Hello, everyone. It's Nick Stone, Head of Investor Relations. Welcome to our Year-to-Date and Q3 2023 Results Conference Call and Webcast for Investors and Analysts. The presentation was sent out to our distribution list by email. And you can also find us on gsk.com. Please turn to Slide 2. This is the usual safe harbor statements.

We will comment on our performance using constant exchange rates, or CER, unless stated otherwise. As a reminder, following the Consumer Healthcare demerger in 2022 to form Haleon, we're representing performance and growth of the continuing operations for GSK. Please turn to Slide 3.

Today's call will last approximately one hour with the management presentation taking around 30 minutes and the remaining time for your questions. [Operator Instructions] Our speakers are Emma Walmsley, Tony Wood, Luke Miels, Deborah Waterhouse and Julie Brown, with David Redfern joining the rest of the team for the Q&A portion of the call.

I'll now hand the call over to Emma..

Thanks, Nick, and welcome to everybody joining us today. I am delighted to be presenting to you all with another set of excellent quarterly results. Please turn to the next slide.

Sales and profits grew double-digits for the quarter, with sales up 16% to £8.1 billion, adjusted operating profit up 22% to £2.8 billion, and adjusted earnings per share up 25% to £0.504, all excluding pandemic solutions.

Our strong performance was broadly based and benefitted particularly from the outstanding US launch of our RSV vaccine, Arexvy, on track to be a blockbuster in its first year on the market.

This excellent execution together with our drive for efficiency and margin accretion, means we can upgrade our 2023 sales, adjusted operating profit and adjusted EPS guidance. For the year, we now expect sales to increase between 12% and 13%, adjusted operating profit to increase between 13% and 15%, and adjusted EPS to increase between 17% and 20%.

Within sales, we are upgrading the outlooks across all segments for the year, reflecting our clear momentum. Our performance also clearly demonstrates delivery of the strategic choices we've made to invest in prevention, as well as the treatment of disease.

New products launched since 2017 have contributed sales of £7.8 billion so far this year, with nearly 80% of them coming from Vaccines and Specialty Medicines.

Approvals this year for Arexvy and Apretude, together with two important oncology medicines Jemperli and, most recently, Ojjaara, further strengthen this new product portfolio, and offer meaningful sources of profitable growth. So taken altogether, this is a strong and sustained performance heading into 2024. Next slide, please.

This quarter, further underscore the importance and strength of our Vaccines' business. Prevention is an increasing focus for healthcare systems all around the world. GSK is a world leader in vaccines and is extremely well-placed to deliver innovation and offer value to both individuals and payers.

The introduction of Arexvy in the US is evidence of this, demonstrating our strong launch capabilities because with over £700 million of sales and its very first quarter as we protect people at scale from this life-threatening disease, and especially those with comorbidities.

Generating further clinical evidence for Arexvy remains a clear priority and we were pleased to present positive data in adults aged 50 to 59 years at the CDC's Advisory Committee on Immunization Practices last month. We also added to the outstanding clinical profile of the Shingrix this quarter.

Results of the large post-marketing study in China demonstrating a 100% efficacy.

And alongside this, we're additionally significantly expanding availability of Shingrix in China, our exclusive partnership with Zhifei signed last month is going to support and accelerate our goal to Shingrix's annual sales of more than £4 billion by 2026, and with opportunities to expand this partnership further, including potentially with Arexvy.

Our innovation in RSV, shingles, meningitis and pediatrics, all demonstrate our world-leading vaccines capabilities.

And we have further substantial innovation in the pipeline where we have our comprehensive and leading suite of vaccine platform technologies, including next-generation mRNA, our multiple antigen presenting system, or MAPS, as well as, of course, as our adjuvant systems.

All of these offer exciting new opportunities in seasonal respiratory, bacterial and chronic viral infections, and we continue to explore the science beyond infectious diseases. Next slide, please. Alongside delivering stronger shareholder returns, we also continue to build trust by delivering across the six key areas we prioritize for ESG.

This quarter, I'm highlighting our continued commitment to fight malaria with innovation.

GSK scientists working with Johns Hopkins Institute and others published their groundbreaking discovery of the naturally-occurring bacteria that can significantly reduce the malaria parasite load in mosquitoes, indicating the potential to inhibit transmission of malaria to humans.

And we also continue to deliver our environment and diversity, equity and inclusion goals. Further details, along with more, on all six key areas are included in the Q3 results announcement. Now, let's hear more from the team on our progress, starting with Tony and R&D..

Thank you, Emma. My priority is investing in our pipeline and accelerating R&D to deliver new vaccines and medicines to patients. Today, the pipeline comprises 67 assets in clinical development, two-thirds of these prevent and treat infectious diseases and HIV. During the quarter, we've seen continued progress.

In infectious diseases, we're focused on seasonal respiratory viruses, bacterial, fungal and chronic viral infections. In seasonal respiratory viruses, Arexvy received approval in Japan as the country's first RSV vaccine for older adults.

And we also shared positive data for 50-year-olds to 59-year-olds with the Advisory Committee on Immunization Practices in the US. In chronic viral infections, we will present data later this month on bepirovirsen, a potentially transformative treatment for chronic hepatitis B. I'll talk more about these data shortly.

In HIV, the European Medicines Agency approved Apretude as the first and only HIV prevention option in combination with safer sex practices to reduce the risk of sexually-acquired HIV infection in high-risk adults and adolescents.

For respiratory, Japan accepted the regulatory submission of Nucala for chronic rhinosinusitis with nasal polyps, and later this month alongside Luke, I look forward to providing you with insights into our respiratory strategy and medicines at the next focused Meet the Management event.

For oncology, the European Medicines Agency recommended not renewing conditional marketing authorization for Blenrep. As a reminder, given the changing regulatory environment, our expectations remain low for the event-driven DREAMM-7 and DREAMM-8 Phase III trials. We now expect to read these out in 2024.

This quarter, we also reached an exclusive licensing agreement with Hansoh for a Phase I B7-H4 targeted antibody-drug conjugate, or ADC. We believe this has best-in-class potential in ovarian and endometrial cancer with opportunities in other solid tumors.

Lastly, we're delighted with the US FDA approval of Ojjaara, or momelotinib, which is indicated for treating myelofibrosis in adults with anemia, and the approval of Jemperli, our highly effective PD-1 inhibitor, as the first new frontline treatment for patients with dMMR/MSI-High primary advanced or recurrent endometrial cancer.

