Good morning once again. We're delighted to have GSK at the TD Cowen Conference once again this year. Representing the company is Luke Miels, who is the Chief Commercial Officer. Luke, thanks so much for making the effort to be with us today.
Thank you, Steve.
There's a ton going on in your business today, and we want to dig into all of it. But maybe we could start out by you identifying the two or three most important dynamics in the commercial operations that will transpire in 2025.
Sure. So I think number one is Blenrep, the launch of that. We have the PDUFA in July. Second would be the introduction of Nucala into COPD. And I think the third one would be just extracting more from Shingrix overall. But I can add to that list. You've asked for three.
Okay. We're actually going to get to Shingrix eventually. But let's start out with number one, and that is Blenrep. So I assume the review is going well and that we should not be overly apprehensive about the PDUFA. But therefore, describe for us the launch curve. What's the launch curve going to look like?
Yep. I mean, I think it's an unusual case because it's a relatively rare event that you relaunch a product. And the data that we've generated through essentially the relaunch program, so DREAMM-7, DREAMM-8, is very compelling. But there is an art to using Blenrep. It's relatively simple to use versus options such as CAR-T and, I would argue, bispecifics. But we want people to have those first five patients a really good experience, understand how to manage the dosing, when to dose hold, when to infuse based on the patient's status of their vision. And so it'll be a tiered introduction. We'll initially go to HCPs that have used HemOncs, that have used the product in the past, and then we'll expand out. But ultimately, the destination, of course, is to use this very broadly.
Our arguments why this can be used very broadly, if you really need to look at the options that someone treating multiple myeloma patients has in second line today. The assumption is in the U.S. that you're going to be using a CD38 in first line. And so your choice in second line is a CAR-T, which is a minority of patients in a minority of centers, or a bispecific, which they don't have a label there, of course. They don't have survival data there. But they're really your primary choices if you're looking at chasing efficacy. Or you have Blenrep. And with DREAMM-7, we're projected to have a 33-month incremental survival benefit over and above Daratumumab, which is obviously very compelling. But there's an element of Blenrep's profile, which is blurred vision. When we first introduced the product, there was a lot of questions around it.
We've now dosed over 7,000 patients. Every patient that's had any ocular issues, any blurred vision, it's been completely reversible to date. And so what we want to ensure is that physicians understand how to dose the product and when to dose hold and when to start. And that's why that process there is going to be a little bit slower.
Okay. I should have mentioned at the outset, should you have a question anywhere along the line, just raise your hand and we'll call on you. So, Luke, you mentioned that the first targeted physicians will be experienced or advanced HemOncs and so forth. But what's the nature of the first types of patients that will be put on this drug?
Yeah. I mean, the aim, of course, is second line. That's where the label is. There's patients who are largely in the community. This is ultimately, we think, is going to be the choice for community oncologists. Because, again, if you look at the options, and that's 70% of the patients in the U.S., by the way. So CAR-T is an absolute minority. I think most CAR-T clinics have a capacity for about 250 patients a year. If you want to use a bispecific, you've got to admit the patient to hospital. You've got a complex dosing titration regimen, and you have a pretty severe and unpredictable infection risk. Whereas with Blenrep, which, again, it's likely to come down with bispecifics, but it was still 20% in their poster with Grade 5 fatal infections at ASH this year or last year.
With Blenrep, you're looking at managing eye-related side effects. If you treat 100 patients in the community or an academic setting, two-thirds of them are going to have no visual disturbance. That's the key thing that is often lost in these discussions. Two out of three have no impact on their vision. The one-third that have an impact on the vision, the bulk of them, it's mild to some disturbance, say, 20/50. If you look at the time that they have that disturbance, around 11% of the time that they're on treatment. It's for periods around dosing. What we've also learned is that if you dose hold, you can get that patient to normalize relatively quickly, and you're not sacrificing efficacy. We've shown that through DREAMM-7. That protocol is now being used in our first-line approach.
And if you look at people that have severe visual disturbance, say, 20/100, 20/200, it's about 2% of patients. So it's dramatically less. And a number of these patients can get to a steady-state infusion of one infusion every 10 to 12 weeks. You don't have to bring them into hospital. You don't have to infuse immunoglobulin. So it's a much simpler regimen once you've got the patient up and going. Hence, we ultimately aim to be the choice for community-based HemOncs.
