Ladies and gentlemen, thank you for standing by. Welcome to the Sanofi fourth quarter and full year 2019 earnings conference call. I would now like to turn the call over to Felix Lauscher, 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 fourth quarter and full year 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 contain 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 document on file with the SEC and also our Document de Reference 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, John Reed, Executive Vice President, Global Head of R&D and Jean-Baptiste de Chatillon, Executive Vice President and Chief Financial Officer. Paul will update you on business performance. After which, John will provide an update on R&D. Jean-Baptiste will then review the financials.

After concluding remarks, we will close with a Q&A session, during which we will be joined by members of the Executive Committee. With that, I would like to turn the call over to Paul..

Well thank you, Felix. Beautifully done. Welcome to the call of Q4 and full year. We have got quite a bit to get through. I think news flow is particularly good and we went into a bit of detail. I am, as Felix said, joined by wider members of the Executive Committee. So Olivier Charmeil, which if we need to focus on China.

We have Bill Sibold for Dupixent and immunology and the specialty business. Alan Main in consumer health, David Loew on vaccines. And Dieter Weinand for primary care and diabetes. So we are well represented and we look forward to getting through the conversation. So let's hit the key achievements.

3% on the topline, 7% on EPS, I think strong performance, lot of good discipline from the organization to deliver those numbers. Our pipeline innovation continues at some pace. So there is a little bit of interest in the BTKi. John will go into some detail in his session.

But I think as you will appreciate, we want to save the full data set for the presentation at up and coming Congress. On accelerating efficiency, we were almost a full point down on operating expense.

So that is the discipline that I referred to and it is going to essential that we continue with this level of reallocation of resources and discipline to deliver on our short, medium and long term objectives. That long term objective in terms of BOI margin were about 120 basis points for the year. I think 25.8% to 27%.

And you know that we are tracking to our overall goal of 30% in 2022. As for the Executive Committee, it is worth sharing with you on the next slide a little bit of an update. We went through the strategy and prioritization exercise as an ExCom throughout the back end of last year. I will just say simply, thank you to the ExCom for thinking enterprise.

As we outlined this strategy, it was quite clear that we wanted to allocate more of our central expertise into our business units and increase the accountability. With that, the impact was that we became a reduction other up from 14 to 10 Executive Committee positions. Of course, there was some personal impact that is structural.

I wan to thank those on the ExCom that will leave the organization but contributed in a very energetic way to making sure that we have a strong legacy from their work and we can get done what needs to be done over the future. One additional role perhaps in there is the Chief Digital Officer piece which was a hybrid role with medical.

What we have done is single it out. We have done that because I think we are a little bit behind in our agenda on the digital understanding and language capability internally. So in the short to medium term, that role will have a bias towards helping us improve our user experience and data science management internally.

We could skip on to the next slide. Thank you. Overall, you know, some very strong underlying performances. Specialty close to 23% and it heightened there 11% in onco and 7% in rare diseases, a very strong performance indeed. General medicines, whilst declining, I will talk about how it's stabilizing a little bit later.

We are beginning to see the impact of course of the VBP in China and the continued decline in diabetes, although moderating and I will touch on that. Vaccines' overall performance continues to stay within the boundaries of our mid to high single digit. Strong Q4.

Of course, there is a phasing and some other bits and pieces that we can get to but fundamentals stay strong in vaccines. And of course, consumer. I think recognizing that it's a little bit overdue making it as standalone and giving it agility and speed an optionaility and we took a hit on the Zantac recall amongst other things.

Overall, this is our new shape. We will report figures again in Q1 in this shape and we will give you figures per quarter for 2019 so that you can make a more accurate comparison. We will do that ahead of Q1. Moving to next slide and Dupixent, in particular, you know 152% growth, which is an incredible performance, a truly incredible medicine.

We will spend a few slides on that going a little bit deeper. Script trend up, TRx up over 100% already as we enter 2020. So the underlying demand is really where it needs to be. We feel that we are well on our way to delivering on that overall ambition that we have. We are annualizing at €2.7 billion. And you know, we are not even fully launched yet.

I think it gets forgotten. We will cover it that really we are principally only atopic dermatitis ex-U.S. and with asthma and other indications coming on board. So that's good set up. Vaccines, we talked about it. It was a very strong Q4, but the underlying is good. And then on the pipeline, so let's mention the BTKi for a moment.

I think, depending on what you read for the future value of the market in multiple sclerosis or indeed the B-cell depletion part of that, I think the general consensus would be roundabout $20 billion marketplace in the near term future for multiple sclerosis.

It goes within that depending on Ocrevus and other B-cell depletors, there is a chance that ultimately about half that market, maybe even close to $10 billion, will be in B-cell depletion. The PoC readout is quite an important moment for us. We have flagged it at our Capital Markets Day back in December. We hoped that it would get to a good place.

And as you have seen, it's met its primary endpoint and a safety profile within our expectations. So with that said, it will be the oral that crosses the blood-brain barrier in MS. We have shot at doing something incredible with the microglia for example.

So we think we are setting ourselves up very, very well indeed to do something outstanding for patients and something I would say transformational impact for the company if this comes through Phase 3 in the right way. At Dupi, just at the end and John will touch on this, we have three studies that have been kicked off.

So we feel that the news flow would just get stronger and stronger and stronger. So we mentioned the rollout of Dupixent. And you know, the last few quarters have been averaging an incremental Euro gain of over €100 million per quarter. Now, expectations are high. And I think it's also worth mentioning out TRx are strong.

There is a little bit of patient assistance reset in January, maybe even early February. So whilst we expect to see a little bit on the dollar side there, we are very bullish about what 2020 looks like. And we know we will gather momentum and we know underlying demand is very, very strong.

So we are launched in 34 countries, still only predominantly adult atopic dermatitis. We have got 89 more launches, I think, or something like that to go.

We are delighted the FDA has accepted Dupixent for priority review in the pediatric indication, not least for the children who will benefit, but actually you know this is just another reminder of how important safety is in this disease area and why it's important that physicians can have confidence as can parents and children in having the right safety profile.

And we think we are very definitely unique. We submitted in atopic in China and whilst we sort of transform our business in China towards a specialty one, that will play a significant part. Moving on. Biologic leadership for Dupixent across all specialties is a very real thing.

