AstraZeneca PLC (AZN) 2018 Q2 法說會逐字稿

Welcome to First Half Year Results Presentation Conference call and webcast.

We are here in London and we are live with a number of people present in the room, but we also have more people joining us by phone and by webcast.

As always, the presentation is available on astrazeneca.com, on our website, for you to download.

And we know that there are competing events today that's probably reflected also by the attendance in this room.

So we thank you very much to all of those who are able to join us today.

So if we move to Slide 2, this is our usual Safe Harbor statement.

Moving on to Slide 3. So we plan to spend around 30 minutes on the presentation and then that will leave us plenty of time for Q&A.

For those on the phone, (Operator Instructions).

Thank you very much in advance for trying to stick to this very discipline.

Today I'm joined as always by Dave Fredrickson, who is our EVP, Head of the Oncology Business Unit; Mark Mallon, the EVP of Global Product and Portfolio Strategy Medical Affairs and Corporate Affairs; Marc Dunoyer, our CFO; and Sean Bohen, our Chief Medical Officer and the EVP of Global Medicines Development.

So if we turn to Slide 4, this is the agenda and we'll cover all the aspects of our half year announcement today.

So moving to Slide 5, I wanted to start with this slide because a really -- key message I wanted to leave with you today is that the strategy we've been pursuing and implementing for the last 4 years or 5 years is starting to bear fruits.

And it's been really a long journey as all of you know, and that journey is not finished.

We still are facing substantial headwinds coming from patent expiries and there's still a lot of hard work ahead of us, but the new products are starting to have an impact on our top line.

And the important point here is you can see that those new products that we define as Oncology, New CVRM.

New CVRM is essentially diabetes and Brilinta to which we will add LOKELMA and roxa in the future and essentially exclude the old CV products, IMBRUVICA, Crestor.

In Respiratory, Respiratory is the totality of the Respiratory portfolio.

Collectively, these products grew by 19% in Q2 and 14% for the first half.

So you can see here a nice acceleration in the second quarter and a very nice growth for the first half of 14% and there is more to come, of course, because those products -- many of them are still in launch phase.

When you see the other and the other is pretty simple.

It's essentially Crestor having this big impact.

The others are declining 32% in the quarter and 25% for the first half.

And as I said, it's mainly Crestor in Japan and Europe.

The dynamics in the European and Japanese marketplace have changed as it relates to generics.

And when you lose patent protection now in those regions, you really decline very, very rapidly.

There is still, of course, an impact of Seroquel and Nexium but those are the older products.

Now you can see the growth.

The second point I want to make on this graph is the so-called new, the first line on this chart now represents 70% of our sales.

So 70% of our sales grew by 19% in Q2 and the balance 30% declined by 32%.

And that balance, the so-called others, will start stabilizing moving forward because what's left will be what's marketed in China and the emerging markets.

The Japanese, European and U.S. piece will be more or less gone by the end of this year.

So if you project yourself into 2019, we should no longer have this headwind coming from the rest of the portfolio or much, much lower headwind and then the full impact of the growth of the new product should come through.

So I wanted to start there so you see that we are definitely in -- at a pivot point.

So if I move to Slide 6, looking at the details.

So the product sales declined by 2% for the half year, 1% for the quarter.

And the 1% is the result of the 2 numbers I just showed you.

There is an impact for the first half from the divestments that is about 2%.

So in fact, we would have been flat if -- without the divestments.

And there is a very, very strong performance of our new medicines, but also of China.

We'll come back to this.

Total revenue declined by 5%, impacted by the lower externalization revenue compared to last year.

And then if you look at the new medicines, collectively, they delivered $1 billion of incremental sales versus the first half of last year.

Oncology grew by 37%.

Good sales of Lynparza, Tagrisso and Imfinzi, and we'll talk about those later.

CVRM grew by 9% with nice growth for Brilinta and Farxiga.

Respiratory stabilized.

We see that the decline of Symbicort.

Even though it's still a very competitive market, the decline in Symbicort is lower than in past quarters, and importantly, Pulmicort is growing nicely.

And we now see the impact of Fasenra starting to come through in the total respiratory sales.

And we will come back to Fasenra because it is a very exciting product and a great lunch.

The Emerging Markets grew by 10%, China 24% and the quarter itself grew by 26%.

And you see here, the impact of the great work our team in China is doing, but also the fact that we're getting reimbursement for a number of new products and starting accelerating our growth in China.

Outside China, if we correct for divestments, our growth rate was 4%, 5%, impacted negatively by Russia.

And we think Russia will, of course, stabilize itself.

We believe that you need to take a long-term view with Russia and walk through the economic challenges the country faces today, and we think that in the long run, starting next year, it will grow again, but certainly a challenging economic landscape in China, as you all know today.

Core EPS was $1.17 and we are reconfirming our guidance for the year.

So if we move to Slide 7 now.

The pipeline continued to deliver.

As you can see here, we had quite a number of approval and submissions.

Approval in Oncology, approval of Lynparza in Japan for breast cancer.

The launch, by the way, of Lynparza in Japan in ovarian cancer is going very well.

We got a positive outcome of our ovarian cancer first line study with Lynparza, so great news around Lynparza.

Tagrisso, we got approval for first line in the EU.

Imfinzi got approval in Japan, and we also met the primary overall survival endpoint.

Selumetinib didn't succeed in thyroid cancer.

So you can see here quite a number of very supportive positive news for Oncology franchise.

Also a number of good developments across cardiovascular, renal and metabolism as you can see on this slide, the number of submissions and importantly, the approval of LOKELMA in the U.S.

In Respiratory, unfortunately, Fasenra didn't meet the primary endpoint in COPD and we're working through where does it leave us and what are the next step for Fasenra in that indication.

We, of course, are still very excited about the potential in asthma, but certainly COPD, we have to work out what are the next steps.

And as you know, our BACE inhibitor didn't work in Alzheimer's disease; we terminated the program.

If you now move to Slide 8. The left-hand side graph actually shows you the trend over the last few quarters.

And essentially this graph tells you what I have told you a few minutes ago, is that the impact of the declining older products is progressively compensated by the new products -- the launch of new products.

And so the negative sales growth has been declining all the way down to Q2 being almost flat.

So we hope and we believe that it will continue to improve and the second half should see a growth picture and 2019 should definitely see a growth picture because the impact of declining old products would be very small by then.

On the right-hand side, you see the medicines that are impacting our sales.

And the important message here is that there is not 1 or 2 products that are driving our growth, but several, several that have been either established for some time like Brilinta or new like Lynparza, Tagrisso, Imfinzi and have been established like Farxiga, but can also be new in the next few months if DECLARE is positive, it would bring new strengths and a new force behind Farxiga.

So as you can see here, it's really an engine that is powered by multiple products.

And the only negative really is Crestor that hopefully we get out of by the end of this year in terms of the declining sales in Japan and Europe.

