James Gordon: Great. Thank you for coming, everybody. I'm James Gordon, Barclays European Pharma and Biotech Analyst, and today I've got the pleasure of hosting a fireside with GSK. So we're going to hear from GSK Chief Strategy Officer and Chairman of EVE, David Redfern. Thanks for joining us today, David.
David Redfern: Thanks, James. Always great to be in Miami. Very nice to be here.
James Gordon: And we've got quite a lot to talk about because David's got a pretty broad remit. So I think we're going to try and talk a bit about the strategy for the overall GSK group. But we're also going to talk about business development. And then as chair of EVE, we can also have a chat on HIV as well. So maybe just to start off, though, so you've got a new CEO, Luke Mills, although he's not entirely new because he's been there a while. Any early feedback about changes under Luke? What are we seeing and what changes might we have?
David Redfern: Yeah, well, we're two and a half months in. I mean, I think, I mean, firstly, I think Luke will be much more expressive in the second half of the year. But that said, I wouldn't expect any kind of big strategic shifts in the direction of GSK. I think the therapy areas that we play in, respiratory inflammation and immunology, oncology increasingly a very fast-growing business in oncology in both solid and uh hemological tumors and pretty much everything infectious disease obviously we have a big vaccine business um as well as hiv and increasingly and things like hepatitis b so i you know that is clear i think capital allocation very clear we're very clear on the dividend um investing in the business uh business development you know luke has been a big driver of that with tony wood and i over the last uh few years that continues you've seen us being pretty active on that this year, and the guidance that we've given that Emma set out, he has reaffirmed. So I think you should think of Luke as very much focused on doubling down on execution, driving growth, simplifying the business, and particularly over the last few weeks, really getting into the the R&D pipeline and particularly sort of the phase two assets, so we can talk more about those things like B7H3, B7H4, T-slip program, FGF21 that we got from Boston Pharma, and really digging in with the teams on how we make things like dose escalation, dose optimization decisions in a bolder, quicker way, how we can recruit patients, set up the protocols, run the studies faster. So there's a real focus on pipeline execution, particularly the mid to late stage assets that are really going to drive the growth in the 2030s.
James Gordon: Thanks. And you mentioned M&A, and so you're also heavily involved in business development. So maybe first of all, what are the two deals you've done recently? Because we've had two quite recent deals. So why did you go for those assets? What's the appeal?
David Redfern: Yeah. So we have been busy, and it's very much part of the strategy to continue to invest to build the pipeline, particularly through the 2030s. So the two M&A deals, we've done more than that. We've also done some licensing deals with people like Frontier and um but uh we we bought and have now closed wraps which brings um a medicine for food allergy very similar to zola which is doing incredibly well uh here in the united states but with a much longer half-life and then potentially up to 12-week dosing and a simplified dosing regimen i mean food allergy massive Issue 17 million people here in the US enormous burden on the healthcare cost in terms of hospitalizations and so forth It's obviously builds on our respiratory expertise. We have an allergy sales force and we think uh the wrapped asset uh is an improved version of zola because of the longer half-life and the simpler dosing regimen and also potentially we can access the 25 percent of patients that either through weight or ige level uh zola can't so we're excited about that and that's pretty symptomatic of the type of deals that we're trying to do which is some level of scientific de-risking um so either precedented target or a precedented mechanism but with the potential to be best in class through some differentiation. And in therapy areas where we have a very clear capability and right to win, or very close adjacencies to those. And the second deal we announced, I think only last week, 35 Pharma, a Montreal-based biotech company that has a drug for pulmonary hypertension. So again, builds on our respiratory expertise. We've had drugs previously, Volabris and Flolan, in that area. Again, precedented mechanism, this is an active pathway inhibitor, but potentially spares something called PMP9 and 10, which is involved in increased bleeding risk. So this is, think of this as the tapasept-like, the Merck asset. but potentially with less bleeding. It's very early, I have to say, so there is a bit more clinical risk around this. It's only in phase one, but potentially a very big medicine in that indication.
James Gordon: And I think of GSK as having quite a focus on infectious disease and oncology, which these two aren't in. Is it just chance that these aren't infectious disease or oncology, or is it quite deliberate you wanted to be broader?
David Redfern: Well, it's not chance. I mean, infectious disease, definitely we're very strong in, but we're extremely strong in respiratory, and we're building out adjacencies and things like inflammation with the Boston Pharma deal. We've got a lot of science around fibrosis developed with lung fibrosis, so it's natural to move that into the huge indications of liver fibrosis. So I don't think this is not chance. We're very thoughtful of where we go. We will do deals in oncology as well.
