Sanofi SA

PAR:SAN

Earnings Call Transcript 2021-Q2

[Operator]

Ladies and gentlemen, thank you for standing by. Welcome to the Sanofi Second Quarter 2021 Earnings Call. I would now like to turn the call over to Eva Schaefer-Jansen, Head of Sanofi Investor Relations. Please go ahead, Eva.

[Eva Schaefer-Jansen]

Good morning, good afternoon and good evening to everyone. Thank you for joining us to review Sanofi's 2021 second quarter results followed by a Q&A session. As usual, you can find the slides to this earnings call on the Investors page of our website at sanofi.com. Moving to Slide 2. 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 d'Enregistrement Universel for a description of these risk factors. With that, please go to Slide 3. Our speakers on the call today are Paul Hudson, Chief Executive Officer; the Global Business Unit Heads Bill Sibold, Thomas Triomphe, Olivier Charmeil and Julie Van Ongevalle; John Reed, Global Head of Research and Development; and Jean-Baptiste de Chatillon, Chief Financial Officer. For the Q&A, you have 2 options to participate. [Operator Instructions] With that, I'd like to turn the call over to Paul.

[Paul Hudson, CEO & Director]

Well, thank you, Eva, and thanks to everyone for joining our call. I believe our results in the second quarter are compelling evidence for however Sanofi's transformation translates into accelerating performance, driven by Dupixent and growth across all of our businesses, all of it exceeding expectations. I'm particularly proud of our R&D teams and their achievements in driving visible pipeline transformation. In immunology and oncology, we have impressively strengthened the early to mid-stage portfolio, and Dupixent delivered on a potential new indication in record time. We saw an acceleration of sales and EPS growth with both top line and bottom line growing by double digits to 12% and 16%, respectively, in constant currency. While the strong top line growth should be viewed against the backdrop of the second quarter of 2020 when sales of Gen Med, CHC and [ partly ] vaccines were impacted by the COVID pandemic, the recovery is simply quite outstanding. The primary driver of the strong top line performance in the quarter was an acceleration of growth for Dupixent, a 57% increase in sales, growing impressively both in the U.S. and global markets. Importantly, although Dupixent sales were not as affected by the pandemic as other parts of our business, its sales continue to accelerate with now more than 300,000 patients treated globally. In Vaccines, our other key growth driver, business momentum continued with a 16% increase in sales and growth across most franchises. With the existing franchises performing according to plan or even better, we are increasingly turning our focus on the future innovation in the vaccines business as evidenced by the recent announcement of the creation of an mRNA Center of Excellence. We also saw growth in our other businesses. Gen Med and CHC, both GBUs outlined their respective midterm goals in our recent Capital Markets Day on February 5, and I feel encouraged and optimistic to see the progress that we're making, both structurally and in terms of performance. Since embarking on our savings initiative at the end of 2019, we have already delivered cumulative savings of EUR 2.1 billion, and we continue on our path to unlock operational efficiencies across the organization. The second quarter results strengthen our confidence in our growth trajectory for the year, and consequently, we are raising our full year guidance to around 12% business EPS growth at constant currency. Moving to Slide 5. Today, we also announced the appointment of 3 international leaders with world-class pharma expertise. Brendan will become the new Head of Industrial Affairs. Already with Sanofi today, he has been responsible for the development and acceleration of our biologics manufacturing capacity and is leading some of our world-class manufacturing sites like the Factory of the Year in Framingham, U.S. Roy, who will be joining us from Novartis, will take over the role of Sanofi General Counsel early next year, and he brings diverse experience acquired in private practice and large pharma, coupled with exceptional commercial skills. Viviane will be breaking new ground as the chair of a company that is set to become one of the world's leading API players. She brings 30 years of experience in financial operations in pharmaceutical companies and also serves as an independent director on a number of boards. I'm very excited with these new appointments and a mix of internal promotion and newcomers to our company with a passion for engaging and leading teams across larger organizations. Turning to Slide 6, let us talk about what is at the core of our Play to Win strategy, bringing new medicines to patients in need. Before John provides more insights, I'll give a few highlights of what we've been achieving over the last 18 months to bring our priority assets to patients by beating industry benchmarks in R&D productivity. Dupixent is only at the beginning of its journey, penetrating the large type 2 penetration -- the large type 2 patient population in atopic dermatitis and asthma. And commercially, it is well on its trajectory to deliver on our ambition to exceed EUR 10 billion in peak sales. Since December '19, we have initiated trials in 6 more indications to expand the potential of this amazing once-in-a-lifetime medicine into adjacent type 2 inflammatory diseases. As just mentioned, our latest success is a milestone in chronic spontaneous urticaria, or CSU by meeting the Phase III clinical trial primary endpoints, regulatory submissions for this investigative indication are planned for next year. We presented exciting data from the amcenestrant AMEERA program at ASCO in June, demonstrating its potential best-in-class antitumor activity and safe and tolerable profile. Our first-line program is well underway, and we decided to move into the adjuvant setting. We are thrilled to begin global submissions for nirsevimab, 1 year ahead of our initial plan. This antibody has the potential to protect all infants during their first RSV season. We're looking forward to sharing the positive data from the MELODY and MEDLEY studies with you in due course. Substantial progress has been made with efa and fitusiran, our potentially life-changing treatments for patients with hemophilia, and we're excited to present data from the Phase III studies as early as the beginning of next year. And finally, with tolebrutinib, we're enrolling across our 4 Phase III studies with greater than 95% of our patients retained on the Phase IIb open label extension study. Quite remarkable. We remain convinced in the transformative potential of venglustat as a breakthrough treatment for patients living with lysosomal storage disorders. With our expectation that priority assets are potentially transformative value for the company as a whole, venglustat's revised focus on the LSD indications has led us to reprioritize the resource deployment on those priority assets listed on this slide. Beyond those on the slide, we have an increasing number of other innovative molecules in our pipeline, and we will introduce further priority assets to you as the data continues to evolve. Now turning to Slide 7. Sanofi's diversity inclusion strategy is well embedded in our Play to Win culture with clear priorities. Regarding gender equality, we are on an encouraging path with 40% of our senior leadership roles held by women today. But clearly, our commitment remains for women to hold 50% of those roles by 2025. In the U.S., people of color now represent 31% of the Sanofi workforce. And here, our commitment is to align with the representation of our patient base by 2025, which is estimated to be around 37%. There is great work underway across Sanofi's organization with many best practice initiatives of how we include diverse communities and our workforce. For example, during Pride month in June, many country organizations teams came together to drive local campaigns, providing LGBTQIA+ communities with forums to create a culture of inclusion and equality at work and beyond. While we're encouraged by our progress, we recognize that we are nowhere close to where we need to be. Our journey will only be complete once Sanofi's workforce is fully representative of our diverse society. And now let me hand over the call to Bill to begin the second quarter business review. Bill?