Okay. Now, you mentioned that it will be a tiered introduction. But tell us, after this tiered introduction, what it's going to look like. So will there be inflections, and what will be those inflections? Will it be guidelines, reimbursement, more data? What will drive these inflections?
Yeah. I mean, guidelines are key, of course. And the sentiment around there, we're somewhat limited at this point to what we can do with guidelines because we don't have an approved product. But that is an important component just in terms, particularly with community oncologists and hematologists, HemOncs. But I think the first six months of this year will be more steady-state, carefully accumulating experience. We don't want people just to go rapid-fire with the product. We want to support them so that their first few patients, they have a good experience. They understand that it's a very predictable product, and it can be managed very well in their clinic. And once they accumulate experience, then I think we can open it up. We'll start initially with people that have experience with Blenrep in the past.
Then we'll look at community-based physicians in practices that have a lot of experience or have participated in our programs. Go to them first, and then ultimately the broader community. So a stepwise approach.
Okay, and when would the product be first eligible for consideration for inclusion in guidelines?
I mean, that's really the gift of the guidelines committee. Sometimes they move very quickly. Sometimes they wait a number of months. So it's difficult to predict. But all the members are well aware of the data. I think when you DREAMM-7 is really quite striking. You've got a hazard ratio, which is approaching that of what you achieve with a CAR-T. And as I said earlier, you're adding 33 months of survival on top of what was standard of care in the form of Darzalex, Daratumumab at that point. People have not missed that. We've got updates to DREAMM-7 and DREAMM-8 at ASCO this year. So that timing is helpful. And then further data at ASH at the end of 2025.
Would you push back on the assertion that it should be rapidly considered by guideline committees? Would that be too strong?
I mean, I hope so. But again, we have limited influence, with good reason, right? These individuals need to be independent and seen to be independent. But I would expect it's something that's considered. I don't think we'll be waiting six months. I think they'll be looking at it relatively quickly because of this gap that's opened up in second line. And people do need guidance in terms of what's appropriate to employ in second line if you're electing to use daratumumab in first line.
Okay. GSK has provided a peak sales estimate of GBP 3 billion plus. Can you just dissect that a little bit for us?
Yep.
What's embedded in that in treatment duration, market share? And I assume you're not going to speak to price, but maybe you will.
But the pricing, we are talking to payers about pricing. We'll be intelligent with pricing. But we have a good sense of the price that will provide good access but reward the profile of the product. If you look at the GBP 3 billion plus, that is second line plus. So it doesn't include any potential label that we currently have experiments running for first line. But yeah, the bulk of those patients are in second line. You can model the duration roughly off what we've seen so far with DREAMM-7, as I mentioned before. So 84 months would be an evidence-based timeframe to model. The complicated element is that the dose initially drops relatively quickly in their frequency. So the initial dose is every three weeks, relatively high.
And as I said, many of these patients are going to get out to about half or a third of that every nine to 12 weeks. So again, we've been quite thoughtful around how we price that and looking at an annualized or through treatment costs with payers.
Okay. One more question on Blenrep before we move to other topics, and that is that in your mind, you have a best-case outcome for the REMS. How does that best-case outcome compare to the REMS that was in the original label?
Yeah. I mean, the REMS that was in the original label was onerous. And for those of you that remember, in the adcom, there was a lot of discussion at the time around what is the profile of this product in terms of keratopathy of the cornea. We only had a couple of hundred patients experienced then. We're in a dramatically different point now. So ultimately, it's in the arms of the regulator. But our expectation is there will be some form of eye exam initially. But this is a simple slit lamp examination. And the intent is that it can be conducted by an optometrist. If you look at a typical multiple myeloma patient, 90% of them are within 30 minutes of an eye care professional optometrist because many of them, of course, have glasses. So the capacity to support those people and do that is there.
We also have a huge infrastructure that we're putting in place to help physicians navigate and their patients navigate that as you would with any other REMS program. REMS finally are, I mean, most products in multiple myeloma actually have a REMS program. It's not unusual for that to be there.