The profile for Jemperli was strengthened by the recent interim analysis of RUBY Part 1, which reported a statistically significant and clinically meaningful survival benefit in the overall population enrolled. We aim to present these OS data at a conference early next year. Next slide, please.

Last week, we presented further safety and immunogenicity data for Arexvy to ASIP. The vaccine met its co-primary endpoints and demonstrated non-inferiority in people aged 50 to 59 years of age, when compared with adults of six years and older, including those at increased risk of RSV lower respiratory tract disease.

These data continue to demonstrate the consistent strength of Arexvy's profile in protecting the most vulnerable. We will make a supplementary biological licenses application to the US FDA before the end of this year in time for next year's ASIP to further support potential label updates.

For Shingrix, we continue to build our knowledge with new data demonstrating 100% efficacy in the prevention of shingles in China for adults aged 50 and over, a remarkable result. We expect to publish these data in a peer-reviewed scientific journal before the end of the year. Slide 11, please.

Continuing with infectious diseases, bepirovirsen, our triple-action antisense oligonucleotide, has the potential to be the cornerstone of functional cure for patients with chronic hepatitis B. It inhibits viral replication, reducing viral DNA, and thus the production of viral proteins including hepatitis B surface antigen.

And importantly, it stimulates the body's innate immune system. We believe this triple mechanism-of-action is the reason for bepi's unique profile.

There are more than 300 million people living with hepatitis B and our goal is to provide patients with the first clinically meaningful functional cure for hepatitis B, eliminating the need for continued therapy and ultimately reducing the long-term risk of developing liver cirrhosis and cancer.

We now have two completed Phase II trials, for which data are consistent and demonstrate that patients with low surface antigen have the greatest chance of a functional cure when treated with bepi. In the case of B-Together, this is not significantly improved by sequential Peg-interferon treatment.

However, the recent exclusive license of Janssen's Phase II small interfering RNA-based therapeutic provides a complementary opportunity to develop a potential novel sequential regimen to benefit a broader patient population and potentially drive higher functional cure rates.

Lastly, we hope data from B-Sure will be presented later this month at AASLD. This will demonstrate a durable response for a significant proportion of patients treated with bepi. Our Phase III trials B-Well 1 and B-Well 2 are progressing as planned in 31 countries with data anticipated in 2025. Turning to my final slide.

This slide highlights important clinical data readouts and regulatory events over the upcoming months. You can find a comprehensive overview in the appendix. In summary, I'm pleased with our progress so far this year. We have clear plans to move forward at pace, deliver on our key objectives for R&D and support GSK's overall growth ambitions.

I'll now hand it over to Luke on Slide 13..

Thanks, Tony. In Q3, we again delivered growth across Vaccines and Specialty Medicines in each region with £8.1 billion of sales, up 16% versus last year, excluding pandemic solutions. Please turn to Slide 15.

In Vaccines, we saw strong growth of 34% in the quarter excluding pandemic solutions, led by the excellent launch of Arexvy, which contributed £709 million. On the same basis, we now expect full year Vaccines sales growth to be around 20%.

On Arexvy, I want to highlight the excitement our organization has had behind the launch that we've seen in the US. Following an initial inventory build, we saw high demand and received two out of every three retail prescriptions. In the quarter, we saw around 50% of Arexvy doses were co-administered with flu.

And we're pleased with our commercial positioning in all major pharmacies, including competitive contracts with 11 key accounts. We strategically chose to highlight our 94.6% efficacy in the co-morbid population and that message seems to resonate well with strong HCP brand recognition.

There's a long runway for Arexvy in the US, where during the quarter, we vaccinated more than 1.4 million adults of the 83 million at-risk, and ex-US, as launches are underway across Europe and Canada. In September, we also received approval in Japan. We remain confident in our peak sales being greater than £3 billion.

For the full year, we expect sales to be between £0.9 billion and £1 billion, based on an analogue of flu vaccination seasonality. However, there continue to be unknown factors including annual vaccination patents, duration of protection and what re-vaccination recommendations might be. We will continue to keep you informed of course as we learn more.

Next slide, please. Moving to Shingrix, this remains an important vaccine for our portfolio, up 15% versus last year with the ex-US contribution now representing 50% of sales. In addition to the US, Shingrix is available in 38 additional countries, with less than 3% penetration in most markets, and we continue to have unconstrained supply.

In the US, we have reached the most motivated consumers with 33% penetration of more than 120 million adults recommended to receive Shingrix. We remain encouraged by the growth in retail, which was up 4% in the quarter and are investing in strategic initiatives to actively target consumers and HCPs to access the next tranche of customers.

In October, we announced the deal with Zhifei to co-promote Shingrix in China, and this partnership materially expands the number of Chinese adults who can benefit from Shingrix over the next three years through a company with a track record of driving access to innovative medicines and vaccines in China.

Zhifei has a significant reach across China with an extensive service network covering more than 30,000 point of vaccination versus the current 9,500 we have now. As Emma mentioned, we expect this partnership to support and accelerate our expectations for Shingrix sales to reach more than £4 billion by 2026. Next slide, please.

In Specialty Medicines, including HIV, which Deborah will cover shortly, we've increased our sales by 17% excluding Xevudy. For the full year, we now expect low-double-digit sales growth. Our market-leading medicines Benlysta and Nucala continue to deliver double-digit growth.

Benlysta was up 20% in the quarter, with growth across all major markets and a promising opportunity with updated EULAR guidelines now recommending use earlier as part of a standard-of-care for lupus and lupus nephritis. Nucala was up 19% in the quarter and remains the first and only biologic approved in four eosinophilic diseases.

We expect to see COPD data for Nucala in the second half of next year. Both of these medicines continue to have room to grow with relatively low buyer penetration and lifecycle opportunities, underscoring our confidence in the long-term opportunity for both.

In oncology, sales were up 26% in the quarter with Jemperli now being used in the first-line for appropriate endometrial cancer patients, and Zejula was up 22% due to stocking of our new tablet formulation, providing an improved patient experience. We expect this stock will be utilized by the end of the year.

And on this slide, I wanted to highlight the recent approval of our myelofibrosis medicine Ojjaara.