[William J. Sibold]

Thank you, Paul. Starting with Dupixent on Slide 8. Dupixent delivered in an outstanding quarter with accelerated worldwide growth of 57%, driven by strong performance in the U.S. as well as in the ex-U.S. markets. Annualizing at EUR 5 billion and well on its trajectory to achieve our greater than EUR 10 billion peak sales ambition, Dupixent added almost EUR 200 million of incremental sales in the period versus the first quarter in spite of in-office visits remaining below pre-COVID levels. As we progress into the second half of 2021, we are excited about key milestones, which could make Dupixent accessible to younger patient populations in both asthma and atopic dermatitis, supported by its well-established long-term safety profile. We are anticipating the FDA decision for 6- to 11-year-olds in asthma as well as the pivotal data in our AD trial below the age of 6 close to a year earlier than planned as enrollment completed much faster. We also continued to advance the science into additional inflammatory diseases with the key readouts in prurigo nodularis and eosinophilic esophagitis expected this year. On Slide 9, let me highlight the positive results of Dupixent in patients with chronic spontaneous urticaria announced today. CSU bears the hallmarks of type 2 inflammation and is characterized by hives and/or skin swelling and is associated with intense itch. This chronic disease has a potentially severe impact on quality of life and is typically treated with antihistamines. However, for up to 50% of people living with CSU, their disease remains uncontrolled, and an estimated 300,000 moderate to severe patients are eligible for biologics in the U.S. Putting this into context, the eligible population is as large as the number of patients on Dupixent globally today. The top line results at 24 weeks from Study A of the LIBERTY CUPID trial program demonstrated that Dupixent nearly doubled the reduction in itch and urticaria activity compared to standard of care alone. The trial also demonstrated safety results similar to the known safety of Dupixent in its approved indications. Regulatory submissions are planned to begin next year as Study B of the trial program, a study of patients who remain symptomatic despite antihistamines and omalizumab is ongoing with expected readout in H1 2022. Moving on to Slide 10 and taking a closer look at our approved indications in the U.S., Dupixent has the potential to address the lives of over 3 million patients. Clearly, we are only at the beginning of penetrating the large U.S. market with only 6% of the biologics eligible AD patients treated today. Similarly, in asthma and nasal polyps, we are only starting to unlock the opportunity and have a tremendous growth potential ahead of us. Driven by our ambition to expand into the pediatric populations, we have the opportunity to add an incremental 150,000 young patients in total in our core indications. Separately, we are executing on a robust clinical development program in multiple adjacent type 2 indications, which could unlock additional growth opportunities. These indications combined have the potential to address an additional population of 600,000 patients in the future. Notably, let me remind you that we consider the Type 2 COPD indication an upside to our peak sales ambition and, therefore, have not included this significant population in the patient number for the adjacent indications on this slide. Advancing to Slide 11 and turning to the other Specialty Care franchises. The rare disease franchise continued to deliver growth in the second quarter with higher sales in all reported regions and strong performance from our Pompe and Fabry franchises. Growth rates have to be seen also against the backdrop of the second quarter of 2020 due to COVID when receiving treatment was very challenging for patients. In Pompe specifically, we are looking forward to the FDA PDUFA date for avalglucosidase alfa in August. Our neurology and immunology franchise was down slightly as Aubagio continued to be resilient in the increasingly crowded MS market. The franchise showed strong growth of 14% outside the U.S., offset by the expected lower U.S. sales with recent competitive launches. Rare Blood Disorder grew 17%, excluding sales to Sobi. Franchise growth was mainly driven by increased sales of Alprolix and Cablivi in the U.S. As planned, sales to Sobi were lower in the second quarter, and we anticipate this dynamic to continue into the second half of 2021. As our presence in oncology is reemerging, sales of the Oncology franchise were up 25%, supported by the encouraging uptake of Sarclisa and Libtayo, which collectively achieved more than 300% growth. With that, I turn over to Thomas to update you on the Vaccines business.

