necessarily a topic investors did much gone until, I would say, COVID. And then since then, there's been a lot of work on the COVID side of it. But I still think there's some vaccine specific topics which are not well appreciated. So for the purposes of everybody, can we perhaps go through shared clinical decision-making versus rate recommendation? How does that actually impact commerciality? And why is it so significant priority for you?
Philip Dormitzer
So these are ACIP differences in recommendation. And in a straight recommendation, a full recommendation, it simply says those over a certain age or potentially with comorbidities, all to get the vaccine as opposed to a shared clinical decision-making model, was left to a conversation between the provider, and his or her patient, on whether to get the vaccine. It makes it a more complicated conversation. I mean, you really, you can't simply say CDC recommends you get this vaccine. There needs to be more of a discussion.
Umer Raffat
But who's the provider? Like, if I walk into CVS and I say, I want the RSV shot, then the pharmacist just kind of looks at me, but he really wants to give me the shot. Is that the conversation, or is there like, some sort of a prescription? I don't think there is one to my knowledge.
Philip Dormitzer
Yes. And certainly between physician and patient, there'd be that conversation. I'm just thinking of, I don't want to date myself, but having received the vaccine myself, when I went into the pharmacy, there were no questions asked.
Jeff McLaughlin
I mean, generally speaking, a pharmacist is also a health care provider. So that decision can be routed that way. In most states, I don't think that you need to take a piece of paper prescription to the pharmacy from your doctor. But the conversation with the physician can prompt the decision to go get your vaccine. And in most states in the U.S., I think maybe even all of them you can get a vaccine directly from the pharmacist.
Umer Raffat
My point is, is there, I mean, since you've looked at so many vaccines, is there evidence of step up in volumes when a product transitions from shared decision-making to a full recommendation? Or is it more on market share versus a competitor within that category?
Philip Dormitzer
This is universal right now across the RSV vaccines that are out there. I'm trying to think of precedent. And, certainly, for flu, as the -- if it became more and more simple recommendation, it says just simply recommended for everyone above this age opposed to a more complicated recommendation. Uptake certainly increased. And I'm trying to think of other precedents. I'm looking at.
Jeff McLaughlin
Yes. I'd have to look back at, like, the pneumococcal older adult analog to see how that started out over time. But, it's not unusual for a shared clinical decision making type recommendation to begin with the vaccine. We have one with our meningococcal vaccine for adolescents as well.
Umer Raffat
The landscape too because there's multiple players. There's an antibody. There's some mRNA players coming, et cetera. But just before that, the basis of granting shared decision-making was because your second study was slightly weaker or is that because just how they progressed?
Philip Dormitzer
No. The discussion that took place at that time seemed to be much more around pricing and not so much about the scientific data. That's my recollection of the discussion that was holiday ACIP.
Umer Raffat
Got it. And the pricing here is, how much is it? I forget.
Philip Dormitzer
280 a dose.
Umer Raffat
Got it. Okay, makes sense. And is that comparable for Pfizer as well?
Jeff McLaughlin
I think Pfizer is a little bit higher, but yes the same general ballpark.
Umer Raffat
Okay. Got it. Which then takes me into the study two you guys have, I know I was looking at ACIP twice, RSV associated, low respiratory tract disease, 83% in the first study, 56% in second study. I was curious. Was there anything about the second season which made it less strong in the second season or the first season?
Philip Dormitzer
The second season, there was a higher pressure of infection. It was a stronger RSV season, but I also think that some of this may simply be some weighing of immunity from one year to another.
Umer Raffat
So you took one shot, and it lasted a couple of years that's what I see.
Philip Dormitzer
That's right. So there were both groups that received a single shot and were followed over the course of two years. There were some who also received, one shot the first year and second shot the second year. What's interesting is the boost at one year didn't increase titers, increased T cell responses, but not titers so much.
Umer Raffat
And how would that be?
Philip Dormitzer
Well, that's a very interesting question. So there are no vaccines out there except for those where the virus changes every year, where you boost after one year. So, it did surprise us at the time. But of course, hindsight is sort of 2020. And so, there are going to be a couple of important information that will come out. First is, we will see what the immune response looks like when you immunize at the beginning and then after two years. We will also look at what that does for efficacy.