In addition to a line-agnostic label in the US, regulators acknowledged our unique benefit in anemia, an especially important characteristic for these patients as we know that anemia status from requirements of transfusion directly correlate with poor survival prognosis and quality-of-life.

And as you can see on this chart, if you're a myelofibrosis patient with no anemia, you have a median eight-year life expectancy. Conversely, you have a two-year life expectancy, if you're severely anemic. So, for example, your hemoglobin level is below eight.

We look forward to making this medicine available to patients and have already recorded sales in September. And when these updates, we are raising our full year oncology sales expectations to increase to low-single digit. Please turn to Slide 18.

Finally, our General Medicines portfolio continues to contribute more than £2 billion in the quarter, led by Trelegy, which was up 23%. Trelegy is the fastest-growing triple therapy for COPD and asthma with room to grow as the SITT class still only has 28% penetration of the COPD patient class share in the US.

Overall, General Medicines were down 2% for the quarter due to negative RAR impact, slightly offset by Trelegy demand and continued post-pandemic recovery of the EU and international antibiotic market. Taking everything into account, we now anticipate low- to mid-single-digit growth this year.

And with that, I'll now hand over to Deborah to cover HIV..

Thank you, Luke. Our HIV business delivered sales of £1.6 billion in the third quarter, growing 15%. This growth was primarily driven by patient demand, which contributed 10 percentage points of growth, with the majority of the remaining 5 points from tender phasing in our international business.

Our continued strong performance through this quarter means we are now increasing our guidance for full year growth to around 10%. Our performance benefited from strong patient demand for our oral two-drug regimens and long-acting injectable medicines, which are now 53% of our total portfolio value. Dovato delivered £477 million in the quarter.

Market performance reflects HCP belief in Dovato, which has firmly consolidated its position as the leading oral two-drug regimen. I'd like to spend a few moments describing our expectations around Dolutegravir's loss of exclusivity. In Europe, the composition-of-matter patent expires in July 2029.

In the US, Dolutegravir is protected by a composition-of-matter patents until April 2028, which includes an additional six months of exclusivity, following the completion of our pediatric studies. Dovato and Juluca are also protected by formulation and other patents in the US, which have expiry date after the composition-of-matter patents.

Therefore, we anticipate a longer exclusivity period in the US with Dovato until December 2029 and Juluca until July 2030. Moving to our long-acting injectable portfolio. Cabenuva sales for the quarter were £182 million, reflecting strong patient demand with high levels of market access and reimbursements across the US and Europe.

Cabenuva continues to be supported by strong label evolution and data, which underpins confidence. Patient awareness of Cabenuva is high at over 70% and around two-thirds of switches are coming from competitor products. Moving on to prevention.

Sales of Apretude, the world's first long-acting injectable for the prevention of HIV, delivered £37 million in the quarter, and we are pleased by the momentum across the US.

This, alongside the desire by prescribers, payers and governments for new solution to help end the HIV epidemic, gives confidence that the PrEP market in the US will continue to grow strongly. We were also pleased to receive European approval for Apretude in September.

We're also pleased by the progress of our pipeline, which is focused on innovative long-acting regimens. We have three clear target medicine profiles to provide the world's first self-administered long-acting regimen for treatment, and to provide ultra long-acting regimens for treatments and prevention.

In our recent HIV Meet the Management event, we confirmed that we are currently on track to deliver an every four-month injectable regimen. This would enable us to double the dosing interval, enabling clinic visits to be halved to just three per year, meaningfully increasing the benefit of long-acting regimens for patients and healthcare systems.

The four-monthly dosing and prevention, we said we currently expect approval in the 2026 timeframe, and for four monthly treatments in 2027. We also provided greater clarity on our roadmap to further extend the dosing interval of our long-acting regimens in treatment and prevention to enable every six month dosing towards the end of the decade.

To conclude, we remain very confident in our ambition to achieve a five year sales CAGR to 2026 of 6% to 8% and to maintain our innovation leadership in HIV. This, combined with the continued growth of the long-acting market, gives us the potential to significantly replace the revenue from the Dolutegravir loss of exclusivity.

I will now hand over to Julie..

firstly, the receipt of the Gilead settlement last year of £0.9 billion; and secondly, the increase in working capital, influenced by stronger Arexvy sales in Q3 and lower Xevudy collections. The Arexvy sales will come through in the fourth quarter cash flow.

Free cash flow more than doubled to £1.7 billion in the third quarter and brought the nine month year-to-date to an inflow of £1.3 billion. Cash expectations for the year have improved, but we still anticipate that 2023 cash generated from operations will be slightly lower than 2022 due to the one-off we've seen from Gilead last year.

We confirm our commitment of more than £10 billion of cash generated from ops by 2026. Net debt stands at £17.6 billion with free cash inflow and proceeds from the Haleon stake are partly deployed through business development on the acquisition of BELLUS healthcare. Turning to the guidance on Slide 26.

Given our sustained strong performance across all segments in the business, we are upgrading our guidance at CER for the full year. And as a reminder, our guidance excludes the impact of COVID-19. We now expect sales to increase 12% to 13%.

We expect adjusted operating profit to increase between 13% and 15%, and adjusted earnings per share to increase 17% to 20%. The strength of the Arexvy launch has been ahead of our initial expectations and is the main source of the guidance upgrade.

Q3 sales of Arexvy benefited from strong demand and initial channel inventory build, with TRx volumes representing around one-third of the volumes sold. As Luke referenced, we are projecting our forecast for the season in line with the high-dose flu analogues, and therefore expect full year sales of around £0.9 billion to £1 billion.

There is however, still much to learn given the novel nature of this new vaccine, including annual vaccination patterns, duration of protection, competitor dynamics and what expert recommendations might be, and we anticipate further insight following the end of the US flu season, which will inform our outlook for 2024.

We look forward to updating you further as part of our full year results and remain confident in our longer-term revenue ambition for Arexvy. Turning to the dynamics within upgraded guidance. Within sales, we're increasing our expectations across all product groups. We now anticipate Vaccine growth of around 20%.

Specialty Medicines to grow low double-digits. And within this, HIV to grow around 10%. And General Medicines to grow low- to mid-single digits. Moving down the P&L to operating profit, we now expect royalties to be around £900 million with no change to our expectations for the other lines of the P&L.

To EPS, we expect lower interest expense of between £650 million and £700 million.