Okay. Questions from the audience? Okay. Let's move to vaccines and spend a few minutes here. First, on Shingrix, do you expect U.S. Shingrix to return to growth, plateau, or decline through the end of the decade in the U.S.?
I mean, if you look at the total population that is 50 plus and presents for a regular adult vaccine, it's about 70 million people in the U.S., 72 million-73 million, 4 million are added. Obviously, some people pass away. But steady states are around 70 million. We have 50 million of them already vaccinated with at least one shot of Shingrix. So there's another 22 steady state that we have a good chance of picking up. In the past, the penetration rate for Shingrix, we added about 6 or 7% a year. So we finished last year at around 40%-41% penetration. But what we've said consistently is we expect that accrual rate to drop to a rate of 3%-5% because you've got less engaged people, less motivated. But I do think we can work through that population.
So growth is more challenging, but we can still ultimately capture those patients and vaccinate them over time. The other thing we're doing is shifting the strategy. This has been very successful in Europe. In markets like Germany, we launched a broad approach in the U.S.. If you're this age group, you should consider Shingrix, the shingles vaccine, your risk of shingles as such. What we're now doing is ramping up our efforts. And that was really a retail pharmacy-driven strategy. What we are now doing, we're not abandoning the retail pharmacy strategy, but what we're doing is increasing the investment behind physician education and really looking at subgroups of patients and looking at physicians that have high usage of vaccines but don't necessarily use a lot of Shingrix. And that combination has worked very well in Europe. And that's one that we're actually launching now in the U.S..
We're building a specialty team to target oncologists, dermatologists, cardiologists, groups like that to encourage them to get their patients vaccinated with Shingrix because it disrupts the primary care that they're trying to deliver themselves, whether it's chemotherapy infusions or stenting a patient and then having the recovery post-stent, and we've seen that resonates really well in other markets in the world, so that's what we're doing with Shingrix. Europe is an opportunity to grow. Emerging markets, excluding China, is an opportunity to grow.
All things considered, in the U.S., sales in 2030 are for Shingrix slightly higher than current?
I won't speculate.
That man in the front row there called Mick will throw his laptop at me or something at me. But what I would say is that our aim is to accrue those 22 million people over time. And we are at a relatively early phase in most markets in the world. And if you look at even Europe, I mean, we're just introducing the product into France now. We've got a good restart and an inflection point in Germany. So yeah, this is a very valuable, very effective product. It'll remain like that for a number of years. Okay. Let's move to Arexvy. What data points does ACIP need to see to consider a booster dose for the Arexvy vaccine?
It's difficult to speculate. And of course, there's a lot of variability in this environment right now. We will have the 36-month immune data study 004, 0004, hopefully presented to ACIP in June. But I think they're going to want to see breakthrough infections. All of our modeling indicates that's going to happen. This is not a one-and-done vaccine. For simplicity's sake, we model five years. And historically, ACIP has dealt in prime numbers, so one, three, and five. So I think it would be judicious to model a five-year vaccination cycle, which is a remarkably effective vaccine for high-risk individuals. And so I think there's some strategic patients needed here. The product is very compelling. We're having good success outside the U.S. in terms of contracts and reimbursement, obviously different systems to the U.S.
But yeah, I think in time, the benefits of this product will be apparent in the U.S. setting. And I think in time, we'll see revaccination. And in time, we'll see an expanded population. But it's just not going to happen tomorrow. And it's not going to happen in 2025.
Okay. Let's move on to one more vaccine, and that is, what are the implications of the delay to the U.S. ACIP recommendation for MenABCWY, and that was supposed to occur this month, and what's the path forward now?
Yeah. I mean, we were not expecting that, of course. This initial meeting was not as important as the second meeting that was expected in October. When Pfizer's pentavalent was approved, ACIP said, "Look, we'll put it in a context of shared clinical decision-making, but we want to come and revisit this schedule and move it to more of a risk-based." And that's why you've seen relatively low uptake of their pentavalent. And I don't think we would see a dramatic uptake of ours until you move to really looking at segments of adolescents that are going to be in high-risk environments for meningitis. That being said, we have an outstanding business with the standalone B vaccine. We get 76% of the market. It's perceived to be superior to Pfizer's product. Remember, we cover about 110 strains. So it's the preferred B.