And then following that, there will be additional studies where we hit look at a three year interval and even a four year interval to see how far, you have to wait from both animal studies and human immunization experience. The longer you wait between a prime and a boost, the better the response to the boost is. And of course, there is lots of interesting scientific discussion about why that is.
For example, in infants, who have maternal antibody, but have not seen a pathogen before, while that maternal antibody is there, you can boost T-cells well or you can immunize to elicit T-cell responses, but not antibody responses so well. So, the presence of antibody does seem to suppress subsequent antibody response. So, you seem to let things fade a bit. The details of the science aren't so clear, but the phenomenon is pretty clear. So, the anticipation is we will have to see how long you have to wait before you have an effective booster.
Umer Raffat
Makes sense. Makes a lot of sense. Okay. Excellent. So let me just get it right. Year one 83% efficacy. Year two, it was in the low 50s. And again, the difference was a lot of patients did not take a shot that second year.
Philip Dormitzer
Correct.
Umer Raffat
For the subgroup that did, was the efficacy again in the 80s in that second year? Was that broken?
Philip Dormitzer
No. No. The boost after one year, it didn't do much. It did not increase efficacy. It did boost antibodies a bit, but not nearly to where they were after the first dose. And so, we will now -- we will be, later this year, we will have the data on what the two year interval boost does for efficacy and for immune responses. And then at the end of this season that we are entering now, we will see what the efficacy is with a single dose and with a two year boost after three seasons.
Umer Raffat
Got it. That makes sense. So I guess, when is the next big data update on this one versus two shot issue? Because I guess, ultimately, the question we are getting at is, how often should we be taking shots.
Philip Dormitzer
Exactly. And so it is a booster interval question now. We need to set the timing for the second dose. I don't know the exact date of those data, but it shouldn't be that long for the second shot immune response and efficacy data.
Umer Raffat
From the existing two trials.
Philip Dormitzer
From the existing trials, so we have the existing trials that are continuing and we are going to be looking at the intervals. And then we have extensions, so we can look at every three year and every four year dosing. So, we really set that interval. I think my guess is that the third year data will be very important when we see the every three year interval.
Umer Raffat
And when you say three year data, you are referring to shot at the third year and track for a season after?
Jeff McLaughlin
So, we will have the shot at two years, and tracking afterwards and the shot upfront, and then tracking for efficacy for three years after that first shot. So I think we will know quite a bit at the end of that.
Umer Raffat
Jeff, when you guys put some of this stuff out, do you intend to break it out like that? I didn't again, as I was going through some of this data, it wasn't very clear if it was shown like this. But is that the intent to show in tables like folks that only got it once, tracked for two, three years, folks that got it a year or two, tracked for a year?
Jeff McLaughlin
I mean, I think the focus needs to be once we have all in hand that we need to have is this a vaccine that should be administered every two or every three years. And when we have that much information then we can show the evidence that supports that. And then you have to bring it to the public health officials and share it with the ACIP, and showcase what you've got in that regard and eventually at a clinical Congress as well.
Umer Raffat
And this is data like this is important next year, for example?
Philip Dormitzer
Certainly, the immune response data for the two-year interval boosting will be there. We need to wait…
Umer Raffat
When you say there about a potential ACIP in first half?
Philip Dormitzer
Yes, I don't think the ACIP is likely to make a decision on dose interval at the next meeting for the reason that there's still more data to come in. So that might be delayed a little bit just because they're likely to wait for more data and also to see the season three efficacy data, and that has to wait until the end of this RSV season, which will be sometime in the spring.
Jeff McLaughlin
And the other thing is that because this is the first year 2023 of RSV vaccines. The ACIP knowing that you don't need to dose it at successive years, they don't really need to make a decision until 2025.
Umer Raffat
So, the next big data update is titer data as well as end of RSV season data on efficacy. And when you see that data, just so I understand, the first metric you look at is low respiratory tract disease or are you looking at the medically attended?
Philip Dormitzer
Yes. The primary outcome is low respiratory tract illness.
Umer Raffat
Okay. Not the medically attended because the definition could be a little different.
Philip Dormitzer
It can be a little bit different but the primary is, low risk for tract disease, but we also track medically attended, but not as the primary endpoint.
Umer Raffat
So is it your expectation that some of your competitive programs like Pfizer might need annual dosing, while you don't, which ends up becoming a big differentiation commercially?