In terms of currency, if exchange rates were to hold at the closing rates on the 30th of September for the rest of the year, the estimated adverse impact on sterling turnover growth for the full year would be minus 2% and on adjusted operating profit growth, it would be minus 4%.

Finally, we remind you of a few modeling assumptions in 2024, namely the impact of AMP cap, the loss of Gardasil royalties and the tax rate likely being a couple of percentage points higher due to OECD legislation. More details on these are included in our pre-quarterly aide memoire, and I look forward to guiding more fully at the end of the year.

And thank you, and with that, I will hand back to Emma..

Thanks, Julie. Turning lastly to Slide 27. So, in summary, we are seeing strong and sustained improvements in our performance. This quarter marks the seventh consecutive quarter of competitive sales and profit growth, which supports an upgrade to our guidance for the year.

We also remain very focused on strengthening our pipeline and our longer-term outlooks with progress in vaccines, developments of our long-acting HIV portfolio and new prospects in respiratory, all pointing to new growth opportunities for GSK. We have strong performance as we enter 2024, and we look forward to keeping you updated on our progress.

Thank you for listening. And let's now please all move to the Q&A..

Thanks. [Operator Instructions] With that, I'd like to take our first question from Graham Parry. Graham, over to you..

Great. Thanks, Nick. Thanks for taking my question. So, I'd start with Arexvy. So, it's question on the level of discounting in the initial launch. So, two-thirds of your £709 million was inventory and you've administered some, I think, 1.4 million, 1.5 million doses.

That means underlying sales are in the sort of £230 million to £240 million range, and that would imply net price probably more than 30% below the list price.

So, can I just check that's the right sort of ballpark? And is that mostly wholesaler discounting or retail pharmacy discounting to drive the initial inventory build and something which we might see sort of ameliorates little bit over time, or is that just kind of where the competitive nature of the market is at the moment? And then secondly, I know, Julie you touched on this, but dynamics into next year, just be interested [Technical Difficulty] you obviously won't have the initial inventory build, but how much of that inventory do you think is just sort of [Technical Difficulty] you don't have the return of the patient -- people you vaccinated this year.

So, any thoughts you have so far on how far penetrated you are into the easy wins of the more elderly comorbid et cetera, and how much tougher it might be to get return or to new people to get vaccinated next year? Thank you..

Thanks, Graham. Well, we'll come to Julie in a minute on guidance and thoughts around next year, although obviously, we will mainly be giving you thoughts around next year when we come to February 2024.

And I would just remind everybody that whilst we are absolutely delighted with the fast and competitive start here on RSV, it is just the start, it's the first season, and we remain very ambitious to the £3 billion, at least that we expect this asset to represent.

But let's go to Luke first, noting, Graham, you will fully understand we're not going to be declaring all our commercial details on this call.

But Luke, do you want to comment more broadly?.

Yeah, Graham, thank you. I mean, I think we've been quite disciplined taking a longer-term around pricing and contracting and it's landed quite well. I won't give you any more color than that in terms of the percentages at this point because I'm sure our friends in New York have probably got up a little bit early this morning.

But what I would say is to build on Emma's point, I think in the short-term, things are uncertain. We're very happy with the launch. In the long-term, we're very certain. I think so far, if we look at some of the metrics which I can try and help you with, it's about 50% co-administration with flu. This is a very large overlap with that population.

And interestingly, around 15% of people are getting free shots when they come into the pharmacy. 85% is that 65 to 84 age population. So again, very similar to high-dose flu.

And I think for the rest of the year, in terms of demand, you're still seeing good market research in terms of HCPs recommending it, so it's about 64% based on our latest market research, which is encouraging. And of course, the CDC is advising doctors to keep going. So that's on a positive side of the ledger.

But the fact is this -- our working hypothesis that this is more of a flu-like trajectory. And as people start coming into pharmacies and we see a reduction in staffing levels of pharmacy who actually deliver these vaccines, then we're going to see a drop-off in demand. And that's our hypothesis at this point.

We'll obviously have a lot more color in Q4 to give you an update. And then as Emma said, I think we're very, very confident in terms of the £3 billion number that we have outlined in the past..

And obviously, looking forward to running forward with that 50-year-olds to 59-year-olds data too, which is another potentially meaningful cohort.

Julie, anything else you want to add?.

No, I think actually Luke has covered it extremely well. I think we've obviously looked at the levels of stock in the channel. We've looked at the rate of immunizations. We've seen a correlation with flu as Luke mentioned very, very close and that's really informed our guidance. And in terms of 2024, I mean.

I think we're going to -- as we come through the US flu season, we are going to have a much clearer view of 2024 when we give our full year results. So, we will definitely update you at that stage, more fully..

Thanks. Next question, please..

Okay. Next question is going to be from Kerry Holford at Berenberg. Kerry, over to you, please..

Thank you. I have a couple of questions for Tony, please, within R&D.

So, firstly, on bepirovirsen, so now you've got the full reach of your Phase II data, and you've recently signed that deal with J&J to look at sequential therapy, do you still remain confident you offer hep B patients the functional cure, at least a proportion of them? What do you expect that J&J siRNA to add here? And do you stand by your more than £2 billion sales target for that asset? And then secondly, a broader question on R&D budgets.

So here, we've seen significant growth in your budgets over the past 18 months or so. And based on the pipeline you have ahead of you, are you broadly happy with the annual budget that you've effectively been given this year? The run rate looks to be about £5.5 billion.

Or should we expect that R&D budget to continue to grow in the sort of low-double-digit range that we've seen year-to-date going forward? Thank you..

Thanks, Kerry. Let's get started with HBV, and then I'll comment on the pipeline, but perhaps, Emma, you might want to make your comment on R&D budget. So, first of all, look, I'm really pleased with this deal, Kerry.

Let me just remind you because I'm going to anchor it in what we are -- what we know about bepi and becoming increasingly confident about that is in the context of monotherapy on top of nucleoside treatment, that we achieve a durable functional cure for a significant proportion of the HBV population, the chronic HBV patient population.

And that's for individuals that have a surface antigen count of less than 3,000. Just as a reminder, that's about 40% of the 300 million individuals who are living with chronic hepatitis B. To put it in a nutshell, what the new deal with the J&J siRNA does is takes the broader population down to that target population of about 3,000 and below.