[Thomas Triomphe, Executive VP & Head of Sanofi Pasteur]

Thank you, Bill. Vaccines delivered another strong quarter with 16% growth, demonstrating that our business is progressively getting back towards the pre-pandemic trajectory. The U.S. business performed particularly well, growing 84% in recovering from a low Q2 2020, in particular, the Meningitis franchise that was already off to a good start in Q1. We launched 2 important new products in the U.S. this quarter. MenQuadfi, the only FDA-approved meningococcal vaccine indicated for individuals above 2 years of age and Vaxelis, the first and only the first and only hexavalent pediatric vaccines in the U.S. Outside the U.S., sales were negatively impacted by lower birth rates and by ongoing COVID-19 immunizations that have been prioritized over routine immunizations. Flu had a solid performance, up 9% versus Q2 last year, and we continue to plan for a record northern hemisphere flu season in terms of sales. From a phasing perspective, for this Northern Hemisphere season, we still expect around 50% of those sales to occur in the third quarter of the year. Also, we initiated our global Phase III study for recombinant COVID-19 vaccine candidate. We assume to collect sufficient events by Q4 of this year to read out the data. Meanwhile, a rolling submission process has already started in the EU. For the remaining COVID-19 vaccine candidate, we continue to expect Phase I/II data in Q3 of this year. On Slide 13, let me explain how Vaxelis will simplify routine infant vaccination in the U.S. Prior to the Vaxelis launch, infants received a pentavalent vaccine plus a separate vaccine to protect against 6 diseases. Altogether, this represents 5 or 6 injections in the first 6 months of age. This is shown on the left part of the chart. With Vaxelis, we can now reduce the number of injections required from 5 or 6 down to 3 injections. As you know, hexavalent pediatric vaccines have been launched in other Western markets and have taken a majority share within 3 years of launch. We do expect Vaxelis to capture significant market share in the U.S. from both available pentavalent vaccines. For your reference, Pentacel, the Sanofi pentavalent U.S. brand, represented around 2/3 of our 2020 PPH US sales. Importantly, Pentacel sales will not completely disappear because of the booster regimen shown on the lower part of the slide. Infants will receive Vaxelis for the primary vaccination, will likely receive a Pentacel booster dose to continue immunization with consistent antigens, meaning that while Vaxelis sales will replace Pentacel in the primary series, Pentacel is likely to become the booster of choice at 18 months of age. Vaxelis is commercialized through our joint partnership with Merck, leveraging both companies' existing commercial teams instead of setting up a separate infrastructure. Sales are recorded by the joint partnership with Sanofi booking 50% of the profit. I'm glad to share today that this setup is profit-making from the very start. Let's now talk about Sanofi's mRNA Center of Excellence on the next slide. We did recognize the potential of this technology before the COVID-19 pandemic, signing the initial portfolio developed through the Translate Bio agreement in 2018. From that time, we saw mRNA as an additional tool in our vaccine toolbox. Sanofi's mRNA Center of Excellence will accelerate the development and delivery of the next-generation vaccines by bringing together 400 dedicated employees in both in the U.S. and France with end-to-end expertise from R&D to CMC and from manufacturing to regulatory filing. We will be science-driven and explore both unmodified and modified mRNAs to get the best possible constructs. In parallel, we recently invested in an evolutive vaccines factory, a very innovative industrial concept, versatile enough to accommodate mRNA manufacturing in addition to other technologies. With this investment in mRNA, we are looking forward to delivering an innovative next-generation of vaccines beyond pandemic with the ambition of a minimum of 6 clinical candidates by 2025. With this, I now hand over to Olivier for General Medicines.

[Olivier Charmeil, Executive Vice President of General Medicines]

Thank you, Thomas. In General Medicine, we are extremely pleased with the performance of the second quarter, which reflects on the execution of our strategy. Our core assets delivered 12% growth during the period. The 6 key brands in our core asset portfolio reported solid growth in the quarter. Lovenox was up 25% and continued to benefit from inclusion in the WHO guidelines for the treatment of hospitalized severe COVID-19 patients in addition to a low base last year due to deferred elective surgery. Toujeo grew 8% due to the launch execution in China and continued strong adoption in European markets. Toujeo remains on track to reach blockbuster status. Plavix returned to growth in the second quarter and grew in both volume and sales in China, up 8% in sales more than 1 year after its inclusion in the VBP. On the other key brands, let me point to differentiating data for Soliqua presented at ADA in June. The SoliMix study demonstrated improved blood sugar control without weight gain for patients and therapy with Soliqua versus premixed insulin. We believe this provides us with the opportunity to further drive growth of Soliqua in large markets where premixed insulin are still widely used. So broadly stable sales performance of our noncore portfolio benefited from the pricing environment this quarter, offsetting the loss of revenues from our strategic portfolio streamlining initiatives. Turning to China. Sanofi participated successfully in the VBP Wave 5, bidding for Eloxatin in June with implementation expected in the fourth quarter. We do not expect significant sales impact on the full year from the VBP Wave 5, but we remain vigilant to learn about any potential mechanism for the inclusion of the insulin class. Part of the transformation of the General Medicine business continues to be the streamlining of our tail products and reduction of our geographic footprint, and we delivered on this commitment with recently announced product divestments and a more simplified infrastructure in European countries. Overall, we are confident in our strategic execution and on track to deliver on our commitment to stabilize sales by 2025 as compared to the 2020 pace. With that, I hand over the call to Julie.