James Gordon: And in terms of the scale of deals you do, I said these are sort of moderate-sized deals rather than massive deals. Is that also quite a deliberate thing that rather than wanting to do one big bet, you want to have quite a broad portfolio of assets?
David Redfern: Yeah, I think so. I mean, we'd never rule out doing a bigger deal if the returns and the styles aligned on it. But I think we've been pretty active doing a series of these sorts of deals. What we're really trying to do is drive – meaningful growth through the 2030s. I mean, that is what is behind all of this. I think the pipeline is building up extremely well to be able to do that.
James Gordon: And would you consider doing deals for assets that would launch this decade, or you think that the outlook is strong for this decade, such that it's only really post-2030s you want to be having a boost?
David Redfern: We wouldn't rule it out. I mean, we clearly bought Sierra a few years ago now, which gave us Momolotn and Majara. in myelofibrosis, and particularly myelofibrosis patients with anemia, which is a significant proportion of them. That was a very late-stage asset. It's doing incredibly well. But there aren't that many unencumbered, really late-stage assets, and they're extremely expensive. So I think we're in a pretty good space doing what we're doing. Makes sense.
James Gordon: If we could switch to talking about new product launches, because there's a few things going on there. I hosted a panel yesterday which was about respiratory, which got a lot of interest, and we were talking about longer-acting therapies in respiratory. So you've got Extensa, a longer-acting IL-5, a six-monthly. How should we think about that fitting versus the other drugs that are already out there that are biologics that are shorter-acting?
David Redfern: Yeah, I mean, we're super excited about Extensa. Every six months, they sink. I think that is very significant compared to the shorter acting R5s, which are four to six weeks. The thing about severe asthma is it's very under-penetrated with biologic agents. Only about 27% of asthma patients take a biologic agent. So there's a real opportunity for increased biopenetration market development here. And I think all the feedback we're getting And as I say, it's early days, but the qualitative feedback from physicians, the mood at ERS, six-monthly dating will be extremely helpful in increasing that penetration. We will, of course, get some switches. I mean, there will be patients that will naturally want to switch from every month to every six months, obviously a lot more convenient. But we're really focused on driving Accenture into that bio-naive population. Early days, but everything's on track.
James Gordon: And I think there was a study that came out that showed it wasn't quite non-inferior as an extensor to Nucola, but does that impact how you plan to do the launch?
David Redfern: We're pretty relaxed. I mean, that was the Nimble study. It wasn't statistically powered to show that the switch indication is in the label. All of that was disclosed to the FDA. So I don't think we don't anticipate that will impact the launch. And it reinforced actually the safety data of the product, so we're pretty relaxed about that.
James Gordon: And is this a category where it can take some time to get insurance coverage, and that's a bit of a headache?
David Redfern: Well, there's nothing particularly unusual about it. I mean, it always takes a quarter or two to go through the discussions with the insurance companies, but we expect this very much to be in the ordinary course. I think the payer proposition for it, given the burden of severe asthma exacerbations often lead to hospitalizations and so forth, So we don't anticipate anything being particularly difficult or unusual. It always takes a quarter or two. And the other thing I'd say about Accenture is it's part B. There's about 25% of severe asthma patients that are Medicare patients here in the United States. That's very different actually from COPD, where Medicare is the majority of the patients. We are also in the process to get the J-code, which will take a few months. But, you know, everything on track, all in the ordinary course. And I think we're very excited about the potential. And, of course, we're talking about severe asthma. We've started the studies now in COPD as well.
James Gordon: And maybe just on that, so we also talked about COPD yesterday. So you've got the only IL-5 approved for COPD. How's that launch going?
David Redfern: It's going extremely well. I mean, we showed some data at Q4. There's been a big spike up in Nucala, MBRX. I think there's also probably a halo effect from the COPD indication across asthma and nasal polyps. So, yeah, Nucala is doing very well. I think the metric that is really resonating is a 35% reduction in in hospital exacerbations leading to hospitalizations. And that's what you're really trying to do because it's a progressive disease. It's incredible the burden of COPD. If you go into any emergency hospital, how many patients have COPD? and taking up resource. 10% of patients that are admitted never come out of hospital. 50% die within five years. So there's a real unmet medical need to come up with new agents.
James Gordon: Well, actually, just on that point of new agents, there's some other mechanisms as well. So we've got Dupixent, a 413 that's approved for COPD. But then we're also soon going to get some data for IL-33. I believe T-slips are also in development. I think you've got quite a few, including some longer acting versions, going after all those targets. So When could you broaden what you're doing in COPD and how do we segment it?