If you look at Slide 9 now, you can see here the impact of each individual new products on our total growth.

As I said earlier, we generate an additional $1 billion of additional sales for the first half, and collectively, these products grew by 69%.

Just like to attract your attention to Tagrisso.

On the basis of Q2, we are getting close to a run rate, annual run rate of $2 billion.

So not exactly $2 billion, but not far.

And so it's really a product that is growing very rapidly and has enormous potential moving forward as we roll out the first line indication and we get reimbursement for it across the world, including China.

We hope this product has tremendous potential.

But Tagrisso is not the only product.

Imfinzi, you will hear more from Dave a little bit later.

Imfinzi demonstrated pretty rapid launch trajectory, and we're very happy with the development of this product in the U.S. marketplace.

And the other products also drove growth.

So if you start -- if we move to Slide 10, you got a summary here of our sales by franchise.

Oncology grew by 40% for Q2, 37% for the half year.

New CVRM 9%, both for Q2 and the half year.

Respiratory was flat for the half year but grew by 7% in Q2.

And this is linked to the fact that Pulmicort is growing and we will resolve the supply issue in China, in particular.

Symbicort is stabilizing and Fasenra is adding to the growth of the Respiratory franchise.

And then others, as we saw a minute ago, are clearly collapsing, declining 32% in Q2.

Importantly, again, here, China grew by 26% in Q2 and 24% year-to-date.

We can talk more about China during the Q&A, but it's certainly a very, very nice performance and the team there is doing a fabulous job.

Moving to Slide 11, we'll now stop here and ask Dave come here and give you some highlights about the development of Oncology franchise.

Great, thank you, Pascal.

I appreciate very much and it's really a pleasure to be here today to talk about our new generation of medicines.

I'll start first and update on Oncology and then Mark will come up and speak through CVRM, Respiratory and Emerging Markets afterwards.

So if we could turn please to Slide 12.

So as Pascal mentioned, in the first half, sales in Oncology were over $2.6 billion for the half.

Oncology was at a growth rate of 37% for the half and now represents 27% of total product sales.

I think also what this graph depicts and really importantly, in the second quarter for the first time, we had greater contribution of new Oncology to our sales than we did for our mature products and you can see that depicted by the colored graph versus the gray shaded on the right.

The 4 new medicines, as Pascal spoke to, delivered about $0.7 billion or $700 million in additional sales versus the first half of 2017 and this really came from accelerated growth globally on Lynparza with a promising launch in Japan that I'll mention too in a second.

In Tagrisso, we saw sustained high growth across the globe and really a very encouraging start to our first line launch within the U.S.

With Imfinzi, we saw a near doubling in our sales in lung cancer and Calquence continues to progress solidly as we've have seen an increase in the BTKI naïve patient utilization.

I won't talk much about Faslodex after this, but I do want to note that Faslodex continues to perform, benefiting from the expanded label with novel combinations in breast cancer.

If we turn the next slide.

So on Lynparza, what we saw were sales in the first half of $269 million and there was growth across all of the regions which you can see pretty clearly here on the slide.

In the U.S., sales were $149 million for the half and also we saw sequential growth coming as well.

Growth came across both our own ovarian cancer where we continue to see strength from the launch of the tablet formulation in our broad ovarian label, but also emerging utilization and continued utilization within breast cancer.

The majority of our uses in ovarian, as I mentioned before, and Lynparza continues to be, in the United States, the leading medicine in the PARP inhibitor class as measured by total prescription volumes.

In Europe, sales were about $87 million or up 36% versus the prior year, and again, this reflects strengths that we have in increasing our testing rates, lengthening duration of therapy and the broad label that we've got within ovarian cancer with the tablets.

I alluded to it before, but we're very excited about what appears to be a promising start to a launch within Japan, already at $10 million in sales.

But I think, that, more importantly than the sales number, what we see is that we've opened up in Japan 85% of accounts.

We've done that with a very rapid pace and the market shaping work in order to establish the importance of BRCA and to establish the importance of PARP inhibition has been really quite impressive, and I think that, that's created a pent-up demand so that when we launched, we launched with lots of enthusiasm.

In terms of upcoming milestones, we look forward to the presentation of the results of the SOLO-1 study, which we expect in the second half of this year and also in China, a second half regulatory decision in ovarian cancer, which would be the first opportunity to bring Lynparza to China.

With that, if we could please turn to the next Slide 14.

So as we move to our lung cancer portfolio, I'd like to talk about Tagrisso, which is our #1 medicine in our Oncology portfolio.

For the half, we had $760 million in sales and really very importantly, and I think impressively, these are sales that come across 75 different countries worldwide in which we are approved, in which we've established a very good mechanism for driving, testing and driving results across the globe.

The U.S. obviously the largest portion of that with $341 million in sales for the quarter, we saw -- for the half, excuse me -- we saw strength in our second line business but of course, it was the frontline business and the growth that occurred there following the approval in April that is really I think the drivers we pivot towards first line.

In the U.S., Tagrisso is now the market leader in the first line in terms of new patient starts in the first line EGFR mutated setting.

Europe demonstrated a strong half with growth of 63%, though the quarter was softer.

And just to explain a bit of the dynamics behind that, volume growth was good in Europe for the quarter.

It was offset by some price declines that were largely due to adjustments to access agreements and there are some retrospective aspects of that.

We don't expect that to carry through going forward, but it is something we experienced within the quarter.

Importantly, within Japan, which you will recall in last quarter had sequentially moved to stable or softening growth.

Japan returned to growth in the second quarter, which we think is promising, especially because that's ahead of a frontline approval within Japan, which we expect in the second half of the year and with the subsequent launch immediately afterwards as price has already been established.

Within China, worth noting that we expect a regulatory decision for next year.

If we could turn the page to Slide 15, please.

So now turning to Imfinzi, we are very pleased to see in the second quarter that the approval or following the approval for the PACIFIC indication in unresectable Stage III non-small cell lung that we really are at an inflection point in terms of sales.

Sales for the half were $184 million, but importantly, in the quarter, it was $122 million.

The vast majority of these sales are from the lung indication, a very, very small portion coming from bladder.

And we do see that roughly half of the PACIFIC eligible patients in this setting are getting immunotherapy and the majority of those are getting Imfinzi.

I think if you take a look over onto the right, what you can see on the underlying patient dynamics is that in June, we neared 10,000 monthly infusions in the United States and that's a near doubling from where we exited from the first quarter.

So you can really see the good velocity within this business and that's reflected too in growth and new starts as well as in total scripts.

We did in the quarter see our first sales outside of the United States and we have additional approvals that have been obtained in Japan, Canada, Switzerland, India and Brazil.

And we expect over 40 more countries to be approved as we move into the second half and as we saw with Tagrisso, I think, that's the real opportunity to really even get an opportunity to see even further sustained growth.