[Julie Van Ongevalle]

Thank you, Olivier. I'm very pleased with our return to growth in the second quarter, not only versus last year, but also on a pre-COVID comparison. And I'm happy to say this strong performance is, to a large extent, the result of the new focus on our key brands and markets that we shared with you in February. The double-digit growth in the quarter also reflects the strong recovery of the CHC market against a low basis for comparison of the prior year when person pharmacy traffic was significantly impacted by the pandemic, coupled with the unwinding of the high inventory at the consumer level. Our priorities put behind our wellness categories are driving growth, with digestive wellness performing particularly well in the second quarter, led by our brands in Enterogermina, Buscopan, Dulcolax as well as Essentiale in liver care. I'm also encouraged by the acceleration of our sales through the e-commerce channel with significant growth from some brands and in key markets. Importantly, we execute on our strategy to reduce the complexity of our portfolio. We recently signed a couple of meaningful divestiture agreements which enable us to increase focus on our strategic brands. Another very important step to note is that to date, 10 legal entities have successfully become stand-alone, which is in line with our road map to create a fast-moving consumer health care entity with agile and adaptive ways of working. In summary, both the return to growth of our CHC business in the second quarter as well as the advancements on our strategic road map increase our confidence in the value of our business. With that, I'm happy to hand it over to John for an update on transforming R&D.

[John C. Reed]