We are already number two in the market in derms and you think how long Humira has been around, I think we have a realistic expectation to be the leading biologic in the dermatologist's office. Likewise in allergists. We are already the leading player in NBRx and it reflects very well on the overall profile of this medicine.

And then finally in asthma and in pulmonology, time aligned, we are outperforming the IL-5s in this class. So I think what you have here is really unique medicine.

You have it at an incredible time with a rich news flow to come and you have what is market leadership position or specialty leadership positions that you really don't get to unless you have a winning profile. Just to go another slide further into Dupixent. The last slide on Dupixent, but I think it's worth spending a few moments on.

You know, we are really starting to put together the real evidence that matters to patients and to prescribers. You know, there has been a little bit of misinformation floating around from our competition that Dupixent has an effect after the first dose, after first dose. And that's across a number of important endpoints.

And in that we could include lesions, itch, quality of life. You know, this medicine works very, very quickly. Another reason why it's becoming the leader in each of the physician populations, but after the first dose and you could see that it's separated from placebo and I think it was CHRONOS, our pivotal study.

I just wanted to be in no doubt about how fast it works and the impact it has on patients. There is also a durability point, which I think the longer and more mature these markets become in biologics, you can see that this is a response that is maintained and over a long period of time, you have to think 148 weeks that you can see there.

And we have just added, I think it was Maui Derm where we presented the three-year data on continuous incredible efficacy. So you know, the foundation stones are very, very strong for what we are doing with Dupixent across multiple geographies, multiple indications and multiple specialty groups. Moving on to vaccines.

You know, as I get to know vaccines better, I am delighted and in some ways privileged to be involved in this part of the business. We are growing high single digit and beyond across every single area we play with vaccines. Two of our areas PPH and influenza, we are close to the equivalent of mega blockbuster status. We are close to €2 billion.

And I think that says a lot about how the business is performing in its run. We are very happy to see this broad growth. We may get to it in the Q&A.

But you should also know that the team has offered up its expertise in Coronavirus, coordinating with CEPI, with other government institutions to make sure that anything and everything we can possibly do, we will do. And we hope on one particularly strong that we have a meaningful initiative to be able to announce something in the next several weeks.

In flu, we have a very successful differentiation strategy. You know, improved vaccination rate is a part of it and it's very important that I think people understand that there's still some way to go actually in some markets to make sure those who really need to be vaccinated get that. And it's another opportunity for us.

And then on the value upgrade piece, we are expecting these to be a significant growth driver in the coming years and Fluzone High-Dose QIV launch in the U.S., Flublok and HD expansion to Europe where we are fully differentiated and haven't been available so far is going to be an essential part of that story too. Moving on to diabetes.

We have been in a double digit decline and not because of lack of excellent work. Our volumes have continued to be impressive but the price pressure, particularly in the U.S. has taken its toll. Now whilst minus 8% is still significant, it is moderating.

And I think that's an important piece to understand of our underlying business to know that the drags on the business start to slow down. So where we are moving on the topline is real growth that is not being weighed down and I look forward to getting to that point.

Just to point out the impact on that the VBP on Amaryl in China, we chose not to tender, didn't need to and any impact of that is already in our assumptions for 2020. The full year impact of the WAC reduction for Admelog from July 2019 and we may catch up in the Q&A on the risks of biosimilar competition across the glargine franchise.

All of it already contained within our thinking.

As for China, just starting with Amaryl but I think it's worth mentioning, just to take you back for a second, if you go back and look at what we said in Q3, we were quite explicit that there would be a Q4 impact on price that would be taken just because the price hasn't changed and the inventory was already in play and that's okay.

We are right where we expected to be. There were no surprises there. Now we guided to a 50% decline of Plavix and Aprovel family and we are again right pretty much where we expected to be.

I think it's worth saying and this is going to be a little bit more complicated because of course of the difficult and complicated challenge for China and beyond the borders with Coronavirus, as problematic as that is, we are trying to make sure that we can still support and provide medicines for patients across China. It is a priority.

We are pulling out all the stops, like I am sure all companies are. But a little bit of context. We started the year on the demand side, just to share some of the couple of comments, that we picked up strongly from the VBP brands. So while we are not declaring any type of victory, we did say at Q3, we hope to grow volumes throughout the year.

That will come and just gather pace. We hope that that will help us offset some of the loss just from the straightforward price cut. It's a little bit complicated because we like to show more as we go through quarter one into Q2. We will see how easy that is to tease out based on what else happens given the Coronavirus and the impact.

But we like to think that we started quite well. I mentioned that Dupixent has already been submitted but I should probably add Praluent and Fabrazyme were approved and that's again part of our move towards specialty over the long term in China.

As for consumer health, maybe I will just finish here to say, the Zantac impact is real and accounts for more than half of the 5% decline in Q4 2019. We are a multi-local business and it's one of our global brands. And we took a hit and we will work hard to get back to where we need to this year, that's for sure.

But with some healthy pruning and some, how shall I put it, some increased regulatory requirements, we will just use some time to make sure we get the business fit for purpose for the long term. Making excuses, we can do more. Our desire is to get back on or above the industry growth rate and we want to gather momentum as we go further along.

A last comment, not on this slide, but I am also very cognizant I am new into this role, I have spent quite a bit of time understanding what our environmental effort is in the company. In some ways, renewable energy, wastewater management, we are doing an incredible job at Sanofi and not a story well told, but it's reality.

We thought about sharing something on climate or CO2 emissions at this. We will actually defer it to Q2. No other reason than we would rather put out here some very real objectives that think we can deliver.

It's quite clear looking across our peers and further and more wide that there is a lot of aspiration and hope in where people are by 2025 and beyond. I think we are asking the team to spend some time to properly calibrate what is actually going to be achieved on what timeline and we will share that with you at Q2, if not at before then.

With that, I think I will hand to John Reed and I look forward to bringing this back around after John and Jean-Baptiste.

John?.

Thank you Paul. Well, good morning, good afternoon everyone. I am pleased to update you on several important pipeline advances at Sanofi. What's particularly striking is that these have all occurred since we met at Capital Markets Day, which I will remind you was less than two months ago.

This speaks to an R&D organization that is gaining real momentum as we deliver with pace on our new strategic framework at Sanofi R&D.