So, you should expect, and we're excited about the prospects, therefore, of seeing both an increased coverage in an ITT population and also a deepening of the therapeutic effect. And this is important if you look at the mechanism of action of the J&J siRNA.

It works in, excuse me, a complementary fashion to bepi, so further lowering viral DNA and the consequences of that, as I mentioned in the presentation. The other important thing is that we've built a complex PKPD model around response, which this will add to.

And in addition, using AIML and some really deep phenotyping on nearly 500 patients, established an understanding of the immune status required at the beginning of treatment for response. We're going to continue to add to that because with the deal in question, we get a number of ongoing Phase II studies.

So, I'm really very pleased about where we are with that particular deal. For me, it strengthens my expectations in terms of our ability to deliver a functional cure for a broader population of patients living with this disease.

Let me just in terms of the question about R&D budget and growth, perhaps I'd just say a few brief things about the portfolio and then hand over to Emma. So again, I'm really very pleased with where we are on the portfolio.

Emma mentioned the strength that we have in our growing vaccines portfolio, particularly next year, as you'll see, more data coming from our mRNA platform, from MAPS, and we have a number of important studies, like, for example, therapeutic herpes simplex vaccine readout on POC that will again continue to hopefully deepen the importance of our adjuvant technology that is underscoring, I think, the fantastic clinical performance we see for Shingrix and for Arexvy.

Luke and I will say more at Meet the Management about the cornerstones of depemokimab, Nucala and camlipixant. In our respiratory portfolio, of course, I just mentioned bepi.

And then moving again just briefly into oncology, Jemperli, most recently through the OS data that I mentioned earlier, continues to show its credentials as a very highly effective PD1 inhibitor. And with all of that in place, I think we're well set with regards to our future ambitions and the budget required for that ambition.

I'm in good shape about it.

Emma?.

Thanks, Tony. I mean, I think that there are two important things to emphasize strongly here. First of all, we've been very clear in our capital allocation framework. The number one priority for the company is to invest in the pipeline, organic and inorganically.

And that is why, over the last five years, you've seen a significant step up in our R&D spending. What matters is not how much you spend, but that you spend it super smartly and then that is ever-improving and we're continuing to fuel competitive, profitable growth for our shareholders.

So, the first thing is it is a priority, but it's about how we spend it. And I think we are broadly at more industry norm levels in terms of spending, but very much focused on the returns of that. And the second thing is we are absolutely committed to profitable growth and we're in that chapter now.

We're now in, I think, seven consecutive quarters of competitive growth. Glad to upgrade guidance for the year. Very confident about our '26 outlooks and our double-digit profit CAGR. This year, we expect R&D spend to increase slightly below our turnover levels.

And we're not going to set an explicit target around that, but you can be very confident that the outlooks we previously laid out, we're completely committed to and delighted about our progress against. Next question, please..

Okay. The next question is from Simon Baker at Redburn. Simon, over to you, please..

Thank you, Nick. Thank you for taking my questions. Two, if I may, please, both on the pipeline. And apologies if I missed it, because I did lose sound at one point. But it looks like depemokimab is running slightly ahead of previous expectations. I just wondered if you can give us an update there on the [SWIFT] (ph) and the SWIFT-2 study timeline.

And then secondly, on the Hansoh ADC, I wonder if you could just elaborate a bit on what attracted you to that asset. Obviously, we've not seen much data. You all have seen more than us.

And I was wondering if it was data-driven or whether it was driven by the fact that the payload and the [linker bar one or two carbons] (ph) is identical to Dato-Dxd and therefore gives you a high level of confidence in the potential of that ADC. Thanks so much..

Thanks. Well, I'll come to Tony on both of those. But just a flag, please do join us on the 30th of -- or at least Tony and Luke, I should say, on the 30th of November when they will update you on some -- the very exciting scale assets we have in respiratory, obviously our homeland and our heartland, including [depe] (ph) and camlipixant as well.

But Tony, you might want to comment a bit more on the trials that are ongoing and then also on the ADC, which is obviously completely in line with our [Onc] (ph) strategy..

Sure. Thanks, Emma. Hi, Simon. Yeah, I'm pleased with the progress we're making on SWIFT-1 and SWIFT-2. As you've spotted, we've seen a slight acceleration in that, that was associated actually with also an acceleration in the ANCHOR study for nasal polyps. What that means is that the safety database that we need to underpin the file is now complete.

You should expect, though, that we'll stay on schedule with regards to the analysis and publication of the data and I won't be doing that until we get the results for the second SWIFT analysis, which still places us in the first half of next year.

As far as the ADC deal is concerned, Simon, so, yes, as you quite rightly point out, in terms of linker payload, there are similarities to Dato-Dx and therefore we derive confidence from the improved profile that you see for ADCs carrying that linker payload. Two important things, though, to stress in the context of this deal.

One, the antigen B7-H4 is selectively expressed on gynecological cancers. That's why we went after the mechanism in line with our strategy for focus on women's cancers and heme. And lastly, in that area as well, there is ample evidence of use of topoisomerase inhibitors as standard of care for chemotherapy.

That's related in part probably to the fact that you see a lot of DNA instability in those cancers, and as I'm sure you're aware, topoisomerases work on that mechanism..

Thanks, Tony. Next question, please..

So, next question is going to be from Andrew Baum at Citi. Andrew, over to you, please..

Hey, Andrew..

Andrew, you're there?.

Yeah, I'm sorry about that. Two questions, please. One for Luke and the other one for Tony. So, for Luke, could you talk to the impact of the removal of the Medicaid cap, the MP cap on your Gen Med business, particularly respiratory next year in terms of quantifying the impact on revenue and earnings. And then for Tony, or I guess Kim [ph], if she's on.

There was recently reported the ATHENA cohort with Cabotegravir+Rilpivirine. There was a number of cases of viral rebound resistance, particularly in patients with high BMI or weight gain. Should we expect any label change as a function of observations in that cohort? And it was limited number, but still it was notable and remarked upon. Thank you..

Thanks, Andrew. We'll come to Deborah actually on the HIV pipeline first and then Luke back to you on AMP cap..

Thanks, Andrew. So the ATHENA is a cohort study. It was presented at EACS eight to ten days ago. Actually, the finding is exactly in line with our clinical studies. So, as you know, there are kind of three characterized things that give you a higher likelihood of failing with Cab+Rilpivirine. Weight is one, so high BMI is one.