Thank you, Julie. Turning to Slide 16 now. When I joined the Sanofi team in mid-2018, we set out to fundamentally transform our pipeline and bolster productivity of the R&D organization. Moreover, we aimed to accomplish this transformation with a flat or even declining budget by making the necessary trade-offs and mandating far more focus. Key to this ambition has been the rigorous prioritization of projects. I'm proud to say the productivity of Sanofi R&D has doubled, and this is reflected in the pipeline. Comparing the 2017 Sanofi portfolio with the 2021 shows the results both in quantity and most importantly, quality of molecules in development. With respect to quantity, we've achieved an 80% increase in the number of NMEs in development without increasing our budget. And with respect to quality, 89% of our molecules in development now have a clear first-in-class or best-in-class target profile. A few examples of molecules that began their development journey since 2018 are listed here, ranging from our oral selective estrogen receptor degrader amcenestrant for breast cancer to our brain-penetrant oral BTK inhibitor for multiple sclerosis to our exquisitely engineered extended pharmacology Factor VIII replacement for hemophilia A efa; two, our non-alpha interleukin-2 molecule for immuno-oncology created using a recently acquired synthetic biology platform that I had been monitoring for a couple of years waiting for derisking data that provided the confidence that pounds on the opportunity. In addition, our IRAK4 degrader, in collaboration with Chimera, recently achieved clinical proof of mechanism. The reinvigoration of the Sanofi pipeline has been greatly accelerated through M&A with 6 innovative companies bolted on. These are supplementing our pipeline and importantly, adding drug discovery platforms contributing to improved research productivity going forward. Today, our drug discovery toolbox is much more diverse going beyond small molecules, insulins and recombinant enzymes to add platforms in antibodies from Ablynx, fully human monoclonal antibodies from Kymab, synthetic biology inspired recombinant proteins from Synthorx, mRNA delivered in vivo into selective types of cells using highly engineered nanoparticles from Tidal, universal NK cell therapies for immuno-oncology from Kiadis and even new twists on small molecules from Principia. Moving to Slide 17. Among our late-stage oncology assets is amcenestrant, our oral selective estrogen receptor degrader or SERD. This molecule has the potential to become a best-in-class endocrine backbone therapy for hormone receptor positive breast cancer. What makes amcenestrant best-in-class? Well, it's all about the structure of the molecule, setting amcenestrant apart from competitors. You can think of SERDs as having 2 components: a core scaffold that binds the estrogen receptor shown in the box and an arm shown in green that engages cellular protein degradation machinery to eliminate the [ ser ] receptor from cells. Now Sanofi's degrader arm is a bit different from competing SERDs, but our scaffold is entirely different. As a result, amcenestrant possesses competitive efficacy, but without the side effect baggage of competing SERDs. This best-in-class tolerability profile really matters when treating early-stage breast cancer, particularly in the adjuvant setting, where women can be on therapy for 10 years. We've launched a broad program to assess the efficacy and tolerability of amcenestrant across all lines of therapy from early to late. Our fast to market opportunity is found in the study we call AMEERA-3 in late-line metastatic breast cancer. This is a high bar challenge for amcenestrant, particularly in a world where most women will have already failed in aromatase inhibitor combined with the CDK4/6 inhibitor. But if successful, AMEERA-3 could bring amcenestrant market within 7 years, well ahead of standard industry cycle times. We anticipate the event-driven readout for AMEERA-3 in the second half of this year. Our Phase I data showed a respectable 36% clinical benefit rate, which rose to 64% for patients who had not already received fulvestrant or a kinase inhibitor. Treatment-related adverse events were mostly Grade 1, some Grade 2, but unlike competing SERDs, no Grade 3. AMEERA-5 in frontline metastatic breast cancer compares CDK4/6 inhibitor palbociclib in combination with either our amcenestrant or an aromatase inhibitor. We expect this trial to be fully enrolled faster than planned if the enthusiastic response from the investigator community continues at the current pace. At ASCO last month, we presented our pilot data for amcenestrant combined with palbociclib, reporting an overall response rate of 34% and an impressive clinical benefit rate of 74% for this combination. Again, our safety profile was consistent with best-in-class tolerability. Today, we are the only company having demonstrated encouraging Phase I combination efficacy data at the Phase III dose. For early breast cancer, our first foray into the adjuvant setting is set to begin towards the end of this year. As announced at ASCO, we're pleased and honored to join forces with some of the world's leading oncology corporate groups working on breast cancer to conduct a seminal trial in aromatase inhibitor intolerant patients whose tumors have high-risk features. Our study will put amcenestrant head-to-head against tamoxifen. While representing a subset of the adjuvant population, this study design affords the opportunity to reach the market relatively quickly by adjuvant standards. Recognize that an estimated 30% of women with early-stage breast cancer fail to complete the prescribed 5 years of adjuvant therapy due to tolerability challenges with the aromatase inhibitors. Now on Slide 18, please. I can point to several other examples of our progress in oncology that also occurred in Q2. First, SAR'245, a potential best-in-class non-alpha interleukin-2 molecule from the Synthorx platform now being tested in several oncology indications and contexts as monotherapy and as combination therapy. In our broad Phase II program, we are leveraging '245's impressive ability to selectively expand effector T cells without undue expansion of immunosuppressive regulatory T cells by combining '245 either with our cemiplimab or with Merck's pembrolizumab. In addition, '245 will be tested in combination with ADCC-competent antibodies such as cetuximab to leverage the impressive NK cell expansion that our molecule stimulates in patients with very well-tolerated doses. In the second panel, SAR'881 is a trailblazing entrant into the frontier of checkpoint inhibitors, partnered with Beyond Biosciences. '881 targets ILT2, a checkpoint receptor found principally on myeloid cells and NK cells as well as a subpopulation of PD-1 negative exhausted T cells. That molecule just entered Phase I, and we are anxious to combine 881 with other molecules in our portfolio. In the third panel, Sanofi's first entry into cell-based therapeutics is represented by the universal NK cell platform with the objective to bolster our emerging focus on NK cell-based immunotherapies. We expect these universally compatible NK cells to combine well with other molecules in our portfolio. And finally, in the fourth panel, I would highlight our antibody drug conjugate molecule, tusamitamab ravtansine, our potential first-in-class CEACAM5 targeting ADC now in Phase III for advanced lung cancer. Tusa aims to not only become the standard of care for patients with CEACAM5 high expressing tumors in second line post immunotherapy but also to become the cornerstone of therapy in first-line non-squamous cell lung cancer in combination with a PD-1. Looking beyond lung cancer. This quarter, we started a basket trial in additional CEACAM5-expressing tumor types, namely breast and pancreatic. My final slide, Slide 19, list of pipeline milestones expected for the second half of the year. It includes potentially registration-enabling pivotal trial readouts for Dupixent in 3 new indications. You've heard about one of those from Bill. We have pivotal trial readouts also where our internally invented anti-CD38 antibody Sarclisa in treatment-naive frontline myeloma and for our internally invented oral SERD amcenestrant in late-line breast cancer. And for rilzabrutinib, the oral BTK inhibitor acquired from Principia, which will read out later this year for a dermatology indication. We also expect to put an additional 5 molecules into the clinic in the second half of 2021, including some really interesting multi-specific nanobodies. Finally, I would mention with pride that the FDA approved fexinidazole for the treatment of African sleeping sickness. Fexinidazole was discovered in our laboratories in Frankfurt and developed in collaboration with the nonprofit organization, Drugs for Neglected Disease Initiative. It represents the first convenient oral therapy for African trypanosomiasis, a milestone in Sanofi's long-stand commitment to eradicate this neglected tropical disease. The FDA will issue a priority review voucher for this accomplishment. And with that, I hand over to our CFO, Jean-Baptiste.

[Jean-Baptiste Chasseloup de Chatillon]