Philip Dormitzer
I think we're just going to have to let the data speak for themselves. I mean, there is a difference and that we do have an adjuvant of the vaccine and we'll have to see...
Umer Raffat
Pfizer doesn't have an adjuvant?
Philip Dormitzer
Pfizer doesn't have an adjuvant, yes.
Umer Raffat
And what's the adjuvant for you, is it aluminum?
Philip Dormitzer
Same one as Shingrix.
Umer Raffat
Okay.
Philip Dormitzer
As one though at half the dose level that's in Shingrix for better tolerability.
Umer Raffat
So you think that's what's driving maybe the lack of titer boosting too, potentially, because there's a residual level of titers hanging out from the very first dose, but also why it's more durable potentially?
Philip Dormitzer
Yes. I don't know that the increase in lack of increase in efficacy or on the modest increase in antibody titers after the first boost. So, it's a differentiator between the two vaccines, but we'll have to see as we go into subsequent time points, if it becomes a differentiator or not.
Umer Raffat
Any last question, Jessica, on RSV [indiscernible]?
Jessica Hui
One question I have is, I know after seeing the second season data, you guys raise the price for the dose. I guess, in a scenario that, immunity doesn't wane into the third season. Would you guys consider a price change to take into account that this is a vaccine that can last three years?
Philip Dormitzer
Well, I mean, we're not going to comment on anything about our pricing strategy, but just to point out that the analysis that we did for health outcomes purposes was based on only one year of data initially. But then once we had two years of data, we did a new analysis for health outcomes purposes. And then that's what drove the final decision on pricing. So, we didn't raise it. We just launched it at a price that reflected the benefit of two years of data. But we wouldn't comment on strategically, there's so many different things to weigh in terms of how you go about the pricing strategy.
Jessica Hui
And if I could just ask one more follow-up, I know you guys have data from like a co-administration study with high dose and adjuvanted flu vaccines. Given that, the CDC has already seen some sort of safety signal with COVID vaccines and high efficacy flu vaccines administered the same day, some sort of like ischemic stroke signal, the P value kind of wavers between lower than 0.05. Have you guys seen any sort of safety concerns of co-administering your vaccine with like an adjuvanted flu vaccine?
Philip Dormitzer
No. We've done the co-administration studies and that we have --our co-administration is allowed, and then there's been no important safety signal there.
Umer Raffat
Maybe one last one. On the adjuvant you are using, I know, this point has not been commercially relevant, but Pfizer is trying to drill that. You said AS01, which is a standard? How is that different from AS03?
Philip Dormitzer
Okay. So there are different adjuvants. AS03 is the adjuvant we typically use, example, for pandemic purposes.
Umer Raffat
For the COVID vaccine?
Philip Dormitzer
It was distributed for COVID and in the past for flu whereas AS01 is the adjuvant that is in Shingrix at double the dose that we have it in the RSV vaccine.
Umer Raffat
Got it. Because the reason I ask is, if I remember correctly, AS03, there was some underlying causality about the link between narcolepsy increase and AS03. I wonder if some of those. If I was your competitor, I would be looking and digging for that type of information.
Philip Dormitzer
Yes. So, it's a different adjuvant in this case. And the narcolepsy was particular the pandemic flu vaccine has not been seen, generally. It was a special subset of people. And actually, it has it's actually tend to be Northern European teenagers where that was seen. So, it was not seen generally different.
Umer Raffat
Northern European teenagers?
Philip Dormitzer
Yes, it seemed to be an idiosyncratic reaction. There's been a lot of back and forth…
Umer Raffat
That's where we do our recruiting for our team by the way.
Philip Dormitzer
And there's been a lot of scientific trying to figure out how real was the signal because ascertainment bias comes in very quickly once you declare a signal on it.
Umer Raffat
Excellent. Alright. Well, listen I think, we got through all the key issues. Oh, one last. So narsoplimab versus Moderna, how does that tie into the bigger picture? I know people are thinking about it as a GSK Pfizer thing but this is a more complex picture here as well?
Philip Dormitzer
Yes. And the antibody is primarily for infants because you'd have to dose too much to determine in adults, so it's not pertinent to the adult market. But for the infant market, there's narsoplimab. And we are not targeting this vaccine to the infant market. We're looking just at a little bit of the vaccine.
Umer Raffat
And why is that?