So we can offset any delays there because it just means the uptake of the pentavalent is going to be delayed. The other critical thing is the compliance rates when you get into the B vaccine strains are relatively low. It's about a third of adolescents that get it. Again, a risk space would be, okay, your son or your daughter's going off to college. They should really get a vaccination. And the pentavalent for that middle vaccine increases compliance, makes things simple. And there's a history of that in pediatric vaccines. And the B that they use in the middle pentavalent, they have to use the same B for the follow-up B shot, which again is very helpful for us because they prefer to use our B, which places our pentavalent when it's eventually approved by ACIP in a strong position.
Is there a path for preferential recommendation of your vaccine?
ACIP is historically very reluctant to separate out vaccines. I mean, people forget this, but Shingrix has only got a preferential vaccination recommendation by one vote at ACIP, despite the fact that you had, I think it was 89% efficacy, more durability versus Zostavax, which was about 50% efficacy and relatively short duration. So there's a reluctance to do that. It's in the interest of competition and supply stability. So I would not expect that. Now, in European systems, they are more driven by raw clinical data and relative differences, price as a component. But tender specs and things like that can be more targeted around the evidence that you have versus extrapolating or assuming class effects, which ACIP is more typically inclined to do.
Before we leave vaccines, any questions from the audience? Okay. Let's just briefly touch upon Benlysta, and then we'll go to Depemokimab. When you look at Benlysta today, what % of sales are in lupus versus lupus nephritis?
Yeah, it's 60-40. So 60:% in SLE, 40% in lupus nephritis. If you look at the subcut IV split, it's actually 60-40 as well. So 40% of those patients are coming in on a regular basis for an infusion, which is important when we look at longer-acting B-type programs in the future. But I mean, Roche obviously presented Gazyva data. I think that data was pretty much what we were expecting. It's in the range of Benlysta in terms of efficacy, but you have a far more complicated toxicity profile, black box on pregnancy, etc. I think lupus nephritis will continue to grow. The guidelines in the U.S. have just shifted. We had global kidney guidelines, European kidney guidelines for a year or a couple of years now favoring the early use of Benlysta.
And the U.S. guidelines have now just shifted last year, encouraging, and are very clear that Benlysta should be used initially. So our market research indicates that physicians see it as a refractory later-line option. And that Benlysta is perceived to be the ideal balance of efficacy and non-toxicity profile, tolerability profile for those patients.
This would not be unexpected, but Roche thinks the guidelines will be revised in that Gazyva will be the drug of choice. But you believe the data is such that Benlysta will not be at a disadvantage.
Yeah. I mean, they miss their secondaries. The efficacy rate is not dramatically different from if you allow for cross trial. It's really in the realm of a similar profile. Rituximab, we know the heritage of rituximab there. So again, our view is at least what we're hearing is that no, Benlysta will remain the favored agent to be used in those early patients.
Okay. Why don't we move to Depemokimab? And I think there was some news this morning. So in case anyone missed it, why don't you just recap what the news was today?
Sure. So I mean, we are filing. The initial launch will be in severe eosinophilic asthma, but also nasal polyps. And that is an interesting area. The bulk of the value, of course, is in severe eosinophilic asthma. And Depemokimab, we think, is going to be very disruptive in that setting. It's a twice-yearly long-acting IL-5. This is, we think, compelling for a range of reasons. Firstly, the IL-5 target is well known. You've got mepolizumab, which is ours. Nucala. You have benralizumab from Astra. It's well characterized. The profile of the product, if you look at the publications, is typically close to placebo. So it's well known by pulmonologists. The challenge is, if you look at penetration rates of biologics in severe asthma, I mean, these are very refractory patients. It's about 28% in the U.S.. And there's a range of reasons for that.
Insurance, if you look at lives covered, is about 95% or higher. So it's not an insurance issue. And the other challenge we have is if you look at the stats, and it's the same for GPs and other biologics in severe asthma, typically someone who started on the 1st of January, you lose about a third of those patients by the middle of the year, and you've lost two-thirds of them by the end of the year. So what's attractive about Depemokimab is the physician has complete control of the patient. Our intent is to launch it into Part B, B for Bravo, so physician-administered. And so we also know there's a lot of patients that would be open to a biologic if they didn't have to inject it themselves. And then you've also got adolescents, pediatric patients where their parents are having to do this.