Thank you. Thank you, John. On Slide 21, turning to our financial performance. Company sales increased 12.4% in the second quarter which helped to drive a 16.4% EPS growth in the period. We are improving on our gross margin, improving 40 bps in the quarter, 70 bps at constant exchange rate, resulting from our favorable portfolio shift to Specialty Care products and efficiencies within industrial affairs. This improvement more than compensated for lower gross margin in the Vaccines unit that was affected this quarter by product destructions with limited remaining shelf life due to the pandemic. R&D spending increased during the quarter, driven by advancements of our priority assets. We also continue to add R&D spend from recent acquisitions with the 3 deals closing during the quarter, partially offset by operational efficiencies. Higher SG&A spending was driven mainly by investment in advertising and promotion behind our Specialty Care products but also needs to be seen against a low level of spend 1 year ago.Other operating income benefited from capital gains on portfolio divestments of around EUR 50 million. In the same period last year, we booked EUR 157 million gain on the revaluation of the retained Regeneron shares. And lastly, our EPS growth continues to be supported by the anticipated lower effective tax rate of 21%, which we guided to in February as part of the full year financial guidance. On Slide 22, we believe that our strong performance in the first half puts us on the right path towards meeting our communicated midterm finance target -- financial target with BOI margin of at least 30% in 2022. Driven by a 7% top line growth, we increased the BOI margin in the first half of 2021 by 100 bps to 28.3% or 160 bps at constant exchange rate. If you would exclude the product portfolio divestment related capital gains from the other operating income and expense line, both in the first half of 2020 and 2021, the underlying BOI improvement at constant exchange rate reached 170 basis points. This is achieved solely through sales growth, shift in product mix and efficiencies. The underlying improvement in BOI is expected to continue with Dupixent as a primary driver. We now expect Dupixent to be accretive to BOI margin for the full year of 2022 instead of by the end of 2022, as previously communicated. Importantly, we also have plans in place to deliver significant COGS improvement on Dupixent from 2023 onwards. On Slide 23, I will now provide an update on our savings initiatives. As of H1 2021, we have achieved around EUR 2.1 billion of cumulative savings, adding another EUR 450 million savings in the past 6 months. We continue to make strong progress, especially in the area of smart spending. We expect that COVID related savings of EUR 230 million are not permanent, so those need to be seen in addition to the overall EUR 1 billion target. Savings added to operational excellence were generated mainly in manufacturing, and this will also be the main area for future savings to reach our goal of EUR 1 billion next year. We remain on track to achieve our target of EUR 2.5 billion savings by 2022, with most of this year's or next year's savings to be reinvested behind our growth drivers on key programs in R&D. Moving to Slide 24. Free cash flow continues its positive trend. Compared to the 2018 base, it has increased by more than 100%. This is again driven by Sanofi's solid business performance and smart spending initiatives. The comparable period in 2020 benefited from larger asset disposals not repeated in 2021. And in addition, we had significant cash outflows in the first half of 2021 to finance M&A on business development deals. As a matter of principle, we stand by our midterm target concerning free cash flow, which we intend to continue to maximize while investing in science. On Slide 25, we summarize expected dynamics for the second half of 2021. For Pharma, we expect continued growth from Dupixent and Gen Med core assets. For Lovenox, in particular, we expect growth rates to slow. The latest round of China VBP will be implemented late Q3 to Q4 this year and uncertainties remain around the mechanism for insulin class inclusion. For vaccines, we expect another record flu season and continued recovery of meningitis on the accounting of Vaxelis on lower birth rate may affect PPH sales. In Consumer Health, we expect to make further progress on business simplification, similar to what we saw in the first half. In terms of non-sales items, we expect to continue improvement in gross margin. With the expansion of our pipeline, R&D spend is likely to trend in line with the increase in the first half. On a separate topic, we plan to host a vaccine investor event in Q4 of this year, where we expect to discuss our industry leadership and our emerging pipeline. On Slide 26, based on the strong results of the first 6 months of the year, we are raising our full year guidance for 2021 business EPS. We now expect business EPS to grow around 12% at CER. The outlook regarding foreign exchange impact continues to be negative by minus 4% to minus 5% based on July average exchange rate. So let's open the call now to Q&A. I hand it back to Eva.

[Eva Schaefer-Jansen]

Thank you. So we will now open the call to your questions. [Operator Instructions] We will take the first question.

[Unknown Executive]

Thank you, Eva. So we will start the Q&A with Peter Verdult at Citi. Pete?

[Peter Verdult, Managing Director]

Pete Verdult, Citi, have 2 questions. Just for Paul or J-B. I realize it's not going to be today, but when is the earliest you might think to update the market on your midterm financial targets? I only asked this question in light of the business trends you're posting, the fact that you've absorbed the hit from the Regeneron stake disposal and increased R&D from M&A and you're now guiding to Dupixent being accretive sooner than previously expected. So just an update there. And then very quickly, just a quick strategic one for Paul. KOLs love to pick one, but a consistent message we hear is that the need for an oral -- efficacious oral with a safe, clean side effect profile is the biggest area of unmet need. Now JAKs hit on efficacy, but we could debate and probably agree that safety is not as clean as was hoped. So just strategically, outside of JAKs, what would your interest level be to add an oral mechanism to your atopic dermatitis if that sort of profile does emerge over the coming years? That's the question to you.

[Paul Hudson, CEO & Director]

Okay. Pete, thanks so much. Maybe J-B, midterm guidance and how we're balancing investment in R&D and outperforming and how we're going to navigate that.

[Jean-Baptiste Chasseloup de Chatillon]

Yes. Yes, thanks. It's important to reiterate our conviction on our midterm target. We said we will be trending towards 32% BOI margin by 2025 and 30% in 2022. And this is for always the same reason. You see how we move forward. We reinvest our savings to stimulate the growth and to enrich the pipeline. You will see more of that. And it's -- that's why we are not looking at beating those expectations in terms of BOI margin, because the priority is how to reach another level of growth in the midterm. So priority to the science, priority to the pipeline, priority to growth.

[Paul Hudson, CEO & Director]

Thanks, J-B. Peter, in answer to other question, Dupixent sets a very high bar on safety and efficacy. You've seen we've added CSU, at least the data today. We're very excited about the long term with Dupixent. You'll also know from what we presented, I think, on February 5 that we're excited about some of our adjacent mechanisms. 2 of them, rilzabrutinib will go into atopic dermatitis and our IRAK4 degrader will also be in atopic dermatitis. So we recognize there may be a place for it, but let's be clear, I think Dupixent sets a very high bar. Of course, adjacent, again, we have the OX40-Ligand injection with the Kymab acquisition. But we know patients will -- are very interested in orals, but we also know safety and efficacy are the #1 reasons to choose. We feel over time, and we laid out in February 5, we've got the full picture for whatever patient need will be but importing safety and efficacy over the next decade plus.