The updates I wish to share concern our brain-penetrant BTK inhibitor, '168, for MS, Dupixent, our best-in-disease antibody for Type II inflammatory diseases and our recently acquired engineered interleukin-2 molecule, THOR-707 for immuno-oncology. I will start the BTK.

As the saying goes, I don't like to choose a favorite among my children where in this case the molecules of the Sanofi portfolio are my children. But if I had to pick one item to highlight, it would be the positive proof of concept with our brain-penetrant BTK inhibitor '168, which is really tremendous news for us.

We spent some time at the Capital Markets Day explaining why we believe the profile of this oral small molecule could position it to be the best-in-disease treatment option for patients across the multiples sclerosis spectrum. Well, the new data we have in hand absolutely support our huge excitement. Let me remind you of the concept here.

So what is it that makes our BTK inhibitor different? First, when you look at BTK, we know from human genetics that BTK is required for B-cells to function. Second, we know from preclinical studies that B-cells are an important target for treating MS. With an oral drug like '168, we can shut off, but not kill the B-cells.

We think that modulating B-cells is preferable. So we do not kill the B-cells, we just put them to sleep for a while. This contrasts with the potent B-cell depleting agents such as Ocrevus, rituximab, epratuzumab.

This point of differentiation could potentially be highly important in clinical practice if the patient develops an infection while on treatment and you need their antibody response to bounce back quickly. So you may say to me, well, John, there are other BTK inhibitors in developments and some are already in Phase 3.

However, I would remind you that '168 has an advantage among more advanced BTK inhibitors because it crosses the blood-brain barrier. Remember, that we establish the CNS exposure in Phase I with receptor occupancy and CNS pharmacology studies. That brings me then to the second key mechanism for BTK.

In addition to its expression in B-cells, BTK is also expressed in resident inflammatory cells in the brain called microglia. Growing evidence suggests that these microglia cells are responsible for the persistent inflammation in the brains of MS patients, particularly in progressive forms of disease.

By inhibiting BTK, we can quiet the microglia as a second point of intervention in addition to silencing B-cells in both the periphery and in the CNS. Hence, we expect to improve upon the efficacy of other BTK inhibitors that are not brain-penetrant.

The final point of differentiation and this is also usually important is that '168 appears to be an exceptionally selective BTK inhibitor. And as a consequence, we did not see in Phase I the off-target safety issues experienced by some competitor molecules.

So the wonderful news today is that our hypothesis is supported by the results of the Phase 2 PoC data in relapsing MS. I am limited in what I can disclose today, but suffice it to say, we did meet the primary endpoint which was a reduction in the number of new gadolinium-enhancing hypersensitive lesions at 12 weeks as detected by MRI.

Additionally, secondary brain imaging studies also show promising results. The caveat of course is that these imaging endpoints are surrogate markers, but the results give us the confidence to go forward and we have pulled the trigger on the initiation now of our part Phase 3 trial program, which we expect to start around mid-year.

In addition to meeting the primary endpoint, the safety profile was consistent with what we saw in Phase I, suggesting a very well-tolerated medicine. Importantly, no patients discontinued treatment due to adverse events. And also, currently 95% of those patients eligible have rolled into an open line extension phase and remain on study drug today.

We look forward to presenting the full results in an upcoming conference. As an aside, we PoC with this molecule just one year after we submitted our IND and we anticipate starting the Phase 3 program less than two years from IND. So this demonstrates our renewed commitment at Sanofi R&D to delivering with urgency.

Where we see the potential to transform the practice of medicine, we will move fast and we will invest to deliver with a pace that reflects the urgency that patients feel.

The magnitude of the medical need is illustrated on slide 20, More than 1.2 million MS patients in the USA and EU part alone, of which roughly one quarter have progressive forms of disease where therapeutic options are few or none.

With the dual mechanism of our brain-penetrant BTK inhibitor with actions not only on B-cells but also on microglia and coupled with this potentially well-tolerated safety profile, we think we have the opportunity to deliver the best-in-disease molecule across the entire spectrum of MS including relapsing MS, primary progressive and secondary progressive.

We will now move swiftly with our comprehensive Phase 3 program. The data of the proof of concept study have defined our precise dose for the Phase 3 studies. And as soon as the pills are packaged at that does and then shipped to the sites, we will be ready to start.

You will also note from the slide that we are using Aubagio, our own medicine as a comparator in the relapsing MS study, which you can take as a clear signal of our confidence in this molecule. In terms of timelines, we are targeting regulatory submissions in the 2024 to 2025 time frame beginning with relapsing remitting diseases.

As you know, Sanofi has a proud tradition in MS but what you may not know is that Sanofi has the number two patient share globally. So we have the tradition and the expertise to make this potentially transformative drug a major commercial success, if we delivered a game changing profile to which we aspire.

Let's move now to the star of the Sanofi portfolio, Dupixent, on slide 21. We talked in December at the Capital Markets Day about the potential for patient benefit in additional Type 2 medium inflammatory diseases beyond atopic dermatitis, asthma and nasal polyposis, where Dupixent is already approved.

We have systematically explored potential opportunities for Dupixent using machine learning and AI, mining public data and leveraging our proprietary real-world evidence database that we call Darwin where we have access to around 450 million live medical records.

In dermatology, we identified three additional indications where we see a strong biologic rationale for testing Dupixent and where we have obtained anecdotal evidence of striking benefits from investigator studies. These indications are prurigo nodularis, chronic spontaneous urticaria and bullous pemphigoid.

Each of these is an allergic skin disorder that severely impacts the quality of life for patients. In total, we estimate there are over 400,000 patients with these conditions in the USA alone who would be eligible to receive a biologic. So the news today is that we have started registrational studies in each of these three indications.

The timelines of the studies are relatively rapid and if positive, we would be in a position to submit each for regulatory approval over the 2021 to 2022 period. And beyond dermatology, we are also starting a new study in bronchopulmonary aspergillosis and continuing our ongoing programs in COPD and in eosinophilic esophagitis.

We have estimated submissions in 2022, 2024 timeline. In fact, this year, we will obtain data from Part A of our pivotal study in eosinophilic esophagitis and we also plan to start a pivotal trial in eosinophilic esophagitis in pediatric patients.

To close here, we really are just at the beginning of our journey with Dupixent with the potential for this medicine become to standard of care across multiple diseases where Type 2 inflammation plays a role. Moving to slide 22.