So as I turn then to my last Slide on 17, and the hematology franchise, I just like to reflect continued progress we're making in hematology.

It's a platform that we are building for years to come.

Calquence continues to perform well with sales of $20 million in the half in our faster markets, second line relapsed recurrent mantle cell lymphoma indication.

We have about a quarter now of new patients starting on Calquence within that indication, within the market, and we look forward to the chronic lymphocytic leukemia data readouts, which is really where the larger market opportunity is, and those readouts we're expecting in 2019.

Finally, moxetumomab is our first potential antibody drug conjugate or ADC, and we expect the regulatory decision in the third quarter for this very niche, but also very high unmet need disease of hairy cell leukemia.

So with that, I bring a close to the Oncology section and I will turn it over to Mark.

Thanks, Dave, for that exciting overview on Oncology.

I'm very pleased to be here again talk to you about starting with New CVRM, our medicines in cardiovascular, renal and metabolism.

Sales were up by 9% despite the intense competition, as Pascal highlighted, with first half sales at $1.9 billion.

Farxiga and Brilinta continued to remain strong with double-digit growth across all regions.

And Brilinta, if we move Brilinta specifically first, delivered sales of $609 million with 18% growth in the half driven by volume growth in the U.S. with sales of 20% and double-digit growth continuing across the regions with Emerging Markets up 17% and Europe up 14%.

So we continue to be very pleased with the performance of Brilinta.

Farxiga delivered sales of $639 million in the half with 36% growth and maintained market share leadership globally with 41% of volume share.

Farxiga growth of 29% in the U.S. exceeded the SGLT2 class growth, however, we are seeing some slowdown in the global class growth and we look forward to the declare readout in the second half of this year as the next major event for the brand and for the class.

Ex-U.

S., where we have 58% of our global sales for Farxiga, we have seen encouraging performances with volume-driven growth increasing in Europe, which was up 28%, and in emerging markets, which was up an impressive 59%.

And in China, despite not being listed on the National Reimbursement Drug List, we were pleased to deliver reimbursement in 7 provinces and discussions are continuing in a number of other provinces.

So very excited and encouraged by the launch of Farxiga in China.

And finally, turning back to the U.S., in the fast-growing GLP-1 market, our autoinjector Bydureon BCise continues to perform well, returning the Bydureon franchise to growth with 5% growth in the quarter.

And what's exciting to see is roughly half the patients for Bydureon BCise are new to the GLP-1 class and about 1/3 are coming from the Bydureon pen as a switch.

Now turning to Respiratory, if we go to the next slide.

As Pascal mentioned, growth was flat in the first half of the year versus 2017 with a very encouraging 7% growth in the second quarter.

The performance was driven by moderation in the decline of Symbicort in the U.S., solid growth of our inhaled products in Japan and Emerging Markets and the strong launch of Fasenra, the first of our leading Biologics portfolio in Respiratory.

So on Symbicort, product sales were down 10% with a reduction of the decline in the quarter, which was down 8%, mainly due to the U.S. pricing pressure slightly moderating and our strong share performance within the ICS/LABA class.

U.S. sales were down 21% with the quarter down 14%, whilst Europe was down 8% in the half.

And in Emerging Markets, as mentioned, Symbicort exhibited continued growth, up 10% in the half.

Pulmicort was up 6% with Emerging Markets the driver of the growth, up 15% and then 37% in the quarter.

And the Pulmicort supply delay that I mentioned in the first quarter that has been in China, that has been resolved, as you can see from the sales results.

So now I'd just like to take a moment more on Fasenra, which we're very excited about.

So Fasenra continued its very strong start with sales of $86 million in the half.

The launch continues to perform in line with our expectations given its highly competitive profile.

And in the U.S. and Japan, Fasenra is now the leading novel Respiratory Biologic in terms of new patient starts.

U.S. sales were $67 million and Japan, which launched during the quarter, delivered a strong early uptake with $11 million in sales.

Europe sales were $8 million with the majority coming from Germany, as we continue to roll out launches to other countries.

Now the successful launch has been driven by the strong clinical profile of Fasenra and we continue to hear feedback from physicians on the positive impact Fasenra is having in patients even already.

And the success has also been driven by excellent execution of our teams and an industry-leading support program to help physicians and patients get appropriate reimbursement for Fasenra.

And finally, we're working very hard to help improve the diagnosis of severe asthma and to make sure patients are referred to appropriate specialists to get the right treatment and to manage their disease.

Less than 1 in 10 asthma patients eligible for Biologics therapy are actually receiving the treatment.

This represents a huge opportunity to improve patient care and obviously, it represents a really exciting opportunity for Fasenra to continue to grow.

We look forward to, as I said, other countries coming on board throughout the year.

Let's move to Slide 20.

And so wrapping up our growth platforms, a deeper dive into Emerging Markets.

Emerging Markets continues to track in line with the long-term performance target, delivered 10% in the half, 10% growth.

China delivered, it's been mentioned a couple of times, strong performance again with 24% growth in the half and it benefited from the products that we added to the NRDL in 2017, and of course, the very successful and ongoing launch of Tagrisso.

And we continue to partner with physicians to develop centers of excellence to ensure better disease management in diabetes, chest pain and lung cancer to name a few and this is leveraging, again, our concept of the -- leveraging the Internet of Thing and creating really an echo sphere around these key diseases to make a big difference for patients and engage as many partners in helping to improve care.

And outside of China, we continue to see the impact from general economic conditions and divestments, which amounted to 7% to 8% of an impact on growth.

The Russia headwinds did continue.

As I mentioned in the last quarter, business was impacted by both cost and budget pressures within the healthcare system.

And we did experience manufacturing capacity constraints in the Middle East and Africa.

However, strong performance of our main therapeutic areas in Emerging Markets continued with Oncology up 37%, Respiratory up 13% and New CVRM up 32%.

So in summary, a portfolio of several potential blockbusters with Emerging Markets, I think we clearly are continuing to demonstrate the [Krayer–Marshall] capabilities to make all of these opportunities major successes for the company and that we're absolutely doing the best we can to get these new medicines to all of the eligible patients that could benefit from them.

And with that note, I would love to have Marc come up at this point.

Thank you, Mark, and hello, everyone.

I'm going to spend the next few minutes to walk you through our financial performance for the first half of the year as well as our unchanged guidance.

So if you want to turn to Page 22.

As usual, we will start with the reported P&L before turning to the core numbers.

Pascal mentioned earlier, product sales declined by 2% for the half with a growing contribution for new medicine and strong Emerging Markets were offset by the ongoing impact from the loss of exclusivity for Crestor.

The lower-level of initial external revenue in the half drove a decline in total external revenue of 54%.

I want to be clear that we remain focused on creating further external opportunities in the future.

As we rapidly across approach our return to growth, I'm pleased that we reduce restructuring cost in the half to $187 million from $496 million in the first half of last year.