And then obviously A6, A1 sort of subtypes. And then lastly, if you're resistant to Rilpivirine. So, we clearly guide that those patients if you have two of those risk factors, you're more likely to fail. We guide that, and that's exactly what we saw in the ATHENA study in terms of the characteristics of those that failed.

And it was in proportion with what we saw in the clinical study, which is obviously less than 1%. So, no surprises whatsoever. Exactly what you would expect. And it just makes it more important that we continue to communicate through our sort of multivariate analysis data for whom Cabenuva is right and who probably shouldn't be taking the medicine.

But it's a tiny proportion of the overall patient base that will get benefit from this medicine..

And nothing new.

Luke?.

Sure. Thanks, Andrew. I mean, as I said at Q2 that the exposure is US$700 million. But of course, we've had notice. So, we've got authorized generics in place. We've done some withdrawals that we've announced. We've done WAC adjustment with Lamictal. The other products impacted, of course, are Advair and Flovent and Serevent.

Look, I think the impact is going to be sizable. We've started to reflect that in RAR adjustments now, but we need to judge to see what level of returns ultimately come back.

There's also some variables in terms of the percentage of switch to authorized generics, but we do have competitive generics, for example, with Flovent, so they may pick up more volume, making it a bit hard to forecast. So, long story short, I mean, we've been prepared for this. We've been working on it for a couple of years.

I think we're in the strongest position possible. But there is going to be a material impact on that US$700 million, and that's why it's reflected in the outlook for General Medicines next year..

I mean, that's the really important point, is it's a '24 hit, but it's all included in our medium-term guidance of being broadly flat in this business, where we've obviously seen a nice uptick in performance, not least as Trelegy continues to power forward and lead the way. So, all factored in and planned for. Next question, please..

So, next question is going to be from Richard Parkes at BNP Paribas. Richard, over to you, please..

Hi, Richard..

Thanks, Nick. Yeah, just a couple of questions. Firstly, on Arexvy.

Can you talk about the unmet need in terms of severe disease in the 50-year-old to 60-year-old patient population just so that we can get a sense of -- and also kind of what you would expect in terms of ACIP recommendations, so we can get a sense of how that label update might impact the opportunity going into next year? And then, second question is on Jemperli.

Just wondered if you could talk about your confidence in expanding the approval into the MMR proficient population. Obviously, I think there's sort of two options there. One is the overall survival data from Part 1 of the study.

So, maybe you could talk about consistency of that benefit across those subgroups? And then, the PARP inhibitor arm of Part 2 of the trial, I noticed you don't include [Zejula] (ph) when you talk about Part 2 as an opportunity. So, I just wondered about your confidence in the PARP inhibitor maintenance arm of that study as well. Thank you..

Thanks. Well, we'll come to Tony in a minute on oncology, but perhaps, Luke, you can talk about the 50-year-olds to 59-year-olds opportunity, which is another 40 million people, by the way, in the US alone. So....

Yeah. I mean, I think there's two advantages. One is just the 40 -- access to the 40 million people. And again, that lines up nicely with the overall Shingrix cohort. So, there's lots of synergies there we can achieve.

And then, there's the broader advantage when we're contracting in the retail and non-retail settings, because we'll be the only one there.

Our expectation at this point is it's going to be shared clinical decision making, but as we speculated before the launch and I think so far that's holding up, that's not been a barrier during this initial phase of adoption.

If you look at that 50-year-old to 60-year-old-plus population, there's a sizeable proportion of them that also have one or more comorbidities. So, it's attractive, and certainly it resonates well with primary care doctors in terms of their support for the brand, which is around 71% in terms of their preference overall for Arexvy..

Right..

Okay. In terms then of RUBY, particularly RUBY Part 2, just -- and indeed the MMRp population from the results that we described earlier this week, important to recognize that the RUBY Part 1 study was not powered to look at OS in the MMRp population, but rather OS for the overall population.

The way to think about this in context of both Part 1 and Part 2 is definitely isolating out the MMRp population, asking under what circumstances are we likely to see the most meaningful therapeutic effect for those. There are, for example, genotype considerations associated with PARP response in the Part 2 population that are important.

I don't want to get caught on the details of those at this point in time. We're still waiting for the readouts, but it's fair to say that the filing strategy that we'll put around Jemperli in first-line EC will take account of all of the factors that I just described as well as the competitive position..

Yeah. I think to build on that competitive position, I mean, I think we're optimistic in terms of how the NCCN may read that. Of course, as you know, GY018 is not designed around an overall survival signal. And it's very interesting, since that initial label, we've gone from 300 to 900 accounts now stocking Jemperli in the US.

So that has a flow-on effect and sales are up 10 times after SGO. And it's intriguing just looking at the marketing shares. If you look at that first-line setting where that was obviously non-promoted initially, I mean, Keytruda was picking up around 40% of that business. [Chemo] (ph) had dropped from 40% down to 27%.

And we had around 13% of that market. So, I think there's an opportunity now to start to make the case versus GY018, the elements of design and the survival signal to try and expand the usage of Jemperli in that setting. So that's something we're quite excited about. And then of course, DUO-E helps inform the thinking around RUBY, too..

Exactly. Just a couple of things to underscore to Luke's point to remind you about GY018, different patient population.

We had a larger degree of carcinosarcoma patients which are harder to treat, and importantly as well the resist sampling frequency for our study was smaller, which obviously is going to pick up failures more quickly than the GY018 case does. So, important to bear those two things in mind when you consider the comparison of the two studies.

And Luke, I think, has guided you correctly in thinking about DUO-E as being informative with regards to how we might interpret the Part 2..

Thank you. Next question..

So, next question is from James Gordon at JPMorgan..

Hello. James Gordon, JPMorgan. Thanks for taking the questions. And I'm going to stick to Arexvy for my two. The first one was about Arexvy and stocking. So, it looks like about £460 million of Arexvy was stock in this quarter. And the guide for this year implies about £200 million to £300 million of sales in Q4.

But what does this assume in terms of stocking unwind in Q4? How much stock do you need to keep in the market to support the product as an ongoing run rate? And also, what are you thinking about ex-US stocking in Q4? Could there be a US-sized stock up that we saw in Q3 in Q4? And the second question sort of leads into that, which is Arexvy and the ex-US launch.