I am delighted to welcome Synthorx into the Sanofi R&D organization and to move their lead asset THOR-707 into our Phase I portfolio. Our acquisition of the company closed on January 23. For those less familiar, THOR-707 is an elegant solution to the conundrum of IL-2.

A lymphokine that has beneficial effects in the new oncology setting, but which unfortunately also results in unacceptable toxicity.

What Synthorx achieved with THOR-707 was to conjugate irreversibly a single PEG chain to a specific site in IL-2 such that the molecule retains the ability to bind to the beta and gamma chains of the IL-2 receptor but not the unwanted alpha chain.

As a consequence, THOR-707 selectively stimulates proliferation of tumor fighting effector T cells and natural killer cells.

What it avoids, unlike some competitor approaches, is the alpha chain mediated stimulation of immunosuppressive regulatory T cells as well as the ILC-2 cells it stimulates eosinophils thus avoiding the vascular leakage side effects associated with native IL-2.

Access to THOR-707 provides Sanofi with the basis for multiple IO-IO combinations including essentially every IO we have in our pipeline as well as those of other companies. We see THOR-707 as an amplifier of the cancer fighting immune engine with broad potential for combination with other IO molecules.

To give specific examples, first we can potentially use this approach to enhance the activity of checkpoint inhibitors in patients with solid tumors.

To use a familiar automobile analogy, when you take the brakes off the tumor fighting T cells with a checkpoint inhibitors such Libtayo, unfortunately for many patients, nothing happens as they do not have sufficient numbers of T cells in their tumors. Essentially, they have no gas in the tank of the immune engine.

With THOR-707, the concept is to expand selectively CD8 positive killer T cells and thereby fuel the immune engine so that checkpoint inhibitors have a better chance of working. We expect to begin the Phase 1B portion of the ongoing clinical studies of THOR-707 very soon where this non-alpha IL-2 will be combined with PD-1 inhibitors.

A second example about which I am even more excited is combining 707 with our emerging pipeline of T cell engagers. These are multi-specific antibodies that bring the tumor and T cell together, activating the T cell and killing the tumor.

Adding THOR-707 should keep the T cells proliferating and help them to survive longer in order to get the job done. And then a third and final example arises from the fact that THOR-707 stimulates impressive increases in NK cells in patients.

So a clear near term opportunity is for us to combine this non-alpha IL-2 with our anti-CD38 antibody Isatuximab, which works in part by recruiting NK cells to kill myeloma cells. Together, this combination could potentially bring better efficacy to patients with myeloma.

On top of that, we have an emerging pipeline of bispecific and multi-specific NK cell engagers which help bring NK cells into the tumor. Again, we expect THOR-707 to amplify the activity of our NK cell engagers for both solid and hematologic malignancies.

In the interest of time, I better move on now but I hope it's abundantly clear that we are enormously excited by the multiple opportunities this molecule brings and the wider Synthorx platform for our IO portfolio. I am going to close now on slide 23, which shows the rich clinical and regulatory news flow we expect in the next 12 months.

Of particular note, with respect to first time new drug approvals, we expect to register two NMEs this year. Isatuximab, our anti-CD38 antibody for myeloma and sutimlimab, our complement pathway inhibitor for hemolytic anemia. You can see we have a lot to talk about over the period as we build the momentum in our Sanofi R&D organization.

And for this reason, I am delighted we will be able to bring you much more information in an R&D Day that we are organizing in June, which Paul provide more details later. So with that, I hand over to Jean-Baptiste..

Thank you very much, John. On slide 25, we delivered excellent P&L leverage in the fourth quarter, helped by the accelerated sales performance Paul described by our efficiency initiatives. As a consequence, the 4.7% increase in sales translated to BOI growth in excess of 20%.

You should note this leverage was achieved despite downward pressure on our gross margin from pricing and mix effects, including the VBP impact in China.

Our efficiency is clear in both the G&A on the R&D line which declined by 1.4% and 0.7%, respectively, in the quarter, while these reductions were achieved with increased investments in our key growth drivers and in our late-stage pipeline. The other line I would like to draw to your attention is other operating income and expense.

There are a couple of elements which I should mention here. In the fourth quarter of 2019, we recognized a one-time non-cash income related to a change in French supplementary pension regulation, but we also recorded one-off provisions in our cost of sales in Vaccine, along with a higher rate of product return in the U.S.

that you can spot in our segment publication. That's why overall, on the quarter, our BOI was not affected by one-time effects. This is a very solid and qualitative BOI delivery which makes us confident that we should pursue our margin expansion in 2020. Secondly, the OI line reflects our accounting for the Regeneron monoclonal antibody alliance.

Here, the outflow in the quarter increased to €241 million versus €65 million in Q4 2018 as the collaboration moved strongly into profitability.

I remind you that this net figure includes three components, Regeneron share of the profit and loss of the alliance, reimbursement by Sanofi of commercialization expenses incurred by Regeneron and reimbursement by Regeneron of Sanofi's development cost.

The breakdown of this component for the full year is set out in a new disclosure in our financial statements and we will provide this on an annual basis going forward. So moving back to the P&L and shifting below BOI. With a tax rate on share count broadly unchanged, our business EPS grew by close to 22% in the quarter.

Looking to 2020, we expect our effective tax rate to be maintained at around 22%. On an IFRS basis, fourth quarter EPS was slightly negative, reflecting additional impairment charges related to Eloctate and Zantac for €1.2 billion and €169 million, respectively.

The second impairment on Eloctate reflects a continued fall in sales trajectory compared with our expectations and takes the total impairment in the year to €2.8 billion. Slide 26 shows that our smart spending initiatives helped our BOI margin to improve by 120 basis points in 2019 to 27%.

But we have plenty of opportunity to drive further efficiencies across the organization and we plan to deliver an additional €2 billion of savings by 2022 to fund both margin expansion and net sales growth. Consequently, we are confident that we are on track to deliver our target of BOI margin of 30% by 2022.

On slide 27, we propose an €0.08 uplift in the dividend to €3 15 which represents the 26th annual increase. The growing dividend is part of our commitment, as you all know, since our last Capital Markets Day. On slide 28, I am turning to our free cash flow KPI, as defined during the Capital Markets Day in December.

