Ladies and gentlemen, thank you for standing by and welcome to the Sanofi Third Quarter 2019 Earnings Conference Call. I would like to turn the call over to George Grofik, Vice President, Head of Investor Relations at Sanofi. Please go ahead, sir..

Good morning and good afternoon to everyone on the call. Thank you for joining us to review Sanofi's third quarter results. As usual, you can find the slides for this call on the Investors page of our website at sanofi.com. Moving to slide two.

I would like to remind you that information presented in this call contains forward-looking statements that involve known and unknown risks, uncertainties and other factors that may cause actual results to differ materially.

I refer you to our Form 20-F documents on file with the SEC and also our Document de Référence for a description of these risk factors. With that, please advance to slide three and let me introduce our speakers today. With me are Paul Hudson, Chief Executive Officer; and Jean-Baptiste de Chatillon, Executive Vice President and Chief Financial Officer.

Paul will discuss the highlights, after which Jean-Baptiste will review the financials. After the concluding remarks, we will close with a Q&A session, during which we'll be joined by members of the Executive Committee. With that, I'd like to turn the call over to Paul..

Well, thank you, George, and good morning and good afternoon, everyone. It's a real pleasure and indeed a privilege to be here on my first earnings call as CEO at Sanofi. Now, I know many of you are eager to hear about my priorities as I settle into the role.

And with this in mind, I will share some of the insights I've gained in my first 60 days in the company. But before that, let's dive into the -- straight into Q3 results. So on slide five, Sanofi delivered a stable performance in Q3, despite the phasing of flu vaccine sales.

This was in line with our expectations and positions us well to meet our full year guidance. Key highlights in the quarter include the continued strong uptake of our now annualizing mega blockbuster Dupixent. While on the downside, we continue to face pricing pressures in Primary Care, as well as the flu phasing.

Additionally, our Consumer Healthcare, or CHC, business was impacted by the Zantac recall. These sales impacts, however, were offset by an increasing level of responsibility in managing our OpEx. And to that end, we managed to hold EPS flat.

And finally, we achieved important regulatory milestones, notably Dupixent in the EU was approved for nasal polyps, as well as for adolescents with atopic dermatitis. So going a bit deeper into sales performance on slide six.

We delivered solid growth, if we adjust for the roughly 3% negative impact of the flu phasing, which I'll remind you will balance out in Q4. And as in prior quarters you can see clearly that our key growth drivers are more than offsetting the declining losses of exclusivity.

Advancing to slide seven and looking at the performance by GBU and by geography. We achieved excellent growth in Specialty Care, beating 20% in both mature and emerging markets and greater than 20% overall.

Vaccines, on the other hand, was heavily impacted by the flu phasing in North America, while CHC growth was constrained by the Zantac recall and by Primary and -- sorry Primary Care remained under pressure in mature markets. Slide eight clearly shows how our strong brands that together are driving our double-digit growth in Specialty Care.

The primary driver continues to be the outstanding launch and continued excellent execution of Dupixent. Sales of this key asset more than doubled in Q3 and are annualizing at over €2 billion. And that we will continue to expand the penetration in adult atopic dermatitis and continue the launch sequence in asthma and additional markets.

Our second biggest driver Aubagio sustained good growth despite the arrival of new competitors and gained nearly half a share point in the past year. Meanwhile, our Rare Disease business continues to drive growth by identifying new patients.

And as the pioneers of enzyme replacement therapy, we continue to build this category, notably this quarter with new patient growth in Gaucher.

Our rare blood disorder franchise was the only real disappointment, as Eloctate underperformed as the brand, of course, completed it's transition to us and we acknowledge there's opportunities, both in execution but we also recognize the challenges to new entrants in the market.

Slide 9 highlights the strong user brand momentum of Dupixent across key customer groups in the U.S. Importantly, there was a 15% increase in NBRx versus the previous quarter. Timeline from launch, we are outpacing other biologic analogues in both asthma and dermatology. You will also note that we launched the nasal polyps indication over the summer.

And on the graph that you can see the uptake of Dupixent with ENTs. Initial positive anecdotes from the field point to the fact that the message around comorbidities such as asthma, resonates well with physicians treating patients suffering from nasal polyps.

We want to build on our momentum with our new DTC TV campaign in atopic dermatitis, as well as an asthma TV campaign which launched as recently as this week.

An important point to remember is the sustained efficacy and safety of Dupixent, as demonstrated in the 76-week data which was recently published in the Journal of the American Academy of Dermatology. And as we all know, safety will be a critical consideration in the dermatologist's office going forward. And now to Vaccines on slide 10.

This clearly illustrates the impact of U.S. flu phasing on overall performance. As previously mentioned the delay in the WHO strain selection plus the U.S. flu deliveries backed by roughly one month. To remind you around two-thirds of our U.S.

flu doses sold were in the third quarter last year, which compares to less than half in this year's third quarter. Consequently, flu sales fell 29%. So this is simply a phasing issue and we expect to more than make-up the shortfall in Q4 and in fact to post higher full year sales than we did in 2018.

Our leading position in flu continues to be based around our differentiated portfolio. And we're particularly pleased with the Flublok performance. Aside from flu, the rest of our vaccines portfolio grew well notably Pentaxim in China. On slide 11 in Primary Care.

Despite good work by the team on volume sales was down due to pricing pressures in diabetes and to a lesser degree from biosimilar competition to Lovenox. I would highlight however that we performed better in diabetes in Europe where the strength of Toujeo reduced the pace of sales decline to 3%. Performance in the U.S.

diabetes business on the other hand was additionally impacted by the 44% WAC reduction for Admelog. Looking to 2020, U.S. payer coverage for our diabetes portfolio is largely maintained. Elsewhere Praluent remains a mixed story due to contrasting legal outcomes between the U.S. and Germany and due to the previously signaled U.S. pricing pressure.