CapEx was also reduced to $486 million in the first half versus $549 million for last year and anticipate declines in restructuring cost and capital expenditure for the full year.

Please turn to Slide 23.

Moving to the core P&L, our gross margin ratio for the first half fell as expected, by 3 percentage points to 80%, driven by the impact of positive manufacturing variances in the first half of last year as well as the inclusion of the profit share from Merck.

The rapid decline in the sale of Crestor in Europe and Japan also had an impact.

The core operating expenses increased by 2%, with a 5% decline in core R&D cost outweighed by 7% increase in core SG&A cost.

Core other operating income declined by 27%, a result of the timing of our divestment for this year.

Our core tax rate was 19%, in line with the indication of a full year core tax rate between 16% and 20%.

Moving now to Slide 24.

As you can see on this slide, it's the lumpiness of the externalization revenues, but it is also worth highlighting that we are -- we have a growing contribution from the collaboration with Merck with $170 million of milestone payments received in the first half.

We also await $400 million later in the year as option payment.

There will continue to be a regular stream of milestones payments from Merck over time, which will reduce the viability in the externalization revenue.

The key part of our strategy is to focus on more appropriate cash generating and value accretive transaction.

And as I said, we remain dedicated to creating further externalization opportunities.

We are also committed to the continued management of portfolio divestments and to increasing the focus of our 3 main therapy areas over time.

Moving to Slide 25.

As I mentioned earlier, our core R&D cost decline by 5%.

Despite maintaining a high level of activity, we continue to deliver benefit from connectivity initiative and efficiencies.

Reinvestment in our business remain one of our capital allocation priorities and I continue to anticipate the stable to low single-digit decline in core R&D costs for this year.

Core SG&A cost increased by 7%, reflecting investment in new medicine launches and increase of formulation resources in China.

H1 2017 saw one of the lowest level of core SG&A spending in many years.

Comparison will, however, become more favorable in the second half of this year.

Consequently, I anticipate low to mid-single-digit percentage increase in core SG&A costs for the full year.

We closely monitor our sales performance.

And if we see that our investment continues to drive excellent results from our new medicine and our business in China, we are likely to be at the higher end of that range.

And I'd like to conclude with a reiteration of our 2018 -- I'm on Slide 27.

I would like to conclude with a reiteration of our 2018 guidance, which is on product sales and core EPS at constant exchange rates.

The product sales performance in the first half was in line with the expectation, and so I have no hesitation in keeping my guidance for low single-digit product sales growth over the full year unchanged.

I continue to anticipate the sum of the external revenue and other operating income will be less than that in 2017 and I want to reiterate my expectation of a core EPS of $3.30 to $3.50.

Finally, our capital allocation priorities remain unchanged given the first half performance, the success of our new medicine and a pipeline that is key to our return to growth.

And with that, I will hand over to Sean.

All right.

Thank you, Marc.

I'll now run through the late stage pipeline events that we've had since the last results announcement and also highlight some recent data presentations at medical meetings.

And as usual, I will finish my presentation with a look forward at our upcoming news flow.

If you could please turn to Slide 28.

So this summarizes active movement in our Oncology pipeline.

We have had strong progress in our Oncology portfolio through this quarter.

More specifically, Lynparza met its primary endpoint in the SOLO-1 trial showing a delay in disease progression or death when used as a first-line maintenance therapy for BRCA-mutated ovarian cancer.

Also, the tablet formulation of Lynparza was approved in Japan for BRCA-mutated breast cancer.

Tagrisso received EU approval for first-line EGFR mutated non-small cell lung cancer.

Selumetinib, as Pascal mentioned, did not meet the primary endpoint in the thyroid cancer trial.

Our ambition now with selumetinib is getting it approved in the unmet medical need of neurofibromatosis type 1.

Finally, for news flow, Imfinzi was approved in Japan for unresectable Stage III non-small cell lung cancer based on PACIFIC trial data.

Furthermore, at a planned interim analysis, the PACIFIC trial met its second primary endpoint of overall survival, which was both statistically significant and clinically meaningful.

And we plan to present this data at a forthcoming medical meeting.

From the right side of the slide, data from our innovative oncology portfolio was again on display at ASCO, where we had 91 abstracts accepted, including 14 oral presentations.

Of those, 7 were best of ASCO presentations.

We presented data from Study A, evaluating Lynparza in combination with abiraterone in metastatic castration-resistant prostate cancer.

The trial showed the potential of PARP inhibition beyond ovarian and metastatic breast cancers regardless of homologous recombination repair mutation status.

We reported response rates and safety data for the immunotoxin moxetumomab pasudotox in relapsed refractory cell hairy cell leukemia patients from our 1053 trial.

For selumetinib, we presented Phase II data from the SPRINT trial evaluating the MEK inhibitor in pediatric patients with neurofibromatosis type 1 and plexiform neurofibromas.

From our early stage pipeline, we presented data from PAKT Phase II trial of capivasertib, a highly selective oral AKT inhibitor, combined with paclitaxel.

The data showed positive impact of the combination on progression-free survival and overall survival in previously untreated metastatic triple negative breast cancer.

We can go now to Slide 29.

In CVRM, last quarter, we received U.S. approval for LOKELMA.

For Farxiga, we made 2 regulatory submissions, one in Japan for the treatment of type 1 diabetes, which is a potential new use of the medicine.

The other was in the EU for Farxiga combined with Onglyza and metformin as a triple tablet for patients with type 2 diabetes.

Also in type 2 diabetes, we made a regulatory submission in the United States for Bydureon based on data from the EXSCEL cardiovascular outcomes trial and we received a positive CHMP opinion for Bydureon BCise, the autoinjector.

At the American Diabetes Association Conference last month, we shared new data on Farxiga in combination with Onglyza and on MEDI0382.

MEDI0382 has a novel mechanism of action.

It is based on a peptide release from the gut, which targets both GLP-1 and glucagon receptors, which are in turn critical to controlling metabolic functions.

In a Phase IIa study, the compound showed significantly improved glycemic control and reduced body weight compared to placebo.

Phase IIb is now underway with data expected in the first half of 2019.

If we can go to Slide -- to the next slide, Slide 30.

On to Respiratory, where we continued our momentum in building an innovative Biologics portfolio, which truly is following the science.

As Pascal mentioned, the launch of Fasenra in severe asthma, Pascal and Mark as well, the launch of Fasenra in severe asthma is off to a strong start.

In COPD, Fasenra missed the primary endpoint in 2 separate Phase III trials in the quarter.

In terms of life cycle management, we are developing Fasenra for administration in the home and we have also begun a new Phase III trial OSTRO for its use in nasal polyposis.

As presented previously, tezepelumab has demonstrated potential to be the best in disease asthma medication based on its Phase II efficacy trial as it reduces several key biomarkers including blood eosinophils, fractional exhaled nitric oxide or FeNO and immunoglobulin.