Well, then I outlined our ambition to increase this important metric to around €6 billion by 2022, an increase of around 50% versus 2018. Well, looking at this slide, you could conclude that we have met our objectives three years early, but this is not exactly right really.

I am certainly thrilled to see the excellent response of our teams to our focus on cash generation because it's already a good success. And I mean it makes me very confident on the progress we can achieve.

But this achievement, however, in 2019 includes roughly €500 million of one-time benefits that really partially belong to 2020, especially earlier than expected flu vaccine collection from customers in the U.S. and later supplier payments in the U.S. due to a system issue. So please take it into consideration in your modeling.

So if we adjust for these factors, our free cash flow would have been approximately €5.5 billion on a normalized basis which is a good performance compared with the prior year and clearly puts us well on track to meet our 2022 free cash flow target. On slide 29, Sanofi met or exceeded each of its financial performance objectives in 2019.

OpEx efficiency and the over-delivery of business EPS, I think, speak to the new culture developing across the organization. On slide 30, we have set out full year guidance for 2020 business EPS to grow by around 5% at constant exchange rate.

You should note that this compares with the slightly restated base of €5 97 in 2019 as the adoption of IFRS 16 this year will reduce our historic business EPS by €0.02. With respect to ForEx, around 1% positive based on January average exchange rate.

When looking at your models, you should keep in mind that our growth profile during the year will be impacted by several important pushes and pulls. On the downside, we will have a full year impact from VBP in China. This will mainly impact year-on-year comparisons in the first nine months.

In addition, our CHC business faces roughly €120 million sales headwind in the first half as a result of the Zantac recall. On the upside, we expect strong growth from Dupixent and vaccines and growing efficiency benefits consistent with the objectives we highlighted at our CMD.

So taken together, these factors suggest that our growth will be weighted to the second half. In addition, you should note that we face a high base for comparison in the first quarter of 2020 as a result of the strong 22% growth we reported in China in Q1 2019. With that, I would like to turn the call back to Paul..

Okay. Thank you, Jean-Baptiste. Thank you to John Reed. Maybe just a last couple of comments. You know, 2019 has been a year of, I think, decisive actions across the portfolio. We are gathering momentum on the growth drivers. We are seeing some momentum in the pipeline.

It's a pleasure to spend a disproportionate amount of time on the science and we hope that going forward, as confidence builds and you see us continue to deliver on our financials, that we can spend even more time on the science with the news flow because that's, in the end, what it's all about.

We have simplified the GBU structure and we hope that that will turn into an enabler for increasing our momentum further in terms of operational delivery. We will push up in terms of the efficiencies and productivity gains. We have laid out what we think. We think we will get 30% in 2022. And you know, that is what we are aiming for.

And we will take the measures necessary to get there. Last but not least and John mentioned it, I think the R&D day in June, I think it's June 23 in London. Hopefully, that makes sense given the other events that are going on around the time and hopefully that's appreciated. We really look forward to spending time with people at that day.

John will be there with his team. You can see the bench strength. You can also get a sense of some of the magic that's going on beyond into rare diseases and other key therapeutic areas. I think that will be a really fascinating session well worth attending. So I think with that, thanks to the presenters.

We have the team here and we are happy to get into a Q&A..

We will now open the call to your questions. As a reminder, we would ask you to limit your questions to two each..

[Operator Instructions]. The first question comes from the line of Peter Verdult of Citi. Please ask your question..

Yes. Thanks. Good afternoon. Peter Verdult, Citi. Two questions, please. One for John and one for Jean-Baptiste.

John, can you just, on '168, tell us where you want to present the data, if all things go well? And when it comes to some of the side effects that are reflected, your competitor BTKs, namely elevated liver enzymes, can you just confirm that that has not been a feature of the data that you have produced so far? I realize you can't go into the data in too much detail today.

But just on that point, any comments you can make? And then secondly, Jean-Baptiste, on cash generation. Thanks for the explanation on the €6 billion and the one-offs. But even taking those one-offs away, free cash is still pretty impressive at €5.5 billion.

So can you just remind us where the biggest buckets of opportunity are and where your team is focused on improving cash generation at the coming quarters and years at Sanofi? Thank you..

So Peter, thank you for your question. I will hand the BTKi question to John, but the most important thing for us now is to make sure that we preserve the integrity of the data through its presentation. So starting off on a journey of showing bits and pieces is, I don't think, it would be really helpful to anybody. But I understand why you ask.

I think John has tried to give as much color as possible.

John, do you want to add anything else?.

I think the main thing, just to emphasize again, there were no terminations or discontinuations rather, in the study. All patients completed the full course. And of those that are eligible to move on, 95% have chosen to move on into the open line extension and are continuing on study drug. So we are delighted with what we have seen so far.

I can't comment on the particulars of the AE assessment. That will have to wait for a conference. And in terms of conferences, we would like to present it at the first opportunity. There are a few conferences coming up.

But that's all subject to the organizers and whether we can sneak into a breakthrough presentation or something like that on short notice..

Thank you..

Jean-Baptiste?.

Yes, Peter. Yes, effectively, it's a very good response. And you know, I apply things that I have done in the past at leading with the team and also with my colleagues, regular free cash flow meeting to really track where our cash is going. You know, it creates a real mobilization. Everybody understands about cash. It's very concrete.

And initiatives are flourishing all over Sanofi in subsidiaries and headquarters everywhere. So remember, of course, it's the improvement in BOI. Smart spending sometimes leads to improvement also in payment terms. It goes to CapEx. We are improving significantly our CapEx spend.

It can be small things like improving when our suppliers are delivering the good to us. DSO, it's really the traditional old tracking of the cash which is starting. It's just the beginning of the journey.

It's very important to us because without the growth we are planning to accelerate like in vaccines, like in biologics which are products with longer transformation time in the plant with a WIP inventory which grows, it's very important that we become very skillful in containing our inventories. We are not good looking to peers.

So we have margin for improvement and we are going to deliver this improvement in the next two years..

Thank you..

Thanks Peter. Next question..

The next question comes from the line of Jo Walton from Credit Suisse. Please ask your question..

Thank you. I have one on the multiple sclerosis franchise and one on Dupixent. On the multiple sclerosis franchise, I noticed that you have chosen Aubagio with your competitor for your BTK. I wonder if you can tell us how you are thinking about this franchise, in that your BTK won't come to the market until after Aubagio has gone off-patent.