And of course when we look to 2020, U.S. payer coverage for Praluent is lower. On slide 12, Consumer Health delivered stable sales despite the continued negative impact of divestments and additional regulatory requirements. Additionally, we carried out a precautionary voluntary Zantac recall following initial FDA safety concerns.

Sales of the brand fell nearly 60% in Q3 impacting performance of the digestive category. In other parts of the business we made good progress. Emerging Markets was again a highlight in our three -- in our other three categories each registered growth.

The highlight of slide 13 is the 10% growth in emerging markets, which remain a core strength of Sanofi. Performance was led by double-digit growth in China and Latin America. And I am particularly impressed by our capabilities in fact by our people and our planning in Emerging Markets. I think it could be the best in the industry.

On slide 14, however, I do want to take a moment to remind you on how the landscape is changing in China for Mature products. So while we delivered 14% growth in Q3, we do expect to see a sales decline in Q4 following the national rollout of volume-based procurement.

The chart shows that our VBP effective products Plavix and the Aprovel family held up last quarter. Looking forward though, we expect a significant sale decrease in Q4 in part through inventory adjustments to pricing. We expect sales of these products to decline by about 50% in 2020.

As you'll also appreciate this is new ground for every company that's in this position. So we'll update as we go forward. As VBP products account for around 40% of country sales this will have an inevitable impact on our overall China performance in 2020. However, going forward we need to work hard on growing volume to return to growth in 2021.

As you think through the broader portfolio you should also note that we have a meaningful percentage of our sales in China in injectable products indicated in the darker blue shading on the chart which may be less exposed ultimately to the VBP program.

Additionally, we expect more than 10 product submissions through the end of 2020 including Dupixent, which will be important for our future growth in China. Turning to pipeline on slide 15.

We are anticipating a number of important milestones in the coming year including first approvals for Isatuximab in multiple myeloma and of our next-generation Meningococcal Vaccine MenQuadfi.

We're also expecting multiple pivotal trial readouts notably for our rare disease assets Sutimlimab, Olipudase and Avalglucosidase as well as for Cemiplimab in basal cell carcinoma. And finally we should receive proof-of-concept readouts for our SERD in breast cancer, our BTK inhibitor in MS and our IL-33 in COPD and AD.

I'm excited by a number of assets on this list. So it's going to be quite an imported year ahead for our R&D organization. And I look forward to going much deeper on several of these projects at our Capital Markets Day in December.

On slide 16, I want to mention the progress we made on sustainability in the quarter and in particular we opened our digital factory of the future in Framingham, Massachusetts.

And whilst the commitment to society and energy and water reutilization are significant at the same time what I love about this site is it makes a significant contribution to lowering our overall cost of goods. So between the environmental impacts and the lowering of cost of biologic production this is a major step forward.

Furthermore we're delighted to be recognized as the third most sustainable pharma company by the Dow Jones Sustainability Index. So with that, I'd like to now hand over to Jean-Baptiste to discuss the financials..

Thank you, Paul on that. Good morning. Good afternoon to you all. On slide 18 we managed to compensate the Vaccines phasing Paul just mentioned by our efficiency initiatives. As a consequence BOI declined only slightly and we achieved modest margin leverage of 70 basis points.

The extent of our new mindset is clear in both G&A and R&D lines which declined by around 1.5% and 8% respectively, while our investment in our late-stage pipeline on new launches is happening. So we are learning to manage our OpEx more efficiently and to reallocate resources to our priority.

Just a line item, I would draw to your attention is other operating income and expense. This includes our share of the profit and loss of the Regeneron monoclonal antibodies Alliance reimbursement of commercialization expenses incurred by Regeneron and reimbursement of development cost to Sanofi.

So combined outflow in the quarter it reached €207 million versus €160 million in Q2 2019. As a collaboration, it's more and more profitable. Looking at our cost line on slide 19. The gross margin of 71.4% decreased slightly on a reported basis by 40 basis points at constant exchange rate.

The reduction reflected a negative sales impact already discussed. For the nine months, we delivered a gross margin of 71.8% at CER. Turning to OpEx. Combined R&D and SG&A expenses declined by 4.1 in the quarter.

If we adjust for the receipt of the milestone from Sobi and the annualization of the EU generic divestment OpEx would have declined on a comparable basis by 1.9%. As I mentioned before, our OpEx performance underscores the new mindset we are implementing across the organization.

For the full year, we maintained our guidance for the gross margin to be between 70% and 71% at CER. Keep in mind, the gross margin in Q4 will reflect the dynamics in China on our usual seasonality from flu vaccines in Q4. We expect OpEx growth for the full year to be now somewhat below 1%.

For Q4, OpEx will reflect increased investments in Dupixent the DTC campaign for flu that we switched from Q3 to Q4 and our continuous investments in our pipeline. On slide 20, we affirm our full year guidance for business EPS to grow approximately 5% at constant exchange rates.

The impact of ForEx is expected to be around 3% positive based on October average exchange rates. With that, I would like to turn the call back over to Paul..

Thank you, Jean-Baptiste. So to summarize Sanofi posted on track third quarter performance led by Dupixent, and more broadly by strong growth in Specialty Care and Emerging Markets. We achieved stable business EPS with the help of good progress on smart spending. And this puts us well on track to deliver our full year EPS growth guidance of around 5%.

So, now before we move to Q&A, I want to say a little about my initial impression as CEO of Sanofi. The first thing to say is that, I've been inspired and I'm humbled by the depth of talent in this organization and its single-minded dedication to improving the lives of patients.

I'm just over half way through a 100-day tour of the company, but already I've had the opportunity to learn from and exchange ideas with hundreds of colleagues in the U.S., France, Germany, Spain, Italy, and the U.K. Next week, I'll be in China indeed for the entire week.