[Unknown Executive]

The next question is from Wimal Kapadia at Bernstein. Wimal?

[Wimal Kapadia, Research Analyst]

Wimal Kapadia from Bernstein. So firstly, just on CSU. Now that you've seen at least the first part of the data, how has your thinking evolved into the potential eligible patient populations where Dupi could be used? Previously, we've talked about [ Xolair ] refractory patients and potentially populations with low IgE. So whilst I appreciate you have not seen Part B of the data, which will be key as you're thinking changed for the potential of Dupi in CSU. And then my second question is just on avalglucosidase alfa in Europe. What sort of delay are we potentially looking at for approval? I'm just curious what EMA's rationale here is. Does it relate to the fact that they don't really see similar proteins with different glycosylation patents as a new substance? And then just tied to that, in terms of decision to ask for further consideration reflect a different pricing strategy for the product, i.e., you're looking for a premium price versus Myozyme?

[Paul Hudson, CEO & Director]

Okay. Wimal, thank you. Bill, I'm going to head towards you for CSU and the potential patient populations in Part A, Part B, maybe before you hand back, you'd like to make a comment on avalglucosidase.

[William J. Sibold]

Yes. So first of all, thanks for the question. You asked from a timing perspective, we would expect that the CHMP reexamination would take place sometime in the fourth quarter of 2021. We're not going to comment too much on any of the specific details. We believe that it's a new active substance. And from a pricing perspective, too early to comment on pricing. Look, we think this is going to be the leading product in Pompe. So we would expect that it would be recognized for that innovation. So then maybe switching to CSU. I mean, look, first of all, we're really just excited about these results in this first Phase III study of CSU. And maybe just to provide a little bit of context here of where we think this sits and what the opportunity is, starting with, this is an indication that has really still a really significant high level of unmet need. And there's really been limited innovation in the place. When you think about it, the last positive Phase III readout was in 2013. So there's a lot of unmet need there. And we have -- we know that a significant number of the patients are uncontrolled. So to give you just an idea of the size here, we think the biologic population should be about 300,000 patients. And those, they have moderate to severe disease, and they don't respond adequately to standard of care, which is antihistamines alone. Now the opportunity with the biologic, it's underpenetrated at the moment. Omalizumab, we think it's about 15% of eligible patients that are currently treated with that. And we expect that the penetration in this indication could double over time to near 30%. Now we also know that with omalizumab that about half the patients are uncontrolled. So we look at this as a couple of -- a few sources. First of all, there is the expansion of the market. There's a profile that we think that is going to be better. Ours is -- has a strong safety profile, Dupixent, no black box and it has at home administration. So we've got the right profile and large market, low penetration, better profile. We're really excited about this. I hope that gives you an idea of what the opportunity is.

[Paul Hudson, CEO & Director]

Yes. Thanks, Bill. Also, it's interesting to watch what the off-treatment durability was, not that we'd ever recommend that, but it's interesting to see how we may be targeting some of the underlying mechanisms in CSU. And I think it's going to be fascinating. I look forward to the Part B and what that tells us, because then maybe we have the complete picture, and that's going to be very exciting for patients.

[Unknown Executive]

The next question is from Jo Walton at Crédit Suisse.

[Jo Walton, Managing Director]

Apologies, I've got 2 questions, please. One on the COVID vaccines and the use of adjuvant. So when your original vaccine is an adjuvanted one, is it a 2-injection regime? Just trying to think how convenient it would be and whether you feel that you will have something that is sufficiently differentiated, but it could be widely used in Western markets? Or whether you feel that the existing vaccines of Pfizer, for example, they're just now so entrenched. But the regulators are not going to be that interested in going for an incremental approach. And my second question is just on the Dupi CSU data. Excellent news that you've got such strong itch data there. Do you think there's anything that you can use to sort of see how that would help against lebrikizumab? Because to understand it, lebrikizumab, one of their key elements is that they can show better itch than is normally seen. So I wonder how you feel of that -- how you compare that?

[Paul Hudson, CEO & Director]

Okay. Thanks, Jo. Maybe, Thomas, you want to comment on what our place could be. I think we have some pretty firm ideas you want to share.

[Thomas Triomphe, Executive VP & Head of Sanofi Pasteur]

Thank you, Jo. So indeed, I confirm the COVID-19 regimen in primary is a 2-dose regimen. But you know that in parallel, we're also testing, sorry, a booster possibility which will be then a 1-dose regimen. And what's interesting, and we've communicated about it before is that we're looking at the ability for the protein adjuvanted platform to be a booster of every -- any single platform that has been used in the primary state. So whether you receive the adenovirus platform or whether you're receiving a manifest from a protein platform, we believe there's a chance for our product to be 1-dose booster for all of these thermostable at [ room ] temperature, therefore. But of course, as we mentioned before, it's going to be Q4 data. So we'll remain completely data-driven. And in Q4, we will read out with the booster data and the primary data, and that will determine where we're going from what from this product.