And then you have also chosen a very tough competitor in the sense that you may have chosen against what will be a cheap generic at the time that you have that launch.

So if you could just tell us how you are thinking about the multiple sclerosis franchise really between now and the BTK and how you would manage that transition? And my second question is just to get a bit of a feel for what you found with your initial DTC in Dupixent. I believe you started it towards the end of last year.

Has it lived up to expectations? What should we be thinking of in terms of that sort of cost going forward? Many thanks..

Thanks Jo. Maybe a couple of comments and I will hand to Bill who built Aubagio, I think. So he will have a deeper insight. I think ultimately the transition is less complex than I think people would imagine.

If we get to market with the right time line, with the right product profile, I think we will bring something that is fundamentally game changing in this space. And that's a fact.

Now the bridge, depending on when you have LOE and where to go, we think, is manageable and retaining the expertise and you can imagine the people, both in the medical and commercial areas, want to be involved early. If you look like you are in the right place on the BTK, then we see no issue with bridging.

We always knew Aubagio would have generic competition in that time frame. And you know this. We have built that into our understanding of the 2025 BOI objective. So we just think it's more of an opportunity than less. Bill, you might want to add to that.

And do you want to talk about the DTC spend for Dupixent? And although it's early days in terms of what it takes over a period of time we invested in DTC in the U.S., give some quick highlights on that..

Yes. Sure. Thank you, Paul and thank you, Jo. So as Paul said, we have spent the last eight years building an MS franchise. And as John showed on his slide, globally we are number two in market share with the franchise. That's taken a lot of work. As Paul said, the bridging isn't such a big deal from our perspective as we have got an excited team.

We have got a lot of activity going on in the specialty part of the business as well. So there's plenty to keep people busy.

To go to the question of using Aubagio as the comparator for the BTK, we have seen it in recent MS studies that Aubagio has been used and I think people have compared against Aubagio because it is really, in many ways, the standard of care in the oral space. It has the only product that's demonstrated an effect on disability in two trials.

And for that very reason, we are comparing the BTK to that. We have set the bar high. But that kind of shows the confidence that we have in the brain-penetrant BTK of ours. So it makes perfect sense. Aubagio is a well-tolerated effective product. We believe that the BTK is going to really become the standard of care in multiple sclerosis.

So we think it's a good comparator there. Regarding Dupixent DTC, I think you are referring to perhaps some of the asthma that started more in earnest last year. We have been conducting DTC, specifically television in AD as well. That has been, we believe, very effective. It's something that we have and will continue to invest in going forward.

I think you have seen in the U.S., this is an important lever. And this is building to be a mega brand and we will have that presence in both the indications in a continued and expanding fashion..

Thanks Bill. Very good. Thanks Jo. Next question..

The next question comes from the line of Florent Cespedes of Societe Generale. Please ask your question..

Good afternoon, gentlemen. Thank you very much for taking my question. Florent Cespedes from Societe Generale. Two quick ones. One for Olivier and one for John. First, Olivier, on China.

Could you elaborate a bit on when you believe that you should see the contribution from higher volumes there? Why Plavix seems to be more impacted than Avapro? And if you could give us an idea of how do you see the impact on Amaryl? Should it be the same vein as for the two other products? And the last question on China.

Maybe if you could tell us if you see any potential disruption on this territory, given the Coronavirus crisis? And then a quick one for John on the IL-33. This year, you will have the proof of concept trial readout in atopic dermatitis.

As Dupixent profile is quite attractive, what do you need to see in terms of efficacy or side effect profile tolerance to really move forward with this product instead of Dupixent and how we will position it? Thank you very much..

Thank you Florent. Coming to Olivier in a moment. Just on the disruption, I tried to touch on it upfront because, you know, we started the year well and we are making, we are putting patients first in what we do. It is difficult to predict what will happen over the next few weeks.

And I think it would be a bit naive of us to say no disruption or try and put a percentage around it. We feel well placed. We don't see business risk. But of course, as it evolves, we are just going to have to recalibrate that. I don't think any company has a choice on that. So we will update as we go along.

I think, Olivier, maybe you want to comment on Plavix particularly or Amaryl..

So on Plavix, as Paul mentioned a little bit earlier, we have clearly early signals, although they are very, of course, premature. At the beginning of 2020, I think, showing very strong shipments. Of course, it's very premature.

So I think we will need a couple of months before we understand what is exactly the trend in volume to respond precisely to your question. I would say that it's probably in the course of Q2 that we will get a feel of how we are able to increase significantly the volume. And we always build our plan on a gradual increase.

So this will come in Q2, Q3, Q4. We are happy in the way we have implemented our new go-to-market model. We have been able to execute in November and December. So for us, it's less of a sales force model. It's making sure that we have the volume pull-through at the provincial and at the hospital level, especially in the bidding offices.

Regarding your question on Amaryl, it's a €130 million product basically. We have decided not to participate to the tender for one reason that is very obvious. There are six generic GQCE. So we thought that there wouldn't be any business case and that the price are going to be very much down.

It's difficult to assess exactly what's going to be the impact due to the fact that we don't know exactly when it's going to be implemented and so probably in the course of H1, but we don't know precisely. In terms of trend, given that the price are going to go significantly down, we are anticipating that the impact could be significant..

Okay. Thank you, Olivier.

John, comment on the IL-33?.

Yes. I guess the takeout message really is we are still investigating the molecule and gathering data in three different indications. We did asthma and we did describe some of those data. We have done a very exploratory study in COPD just to get some baseline information there. And the atopic dermatitis study will read out middle of this year.

And those are all exploratory Phase 2 studies to really kind of establish the profile. In some of the studies, we have done head-to-head with Dupixent and others not. And we are looking for what might be a differentiator or place where the IL-33 molecule could play that Dupixent doesn't.

I would remind you that, for example, with Dupixent, we have separately a COPD study with a Phase 2 that will read out this year. And so that will also be an important piece of data that helps us to compare the two molecules and think about where we go from here.

So all I can basically say is, we are still gathering data and really developing our thinking about IL-33 as we collect those data and compare it to what we are seeing with Dupixent..

Thanks John..

Thank you very much..

Thank you Florent. Next question..

Your next question comes from the line of Graham Parry from Bank of America. Please ask your question..