Philip Dormitzer
We had a non-adjuvanted version of the vaccine in pregnant women, and we saw an excess of preterm births in that study and we stopped it at that point.
Umer Raffat
And Pfizer is developing in infants?
Philip Dormitzer
Development for pregnant women to go into infants and I just invite you to look at their data and the preterm birth those who did not get that.
Umer Raffat
I see. So, it mean, okay. So these vaccines in infants are, okay, there's question marks.
Philip Dormitzer
Yes. But the antibody is for infants.
Umer Raffat
The antibodies for instance. I guess my question is, why is it limited to 50 plus? Why not, perhaps even lower because hospitalization rates are lower?
Philip Dormitzer
Oh, well, for those at greatest risk, there is interest in going lower, particularly for the immunocompromised. There's a disease burn. So, RSV causes substantial disease in infants, and substantial disease in older adults. But the third group is people with underlying conditions either immunocompromising or other conditions such as severe respiratory conditions. So, we are starting with the older adults. We would address infant disease burden in a different way and, but this vaccine could potentially be extended in the future to those at risk.
Umer Raffat
Got it. And what about mRNA, are they going, high and low?
Philip Dormitzer
I believe they are, but I would have to check with Moderna on that, but I believe they are going high and low.
Umer Raffat
Infants as well as adults.
Philip Dormitzer
I think so.
Umer Raffat
And they don't have this big term birth.
Philip Dormitzer
They would be starting older because you have to age deescalate to get down to infants.
Umer Raffat
So they haven't even started infants yet? Or they are in very early stages?
Philip Dormitzer
I'm afraid to have them under sort of address exactly where they are.
Umer Raffat
Okay. Makes sense. Makes sense. But from their efficacy data to-date, how are they positioned versus you guys?
Philip Dormitzer
What I would say is there's no apparent advantage at this point of mRNA over the [indiscernible] subunit technologies. For viruses that change all the time, the ability to match strains more nimbly with RNA appears to be a real advantage when you are talking about viruses that really don't change much year to year of the advantages of [indiscernible].
Umer Raffat
Got it. Makes sense. So, I didn't realize that we will end up spending 20 minutes on RSV. That was way longer than I planned on. But I know there is a bunch of topics. I wanted to go through. Let's go right into your mRNA collaboration with CureVac.
Philip Dormitzer
Sure.
Umer Raffat
There has been maybe let me fill you in on perspective from an investor perspective. There is two things. One, there has been this perception that they have been slow at the development program. GSK folks had to step in to change the strategy from going beyond just the not using chemical modifications to actually doing them. It looks like finally things are starting to work. But even at this point, the COVID vaccine that they have that they showed us data for is on the older omicrons and they are not up to date. I guess, where do things truly stand? And is it truly GSK R&D running the trial design and strategy on their development efforts?
Philip Dormitzer
So, first, it is a collaboration -- so both sides have input. I think the switch using nucleotide modified RNA was very important. There is a clear advantage.
Umer Raffat
Was that your idea?
Philip Dormitzer
I am not the only person who that came from Kati Kariko and Drew Weissman have seen that who got the Nobel Prize, so I haven't come up with that idea, but it was clearly an idea, that is well worth adopting. And, you may or may not know, I was at Pfizer before and sort of Comirnaty was in my [Multiple Speakers]. So, I have kind of done this before.
Umer Raffat
So, you really know the pneumococcal, which I am going to ask you next.
Philip Dormitzer
We can start with pneumococcal too. We are in Phase 2 with both a flu and a COVID vaccine. Our primary goal is getting to the patient. And I think you will see that we are rapidly closing on the leaders.
Umer Raffat
You think you can do infants with this mRNA flu construct? Because it sounds like your other one, which you are currently approved [indiscernible] I think is the name that's not intended for.
Philip Dormitzer
So, the RNA COVID vaccines, they go down way to six months I believe. So, they haven't been down to the youngest babies yet. But, so I see no reason why this RNA vaccine can't have a similar guidance once all the appropriate studies are done, of course, to the existing RNA vaccine.
Umer Raffat
So as you guys sit down with the leadership and the Board internally, is there a goal or a time line set out that, listen, by 2026 or so, we got to have our mRNA vaccines on the mark. Is there anything like that internally?
Philip Dormitzer
I am certainly encouraged by the top of the Company to move that pace here and we are on track.