David Redfern: So we have Nicala today. We're running trials in different levels of severity of COPD patients now, just getting underway, edurance and vigilant trials with Xtendra for six monthly. We also have potentially the six monthly T-slip. We will definitely take that into COPD. And we still remain pretty excited around the science of IL-33. And obviously, we have an IL-33 that we are progressing. And there is obviously the potential to create combinations of those over time. We're doing a lot of work on patient stratification. A lot of AI, actually, has been very helpful. Because COPD was always thought of as just sort of one disease caused by smoking. But actually, you can stratify it in many different ways here. I mean, very simply, the IL-5s are most suitable for eosinophils over 300, maybe T-slips above 150, and IL-33 across all levels. But I think we will get a lot more sophisticated as we move these clinical development programs forward in really identifying different categories of COPD patients these can work for.
James Gordon: Thank you. What if we shift to your other launch, which is BlendRep? Yeah. I don't know how accurate the IQVIA data is, but that looked like a pretty strong ramp initially in Q4. It may be a little bit softer at the beginning of the year, but is that data very reliable? How is the launch actually going?
David Redfern: Again, it's very early days, but we're very pleased with everything we've seen so far. You can't totally rely on IQVIA, although it is showing very strong growth, but it's obviously part B as well, so IQVIA is incomplete. I mean, two things are very important with Blenorab. Firstly, it's an incredibly efficacious medicine. We saw that from the DREAM-7 results, progression three survival, almost three times the standard of care, daratumumab, and a 50% reduction in the risk of death. So it's very meaningful. That efficacy is absolutely resonating with the hematology community. I think there is a real enthusiasm for a BCMA agent post the first line or post CD 38 and the other thing about Blenrep is a very simple infusion takes about 25 minutes to half an hour can be given on an outpatient basis so it's incredibly well suited to the community and here in the US 70% of patients and hematologists are in the community so We're excited about that. It's obviously third line initially in the US, second line in the rest of the world. We're just rolling out, you know, ex-US. The UK was the first market. No hard data points at this point, but everything very much on track.
James Gordon: And is there a lot of work to do in terms of training both the doctors and also ophthalmologists? And so we think at one point GSK had talked about going slow to go fast. Do you need to go quite slow before you go fast?
David Redfern: Yeah, I mean, I think what we mean by that is we're very keen that the early patient experience with both the patient and the hematologist is positive. So, you know, we're encouraging patients. the hemes to be very thoughtful around which patients they put on it initially and then work very closely with them. On the REMS, it's much simpler than BlenRev 1.0. It does require an eye exam each dose in the United States. In the UK, it's just the four doses. But that can be done routinely by a high street optician. It's a very simple slit test. They're very experienced in dealing with cancer patients. We've trained several thousand opticians across the U.S. And the qualitative feedback we're getting from hematologists and the opticians is that process is all working pretty well. And the paperwork associated with it is actually massively simplified.
James Gordon: Great. Well, I definitely want to ask lots about HIV because of your Veev chairman role. Maybe I'll just ask one about the pipeline before switching to HIV. So one of the interesting readouts I think this year is Kamala Pickson. Yeah. So there's two elements. Generally, how excited are you about these readouts for chronic cough? And then the other question was, could there be differences between the two trials? Because I think I've heard a comment from GSK that the second trial might have people that cough even more, like the more acute patients and more severe patients. So how do you think about the two different trials and the overall excitement for the program?
David Redfern: Yeah. I mean, look, refractory chronic cough is a serious condition. We know that there's about 1.8 million people in America being under the care of a pulmonologist. Their pathway there is often quite different. 50% of them have probably seen three other different types of doctors, allergists, GPs, and so forth on the route. And there's really nothing today that really treats it. They're taking a mixture of OCC, cough medicine, Sometimes pain medication opiates and so forth so we're very clear on the unmet medical need the studies Calm one and calm two will read out in the pooled analysis In the middle of the year all of that is on track. You're right come to has got slightly more patients in and more frequent coffers and so You know, there may be a slight difference. I think I'm right in, although it's a pooled analysis, effectively both trials have to statistically hit to ensure that the overall trial hits. So, you know, we'll see in the middle of the year. I mean, I would remind you that the phase two data showed a 34% reduction in cough frequency. The phase three is a 12-week endpoint. um we'd probably expect it to be a bit lower um you know the 15 to 20 percent mark will probably be about par because it's a bigger trial we probably expect a bit more placebo effect but we shall see um we're not too far away now so we'll probably have discussion papers results That sounds good.
James Gordon: In that case, I'd definitely like to switch to HIV. Yeah. To start with, so there was the CROI conference recently where I know you presented quite a few data points. And in particular, I was interested in the data you had for four-monthly, but even more so what you might be able to do for six-monthly. So maybe just briefly, what did you present there? And then what does that say about what your longer-term plans might now look like?