I've also met with important external stakeholders to add further insight to my learning experience. These frank and open interactions have taught me a great deal about the challenges Sanofi faces, but more importantly about the opportunities that lie ahead. Having the right people and culture is vital to seizing these opportunities.

We are in my view a uniquely diverse culture in our industry. As an example, there are 35 different nationalities working in our global innovation center in Barcelona. We should be rightly proud of our diversity, which gives Sanofi a real advantage in our increasingly interlinked society.

As part of my strategic review, the Executive Committee and I have reviewed disease area strategies with an eye toward deeper and much more precise look into our pipeline into competition and into disruptive science in order to define our long-term ambitions and indeed the revenue drivers that go with them.

Fundamental to this, we'll be bolstering our R&D engine. We will have to execute on the new priorities of our refocused R&D organization under John Reed with the ambition to bring first and best-in-class treatments to patients.

To achieve this objective, I believe Sanofi can increasingly leverage, its leading-edge research platforms supported by our rapidly emerging digital and AI capability. It is also clear to me that, there are many opportunities to maintain the best of Sanofi, while improving its productivity and performance.

Even at this formative stage of thinking, I believe we can be more efficient by continuing and amplifying the culture change in mindset on cost and cash flow management, which our CFO, Jean-Baptiste has begun to implement and which you saw clearly in today's results.

So where does this end up? Ultimately, my goal is for Sanofi to be an innovation leader, a commercial leader, a cultural leader, and one of the most attractive investment opportunities in the biopharma industry. It's a big task, but I hope you get the impression I'm completely energized to deliver on this.

Now I understand that many of you on the call today are waiting for the opportunity to ask questions about our future strategic priorities. I've been with the company for a little over eight weeks, so I believe this is not yet the time or indeed venue to have this conversation.

We're currently working as a team with the Executive Committee and the Board on the completion of the strategic plans. There is still a lot of work to do and not everything will be finalized by our Capital Markets Day, but we do look forward to sharing with you our strategic direction at that time.

We would be delighted to welcome you in person at our offices in Cambridge, Massachusetts on December 10. With that, I hand over to George to start the Q&A..

Thank you, Paul. I will now open up the call to your questions.

Joining us for Q&A will be Olivier Charmeil, Executive Vice President General Medicines & Emerging Markets; Karen Linehan, Executive Vice President Legal Affairs and General Counsel; David Loew, Executive Vice President Sanofi Pasteur; Alan Main, Executive Vice President Consumer Healthcare; John Reed, Executive Vice President Global Head of R&D; Bill Sibold, Executive Vice President Sanofi Genzyme; and Dieter Weinand, Executive Vice President Primary Care.

[Operator Instructions].

Thank you. Your first question comes from the line of Peter Verdult of Citi. Please go ahead. Your line is open..

Thank you. Peter Verdult, Citi. Just two questions, Vaccines and Praluent. Just interested in your thoughts regarding Trump's recent executive order to modernize influenza vaccine production.

Just wanted to know where you see the opportunities and threats to your current dominant flu business and confidence that the Vaccines business overall can continue to drive mid- to high single-digit growth rates? And then secondly, Paul on Praluent, market access getting worse as sited by you in the Q3 release, the landscape is getting tougher.

And by our numbers, the product loss-making. You've turned around brands in the past of prior companies. Do you feel you can do the same here? Are all options being considered? Thank you..

Okay. Peter, thank you. Thank you for your questions. I'll come to Dieter shortly. Maybe just a quick comment before I throw to David on Vaccines. It's been an absolute pleasure to get to know the Vaccine business since I joined the company. And whilst I understand it's a long development cycle, the opportunity is in how we're approaching it.

I think it's going to be very interesting for what happens next. Maybe I'll let David take a shot at the Donald Trump comments..

Sure. Thank you, Peter. We welcome of course the executive order, because it helps prepare the U.S. even better. The U.S. is one of the best prepared nations in the world in terms of pandemic preparedness. And we have been longtime working with BARDA to help be really geared up for a pandemic outbreak.

Now the executive order puts an accent on new technologies and here we are well placed. You remember that we have acquired Protein Sciences, which has a recombinant technology.

So we are working as we speak with BARDA to discuss how we are going to expand the footprint in the United States, how we can also prepare adjuvanted versions of this and how we can engage together into the next generation more broadly protective flu vaccines. So we really welcome that executive order..

Thanks, David. As for working on other brands previously, I mean enjoying getting to know the opportunities around Praluent. The access is always a double-edged sword. You do get opportunities even when having slightly lower access than the previous year.

Maybe Dieter, you want to make a comment?.

Yes. Peter, the access obviously is a balance. We -- while we strive to continue to improve access. We are focused on utilization management criteria, which we have significant progress on. That's reflected in the substantial volume growth we have seen in the U.S.

with 9% -- 39% volume growth that does not offset completely -- not completely offsetting obviously the price reductions. And we have seen that to full impact during the year. And the -- we're focused on profitable access improvement and we have hinted towards that already.

As we said, we expect that the pricing decline to stabilize as we go forward hopefully reflecting -- it won't -- that wouldn't be reflected in our sales growth going forward..

Thanks, Dieter. I think it's quite a mature response to be honest on the profitable approach to access..

Thank you..

Thank you. Your next question comes from the line of Florent Cespedes with Societe Generale. Please go ahead. Your line is open..

Good afternoon, gentlemen, and thank you very much for taking my question. Few quick ones. First on the pipeline following the discontinuation of the cemiplimab and your CD38 combo. Why are you so confident and you continue the development with atezolizumab? And follow-up questions on the pipeline.