Umer Raffat
Is there, Jeff, have you guys communicated any sort of like registrational data timelines for the CureVac.
Jeff McLaughlin
We haven't given any detailed timetables.
Umer Raffat
Progressing towards registrational now because I think it was Phase 1, Phase 2 still, but sounds like you're about to initiate something more registrational in nature.
Philip Dormitzer
Yes. So we are looking to move at pace, I would say with Phase 2 data coming out soon, and then…
Umer Raffat
And this will be Phase 2, okay, remind me. This is Phase 2 data on flu plus COVID combined?
Philip Dormitzer
No. So right now, they're separate, but our strategy is to go quickly to the combination vaccine. And I think there could be a market for a RNA flu vaccine alone, but I'd say a new COVID standalone vaccine, there's probably not so much of market for. So, we view right now the COVID as a stepping stone just to the Company.
Umer Raffat
This Phase 2 data's first half?
Philip Dormitzer
Phase 2 data. Yes. I think we should be pretty ended out there in the first half.
Umer Raffat
So, this Phase 2 data is coming up, and remind me, the COVID construct is that updated for the latest, the XB, X, Y, Z, or is it an older one? Because that's always the data, we realize there's older than the older one.
Philip Dormitzer
Phase 1 was older. We've done an update, we may update again for Phase 3.
Umer Raffat
So, this COVID chart data coming up now will be same strain as what's Moderna and Pfizer in the marketplace?
Philip Dormitzer
Yes. We're benchmarking as well. So, yes, we should be able to make apples-to-apples comparisons but not for the Phase 1. But, again, then you can look to the older data.
Umer Raffat
But the Phase 2 that's coming up, that's on the same antigen as the Pfizer, Moderna in the marketplace right now, or is it older?
Philip Dormitzer
The XPB 1.5, I believe, always for the Phase 2, and then we'll update.
Umer Raffat
It is 1.5 for Phase 2.
Philip Dormitzer
Yes.
Umer Raffat
And are you guys in any way, it's a 50-50, I think, with CureVac. Is that right?
Philip Dormitzer
It depends and if you're talking about flu or COVID. So COVID is 50-50, flue is a different agreement.
Jeff McLaughlin
Yes. I haven't looked at the agreement in a while.
Umer Raffat
It's more economics on the flu for you?
Jeff McLaughlin
We have more of the economics, yes, from the initial deal.
Umer Raffat
And there's a lot of litigation between CureVac and the main mRNA players like BioNTech and Pfizer, and there might be some litigation and settlement, but that's not GSK relevant. That's all CureVac, is that right on some of the updated CureVac IP?
Jeff McLaughlin
Yes. We stayed out of commenting on.
Umer Raffat
One last one, is CureVac the only mRNA development you guys have or you have other internal mRNA as well? Because there's been, this is not a question on CureVac, but it's been the question on why didn't GSK just outright have the whole thing in-house because it was not a very large company but it's always been this collaboration?
Philip Dormitzer
GSK, through the Novartis acquisition, has a long history in RNA, and we are, in fact, in the clinic as well, with an internal RNA program as well. Right now, we're just, it's just for the COVID engine for benchmarking purposes.
Umer Raffat
Including on COVID?
Philip Dormitzer
Including in COVID, but that's just for benchmarking. There's no attention to advance a separate COVID, because since the big RNA vaccines out there with COVID, we wanted to see how things compare.
Umer Raffat
Does CureVac not get upset about that?
Philip Dormitzer
We had RNA vaccine development, internally underway at the time of the deal. So since we had an existing program, it was sort of a factor of life at the time when we did that initial deal. And there are many applications of RNA in the future, and not all of them will be covered by our COVID care back arrangement.
Umer Raffat
Any questions on this topic before we move on? Okay. So let's go to pneumococcal. But just before we do, and I didn't know this, did you work on pneumococcal stuff as well at Pfizer's?
Philip Dormitzer
I was more of a bystander adviser. My responsibilities were for the viral vaccine R&D and now it's more broad. So I saw a lot of what was going on, but on the other hand, it was not my responsibility.