And so ultimately, the physician, if they want, can buy and build the product, administer the product, and then the patient's covered for six months, and you don't have to rely on the patient complying. And then within nasal polyps, we've got a battle emerging here against Amgen and Astra with the TSLP there. But I think that it's our market research with the data; it's very attractive to surgeons because most of these nasal polyps patients require multiple surgeries, which is frustrating for the surgeon. And also, of course, the patient is not too happy about it. And so the capacity to, I think it was 88% reduction in surgery with our program is really attractive. And again, surgeons aren't; they're not known for their love of complicated drug regimens.
The capacity to be able to essentially conduct the surgery, inject the patient, discharge the patient, and know that the patient is covered for six months. And you don't have to worry about your office supporting all of that or compliance, etc., or writing letters to the referring pulmonologist. And then you can bring them back in for a follow-up appointment, typically a few months later. And then you can do the second dose, and you've got 12 months of coverage. So again, it just simplifies things. Penetration in nasal polyps is about 14%, which is relatively rapid so far. It's about $1 billion, I think, for Dupixent in the U.S.. So again, these are the areas that we're interested in. We also have EGPA, HES, other indications coming in the next two years. And our intent is to launch a COPD experiment as well.
So you mentioned launching into Part B, which has the advantage of the physician administration and so forth. And you cited the advantages of that. But investors are sensitized to other drugs which launched into Part B and really were not all that successful, most notably Novartis's inclisiran. So why will this be different?
Yeah. I mean, it's a good question, right? And there was bisphosphonates as well as PCSK9. So I think the main element is if these patients don't comply, the odds of them having an exacerbation, being hospitalized; this is a severe disease. These are not people just puffing on Ventolin. These are patients that are being managed by pulmonologists, not primary care doctors. So they're at the severe spectrum of asthma. And asthma is obviously a very dangerous disease if it's not managed. So it's different to lipids where there are other alternatives. And again, it's an auto injector. It's a very thin high-gauge needle. So simplicity: bring the patient in, have the nurse inject them, and then you've got, you're much more confident that that patient's going to be under control.
Okay. On the Q4 2025 conference call, you'll give us an update on access for Depemokimab. What would you predict that number will be?
I mean, our initial feedback is it's going to have very good access. Again, we're not looking for a massive premium versus Nucala. No. And our intent is to target for severe and Dupixent and the TSLIP market. And the incentive scheme for our organization will be geared that way. What we're offering is predictable efficacy, durable efficacy. And the other thing we'll run real-world evidence studies with payers, as we've done with Nucala, showing that compliance is important. And there's an increasing body of evidence, which is being led by Nucala, which is showing that you can actually start to remodel these patients' lungs if you can intervene early enough. And again, compliance is a real problem here in keeping patients on study.
The experiments that we have, we have a study that we'll report out next year looking at people who are stabilized on Fasenra and Nucala, a double-blind, double placebo switched across onto Depemokimab. Again, that is not an in-the-wild environment. You have a nurse following you up. It's the best case there. But we'll run studies which are actually showing people in the real world and what they actually do to comply. And the figures I cited earlier, if they're replicated in the study, then over time, the value of Depemokimab will be apparent to payers.
Okay. Questions from the audience? Let's spend our last few minutes on Camlipixant. What do you think the probability of success of the phase three trials is?
It's good. I mean, for a phase 3 program, a novel phase 3 program, why do I say that? Because we acquired that from Bellus. I was directly involved in that deal. We looked at all our deals. But for me, what I wanted to be convinced of is what have we learned from Gefapixant? And there are chemical profile measurement and study design lessons that are very clear there. So from a profile point of view, I mean, Gefapixant validated the target. It does work to suppress cough. The problem is the primary target is P2X3. But Gefapixant is relatively promiscuous and binds to another target called P2X3, which is present in the taste buds. The problem is that the patients get this taste disturbance, which is a bit like quinine. There are problems with that. Obviously, people don't like that.