Could you share with us, which are the most important milestones on the pipeline? You mentioned that you will be -- there will be three important proof-of-concept studies readout by the end of this year. If you could elaborate on this would be great. And my second question for Olivier regarding China.

Could we have more color on the pharma sector audit process review in this country? Many thanks..

Okay. So we'll come Olivier to you. It sounded more like three questions you asked. But Olivier will come to you shortly. John, question on cemiplimab and isatuximab. And then maybe just pick one or two milestones that are on your mind that would be great..

Yes. Thank you for your questions.

With respect to combining our CD38 antibodies isatuximab with PD-1 or PD-L1, the hypothesis we're testing there is that CD38 plays an important role in the tumor micro environment contributing to an immunosuppressive state and therefore could be a essentially an immuno-oncology opportunity beyond my the role of CD38 as a direct target in myeloma.

Now, the tumor microenvironment of every kind of cancer is different. Really quite unique depending on the type of malignancy and that's why we laid out a broad-based program around eight different types of malignancies to test that hypothesis in a number of context. The first couple of indications prostate and lung have not confirmed the hypothesis.

But we still feel there's merit to continue that work in the other indications. Several of them are hematologic malignancies, for example, where the tumor microenvironment is very different than solid tumors. And so we'll see those studies to their end. They're small signal seeking studies to test the hypothesis.

We've said from the beginning, it's a low probability of success, but we feel that the data -- the preclinical data from our own labs and from the medical community merits that we test the hypothesis in a lean way that would help to determine whether there is a broader opportunity for CD38 antibodies like isatuximab that have unique properties due to the epitope that we target relative to other competitors..

John, a couple of milestones that you're looking out for in the assets..

Well, maybe just to reiterate what was said in -- during Paul's remark is that, our estrogen receptor degrader, our SERD molecule will be completing its analysis in the monotherapy. As the monotherapy in late line, these are patients who have already failed typically three or more therapies. We're encouraged by the early data.

We'll have a more complete data set by end of year and then be poised to move forward. We have already based on the data we've seen, begun our first randomized study as monotherapy in late-line breast cancer. So we're encouraged by the early results.

But we'll have a more complete data package that will allow us to efficiently declare proof-of-concept by end of the year. So that's a very important readout for us. Also mentioned was the anti-IL-33 in COPD. As we know COPD is an indication with great unmet need. No biologics really have been able to crack that problem so far.

We'll have in middle of November, first of our POCs studies Phase II studies. We'll readout and we'll see how we're pairing at that point. So maybe I'll just mention those there's a couple of examples of important readouts..

Thank you, and then, Olivier, China?.

So, Paul, so this Ministry of Finance audit is a sector audit that is currently being performed. The auditors have finished their work but we have not yet received the report. There are more than 78 companies to be precise that have been involved in this audit. Our understanding is that the ministry of finance wants to understand how companies operate.

And the objective of this audit is very much policy shaping. At the moment of time, where there are many, many things that are going on in China. It's oriented and better understanding how companies operate, how the manufacturer produces products, how they promote products. So it's a deep audit that is very much sector-oriented.

And we will be waiting the outcome in terms of policy shaping in the future months..

You want to add something....

Jean-Baptiste..

No. Nicely, you've said it all. It might have some tax impact for the sector in China. But we have no idea so far. Waiting for the report..

Great. Thank you..

Okay, thank you very much.

Thank you. The next question comes from the line of Graham Parry of Bank of America. Please go ahead. Your line is open..

Okay, thanks for taking my question. So, first, again, another one on China. So, obviously, you're talking Plavix and Avapro likely to decline 50% in 2022 due to VBP. Just wonder if you could help us understand the volume and price mix that assumes? And then how you expect that to play out in subsequent years.

So you talked about winning volume to go back to growth afterwards, but what essentially prevents this being a multiyear decline for each of these products? And which products do you think might also get into an expanded program as we roll forward through the years? And then a second question for Paul.

I think there's always been an external view that executive management of Sanofi is being somewhat hamstrung by the Board.

And I know it's too early for you to discuss your specific strategic objectives at this time, but perhaps if you could help us understand your view of your independence and freedom to execute change in the business and really what your mandate that you've been given from the board is? Thank you..

So, Graham, as always, thank you for your pertinent questions. We should -- we'll come to the price volume piece in China. I mean, I think, just by way of a setup, this is new for everybody, right? First of all, secondly, one of the absolute world-class strengths in this company is help manage emerging markets and in particular China.

I think our opportunity to get outside of the big city and drive volume is probably one of -- we're at least in the top two companies to be able to do that. We've suggested that approximately 50% of revenues will be impacted.

But there is some room in that depending on when the provinces roll out their individual programs because it's not all on one day.

And I think that's a perfect opportunity to ask Olivier, where does the volume growth come from?.

So, we deeply think and of course you can imagine that we have taken a sound decision and that's our decision to participate into this bid. It's based on our ability to grow significantly volume. We think that within 12 to 18 months, we should be able to grow volumes like 60%, 70%, 80%, 90%.

And we have a couple of data points now that are quite interesting here. Based on the experience in the seven plus four cities, we have been observing on products belonging to different key area. We have been observing significant increase in terms of consumption.

The second element that is very specific to China is that, the consumption per capital for example on products like Plavix is significantly below the rest of the world and significantly below the countries like -- other emerging countries by a factor of one to two or three or four.

And our performance for Q3 have been a little bit higher than we were anticipating, just due to the fact that we are tracking very nicely in the counties where we continue to see a lot of potential for volume growth in the future. The implementation plan and as Paul mentioned, a little bit earlier this is new to everybody.

The implementation plan province by province is not known. Also, we are starting to see provinces getting organized to be in a situation to execute VBP during the first quarter. But you would understand that of course depending on when it's going to impact into '20, the outcome could be different.