Umer Raffat
I mean, this is not Pfizer questions anyway. I was mostly just orienting. So, obviously, the focus is Affinivax and the MAPS platform internally at GSK. There are several layers to this. I mean, the first one is Pfizer's gone from Prevnar 7 to Prevnar 13 to Prevnar 20 and now going beyond. But the basis of your Affinivax deal is you could do 24 in one clean shot both in infants and adults. However, what Pfizer and Merck are saying in the marketplace is, look, we can go beyond as well. Even though they have a big gating factor for the sheer amount of carrier protein they have to put in there to go beyond, which is why it's not a coincidence. Merck is now doing a separate, I don't know. V116, however valent that is, and as an add-on or an adjuvant shot. Do you foresee some of the traditional players being able to do what you're intending to do with the Affinivax, not seat them with the amount of carrier protein they need to get to that?
Philip Dormitzer
Yes. So, we have a 24-valent program. We also have a 30 plus valent program that's currently preclinical. And when you look at the Pfizer data, as they've gone to higher valencies, what you see is a reduction in the response to each individual component as you go to the higher valencies. And we believe that that is a limitation of the classic glycoconjugation technology. What we've seen in the Phase 2 data for older adults with the glyco complexation or the MAPS technology is we're able to get to higher valencies without the reduction, the level of reduction in response to each individual component.
The physical arrangement of the carbohydrate component and the protein component as we go to those higher valencies is different with the MAPS technology. It's a more ordered kind of arrangement. We refer to it as beads on a string for the MAPS technology as opposed to spaghetti and meatballs, for the glycoconjugation classic technology.
We also have the fact that the carrier protein, it's not an irrelevant for example diphtheria or tetanus blood antigen, but in fact, pneumococcal antigen as well as sharing anti-protein immunity as well. So, of course, because of the anti-protein immunity and just empirically, we're seeing the ability to go to higher levels of valencies without the drop in individual component immunogenicity.
Umer Raffat
So, Phil, I'm just, sort of processing what you just said. It sounds to me like you're saying they may be able to go a little beyond the 20-valent. And again, when I say beyond 20, I'm saying they keep the first 13 in that construct, but they're certainly not catching up too. So, they may get close enough to your 24, but not all the way to 30?
Philip Dormitzer
Yes. And it's 30 plus. We haven't actually disclosed what the actual valencies, but it's the plus.
Umer Raffat
Okay. But you are in agreement that the carrier suppression is a gating factor for those traditional constructs to go well beyond 20?
Philip Dormitzer
Yes. What it says, it's an empirical observation that the response to the individual stereotypes is going down. And originally, the MAPS technology was intended primarily to make it easier to manufacture. It is a simpler technology. And it was an empirical finding in the old adult Phase 2 study that in fact, it seems to also be better at this. We also, as we go higher, we have the option of going to more than one carrier as well.
Umer Raffat
Got it. What's your sense for, and I want to get into MAPS much more specifically. But what's your sense for it from a, because the perception is they control much of the market right now, and it makes it incrementally harder for others, especially if they can expand the valency of their current constructs. What's your sense for if they are at '20, so there's a PCV 20 in the marketplace right now from Pfizer. They want to go broader. There is two ways of doing it. One is what Merck is trying, which is a different construct for adults, where it is broader spectrum. But I don't know how successful that would be because that wouldn't cover infants. A second strategy would be increase add a little more carrier protein so you can add, like, two or three or more serotypes in there. Do you think that's what they are doing? Or are they going down the direction of two carrier proteins? Because then it starts to get very complicated.
Philip Dormitzer
I probably won't comment on the Pfizer program because I have to be very careful there, but certainly our approach is to both go to more carbohydrate serotypes. As we go beyond '24 to consider an additional care approach, no final decision there.
Umer Raffat
The Even for MAPS?
Philip Dormitzer
Even for MAPS. Yes. It is an option.
Umer Raffat
So the perception is, if there is two carrier proteins, it starts the get very risky. I think there was a GSK construct, the 10-valent, where it's two carrier proteins. Is that right? Am I thinking right?
Philip Dormitzer
I don't think.
Umer Raffat
There's a PCV 10-Valent, I forget whose it is, with two carrier proteins, and it's not too strong in data.
Philip Dormitzer
We have a Synflorix is a 10-Valent vaccine. That is not with the new technology. That's with the prior technology. We will have to assess in the clinic, what it looks like with...
Umer Raffat
But it doesn't add more risk a second carrier protein?