As a reminder, the Phase III program called PATHFINDER has begun with data anticipated after 2019.

Next slide, please.

In addition to our innovative medicines, we have also become a leader in precision medicine, driven by a strategy of developing the best medicines for those patients most likely to benefit from them.

Together with our partners, we now have 22 diagnostic tests approved in the U.S., EU and Japan, which supported more than $1.4 billion in precision medicine sales for the first half of 2018.

The biomarkers detected in these tests include EGFR mutation, T790M mutation and EGFR, BRCA and PD-L1 expression, to name a few.

We have several more tests for biomarkers in development and these include tumor mutational burden and homologous recombination repair gene mutations, which we will pair with our innovative medicines.

Hence, as a further result of our portfolio transformation, specialty care medicines now make up more than 1/4 of our first half 2018 sales.

Next slide, please.

This slide summarizes our upcoming news flow.

For Lynparza, we anticipate regulatory submission in the second half based on positive high-level results from SOLO-1 for its first-line use in ovarian cancer.

Following the U.S. approval for Lynparza in germline BRCA-mutated breast cancer at the start of the year, we received regulatory approval in Japan at the start of this month and expect a regulatory decision in the EU in the first half of next year.

We anticipate a regulatory decision for Tagrisso in first-line setting in Japan in the second half of this year.

Moving to immunooncology, we await an EU regulatory decision in the second half for the PACIFIC trial in unresectable Stage III non-small cell lung cancer.

Also in lung cancer, we expect overall survival data readouts for MYSTIC in the second half of this year and for NEPTUNE in the first half of 2019.

Head and neck cancer, we expect data from the KESTREL first-line and EAGLE second line trials in the second half of this year.

Our first-line bladder cancer trial, DANUBE, will have a data readout in the second half of 2019.

In CVRM, data from the Phase III DECLARE trial will be available later this year.

We anticipate a regulatory decision for Bydureon's autoinjector in the EU by the end of the year.

And as communicated by our partner FibroGen, we anticipate data readout for roxadustat in the second half of this year and regulatory submission in the first half of 2019.

In Respiratory, for COPD, we anticipate a regulatory submission acceptance for PT10 and a submission in Japan and a decision from the EU for Bevespi by the end of this year.

Finally, we expect data from anifrolumab in lupus in the second half of 2018.

With this, thank you for your -- I want to thank everyone for your continued support and thank all of the hard-working colleagues in AstraZeneca who come to work every day and make all of this progress happen, and I will hand back to Pascal for closing comments.

Thank you, Sean.

So I'll now move to the last slide, Slide 34.

And just to save us a bit of time for Q&A, we will not cover this slide.

I just want to leave you with one message actually, which is what I said in introduction.

Our strategy is now delivering results and we are at this pivot point where the growth of our new products is accelerating and will soon supercede the decline of the old products.

And these old products, as you know, today, they represent 30% of our total sales and rapidly, they will stabilize and then as of the second half, but also importantly, even more so next year, we will see an accelerated growth of our top line.

And I want to take this opportunity to thank our colleagues around the world.

Many of them are actually listening to us and watching this event.

We rolled out a new technology that is called Workplace and allows them to follow this presentation in real time.

So I just want to say hello to all of them and thank them all for their hard work and their talent.

Over the last few years, they've delivered absolutely outstanding results.

So I'll stop here and open for the question-and-answer session.

And if I may ask you, just ask us simple easy questions so we can impress our colleagues who are listening to us.

Thank you.

Andrew?

It's Andrew Baum from Citi.

Two questions.

First, the administration clearly sends proposal to the White House for amendments or elimination of the current rebate structure.

Could you talk to your understanding, and I know there is limited information, but what you're expecting in terms of number one, our assumption is this is limited to federal sponsored plans, whether that is consistent with your understanding?

Second and the timing and then, finally, the risk that this spreads to commercial plans because general councils or PBMs feel uncomfortable running a separate structure if there is an enforced amendment under the Medicare.

Okay, Mark, do you want to cover this question?

Our understanding I think actually is pretty good.

I don't think we can add much to it based on what we know.

I mean, really there is a lot of uncertainty and not too much information.

It does appear likely to be focused on federal plans, but it will -- it would be a massive change even in that scope.

And so it's -- I think it is pretty hard to predict right now.

Our company is supportive of working with any of the players, including the administration in the healthcare system in the U.S. to find ways to address the concerns that people have around out of pocket cost.

And if there is a way that this could help them, we want to engage and try to make it a success, but we need to hear it, there are risks associated with it as well.

So don't have really a lot to add to this.

I don't know, Pascal, if you want any other points.

The only thing we can also add to this is that if we were able to remove those rebates, suddenly it would create short-term challenges, but in the long term, it would be a good thing for most of the industry really because those create incentives that are not necessarily good for anybody in the long term.

So we will see what comes out.

The ideas that are generated, they tend to change almost on a weekly basis.

We will see what is finally implemented.

James Gordon from JPMorgan.

The question was just on LOKELMA.

And so you've got the U.S. approval, but I think aren't launching yet and maybe not launching until next year.

Just what are the different factors there in terms of continued manufacturing issues versus was the label as good as you hope for, for the products?

Or is it partly about consideration in terms of building a nephrology sales force where you don't yet know whether roxadustat has been successful?

And does it partly reflect that -- some uncertainty around the chances of success for roxadustat?

No uncertainties about the manufacturing.

Label was in line with our expectations and we remain very excited about that.

We've got teams in place and we're starting to lay the groundworks.

The decision to launch in 2019 is all about market preparation.

And I think if you've observed other specialty launches in the U.S., making sure that you've got market access to a reasonable level is crucial and that takes some time.

So we're doing that.

I think this is potentially a transformative treatment for hypokalemia so -- and even physicians understanding of the importance of hypokalemia is a lot of education that needs to be done.

So we're laying the groundwork both from an access and from a science standpoint.

We're very excited about the product.

The label is good.

We have no manufacturing issues.

Everything is going to be a full green light in 2019.

The market has changed, James, in the U.S. as you know.

And getting a good access or minimum level of access by the time you truly start promotion is key because otherwise you are really struggling quite a lot and you've seen many other products have waited a few months before launching to get to a reasonable access and that's exactly what we're doing, but the product should do well.

I mean, there is a big unmet need.

A great product.

As on your question of launching, when we have sufficient access.

Richard Parkes from Deutsche Bank.

I've just got couple of questions.

Firstly on Imfinzi.

So obviously had an incredible launch in the Stage III unresectable lung cancer setting and none of your competition is currently in Phase III studies, but there was a single arm trial of KEYTRUDA at ASCO, which is of broadly similar efficacy and safety.

So I'm just wondering what you think the probability is that KEYTRUDA could have a NCCN compendia listing based on that data and whether that would likely have any impact on Imfinzi use in that setting.