But what you should keep in mind is that, our assumption is that, we will be able to get back to growth within 12 to 18 months. And of course, we are getting organized for that. And in the last few months, first on the manufacturing standpoint, than we had anticipated in order to be in a situation to cope with those volumes.

And second, of course, the go-to-market strategy is going to change very significantly in a sense that it's going to be very much about being present in the bidding offices both in the provinces in the hospital to get the impact in terms of volume through the pull-through.

Long run of course, our growth in China is going to be very much driven by our new products with 10 products that are being submitted within the next 14 months until the end of 2020, 30 products, our indication being submitted by 2025. And of course the big thing here is Dupixent.

To respond precisely to your question on could VBP be expanded to other brands? Our analysis is that, what is going to drive our growth into the future for the non-VBP product is very much injectables.

And we think that we have still a lot of runway on Plavix on of course launches on Toujeo when it's going to be put on the market and of course Clexane. And since the beginning of the year we have allocated significant resources and we see clearly an acceleration on those brands.

So, given the specific status of those brand being injectables, we feel that our VBP like is improbable. The only exception could be in specialty oncology. But the government for the time being hasn't made any call..

Thanks, Olivier. So, just -- we shouldn't underestimate the 10 submissions for sure. And again, I don't know a company better place to pull-through on volume. The question is how fast. And we think more outside of 2020 and beyond. So, I said we'll update you. As for your other question, Graham, I think it was about freedom to operate.

I think was the sort of context of my relationship with the Board and what have you. The conversations that I've had all along from before joining and right through up until as recently as yesterday have been constructive, positive and forward-looking.

I think -- as I get to know the Board, I'm struck by how well informed they are on what we're doing and not only that, how to bring their experiences to bear. I found it incredibly open and only about trying to build a successful organization for the long term and that's the Board and the Chairman.

Of course, we will know more as we go along and as we make choices, but I think so far I've been really pleased with the level of interest and governance and it's very well balanced and in the interest of the company..

Thank you..

Thank you. Your next question comes from the line of Matthew Western of Credit Suisse..

Hello, it's Jo Walton here. I've got two quick questions please. Firstly, I wonder if you could tell us a little bit more about the penetration of Dupixent in the key areas where you feel you've achieved as much penetration, just give us a little bit of background.

And particularly, how it's rolling out in Europe and whether you see any price pressures developing as you add incremental indications to the product? And my second question is for your CFO. Historically, you've told us that you think you can keep the operating expenses to about 1%.

You've obviously done a lot better than that because you're actually managing to get them down at 1%. I wonder if you can tell us a little bit about some of the things that you've perhaps found easier to do and give us some sense as to whether this is a growth rate. This is now a reasonable ambition for future years as well. Thank you..

Thanks Joe. Sorry I think you were wrongly introduced as Matthew Western. But thank you, nonetheless hope we'll get to Matthew too. For dupilumab I think Bill I'm probably going to come your way. I'm not sure how much detail we normally share on penetrations. Maybe a headline for me.

The biologic penetration of eligible patient populations is chronically too low and there's a huge opportunity right across all indications. And as for us, we've created a paradigm in atopic dermatitis. We'll go on to do that in other indications too. I think the scale and scope of the market is significant.

We hope to look at dimensionalizing these things as we go through December 10. Bill maybe a comment on that and maybe on pricing for fallen indications..

Yes. Let me just -- Jo how are you? Let me start with pricing. To-date the innovation of Dupixent has been recognized everywhere in the world. This is -- again as we transform to a best-in-class -- first-in-class product organization. I think that Dupixent is a perfect example of that because it still is on a worldwide basis.

Securing the reimbursement that we had hoped for it's even exceeded that. So good news there, regarding the penetration of Dupi in all the key areas. We don't have specific numbers to give. But let me just try to contextualize it a little bit.

If you -- the way I would describe Dupixent across all indications at this point is that, we're at the very beginning. And as Paul mentioned, we are with this quarter on a greater than €2 billion annualized run rate with aspirations of being a mega blockbuster. And we're at the start on really all the fronts.

Atopic dermatitis, it is a indication that didn't have advanced therapy in the past. And Dupixent is off to an extremely strong start and continues to have strong performance against other biologic launches in other dermatology indications. And we see that around the world in each of the markets.

We've seen -- we've chosen Cosentyx as a comparator and we're anywhere from 3 times to 7 times the launch pace of that biologic and dermatology which is -- was a very strong launch. The other piece, I would mention in asthma and Paul commented on this as well is biologics penetration has been historically very low.

A lot of this has been because pulmonologists haven't had the means to do in office or the interest to do in office injections. The at-home profile of Dupixent and just the clinical profile of Dupixent has really led to an acceleration with pulmonologists as well.

And when you go to 0 basing the launch curve, so comparing us against all the other biologic launches, today we are the number one launch in -- biologics launch in dermatology. We're the number one launch in -- from NBRx again in asthma. And if you look at the specific audience of allergists, we are the number one NBRx biologics across all of allergy.

So I think it's early. We're off to a great start. We'll spend some more time on it in December. But we're -- penetration is low at this point with lot of room to grow..

Thanks Bill. As you can imagine Bill enjoys making comparisons to Cosentyx which I remind him was a great -- still doing well. So Jean-Baptiste questions on cost saving the program overall and the sort of balance.

I hope you can share with people that -- the sort of underlying commitment to lowering our cost to do business, but how we balance out with not missing opportunities?.

Yes thanks. Effectively and it's a good example in Q4 of this year. We are looking at pushing harder on DTC campaigns for flu vaccines in the U.S. for instance. And we are also increasing our cost on the various functions of Dupi. So, what's important for us, and where we -- under Paul's leadership we want to take it one step further.