So, ex-US sales, I think, were only £9 million this quarter, but the product was approved in the EU back in June. And my understanding is you're not capacity constrained.

So, could ex-US start to ramp in Q4 this year? And looking into next year, could we see a big launch for ex-US Arexvy? Could that be a big growth driver for next year? Or is it going to take a bit longer in Europe to get this going? And what are the gating factors to get ex-US Arexvy ramping like what we've seen this quarter in the US?.

Okay. Well, we'll go to Julie first just to deconstruct the guidance for Q4, and then Luke around the globalization. But you're absolutely right, this is a global opportunity. And I'll even include in that, the recent commercial deals we've been doing in second biggest market in the world, which would be an option on that for the future.

And just to repeat, we're very ambitious for this being a multi-billion asset, as we've committed before.

But in terms of the very short term, in its first season, Julie, do you want to comment on the guidance ahead?.

Yes, thanks very much, Emma. So, what we've definitely found so far is of the sales of £709 million, in terms of immunizations into people's arms, we've got around equivalent of about £230 million to £250 million. We were expecting -- I mean, the launch has been massively successful.

We were expecting a stock in at this point, because it's very, very analogous to what's happening with flu. So, I think I'll hand over to Luke in terms of the amount of inventory we expect to carry. Your figure for Q4, by the way, was absolutely spot on in terms of the level of sales we expect to see in the remainder £200 million to £300 million.

And it's all to do with the stocking. So, over to Luke..

Yeah. I mean, if you look at the total market, I think it's about [US$2.71 billion] (ph). And we've got [US$1.7 billion] (ph) of that in arm. Yeah, I won't give too much more color. I mean, as Julie said, it's two-thirds of sales so far. And we'll obviously try and burn through that towards the end of the year to position ourselves well.

What we don't want is empty shelves or any window that Pfizer can get in there. That's why I'm being a little bit cute with the numbers here because it's very dynamic at this point. In terms of EU, look, it's very early days. It's private. We've kept the price in a very tight collar with the US like we've done with Shingrix.

And our expectation is that we need to now navigate access. We've got early wins in Canada. We've got some very encouraging signs coming in Europe and other markets. So, we'll see the full effect of that in 2024.

And of course, the advantage in the European markets like Japan and other international markets is once we get the NIP, then the level of resourcing we need to do to drive patients is significantly lower. And so, from a P&L point of view, it's also very attractive. So, 2024 for rest of world for Arexvy and good start in the US..

And just to repeat, we are definitely seeing increased openness and recognition of the value, literally financial value of investing in prevention.

And so that is and definitely a part why we're seeing this faster rate, even if it's currently in the private market of approvals, because it's just a lot cheaper and there isn't a healthcare system or budget that isn't burdened at the moment, and they have more infrastructure in place, not least through pharmacy channels for distribution in many countries.

So, all of this underpins this broader confidence but with phenomenally tight discipline from Luke and his team as he's alluded to around the shape of the financial contribution plan. Next question, please..

So, mindful, we're at just over the hour mark, and we've still got six individuals with hands raised. So what I propose is that we try and work through as many of those as possible till quarter past the hour, and then we'll close the call there. So, our next question comes from Mark Purcell at Morgan Stanley. Over to you, Mark..

Yeah. Thank you, Nick, and thanks for taking my question. On Arexvy, a little bit more color. I just wondered if there's any early indications of outer seasonal demand for RSV vaccination. Still there may be more of a sort of Prevnar flu hybrid model.

I know you'll know more by the end of the year, but any early indications there? And in pharmacies where Pfizer is fully stocked alongside you, given they talk about how they're not fully launched yet, what is your market share in those pharmacies where both products are present? And then a quick one for Tony.

In terms of the Inflation Reduction Act considerations on R&D, where you have assets such as your IL-18 where you could run parallel trials across a multiple number of indications, do you see the sort of pressure to do that? And on something like IL-5, could you do a bridge study or would you have to do a separate study in COPD?.

Okay.

Luke and Tony?.

Yeah. Thanks, Mark. We're beating them everywhere so far. The aim is to keep that happening. So yeah, I mean -- look, it's really it's interesting. I mean, when you look at pharmacists' prioritization, RSV is up there with flu and COVID. You've seen COVID volumes drop off. And, last week, we still kept growing with Arexvy, which is encouraging.

I was sort of wondering whether it would start to slow down. So, this next couple of weeks, script data will really be interesting. It's more than 90% in the retail setting. And that's another critical component in your assumptions. And we don't actually expect that to materially change.

We think vaccines for maternal in OBGYN and PCP offices will occur, which will be something we'll have to back out in future calculations, but we think the older adults market is going to be very much like flu, very much like Shingrix heading in the direction of retail. So, we'll just see what people's enthusiasm is over the next couple of weeks.

Clearly, awareness is very high. Intention to recommend is very high. So again, I'm very happy to sort of back the truck up with everything that we know in Q4 and give you much more color around the market research that we'll have at that point..

Great, thanks.

And Tony, anything to add?.

Yeah. Just two very quick ones in terms of the IL-18 question. Look, the key question you're asking with IL-18 at the moment is its efficacy relative to [depe] (ph) in atopic dermatitis.

For the medium term, as we build out our biomarker strategy and look for markers of efficacy at Phase I, that's exactly the underpinnings that I would then want to have the confidence to go forward into multiple indications.

You probably have in mind that in the case of IL-18, the Mendelian randomization also points to inflammatory bowel disease, obviously a range of other considerations there beyond just IRA in terms of whether or not that's a path to go. And then lastly for MATINEE and the bridge for depe, let's see where we go when we get the MATINEE results.

Obviously, we're focusing very much on the role of EOS in driving the morbidity and mortality associated with COPD. So, that will be part of our strategy, but I'm focused at the moment on making sure we get the results out for MATINEE and delivering a success.

Emma, any color to that?.

Yeah. Of course any allocation of capital is a combination of probability of success and the assumed forecast. And that assumed forecast now has to take into account the area under the curve, what they really like, format or anything else. Next question, please..

Next question is from Steve Scala at TD Cowen. Over to you, Steve..