Thanks for taking the question. So firstly on the BTKi.

Just thinking about your Phase 3 trial design, what you are pairing that for? Is the target profile to have efficacy benefit over Aubagio similar to what we have been seeing with anti-CD20? And then, ultimately, to replace these in the market which should be consistent with Paul's comments on the news wires about taking half the MS market or the category taking half the MS market? And to that end, do you therefore need to run a CD20 head-to-head further down the line, especially in PPMS? And then secondly, if you could just help quantify the one-off pension expense in the other expenses line and the extent to which there were any other one-offs that offset that on the other side? So how good a base for forecasting is that other expense line? Thank you..

Okay. Thank you Graham. John, I don't know whether you want to go into detail. I am glad, Graham. We are seeing some excitement around the BTKi. Just to remind you and everybody, we think that the market's going to be worth about €20 billion in the time frame at which we will be entering.

We think about half of that will be B-cell depletion and we think we will have to compete within that half and perhaps broader. A lot will depend on the product profile. And you know, we are excited by that at this stage. But we have to wait and see.

You know, in terms of the pairing, John and the anti-CD20 compare, do you have any view?.

Well, we are starting off with, in the case of relapsing, as we said, with comparison with Aubagio, will be our comparator there. We think that's very appropriate. And then in the progressive forms of MS, we will do one study in primary and one in secondary.

And those are placebo-controlled and that's really because, as you know, the standard of care, including the B-cell depleting agents in the progressive forms is really not adding much benefit, unfortunately, for patients. So we feel that that's an appropriate choice.

That will give us a good foundation on which to then make cross comparisons at least and then we can go from there in terms of whether it's appropriate or necessary to do a head-to-head comparison..

Good. Thank you.

Jean-Baptiste, the other expenses line?.

Yes. As I said, the compensation on the netting is not on the same line. One is gross margin, the other one in other expense with no impact on the BOI overall on the quarter. So to model this line, really, it could be depending on the acceleration of the profitability of the return around Sanofi partnership on Dupixent. We will help you guide on that.

It will also depend how quickly we finish our discussion to implement what we presented on both Praluent and Kevzara. But it will be driven really by the Dupixent growth. So that's the best way to look at it. It will be a proportion of the acceleration of this profit generated by Dupixent..

Thank you. Thank you Graham. Next question..

Your next question comes from the line of Thibault Boutherin of Morgan Stanley. Please ask your question..

Thank you for taking my questions. First, a couple on consumer healthcare.

Could you give us an indication in terms of timing for the completion of the carve-out of the business from an operating perspective? And as a follow-up on this, could you give us an update on the regulatory process with the FDA regarding the OTC switches for Tamiflu and Cialis? And then a second question on oral diseases.

Could you comment on the slowdown of the franchise in the fourth quarter, in particular the sales phasing of Cerezyme in emerging markets? Should we see this as a one-off? Or should we expect the growth from this franchise to moderate in the future compared to the kind of mid to high single digit that we saw in recent quarters?.

Okay. Thank you Thibault. I will hand over to Alan with consumer health. I think we flagged about a 24-month journey to carve-out, carve-in, whichever way you want to describe it, to becoming standalone. We announced that in December. So we are a month or two into that process.

In terms of the Rx to OTC switches, is there anything you are prepared to share on the results that doesn't give a competitive opportunity to somebody else?.

Right. As you know, Paul, what we did say at the Capital Markets Day that we would be meeting with the FDA during Q1. So those meetings will take place. And so I think it probably will be more appropriate to do an update on the Q1 call.

So that would be an opportunity for us just to update everybody on what we are planning to do from a trial point of view following those discussions. So probably not today, but perhaps at the Q1 call, we can give a bit more color to that. And as you said, on the standalone project, we have already set up the project teams. We have the launch planned.

Actually, tomorrow, we will meet with all the working groups. We do see a kind of 18 to 24 month time horizon as there's a number of things that we have to consider, particularly around legal entity setup, IT infrastructure and so on which can take a little bit of time. But the teams are fully engaged, very motivated and ready to go..

Yes. I was going to add that the teams are very engaged and motivated and it's great to see. I think we will get some benefits from that and we will update on the Rx to OTC switches and try and perhaps even at Q1, try and dimensionalize what that could look like so people could get a feel for it. Maybe we will have some time to do that.

Bill, Cerezyme?.

Yes. So first of all, Thibault, thanks for the question. I think more representative of the rare growth, in general, is what we did for the year. And there, we had 6.5% growth and actually exceeded €3 billion for the first time. All the franchises are growing well, Gaucher, 7%, Fabry, 5%, Pompe, 8%.

I think you have got to look at Q4 growth as a little bit of a one-off. It's on a high Q4 from the previous year where we had grown over 10%. So looking forward, we think that the performance that we had on the annual basis is more representative of the future..

Thank you..

Thank you, Thibault. Maybe next question, please..

Your next question comes from the line of Seamus Fernandez of Guggenheim. Please ask your question..

Thanks for the questions. So just a couple of things. You guys are updating the guidance for Regeneron sometime after or on the first quarter.

Just directionally, does the 5% EPS growth, I assume that it contemplates that change? But as we think about the move into 2021 and your guidance for 2022, how do you see that change accelerating the profitability of that franchise? Can you just give us a little bit of tenor around that JV? And then for Paul, as we think about business development going forward, obviously the move on Synthorx was timely heading into the Capital Markets Day.

But can you just give us a little bit of a sense of the types of acquisitions or transactions that you are most focused on going forward? Are there particular areas of the business that you are interested to see building out further? Thanks so much..

Okay. We may ask you a clarification question on the first one. I am not sure I heard you correctly..

So you said some maps restructuring?.

Maps restructuring? Is that what you said?.

Exactly. It's the collaboration restructuring. It's just to get a sense of, I assume that the 5% contemplates any benefit from that change.

But how might that, as you see it, accelerate the profitability of the collaboration in heading toward your 30% guidance in 2020?.

Okay.

Then got it, Jean-Baptiste?.

Yes. Absolutely, well, yes, exactly, it's the same spirit as what Regeneron has communicated earlier for both of us. These changes are simplification on reduced governance on some extra costs. So on both sides, it is accretive. Of course, for us, it's less significant. So of course, it is taken into account in this guidance.