Philip Dormitzer
So, every time you add a new antigen, you have to do the safety testing as well. And so, obviously, that will be done. I don't think it is a particularly high level of risk, but every new antigen you introduce you need to do a safety as well as efficacy and immunogenicity assessment
Umer Raffat
Got it. So, Phil, when Affinivax was a standalone private company, you can imagine there were some investors that were acutely familiar with the Company. There were private investors in it, et cetera. And one of the feedbacks was, FDA, because of the theoretical risk, FDA mandated anti-linker antibody testing in the Phase I trial. And then I also heard from those same investors that O&R Phase 2 now, if he's not asking us to do it. Can you talk about that evolution, because presumably it was an important diligence issue in your assessment?
Philip Dormitzer
So, the linker consists of two components. On the protein side, it is a protein called rhizavidin. On the carbohydrate side, it's biotin. And rhizavidin binds biotin very tightly. rhizavidin is a protein from a bacterium that infects plants. It has no homology to any human protein. There is about 22% amino acid identity to chicken evident, which is in eggs. It does list of antibodies.
Umer Raffat
Now, we eat chicken. Is that what it is? So is that from the meat consumption?
Philip Dormitzer
Probably from the egg, there is a fair amount of evidence in eggs.
Umer Raffat
That's why I didn't have egg to eat.
Jeff McLaughlin
In people, who do have anti evident antibodies, those do not cross react, with rhizavidin. And on the biotin side, in these early studies, we looked at both antibodies against biotin, comparing those who receive vaccine, this received placebo. We compared pre-immunization and post-immunization antibody antibodies, and we compared biotin levels, before and after immunization in no case, well, was there a signal.
Umer Raffat
On a group level or patient level as well?
Philip Dormitzer
On a group level, I mean, antibodies go up and down. But if you look at the group level, there's no trend. And so, on the basis of the data we've generated early on, we no longer have to continue looking at those antibodies. So, it was a question that was raised. We've gathered data on it and it looks good.
Umer Raffat
So Phase 1, there was anti-linker antibody tracking. How often was that?
Philip Dormitzer
I think we would have looked pre- and post immunization. I don't know how -- I have to check it out often.
Umer Raffat
And there is no pre-immunization reads that are being taken for your Phase 3 trial?
Philip Dormitzer
So, Phase 3 trial there's no there's no plan for this. Of course, we don't have the finalized Phase 3 protocol yet, but it does appear that we're not, going to have, we will not have to continue looking because we've addressed the question in the earlier stage of clinical trials.
Umer Raffat
And presumably that would be in consultation with FDA?
Philip Dormitzer
Yes, absolutely. The protocols will be reviewed absolutely.
Umer Raffat
And then the other big question on this program has been GSK bought Affinivax and it turns out there's a massive manufacturing problem. Now GSK is working on it, and we don't know when they're going to actually start these trials, and infants are even more delayed. What exactly is going on there? No one really understood.
Philip Dormitzer
So I'm not familiar with any massive manufacturing problem.
Umer Raffat
I'm giving you the investor perspective around this point.
Philip Dormitzer
Okay. I think, I would know about it if there were one. There's a challenge when you're coming up with a 24-valent or a 30 plus valent vaccine.
Umer Raffat
To generate the…
Philip Dormitzer
There's a lot of work to do, because we had the 10-valent vaccine. We were making 10 carbohydrates earlier, but you have to make 14 more for 20 valent and 20 plus more for the 30 plus valent. So, I would say that there's a lot of work to do, but we've not run into any.
Umer Raffat
So, there's a perception that somehow your infant versus adult timing is different. Is that not the case? It sounds like your gating factor is generating stable levels of all 24 serotypes, and that's it. And once you have it, you can do infant and adult. It's not an infant versus an infant?
Philip Dormitzer
No. What did happen in the infant trial is we had a fill finish issue. It just had to do with some quality aspects of the fill finish, and that did, cause a delay in infant trial. So that was stopped, last year. It gives a chance to have a initial look. And then we'll be restarting, this year now, but it was nothing to do with the underlying trial.
Umer Raffat
And what was the initial look?
Philip Dormitzer
So when we stopped the infant trial because of the fill finish issue, we took an interim look at the data. We've not announced it, but I can say we're very pleased with what we saw. It encouraged us to keep it forward on the path.
Umer Raffat
Jeff, you guys didn't press release that, the infant look?
Jeff McLaughlin
No.