It essentially unblinds the medicine, and so the rate that Merck experienced in their program was around 65% of strong taste disturbance and a lot of dropouts and also put a ceiling on the dose that they could pursue. We have about 6% of people in phase two that had some taste disturbance, so relatively mild, and we didn't have dropouts because of that. The other challenge that Merck had was these patients are monitored for a year, so they wear a cough monitor counting the number of coughs, and you use software to compress that. Otherwise, you'd have to listen for 365 days for every patient, and so there were some differences with the agency around that. We actually incorporated that agency feedback into our program.
And then the final one is just looking at the type of patients and cough frequency and using the insights we've got there. So the unmet need is very high. I would encourage anyone, if you're at ATS or other conferences like that and you're talking to a pulmonologist, ask them about the most frustrating part of their practice. There's a good chance that they will say it's chronic cough. These patients typically are coughing for a number of years. They'll go on through four or five other specialties before they end up at a pulmonologist. So typically, it's a disease of exclusion. So no malignancy, reflux, asthma. And then when you look at the options that these patients have, once they actually reach a cough clinic, are relatively low. The most effective is speech therapy. There's not enough of those people.
Anti-cough medicines make you drowsy and are not good long-term. Low-dose opioids, pretty obvious why they're not a good idea. When you look at those pulmonologists and research that we have, only 3% are happy with the options in chronic cough. There's an unmet need there. If we take the most severe population, like the most severe, there are people who are coughing hundreds of times a day. It's about 1.8 million people in the insurance databases in the U.S. Severe population, very synergistic with our respiratory business. We saw around a 34% reduction in cough frequency in our phase two. If we can achieve above 15%, I'd love to achieve that in phase three. But if we can get above 15%-20%, then I think we've got a compelling asset here.
Okay. Great. And we actually are out of time, but let's ask one more question. And that is, so we didn't talk about the oncology business. You got some very important assets here. What do you expect sales of these products to do over the next two to three years? Accelerate, decelerate? So talking about Zejula, Jemperli, and Ojjaara.
Yeah. I mean, I think with PAPs, relatively static, that's not where our focus is. I mean, we have a study for glioblastoma with Zejula, which is, I think, very exciting. We have very high CNS penetration. With that, there's nothing in glioblastoma for the last 40 years. So we did a study there that we're now replicating with a licensing study, pivotal study. But Jemperli is still growing. I mean, if you look at the penetration in endometrial cancer, people are often surprised when I say that we split the market evenly with Merck with Pembrolizumab, which is, I would argue, no small achievement there. And that is continuing to grow. The opportunity for IO in these patients is very high. And we're also looking at non-chemo regimens and experiments there. We also have a program in locally advanced rectal cancer and also programs in CRC with Jemperli.
That's exciting. We just did a deal at Christmas time to buy a product for gastrointestinal stromal tumors. This is a product which is very, very effective at the exons that drive gastrointestinal stromal tumors along with imatinib. But imatinib does not work on the escape mutations. This is an asset that works on the most common escape mutations, which are exons 13 and 17. Also, like camlipixant, very, very specific in terms of its binding behavior. You don't have as much off-target issues with it. We had 200 patients that IDRx had dosed and treated. We really had a good idea of the clinical profile of this. That's an exciting one.
And then Ojjaara, which is a very similar deal, again, looking for a more targeted, very predictable product that solves a problem that physicians have that continues to do well in myelofibrosis. We've just actually started yesterday a study in combination as well to broaden that population. We get about 20% of first-line patients in the U.S. and 40% of second-line patients against ruxolitinib, which again is, I think, probably above what people expected us to do. And then the final thing is we'll have updates over the year for a program called B7-H3. Merck acquired the Daiichi Sankyo program for B7-H3. We have a fast follower with Hansoh. That is looking really quite exciting.
We have two breakthrough designations, or actually three, on small cell, which again is, okay, it's 10%, 11% of patients, but an entry point that we could be very close to Merck there, as well as osteosarcoma, and there's a whole other group of tumors that we're looking at, so it's very targeted. We're humble in our approach here, but we think that we can build this out to be a valuable business and something that's attractive for shareholders and with products that really are doing something over and above what's available for patients today.
Great. Lots to look forward to and monitor. So thank you so much, Luke, for this great rundown.
Thank you. Thanks everyone.