It's a good understanding within the teams of why we are doing it, by better understanding our priorities. So I'd be very happy on the 10th of December to give you more color on the levers we pull to reach that.

But I can tell you already, that when I'm travelling through our different subsidiaries across the world, I can see that it's happening within the teams. It's not a superficial thing happening at headquarters. It's really something that people start to understand these smart spending activities. And it's quite good to see.

I'll come back with more details on color on the 10th..

Thanks, Jean. I think, I'd just echo that last point. I think that, I've been around parts of the globe too. And I think people are getting a deeper level of understanding. And they will do as we go through our strategy. And our priorities about what reallocation like. And what saving in some areas to invest for growth in other areas really looks like.

So it -- we've sort of done the hard part, I think, upfront. And now we'll do the clever work to make sure we can accelerate growth..

That’s only question I have..

Thank you, Joe for the question.

Operator, next question please?.

Thank you. Your next question comes from the line of Richard Vosser with JP Morgan. Please go ahead. Your line is open..

Hi. Thanks for taking my questions. Two please. Firstly, just clearly we heard the good growth from Dupixent but there are some oral products on the horizon maybe fevipiprant asthma and the oral JAKs in atopic dermatitis. So, maybe you could just give us your perspective on the competitive positioning and threats posed by those.

And then second question, just going on to the pipeline. I noticed early you brought another CD38 into development. That's quite a long way behind both isatuximab and Darzalex. So just, if you could give us your rationale and thought process there as opposed to investing in other areas. Thanks very much..

Thanks, Richard. I'll come to John in a moment to answer the question. And I think the question about Dupi about oral challenges between fevipiprant and JAKs. I think, we'll wait and see what happens with the data readouts on fevi. But let's just also remind ourselves that Dupi sets a very high bar on efficacy.

And its safety profile is frankly extraordinary given the nature of the science. So I think there is a -- I think, there's just a very high bar. But I'll let Bill comment. Plus on the JAKs, I think there is some deeper thinking that needs to go on around their own safety profiles.

It's a very intricate balance to launch an oral in -- where safety and efficacy have already been set. And where you are -- where perhaps the side effect profiles are less convenient. But Bill, maybe you have a….

Yeah. No. Paul, that's a great setup. I think that, just to put it in perspective there's now over 125,000 patients globally that have been treated with Dupixent. So it's got a very big head start. And Paul also mentioned, the 76 -- 76-week long-term safety data which again showed nothing new from what had been seen in the clinical trials.

And this whole notion of a pill, a pill's great, if a pill is really effective and really safe. And as we think about the dermatology audience, we know that safety is a really important aspect of product selection as well as efficacy.

And Dupixent has time and time again in different age groups geographically, shown a very strong efficacy not only in clinical trials but in the post-marketing setting as well. And clearly have done the same with safety. So, I think that, we have to see how those profiles of the JAKs and AD emerge.

I think that, our expectation is that there's going to be a class labeling that will be part of those new JAK labels which we all know some of the challenges that have been seen there. So we feel very bullish on Dupixent's ability to continue to compete. We think that we're the best drug.

We've got a big lead and we're only going to generate more and more data along the way. I think, it's going to be really tough for somebody to come in. And we're not going to let somebody come in. And take it away from us..

Thanks Bill. Well said.

John?.

Yeah. Thanks for the question. Indeed, we did put a next-generation CD38 into the clinic. The rationale behind these next, wave of CD38 antibodies is to ask the question of whether they can rescue patients who have failed a frontline CD38 standard of care antibody.

We've engineered into these molecules enhanced properties that enable them to recruit immune cells to attack the malignancy in a more amplified way. The first of those has recently gone in the clinic. We have another one coming along behind that that uses yet another immune mechanism.

What we know so far about mechanisms of resistance to the standard of care CD38 antibodies, is that the levels of CD38 on the myeloma cell are reduced. But CD38 still remains on the myeloma cell, however at lower levels. So the target is still relevant.

And we feel there's sufficient retained expression for most patients that we can still go at that target but with these enhanced antibodies. So there would really be an attempt to rescue patients who failed a frontline standard care agent..

Thanks, John. Next question..

Thank you. Your next question comes from the line of Steve Scala of Cowen. Please go ahead. Your line is open..

Thank you. While it is on Slide 37, fitusiran is not shown on Slide 40 in the R&D milestones. Phase III data and filing was expected in 2020. So is this still on track? Or is Sanofi less committed to fitusiran now? And secondly, regarding the flu vaccine phasing curious why Sanofi was delayed while a competitor did very well in the third quarter.

Is this an execution issue? Or is there some other reason to explain it. Thank you..

So thanks, Steve. I'll let, David in a moment explain why it absolutely wasn't an execution issue just a sheer position of being the biggest player in the market. John just before we get to fitusiran, I will add that it's a really interesting asset we have in this space.

There is a -- it's clearly as we -- as I get to know this area there was a large group of patients that were previously thought to be stable in the factor space that got moved to Hemlibra and other things for a combination of reasons non-factor or convenience, which shows how dynamic this patient population actually is given the disease and administration burden.

So as I get deeper, I get more excited about what could be on offer with fitusiran. But I'll let John talk about the regulatory milestones..

Absolutely. Well thanks for the question. No, the company Sanofi we remain entirely committed to fitusiran. We do feel it's a highly differentiated product. It offers a subcutaneous convenient delivery route for those patients who choose to go with a non-factor solution.

And as you know it is relevant for both hemophilia A and B with or without inhibitors, so really has quite a broad indication possibility. And with the caveats a monthly subcutaneous dosing with a low volume 1 cc and less demand around cold chain because of it being a synthetic RNA sRNA drug.

So for that reason we remain very committed to this molecule. The recruitment of the studies has gone slower than planned. If you may recall that this was this studies were transferred from Alnylam to us. And as perhaps inevitably happens during a transfer a number of things were delayed, a variety of issues that I won't go into here.