And so that's the first question.

Second one, just a quick one on gross margins or a sequential improvement in the second quarter.

So just wondered how that is likely to evolve throughout the rest of the year as the new product start to take greater proportion of revenues?

Okay, Dave or Sean.

Dave, you want to cover the first one, the NCCN?

Sure.

So absolutely, as I had mentioned, the Imfinzi uptake has been really quite strong.

And I think that it is important to note within that, that, as I said before, we've got about half of post-CRT being treated with an immunotherapy and we do see that really the vast majority of that is with Imfinzi, meaning that we're not seeing a lot of other PDX in that particular setting right now.

On your question about the data at ASCO, I mean, your speculation on NCCN will be every bit as good as mine.

What I would say is that I think that single arm studies don't often meet the evidence level that is required for 2-way, which is what is required in order for that to actually translate into public reimbursement within the U.S. It doesn't mean that, that won't be how NCCN chooses, but that's at least my experience with it.

Marc -- I'm sorry, Sean, go ahead.

Dave is exactly right in the setting that we're trying to work here now.

We have NCCN listing based on single arm studies, Calquence has them, but that's the only agent study, okay.

So you know that whatever effect you are seeing is attributable to that.

That's not the case in this disease setting because patients are getting chemo radiation therapy, all of them.

So they're getting an active agent.

And without a control arm, you can say it looks broadly like ours, but you really can't say how it would have competed against the standard of care.

And I think in that setting, what Dave said is really true, it is hard to get a level of evidence.

Marc, do you want to cover the gross margin question?

In terms of gross margin, I think, if you look at the year-to-date gross margin, this would be a good indication for the gross margin for the overall 2018.

So the slight improvement that we experienced in the second quarter may not be lasting until the end of the year.

So I would remain on the conservative side and use the year-to-date gross margin.

Keyur, if I can take 1 minute, I'll take a question online and return to you if that's okay.

There is a question from Simon Baker at Exane.

Simon, do you want to go ahead?

So sounds like we have a technology challenge with the phone line.

How about you ask your question, Keyur?

Keyur Parekh from Goldman.

I have 2 questions, please, one for Sean and one for Mark.

Sean, from your perspective based on your interactions with thought leaders, what do you think roxadustat needs to show that is noninferiority good enough or do you need to show superiority from a commercial perspective?

That's one.

And Marc, can you just remind us what cash flows from operations were for the first half of the year, what do you expect them to be for the full year, and what the swing factor between the 2 halves are likely to be?

You want me to go ahead?

Yes, go ahead.

Okay, yes, so with regard to roxadustat, I think, first of all, it is important to recognize that probably what we need to show is different in the 2 different settings that we're looking at it in.

So in the dialysis setting, where ESAs are the standard of care and have established and with a black box warning, a cardiovascular safety risk.

And the opportunity there is to show superiority from the standpoint of not carrying that risk.

So you will treat the anemia without incurring risk of potentially catastrophic events.

I think what remains to be explored is, if you get similar safety in the trials, you'd still do have an oral agent and then you would look at what is your efficacy in terms of raising the level in treating the anemia.

It's different in the pre-dialysis, non-dialysis-dependent chronic kidney disease because your comparator there is placebo.

So you can't -- it's very unlikely, you can have less cardiovascular risk than no treatments.

So there what you are looking at is noninferiority versus placebo from a safety standpoint by virtue of being not an injectable and an oral starting to extend treatment for anemia to patients who aren't in the intensive healthcare setting.

So in terms of cash generation, we have a general pattern where the first half of the year, we do not for the time being produce large free cash flows.

However, this increases over the second half of the year.

This is further compounded by the external revenues or other income -- generation of other income that could happen at any time, but as I've told you earlier on, on 2018, this would be more truly strong in the second half than in the first half.

So we have a general pattern.

And then I think, 2016 and 2017 would be quite useful for predictions and then you need to compound it with the projection for the externalization and other income in 2018.

I think these 2 sets of predictions have to be made.

You had a follow-up question, Keyur?

So what do you expect full year cash flow from operations to be?

Well, I'm not going to give you the exact number, but it will be a number that is not very far from 2017.

Roger Franklin from Liberum.

Just a question on Fasenra.

I mean, obviously, the thing that stands out this quarter, so really quite incredible performance there, and you called out 2 factors, kind of the profile and the execution.

I wonder if you could just split those out and how much do you think this is down to the profile of the medicine?

And how much do you think this is down to your execution?

I think it is both.

I mean, and I think, again, it is the appropriate time to recognize the U.S. team.

They've done an absolutely fabulous job.

A lot of them actually joined us for this launch.

They came from other companies with a lot of experience in Biologics.

We have a tremendous leader managing, leading this team.

He has done a tremendous job.

On all fronts, from access to commercial to marketing to sales.

And the second aspect is the product.

As Mark told you, and I think one of the key aspects of the product is the speed of action because patients experience benefit very rapidly and they come back to physicians and they relate the positive experience to physicians, which is a positive feedback loop to the prescriber to use the product more.

Mark, anything else you want to add?

Just a couple of points because the answer from me would be both.

It is hard to separate out.

I think that you have to start with the profile.

And what's important is that we're seeing very similar uptakes of Fasenra in Japan, in Germany basically as we launch, extremely rapid uptake and very positive feedback from patients because they're feeling an effect, the benefit, on the first dose which has not always been the case with Biologics in asthma.

So very exciting profile that's clearly sort of fundamental.

The other thing that I would add is that we've been able to leverage our experience in managing -- in other words, helping physicians, patients manage the reimbursement challenge of specialty medicines in getting through prior authorizations, creating the documentation.

We have something called Access 360, which is a group that's an in-house capability that we've built for us for synergies and then for the Oncology launches and it really is best-in-class capability.

The team that works there also needs a huge congratulation.

And what they've been able to do is very significantly, reduce the time it takes between when a prescription is written and when the patient can get reimbursement, and be confident that they will be able to not just have the first dose but actually be able to use the medicine, and I think all of those factors come together have really allowed for a very rapid uptake.

I mean, the German team and the Japanese team have done a fantastic job.

Absolutely stellar launch in all the countries where we have launched.

I think it is important because I remember a year ago, a few months back, people were saying, "Okay, well, it's great you have a pipeline now, but do you have the commercial strength to launch those products?" And I think we can say -- we can say absolutely, yes.

We do have that.

When you look at Tagrisso, you look at Imfinzi, you look at Fasenra and all the other products and they're all doing quite well.

So a commercial organization is very strong.

I interrupted you.

Maybe, James, you wanted to ask a follow-up question.

Yes, so I just wanted to ask in terms of specifically the feedback you got from the physicians on the profile versus LOKELMA, what do you hear from them?

I mean, what the physicians are talking about is what the patients tell them and the things that are coming back, being able to sleep again, being able to get back with activity.