Umer Raffat
And they're very pleased with what you saw. Okay, got it. And the infant looked, so presumably, it was the first one-third or quarter patients, whatever it was, but tracked for three doses, presumably?
Philip Dormitzer
I won't go into details, but we looked at all the data that were accumulated up to that point.
Umer Raffat
That's very helpful, actually. I wasn't familiar with that. Is that well understood, Jeff, that there was a data readout internally on the infant?
Jeff McLaughlin
Phil has said it before.
Umer Raffat
Okay. So you guys have said it in. Okay.
Philip Dormitzer
That's not new information.
Umer Raffat
The Th17 responses are in larger trials. And also I noticed for the -- I realized it's the same serotypes, and I was trying to match them up. And I noticed on serotype 20, you guys use 20b and not serotype 20, so that's technically a small difference versus Prevnar 20 and perhaps even with the backside approach. How relevant is that?
Philip Dormitzer
That, I'd have to go to the real pneumococcal specialist on that distinction.
Umer Raffat
But have you seen that as well, what I'm referring to? That among the serotypes, serotype 20 somehow is not 23 it's 20b. And I wasn't sure why that was?
Philip Dormitzer
Yes, I would have to go back and check into that.
Umer Raffat
Okay. No problem. Any other questions on broadly the pneumococcal, I know there's a lot of interest in this space. Jeff, would you agree this is one of the more questions you guys get broadly on…
Jeff McLaughlin
Pneumococcal it's important, because it is a potentially very large opportunity. And it's incremental for us because though we have Synflorix and it's been around a long time, it's mainly an emerging markets vaccine. So, we've not really been competing in the pneumococcal space.
And I think that because Affinivax was a private company, there's varying degrees of understanding on the platform. So, I think more to do as data emerges, and we can share that externally and it gets presented and published. So, there is definitely interest level.
I mean, vaccines overall, part of the reason why we're here is a high interest area for us. And we spend a lot of time on RSV that's probably the number one question anybody asks us about, so it was good to spend a lot of time on that. mRNA, pneumococcal are kind of new areas for us, so incrementally different, and if you want to spend a little time on Shingrix, that's the other one.
Umer Raffat
So this looks like it just keeps going. So is there room for taking a shot again? Like presumably that could or a new vaccination campaign for you guys to the extent there's any data on that?
Philip Dormitzer
So, there are sort of two parallel options. One is a booster, another is age expansion. And it's a bit of a yin-and-yang because the longer the duration of protection, the more interesting age expansion is and the less interesting a booster is. And we're continuing to collect data on duration of protection, and we're now up to over a decade where the protection looks quite good. So, although both booster or age expansion on the table? I would lean more towards age expansion at this point, but at the point where we start to see waning and…
Umer Raffat
What is the age currently versus what would the expansion looked like?
Philip Dormitzer
So, this is sort of an area of sort of active discussion. We’ll go down to 18 for those at increased risk or immunocompromised. So, there are a variety of options on where you can go. We're actually in some active discussions about where it is. So for those with immunocompromised, you can go all the way down to 18.
In Europe, I believe it's at increased risk, down to 18. So, they're both questions of how far down would you want to go for a broad age based recommendation, and how far do you go down for those who are immunocompromised. And how far down do you go for those who are I'd increase this, but not necessarily immunocompromised. So, there are a variety of options to expand the age indication.
Umer Raffat
Got it. Okay, excellent. Maybe my last point, broadly speaking, since pneumococcal will remain a very big focus from a pipeline perspective since given your positioning there. Are you nervous from the competitive threat from the incumbents as it relates to how broad they can get because ultimately that's really the question everybody's pinning it down to that. If they become really broad spectrum, then maybe your 24-valent may not be as competitive?
Philip Dormitzer
Yes. So, I see that the MAPS technology really does appear to enable us to go to a higher level of valency without the decrease, in response. Second, particularly against, serotypes have been very hard to immunize against such as serotype three. The technology seems to do quite well. And then you have the element of anti-protein immunity as well. So, we think as we push to higher and higher valencies, the MAPS technology will enable us to outpace the incumbents.
Umer Raffat
Excellent. Fantastic. Well, thank you guys for being here. I hope this was helpful and looking forward being in touch.
Jeff McLaughlin
Thanks a lot, Umer. Thanks for having us.
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GSK plc (GSK) Presents at 6th Annual Evercore ISI HealthCONx Conference (Transcript)