But to make a long story short, we have made every effort to try to restore the recruiting time lines. Recruitment now is -- has picked up and we feel like we really now have momentum. The study is about 2/3 recruited right now. So we still have work to do. We will be a bit delayed probably by a couple of quarters.

But it sort of is what it is due to the transfer and all the logistical issues that occurred in the context of that.

But we're excited about what the potential could be and expect that the data will be in probably middle-ish of next year and we'll be in a position then in the second half of next year to share the results from these -- this very broad clinical program going across hem A, B with and without inhibitors..

Okay, John from one of the original team on Hemlibra. And it's great to have the experience we have as a leadership team around the table on what this -- you want to make a comment on why just our sheer scale perhaps is what took a little bit longer..

Thanks, Steve for the question. When you look at how well you're performing on the flu season, you need to look at different factors. One is time to market. One is how many doses are you going to sell in total. And one is are you able to actually sell differentiated doses, which have a higher price level.

So when you look at those three, what we can say is that on the timing we have seen kind of GSK come out of the bar, the fastest. But we need to remember that they have only standard dose flu vaccines. The two other ones [indiscernible] and ourselves, we have a bit more complex vaccines.

We are the only one actually having a high-dose vaccine, which consumes three to four times more of the antigen. So when you prepare for the flu season, it's a more complex manufacturing, that's a small disadvantage. The big advantage is that you're selling differentiated vaccines, therefore at a much higher price, because they offer more value.

And we are doing very well against our internal, let's say road map and against also the preorders that we had, which typically start being finished in March and April. That's when you know how much gets preordered. Then you get some additional orders during the season. We're doing very well there as well.

And then you need to actually look versus are you delivering now according to the shipment plan that you have had. And here we are doing well as well. So, overall, I think this kind of quick out of the bar in effect is not going to be very relevant to us, because everybody was affected by this later strain determination.

And I think we're going to have a very good flu season overall this year..

Great. Thank you. I think it's just worth repeating again that we expect things to rebalance in Q4 and we expect 2019 fill to be higher in 2018. So, thank you David for being so complete on the response.

And maybe the next question?.

Thank you. Your next question comes from the line of Tim Anderson of Wolfe Research. Please go ahead. Your line is open..

Thank you very much. I'm hoping to just get your preliminary view of the Consumer Health business. I'm sure you'll address this in December. Any sort of preliminary view you can give us would be helpful. Second question goes back to Dupixent and competition on various fronts and of any brand basis.

So my specific question here is really on abrocitinib which is Pfizer's product, because it's being run in a head-to-head trial and that's against dupilumab. And that's supposed to report out maybe by the end of the year. It's really hard to see how safety is going to be as good as dupilumab.

But on efficacy, I'm wondering what they may be able to show maybe by the design of their trial. They seem to be messaging that they could have a faster speed of onset and maybe better introduction, which they say is important in atopic derm.

So I'm wondering when you look at that particular trial and that particular program on the efficacy front, what do you think they may be able to show they're better at? Thank you..

So I'll let Bill answer in a moment. As for every CHC as for every single part of our business, I've just been getting up to speed. I'm equally as interested in a deeper understanding of our work on dupilumab as I am in CHC, as I am in vaccines, as I am right across every aspect. We're spending time as a team looking at where our opportunities are.

And we will share more of those in detail on December 10. I can assure you that. So Bill, there was a question I think on Pfizer's JAK, I think it was..

Yeah..

And there was a recognition, I think that the safety profile not be great, but there is -- they're trying to say, there's speed of onset..

Yeah. Tim thanks for the question. Yeah, you're absolutely right. It's -- they're looking at speed of onset around itch at the two-week point. And so we'll see how those read out. I think just a couple of points to make. First of all is atopic dermatitis is not a two-week disease.

It's a chronic disease and how you perform over the long-term is going to be important not only from a safety, but an efficacy perspective as well.

The other piece I would report out is just what we've been hearing from patients that have been treated with Dupixent is that there's a very rapid onset of action and people have commented that after the very first injection they start to have a decrease in itch. And certainly we've seen that in the clinical trials too; it's rapidly onsetting.

So I think that that's certainly a small piece of a much bigger problem, which is the treatment of atopic dermatitis. And we think overall again as sort mentioned comments I made before about the overall safety and efficacy profile, safety is clearly going to be an issue in atopic dermatitis with dermatologists.

And we feel we have the best product from an efficacy and a safety perspective..

Thanks Bill. Very clear. I think if we -- if the analysis is correct and if the class ends up with a black box warning, then we have to be honest with ourselves particularly in dermatology.

If you can get the efficacy with a very, very good safety profile particularly when you look at these patients a lot of them are younger than you really don't want to -- you really have to be very thoughtful about that. So I think we understand the competitive set well enough to know what needs to be done.

Maybe we've got time for another couple of questions..

Thank you. Your next question comes from the line of Wimal Kapadia of Bernstein. Please go ahead. Your line is open..

Hi, great. Thanks very much for taking my questions. Wimal Kapadia from Bernstein. Just following up on Graham's earlier question on China.

Can you talk a little bit about the earnings impact from the drop in sales for Plavix and Aprovel in 2020? Are these products above Pharma division margins and are Sanofi taking any measures to reduce the earnings impact for next year? My second question is just can you talk a little bit about the current OpEx spend trends within the Regeneron collaboration specifically? How should we think about the R&D and SG&A spend moving forward? And have we actually reached peak OpEx spend within the collaboration on an absolute basis? Thank you very much..

Okay. Wimal, thank you.

I think we'll first of all talk to Jean-Batiste a little bit about the China impact of Aprovel and Plavix on earnings? Do you want to make a comment on that?.