I mean, a severe asthma patient, his life is very debilitated, right, they're not able to do any activities of challenge at times and they just feel better.

And one of the things we are doing is actually we are trying to do some research to really capture how it's impacted patients and we've got to plan some additional studies to try to explore that from a scientific perspective because it seems like the impact is really strong.

Yes, absolutely.

People tend to see asthma as a minor disease, but severe asthma is really debilitating and we have so many of those stories of patients coming back and saying, "Look, I haven't been sleeping for 10 years.

I haven't been able to function properly and I took this drug and I sleep.

I sleep the whole night." And sometimes, people come up and they're quite emotional about the experience they're going through because their life, they have their life back.

Unfortunately, it doesn't work in every single patient who is treated, as you would imagine.

But some of those -- many of those patients experience really transformative benefit and the speed at which those benefits come or become obvious is really striking, and I think that's really what the physicians are hearing.

I think the other thing we should also highlight, and again, it's credit to the clinical teams, the medical affairs teams and the marketing and sales teams, we've been very clear about the type of patient that is going to benefit from it.

It's a big portion of patients, but this is for eosinophilic disease.

We've got some very clear indicators about patients that will benefit from that and that's what we are really encouraging physicians to focus on.

And so one thing that also has happened, I think, in almost every case, that first patient that they tried, they saw a positive result.

And this is for certainly true in the U.S., but I think, everywhere.

If you are using an expensive, a little bit out of the ordinary biologic and that first patient you try, it doesn't work, that's a real impediment for sort of future prescription.

And so the teams have done a great job of helping physicians really find the right patients early so that they understand the benefits of it and then they can continue to look for the right patients.

Sounds like we have resolved the technology issue.

So let's go back to Simon Baker from Exane.

Simon, can you ask your question?

Yes.

Can you hear me now?

Yes.

Go ahead.

Perfect.

A continuation on Fasenra.

As we just said, the previous question said, the Q2 performance was considerably more impressive than we were expecting.

So I know it's still early days, but could you talk about how the trajectory of Fasenra launch is going versus your expectations?

I noticed that consensus expectations even by 2023 is still sort of sub blockbuster status.

How does that qualitatively compare with what you expect?

And related to that, how has this informed your expectations and plans for tezepelumab down the line?

Mark, do you want to cover this?

If you ask the question about expectations, you're going to get different responses from different people even in the company.

You had great believers and people who are more conservative as you would expect.

Mark, do you want to cover this?

Well, I think as I said in the opening, another way to phrase it is, it's in line with our high expectations that we had for it and some, at least from my perspective.

We had high expectations.

We knew it was a great clinical profile.

We knew the teams already, but they're doing that and something more.

And we're getting to discussions because we are coming up to the planning cycle and Pascal will be sending targets for us and my colleagues won't be happy if I make that more challenging than it needs to be.

But it's really a great kickoff and we expected it, but it is meeting that and more.

In terms of tezepelumab, I mean, the science and the data that we've seen so far said that we should really move as fast as we can and as comprehensively as we can to understand what this medicine could mean for asthma patients and this only confirms that a right medicine can make a huge difference.

And as I said before, you've got to really focus on the right patients.

And so there are number of patients that aren't going to benefit from Fasenra.

And what we've seen with tezepelumab being upstream, the potential that it could benefit many more patients says we should be moving as fast as we can and certainly doing the right science, and so that's it: What's happening is the studies are up and running and there is a very high degree of excitement within the Respiratory community around tezepelumab.

We have another question, a question on line from Emmanuel Papadakis at Barclays.

Emmanuel, do you want to ask your question?

Maybe take one for Dave on Imfinzi.

You talked previously end of Q1 around half of unresectable patients getting concurrent CRT.

The question I was going to ask is, is that number moving at all before you start think about the half of those then getting an IO agent such as Imfinzi?

And then the second question I was going to take if you allow me was for, I don't know if it is better for Mark or Sean, but it was on the DECLARE study.

Your expectations about that potentially achieving a primary prevention indication as well as the secondary prevention that your competitor -- major competitor in that space already has, would be very interested to hear your thoughts on that.

Dave, you want to cover the Imfinzi one?

And Sean, the DECLARE?

Thanks, Emmanuel, for the question.

Our efforts since launch have really focused in on driving Imfinzi use among those physicians who have already begun concurrent CRT as their standard treatment for Stage III patients.

We have begun also, though, to see some growth in the use of concomitant CRT within the United States.

It grows more slowly and it's something that we will move to put more effort behind, but right now we are really staying focused on making sure that for that on-label population where we see that the greatest opportunity is to have physicians at Imfinzi on to what already is their treatment that they're using for curative intent, which is CRT.

Yes, the question on DECLARE.

Thank you for the question.

So I guess, there are a couple of components there.

You asked specifically about primary prevention patients.

So DECLARE has 17,000 patient trial.

And actually, the majority of those patients have not had a previous cardiovascular event, about 10,000 would be primary prevention; the remaining patients are the secondary prevention.

As you said, the place where this has already been demonstrated with an SGLT2 inhibitor.

With regard to the primary prevention, actually, the end point itself is all of the patients together.

So it will be the patients in totality.

So for the trial to be positive, it has to be everyone.

And it is our hope that if that's the case, then an indication would reflect the trial that was done.

So I think, that's the answer to that question.

You asked a little bit about confidence.

I think both the secondary prevention established data and then as our real-world evidence work, I would say with looking at SGLT2 inhibition and practice heavily -- fairly heavily enriched in some populations for patients receiving Farxiga also supports the idea that SGLT2 inhibitors in general and Farxiga, in particular, is quite potent for helping to reduce cardiovascular risk particularly related to heart failure.

Emmanuel, any follow-up?

So just a follow-up on Fasenra.

So my assumption is that GSK could start using external medical KOLs to market the drug contrary to their existing strategy.

Given where they are positioned and given it is difficult to relaunch a product, is that something that concerns you from a competitive point of view?

And if that isn't a concern because it is too late, then what do you think the risk of your competitor playing the pricing card given the density of competitors in this space and given the PBM market?

So let me make a couple of comments and certainly others and Pascal can jump in here.

So I can't comment on sort of more GSK's practices, how they might change or evolve.

We remain very confident in the future prospects for Fasenra based on as we've been talking about the profile of the product and the capabilities of the team in there.

We've got ambitious life cycle management plan and also additional Phase IV studies to continue to build on the profile of the product.

And I think we're going to continue to build our capabilities in the U.S. and around the world.

In terms of what options they might do to improve the competitiveness, I don't know, those are the things you've highlighted, are potential levers.

I think we don't feel the success that we're having, we don't feel that -- we feel the price that we have for Fasenra is in line with the value and the differentiation, and so, we are going to keep focusing on the levers that I think really will make a difference for the patients and for the performance of the brand.

You think about what the potential for Fasenra is, and what's the most important factor, it's actually the thing I mentioned at the end of the -- section.