Thank you very much. I'm just curious of Arexvy shipments in October support your conservative guide for the full year. So, were they essentially zero? I would note that in the first quarter of 2018, GSK called out stocking for Shingrix and then went on to beat in 10 of the next 12 quarters in the US.

Second, I know you're beating Pfizer in RSV everywhere, but to what should we attribute the success they have had? Previously, you've said that you have a better vaccine, you're stronger in the commercial setting, yet they put up a big number as well. So, to what do we attribute that? Thank you..

Well, I'll ask Luke to overlay, Steve, but thanks for the questions. And this is the first season that we've been through. We've given our guide for the reasons that I won't repeat since we're under some timing pressure, but we will know a lot more in Q4. And obviously, we remain extremely ambitious for this.

And our competitive focus is to make sure that not only the size of the market is big, which is where we welcome competition, but that we are able to effectively reach the patients that need us, which is this more vulnerable [indiscernible] cohort.

Luke, anything you want to add?.

Yeah. Look, I think Shingrix is a different case, right? I mean, I was in the middle of that, we canceled the global launch. We redirected all of the volumes to the US. And we also in the middle of the later year had some synergies in manufacturing, which were surprising upside in terms of loss rate and packaging.

So that's why we're able to get that volume ahead for Shingrix. Look, I think in terms of us versus Pfizer, firstly, it's great two companies are out there driving volume because this is an awareness game. No one had heard of RSV if you're a person in the population before that. So, having two companies promote, it's good.

We have enormous respect for Pfizer. We like competing with them. They are a strategic competitor for us if you look across PCV, meningitis, RSV and potentially shingles at some point. So, it's nice to have this strong start. And again, yeah, we want to keep this going..

Next question..

Yeah. Next question is from Peter Welford at Jefferies..

Hi, thanks. Yeah, I'm afraid I'm sticking with Arexvy. Can I just ask quickly, you mentioned that retail was over 90% of the volumes so far. Curious, why you're so confident that, that mix will continue? I mean obviously Shingrix, it's varied over time.

But I think your competitor made some comments that they think potentially in the fourth quarter and the back half of the season, it's going to switch more towards the non-retail segment where they see perhaps a greater competitive advantage.

I wonder if you could comment I guess on both of those, both from the competitive advantage point of view and also how potentially this could change I guess during the course of the season? And then just secondly, I wanted to stick with vaccines, but wondering if Tony could possibly give us an update at all on how you're thinking about mRNA.

I know we come back to this almost every quarter. There obviously have been some competitive developments in there.

So, I wonder if you could just give us a quick update on how you're looking at your strategy and updates from news flow we could get for your mRNA portfolio in 2024?.

Yeah, we're very excited about mRNA. So, I'm going to come to Tony first. And remember the 90% is all the rest of adult, but we'll come back on that to Luke in a minute. But Tony, mRNA..

Yeah. So, just very quickly then, very pleased about the platform and how it's moving forward. We're now moving into Phase II in both COVID and flu.

And Phase II program for flu is -- includes a range of options and doses that we've deduced from our Phase I study, looking at up to 8 antigen components, which we feel is the path forward to, I presume, resolving the B strain coverage question that exists.

Also worthwhile pointing out that, that's likely to become a slightly simplified proposition as the B/Yamagata strain is probably going to be removed in '24. But more on this when I've got the readout from the Phase II data..

Luke, anything you want to add on that?.

Yeah, Peter, I mean, I just sort of look at it at a macro level. You've got 83 million who are over 60-years-old, you add the 50-59-year-olds, that's another 40 million, so that's 120 million. We think 90% of those are going to still come through. If you look at a typical birth cohort, it's 4 million a year.

So, if I look at between now and the end of the year, that's about 1 million pregnant women. And then, it's unknown how many of those will get a vaccine. There's the influence, the availability of the antibody as well.

I think the other thing to keep in mind, and we're seeing this with Shingrix, is there are a lot of practices that are driving patients to pharmacy because they are -- they don't want to navigate the IRA dimensions and then have a separate track for the commercial patients.

So, they're actually sending patients through to the pharmacy rather than sort of persisting with that themselves. So that's a bit unknown, but definitely those maternal vaccines will be given at OBGYN offices where you don't have the label there. So, we'll need to exclude that from our market share calculations going forward..

Thank you. We've got time for....

We do have time for one more. So apologies to those of you that we won't get to, but our last question comes from Emily Field at Barclay. So, Emily, over to you..

Oh, thank you so much for fitting me in. And maybe I'll just ask one last one about Ojjaara.

I was wondering if you could provide some context about how you're thinking of speed of uptake of this launch, particularly now that you did get the line-agnostic label? And if you're expecting more sort of upfront usage for just second-line usage? And any early indicators you could give us? Thank you..

Luke, straight to you..

Sure. Thanks, Emily. So first, we've got about 172 patients on so far. The bulk of those are sort of jacked failures, highly anemic, so pretty severe cases. So that initial bolus, I think, we'll work through. Our working assumption is that between 40% and 50% of patients presenting are anemic at diagnosis.

And as you know, we've got an outstanding recommendation there in terms of 2a and the most competitive profile on that subgroup. And we also know that around 46% of patients require a transfusion within one year of diagnosis. So that's our target. That's our target market.

We think right now, yeah, third-line, it's a couple of months, but we'll work our way up. Second-line, typical treatment length is 18 months, but we should be able to start to penetrate in 2024, that first-line where typical treatments around 26 months of duration.

And we got the NCCN data into them two hours within an approval and we were very happy with the recommendation. So, so far so good. A lot of academic interest. That's about 55% of the volume right now, 45% in the community. Of course, we expect that to change in time. But yeah, a lot of excitement and this is clearly a visible problem for haematologists.

And yeah, they're very supportive of momelotinib. So, so far, so good..

Wonderful. Thanks, Luke. Well, look forward to coming back to more of your questions over coming days and weeks. I just want to leave you with the recap that we are delivering strong and sustained performance momentum with another quarter of double-digit sales and earnings growth.

This is broadly based performance, but of course benefiting specifically from the very fast start of Arexvy, which we're looking forward to seeing its progress ahead.

I'm pleased to have an upgrade, but also really delighted with the momentum as we look ahead to delivering our '26 results and continuing to strengthen that longer-term outlook as we keep progressing the vaccines pipeline, longer-acting HIV and exciting prospects in respiratory. So, thank you to everybody. We look forward to catching up soon..