Yes. As we've disclosed in the past, the level of gross margin in China is accretive to -- globally to Sanofi. And so it will have an impact on 2020 that's for sure. We are not going for the reasons that Olivier Charmeil gave just before we need to know exactly what's going to play.

What we know as of today is that we are placing our self as a volume player to get a clear rebound of our growth in China from 2021 which is a good position to be in. So, too early to give a precise impact on earnings on 2020..

Olivier, do you have anything to add?.

No, I will just add that we are shifting our go-to-market strategy and this positive process started in the last few months. And the second element is that since the beginning of the year, we have reallocated significant resources behind our growth driver and we are starting to see on some of the brands an acceleration further to this reallocation..

Yes good. Thank you. And just to repeat what I said a few times already which is this is new ground for everybody. We've tried to give a sense of a potential impact. But I think we have to accept that when you go into these tenders, you understand what margin you have and what's expected on volume and what breaking out of that would look like.

I think we are betting on ourselves a little bit. And I think again we'll adjust as we go. We're communicating further bids on those numbers. For OpEx spend trend and R&D with Regeneron, I would say overall with the relationship, I think we're adjusting between brands. And I think that has been very helpful.

I don't know whether Bill you had a specific comment to make?.

No, look just in the context of Dupixent, again, thinking where we are the broadest launch that we have is adults with atopic dermatitis where we're launching literally around the world with several more markets to launch even in 2019. Asthma, we are just getting started. We have only two markets in Europe where we're launched.

So, Europe still has to roll out. Otherwise, it's really the U.S. and Japan. And then now with the recent approval of nasal polyps in Europe, we'll be launching there as well.

So, we are still in the process of launching a mega blockbuster on a global scale and we will continue to invest to make that the mega blockbuster that we expect it to become and we will support it with clinical trial work. So, there's more to come with some details.

But overall as you know we've got a lot to do with Dupixent to make it the brand that it can become and we will adequately invest..

Yes. And just maybe to add as well these are specialty deployments in markets across the world. They're not large primary care field deployments. That can be 10s and 15s and even in large markets.

So, one thing I can assure everybody is that whilst we are very considered about how we deploy, we expect to deploy to win and we have to set ourselves up to achieve that.

Maybe we have time for one last question?.

Thank you. Your final question then comes from the line of Thibault Boutherin of Morgan Stanley. Please go ahead, your line is open..

Yes, thank you for taking my question. One question, the gross profile in China in particular.

Could you walk us through the new product growth opportunities in China in terms of significant new filings launches and energy and reimbursement opportunities which you expect could offset the pricing pressure on Plavix and Avapro? So we saw recent approval in the Genzyme business including Aubagio and Myozyme.

And I think that Aldurazyme Praluent and Fabrazyme are currently under review by the Chinese Healthcare Authority. So, in connection with that, I think Paul you previously talked about investing in digital in China.

And in combination with a significant unmet need for Dupixent in AD and in asthma, what do you think about the growth profile in the medium term in China after the results of next year?.

Okay. So, maybe I'll start with that and offer Olivier the chance to talk about the 10 submissions. And I think we'll provide by the way more color in December as to the -- what we hope to expect.

On the digital piece, I think what sets China apart in many ways is the fact that there isn't a traditional infrastructure of primary care physician office and access to healthcare for the entire country. So, you know probably as well as I do that there's 500 million-plus people who really don't have everyday access to healthcare.

Why is that important? That's important because in many countries when you introduce digital, you're trying to undo or replace a sort of terrestrial alternative and that can take a lot of energy and effort.

In China, it's -- we're being encouraged and rightly so to leapfrog to what does getting access to medicines look like in a digital heavily smartphone-penetrated 4G fast-moving rural world. And that means that there are chances to bring AI and algorithm-derived triaging of patients much earlier in the equation.

So, we have a very strong digital presence in China and collaborations, a very strong Tier two collaboration, which is what excites us about helping use low marginal cost initiatives to pull in patients on a large scale, which is one of the reasons why we felt comfortable going into tender. Now there's a lot of learnings along the way.

But there is a very favorable local environment to trying to make that work. And we'll play our part in that I think.

Olivier, if you'd like to talk a little bit about the submissions?.

Yes. So, where we see the growth in the upcoming quarters for our business in China beyond what I mentioned a little bit earlier which is the acceleration of the growth of products that are injectable like Lantus or Flexon where we see -- and Renvela where we see significant potential for growth with very strong double-digit growth.

So, regarding the submission in the next 12 months, it's definitely 2-0. There are a couple as you mentioned of rare disease product. Dupixent is going to be an important play here.

We are expecting to submit in the upcoming months with a potential approval at the end of 2020 beginning of 2021 with a very fast track to reimbursement, given the very strong unmet need. We are in discussion on the reimbursement of Aubagio and we have three products that are currently being reviewed by NRDL.

And we are expecting to get reimbursement for Aubagio and better. If we are looking a little bit ahead of the curve beyond 2021, 2022, we are expecting to get Soliqua in 2021 to 2022. And of course the new products from oncology are coming between 2023 and 2025..

Thank you, Olivier. So, I think, we'll probably say that's the end of the questions. Maybe just some closing a couple of comments. I'll repeat what I said upfront. I'm very excited. I'm privileged to take this role at Sanofi.

I can tell you after eight weeks, as I get a bit deeper, I see plenty of opportunities and we look forward to sharing with those, with you in detail in December 10, if you can join us.

There's some incredibly talented people in this company, some great opportunities and I think I and the team have a lot of energy for what happens next and the great next chapter. So, thanks for joining us for the call today and we look forward to seeing you in personal, we hope on December 10..

Thank you. That does conclude your conference for today. Thank you all for participating. You may all disconnect..