Less than 1 in 10 severe asthma patients that are eligible for Biologics actually get a biologic.

And we certainly see the potential for this class of biologics to get over 30% of severe asthma patients or more.

And so as we continue to move on, we'll continue to emphasize the profile of the product, but we're going to be and we're already upping our efforts onto really helping reach those patients in the U.S., through consumer advertising, through major medical education programs to really reach those patients and get them treated.

That's the biggest opportunity for Fasenra.

I think we've got a product that will sustain its leadership in the IL-5 category.

But what will really determine the potential is how good a job we get to the patients today that should have access to a biologic but aren't having it.

I would only add 2 comments actually.

Number one, if you are in a diabetes market, an antidiabetic agent can be differentiated, but for the patient, it just reduces glucose.

So they don't really necessarily feel the difference.

Here, if you have a differentiated agent because it works faster and you have a stronger depletion of your eosinophil, the patient feels better, the patient really experiences the difference.

So when you have more differentiation, the price leverage is harder to play.

But also the second point is more technical, is in part B, as long as you are in Part B, price strategies don't -- are really short-lived.

As you know, 6 months later, your price is reset down.

And so basically, you don't get much out of a price reduction.

You get a bit of an advantage for 6 months on top of it, and you have to make sure -- you theoretically should make sure your customer know about the price difference.

In fact, you can't even -- you can't do it, of course.

It's not compliant and you can't promote it.

So your benefit is limited and it is short-lived.

So I think, the price question is Part B, there may be some, but for the reasons I have described, there should be a limit.

Part B and Part D on Fasenra?

No, when you move to Part D, that's a different story.

We are in Part B.

You are in Part B.

If you have a -- if you move to Part D, because you have a different administration, say, home administration or whatever then at that point, of course, the Part D mechanisms can put more pressure on price.

But in Part B, it's really hard.

I mean, it's possible, but it is more limited.

Let me take 2 questions on line here.

One from Jo Walton at Crédit Suisse.

Two quick ones.

One, I'm afraid, again on Fasenra.

It's coming back to something that you just mentioned.

You are looking for home administration and I wondered how important you felt getting home administration at some point in the future would be to unlocking some of that 1 in 10 or moving from the 1 in 10 with Biologics to a much higher number?

And the second one was on China and Pulmicort.

You've managed to solve the supply constraints.

You had an extraordinarily strong 2Q.

How much of that was refilling the pipeline and how much of that is an indication of underlying demand going forwards?

I don't know that we have the answer to your second question.

Maybe Mark Mallon can give you some insights here.

But I guess, a simple way to look at it would be to say look at the first half because it sort of normalized across the 2 quarters, but Mark, if you have anything more on Pulmicort and also if you want to cover the first question?

I think looking at the first half in total is probably the right way to go for Pulmicort in China.

And then in terms of the home or self-administration as a life cycle plan, I think it could be another tool in helping expand the class, expand capacity.

The severe asthma centers are limited in many countries, and so how many patients they can actually see.

So there -- I think both will be -- continue to be important, some physicians or patients will prefer to continue to have an in-office administration.

Others would prefer in-home administration.

So it will meet the unmet needs, and so we are definitely pursuing it aggressively, and I think it can play a role in getting to more patients.

Thanks, Mark.

One thing we kind of don't mention maybe enough is, as a reminder, Fasenra is an injection every 2 months.

So that is a reasonable pace or reason, if you will, for the patient to go back to their physician.

They don't have mild to moderate asthma, they have severe asthma.

Seeing a physician every couple of months for an injection is not necessarily a bad thing for the patients.

So the benefit of home administration is there, but it is not as strong when you have a product like Fasenra.

So we'll take the last question.

Sachin Jain at Bank of America.

Just 2 quick ones.

You framed in your instruction a slowdown in the SGLT2 market.

My mistake, it's down sort of 5% volume growth from mid-teens.

Maybe if you just provide your perspective on reasons for that?

I guess, it is a little bit surprising given the cardiovascular data that is out there for this space.

And then secondly, on roxa, for Mark, sort of a follow-on from the prior question, which of the 2 opportunities pre-dialysis versus dialysis are you most excited by and do you think you could penetrate the quickest if the data came through as a base case as noninferior in both scenarios?

So I'll take the second question first actually.

I'm excited about both opportunities.

It's hard to say, which one.

And I think in terms of penetration, I think, if we deliver on the target part of profile for the dialysis, I mean, this is potentially a transformative opportunity.

Again, if we hit the profile, got the elimination of the concerns around the cardiovascular risk.

You've got an oral therapy.

One from the studies that we've already seen in China on hemoglobin control works in full range of patients, not impacted by things like information, not having to deal with iron.

It's really a benefit for patients in a dialysis setting.

There will be -- of course, we have to go through that market access discussions and we've started that work, but I think, the uptake could be there very rapidly.

But in the NDD, that will probably be a slower build because we have to create that market.

But again, if it hits the target profile, I mean, the benefits can be -- are going to be very significant for patients, right.

Living with anemia for many years has a number of negative consequences.

And so we'll have to educate and create that market, but that, say, will take time, but it's a chance to impact a huge number of patients in Stage III and Stage IV renal disease.

In terms of the SGLT2 class, I think, the short answer is that because we've had some side effects like the DKA, like with one of the competitors where there've been some reports of amputation, there was a labeling change, that makes it -- and SGLT2 is not -- it's in primary physician care physician's mind, not a specialist mind, not quite as easy to use as something like a DPP4, which is an excellent medicine for treating -- managing glucose.

And so but we still have a lot of work to do to making sure that they really understand the benefit.

And as Sean was saying, right, the initial studies was in a pretty limited group of patients with pretty significant CV risk.

And so for primary care physician, it's a little bit of a question.

Do I really see those patients?

And so the combination of the 2 I think have been a factor in the growth.

This is, I would say primarily, mostly in the U.S. and a few other countries.

In many countries, actually the class code is, I should have probably clarified, this is good.

And I think really, DECLARE, if it reads out positively, will help to address on all of those fronts because it will strengthen the cardiovascular benefit profile.

And if it reconfirms the safety and tolerability profile of Farxiga, I think, will also help in terms of physicians feeling confident.

So I think, we can actually improve the overall risk-benefit kind of working both sides of it.

DECLARE is key because of the cardiovascular events, but also because of the safety database that will come with it.

And if we get behind -- if the study is positive and we get behind it, we certainly can go over the class that has enormous potential.

So we stop here.

And thank you for all your questions.

I just want to close by, again, thanking my colleagues from around the world and leaving you with this message, again, that our strategy is working.

We are finally getting to the point where our new products are growing rapidly.

And I know I'm repeating myself, but we can't say it often enough.

Another few quarters and we will be done with those patents expiries and we'll be in a very, very different place.

Thank you very much for all your interest and your patience.