And since we broadly decided this change in December, as we said in the CMD, so yes, it's a positive. It's embedded into our guidance. But it's not so significant in the overall scheme for Sanofi. But it goes in the right direction..

I think there's a great spirit, by the way, between ourselves and Regeneron in trying to simplify things. We recognize that it's better to do these things like this and be more agile in a partnership and I think we will only get benefits from that. Some will be financial, of course, both sides ultimately. But often, it will just be speed.

It will become important. As for deals, as much as we love you all as an audience, we didn't do a deal just to achieve a good news flow for Capital Markets Day.

I think this deal has been tracked for a while and for the fundamental belief that it could, although early, if it works, it could change what happens in oncology and particularly the IO-IO piece. I think, John beautifully described the Synthorx deal with putting gas in the tank.

And I think as we get closer to launch in a few years, people will be excited to have a new approach to what could become a definitive play in combination. And I think, you know, it's hard to say, but I think we are more excited about mechanisms, new mechanisms, complementary mechanisms, things in combination.

John mentioned the CD38 and the PD-1 in combination. There are BD opportunities where you can really get to amp up your own existing pipeline by pulling forward incredible and unique data. So we are excited about that.

Really, it's an interesting time for the company because whilst we go on this BOI journey and we have between vaccines and dupilumab, we have an opportunity to be able to maintain a really positive growth trajectory. So it allows us, I think, from a BD or even M&A perspective, to go after science in a more determined fashion.

I think we are all here because we think that's the right thing to do. And where possible, we would rather do that than look at things that will have short term transformational P&L impact. It's not necessary. It doesn't mean we will never do these things. But I think we are more interested in things like we have just done.

And hopefully, you will see over the months and years that we do more like that. But we will see. So thank you, Seamus. I think we covered everything on your question. I think we still have time for a couple more questions, if you would like.

Jean-Jacques?.

Your next question comes from the line of Jean-Jacques Le Fur of Bryan, Garnier. Please ask your question..

Hello. Thank you for taking my question too. The first is for probably for Jean-Baptiste on the share buyback. I saw that you initiated some buybacks all along January. So I am curious to first understand the purpose of this buyback and if it is the start of a new program for the full year? That's my first question. And the second one is on Kevzara.

Now you have the global rights. Do you intend to start new commercial initiatives or anything else to accelerate the sales growth of this product? And when could we see a positive impact of potential such initiatives? Thank you..

So maybe, Jean-Baptiste, share buyback?.

Yes. Well, very nice to see we are closely monitored. You are perfectly right. We are executing a share buyback all along January which is exactly along the lines of our commitment during the Capital Markets Day to make sure that we neutralize the dilution of any plans or share plans or stock options which will be exercised.

So that's what we are doing now. It's a good moment because share price was favorable, is favorable. So we are executing it right now. Nothing new, nothing different from what we have said..

As for Kevzara, I mean, I think our first objective was simplification and accountability. We are looking at now which way to go next. Some ideas on the table. But I think, frankly, we have to decide what is actually possible and what is a sensible investment to make when there are other very attractive opportunities in the pipeline.

So I would read that the reframing of the relationship was more about simplicity and efficiency, particularly with Kevzara..

Thank you..

One last question then, I think, if that makes sense. Thank you..

Your last question comes from the line of Wimal Kapadia of Bernstein. Please ask your question..

Thanks very much for taking my questions. Wimal Kapadia from Bernstein.

So could I ask a little bit about sutimlimab in cold agglutinin disease? So how should we think about pricing for the product? And then what level of penetration should we assume that given that the spectrum of patients in CAD is relatively wide and some patients exhibit compensatory mechanisms undergoing hemolysis without the need for therapy over long periods? And my second question is on vaccines.

I just want to get a good sense of how Sanofi thinks about differentiation for MenQuad. We have seen some of the competition, some of which is Nimenrix now not having a significant uptake.

So what really differentiates your asset to give you confidence in this market? And then tied to this, how much of a threat are pentavalent vaccines longer term? Thank you very much..

Okay. Good. I am glad to get those questions actually, particularly to get David on the hook on vaccines.

But Bill, before we do that, do you have any comment on pricing?.

Yes. So thanks for the question. Not going to comment directly on pricing, but this is an ultra-rare disease. Just to give you a sense of the scale, we think there's about 5,000 patients in the U.S. and 5,000 in the EU and a couple thousand in Japan. So it certainly qualifies as being ultra-rare.

And this is a serious disease and we have spent a lot of time collecting data which just demonstrates just the impact that the disease has. And there's a 55% increase in thromboembolic events. That was from work that we did in the U.S.

We know that the mortality risk is more than doubled with the disease and there's an 8.5 times rate of arterial thrombosis in some work that we have seen in Japan. So what we are going to be doing is spending a lot of time on the education of the seriousness of the disease.

We think that we will be able to identify the patients, but it's more getting physicians to act with the new medication that will be available. But we are excited about it. It's got very good data and more to come on that later this year..

Thank you. Thanks Bill. David, on MenQuad and the pentavalent question..

So MenQuadfi is going to allow us to really expand beyond the United States where we are mainly selling today Menactra. We didn't have the full range of the indication on Menactra which didn't allow us to go in all the countries around the world. So MenQuadfi is going to solve that problem. It's going to have a label which is very broad.

It's fully liquid. And when you look at the Phase 3 results that we have published, you can also see that immunological responses look very favorably in comparison to all the standard comparators. When it comes to pentavalent, we are developing also a MenB candidate.

However even if a pentavalent comes from a competition, it's not going to take the market because only certain patient populations are going to be eligible at a certain point of time to be vaccinated with a pentavalent.

And so the physician, in any case, will have to then think, do I rather go for what we believe is a best-in-class quadrivalent and a separate MenB? Or do I want to go for convenience and give it a pentavalent? So in that niche of where pentavalent can play, that's going to be a key question.

But we don't think it's going to significantly change the market..

Great. Thank you very much..

Thank you. Thank you to everybody. Thanks for joining, for dialing in. Just to remind everybody, June 23, London R&D Day. It could be quite exciting. And you can get to see some of the stuff we don't get to talk about always on these calls and also meet some of the incredible teams that support John in our R&D effort. Thanks again for dialing in.

Thanks to the team. We look forward to joining you again in end of Q1..

That concludes the conference for today. Thank you for participating. You may all disconnect..