David Redfern: Yeah. So actually, James at CROI, we didn't present much on four-monthly, but for both PrEP and treatment, four-monthly very much on track. So the PrEP will read out this year and hopefully launch next year treatment is about a year later than that we will start the pivotal bridging study later this year what we really presented at CROI and what we're very excited about is our six monthly treatment options and we presented PK data on our third generation integrase 184 which we'd already shown has a very broad resistance profile against all much broader set of mutations than cabotegravir or dolotegravir, which has been very well received by the community and by the KEEs. We showed PK data on that that showed that we're very confident of going to a six-month formulation. And similarly, 499, our capsid inhibitor, which is very similar actually to lencapovir, but with less drug-drug interactions, we showed PK data on that. uh which is very affirming to a six month formulation so the next stage now um is to is to test six monthly formulations of those in infected individuals so i think um and then the third piece of data that we showed uh from r d was our neutralizing antibody N6LS. We showed four-month data on that, but we've got data coming in six months. And again, that was very effective. So we've got some options of how we build a six-month pipeline here. But I think we've got growing confidence that we're going to potentially have a best-in-class six-monthly treatment. And there's more clinical work to do. We will do a meet the management event at some point in the middle of this year and go into a lot more detail around this.
James Gordon: And why would you pursue one of the six-monthly options versus the other? So my understanding is that a broadly neutralizing antibody, it wouldn't work for absolutely all strains of HIV, and you still need to get the six-month data, but you've got some four-month data that looks encouraging. But the capsid, you've already got six-month data, and it could work for everyone. So why not already just go forward with the capsid?
David Redfern: Yeah, that's a very good question, and it's a question that we are still thinking through. There's no doubt, you know, the capsid is going to be broader, and I think 184 plus 499 has the potential to be a very significant medicine. With the antibody, there's actually been quite a lot of science over the last year or so around the impact of antibodies on the latent reservoir in HIV, even in patients who are virally suppressed. So there's work going on to look to see whether there are particular patient groups that that might be potentially important for and I think and I know Andy Dickinson was here before Gilead it's all about having options you know it's a bit like we had Jaluka and Devato there are a diverse group of patients and having different combinations that could be important for different groups I mean to that point it's a big opportunity and they both sound interesting could you just take them both forward we could yeah so watch this space and we will update you later in the year
James Gordon: And actually, so we had Gilead on first, and there's been some talk about less frequent orals. So I don't believe you've announced a less frequent oral program, but you've got a third-generation integrase that looks very effective. Is it the sort of drug that could be made into a less frequent oral?
David Redfern: The PKL184 is such that that's probably not the optimal medicine to be in a more frequent oral, but we are certainly looking at possibilities in that. I think our main focus is very much six-monthly, but we are open-minded on other things.
James Gordon: And what about the route of administration? Does that matter? Because some people have noted your products at the moment are intramuscular, some competitors are going for sub-Q. But then if you're talking about something where you've only got to get it twice a year anyway, how important is whether it's IM, IV, sub-Q?
David Redfern: I think... I think it's very important in PrEP. We haven't got on to PrEP, but there's no doubt that Yes2Go, even though it's doing well, there are quite a lot of nodules, issues from the sub-key formulation. I think in treatment, our aim is very much to develop an IM formulation. We'll have to see. I think that's definitely possible for 499. We've got a bit more work to do with 184. but there is less pain, there's less nodules associated with IM in our view, and all the research we've done. But I would say, I mean, the thing that's underestimated a little bit, the chemistry around these long-acting formulations, integrase chemistry itself is very complicated. I think part of the secret sauce of VEEV has been its integrase chemistry both inside VEEV, but also with our great partner with Shionogi. I think we've got real competitive advantage there.
James Gordon: And if Gilead is able to bring along a once a week PrEP as a pill next year, do you think that would be a big challenge to Apertude as a two month or a four month injection?
David Redfern: I think in the PrEP market, I mean, I agree with Gilead. I mean, the PrEP market is growing strongly and having a second entrance in long acting is absolutely helping that. I think having different options is always good. At this point, Apertude is continuing to grow very strongly along the along the lines of the last couple of quarters. I think if there is a once weekly, I'm not sure that's necessarily coming next year. I mean, it was cannibalized the daily orals for sure. But, you know, we're focused on long acting.
James Gordon: Great. Well, I'm looking forward to this HIV event and hearing more. And with that, I can see we're out of time. So thanks a lot for joining us.
David Redfern: Thanks, James.
James Gordon: Thanks, everyone, for coming.