[Paul Hudson, CEO & Director]

Yes. Thanks, Tom. I think we're all expecting there's enough volume of vaccines for primers. There will be certainly as we go through the remainder of the year worldwide, in fact, that we see our role mainly as a booster, our data is strong. I think we're going to play a very interesting part. And we're optimistic that, that will be the case. And that's -- I'm not sure -- but as a booster, it would do wonders. On your other point on Dupi, I can toss it to Bill. I think our data is really strong in CSU, right? And I think we'll still get to get to Part B. I mean we're really pleased with the data. I can't stress that enough and the size of the unmet need is significant, really significant. We've said it before, but lebri and the other IL-13s, they're only half the answer. We're an IL-13, IL-4. You've seen lebri, I think discontinued or failed from recollection in asthma. And so you start to understand the importance of treating type 2 inflammation. I think we have best in class, frankly. Bill, do you want to add something?

[William J. Sibold]

No, I agree. Just the read over, it just supports our efficacy in a disease with itch. And as Paul said, IL-13, it's an incomplete profile, right? I mean it all come -- it comes back as we think about this asset to the fundamental biology of the IL-4, IL-13, and we think that's just so key. And you're seeing these continued readouts in disease after disease that rely on that mechanism of action. So positive, great opportunity for us, just continues to fill in the picture for what the potential of Dupixent is.

[Unknown Executive]

The next question is from Geoff Porges at Leerink. Geoff?

[Geoffrey Craig Porges]

Just to follow up on an earlier question first on Dupi. The injection frequency in addition to the injectable administration is an issue, and many of your competitors with large biologics have adapted their product profile to reduce the frequency of dosing. I'm wondering if you have a project internally to potentially pursue that, that would actually also act as life cycle extensions? And then wondering if you could talk a little bit more, John, about rilza. It's something you didn't really highlight, but you're going to have the pemphigus readout by the end of the year. And to what extent -- or asked a different way, what are you looking for in the pemphigus readout that would potentially tell you about the likelihood of the drug succeeding in some of those much larger indications that you've talked about, say, asthma and atopic derm?

[Paul Hudson, CEO & Director]

Bill, dosing interval, Dupi?

[William J. Sibold]

Yes. Look, I think, Geoff, thanks for the question, first of all. Look, you've got to look at the whole profile, right? Because people are taking the product for efficacy, first and foremost, safety and then you look at convenience. And that's why we've gone back to the JAKs a bunch of time. That may be a convenient way to dose, but it's going to be a -- if it makes it to market ever, a highly black box broad immunosuppressant. So you can have something which is incredibly convenient to take. But if it is -- has bad side effects, it isn't going to make the difference. So we think that the profile that we have with Dupixent, and it continues to play itself out time and time again in every indication in every geography, that dosing is not a challenge for us. It's the whole profile of the drug that people are looking at, so we feel extremely confident in being able to compete with anyone who enters this market in the foreseeable future with the profile that we have, including that frequency.

[Paul Hudson, CEO & Director]

Well said, Bill. We -- I think what surprises most of you -- it surprised me when I joined the company, it's very rare that the first to launch in a major disease is first and best. And you have to get your heads around that a little bit, because we've touched on the IL-13s. Half the answer. We look at IgE, black box. We look across and we say, everybody has got something that they have to be working on or to communicate. We have great safety. We have excellent efficacy right across all these indications. And normally, that comes later in a disease. We've gone out front. It is the best medicine. If you look at the development of the sales performance as we really crushed Q2 and go on, it's basically stood on the top of safety and efficacy. It's an incredible profile. I think we just have to accept that first was best, and that's an unusual situation, I know. John, rilza, read across from pemphigus to potential other indications?

[John C. Reed]

Yes. Thanks for the question. Rilza is -- has broad potential in several contexts, but pemphigus is a classic autoantibody-driven disease and our Phase II data showed -- tested the mechanism of rilza there and we're quite impressive, and that's what caused us to move into the Phase III. We have similarly impressive data in another autoantibody-driven disease, namely ITP, immune thrombocytopenic purpura. So a couple of examples there where the molecule has achieved proof of concept, and we're in Phase III for both of those indications. And we're doing more in autoantibody-driven diseases, because -- based on the confidence building data we've seen in those. In terms of the extension then into some of the other indications, I think there are some similarities in some cases, and then there are differences in others. And that's why we're doing the -- we're intending to test rilza across a number of indications. The interesting thing about rilza is that it has ways -- it has several mechanisms by which you can interfere with allergic and autoimmune activity, blocking B-cell receptor signaling, blocking FcR receptor signaling. It's the 2 main mechanisms but others as well. So I think there's a strong rationale to pursue rilza across these indications. It's nice to have an oral as well in our portfolio as we try to probe some of this type 2 inflammatory landscape.

[Unknown Executive]

The next question will be from Graham Parry at Bank of America.

[Graham Glyn Charles Parry]

Firstly, on mRNA vaccines. So Sanofi started Phase 1 [indiscernible] monovalent mRNA and the Pfizer Biotech talking -- bringing into clinic with quadrivalent. So does that put you behind, because you try to be sort of careful about getting the right dosing levels. And then, secondly, just on the differences in some of the competitors to trials? So AstraZeneca has announced the [ SERENA-6 trial ] looking at ctDNA is that one mutation...

[Paul Hudson, CEO & Director]

Graham, I think we've lost you a little bit. Maybe you want to dial back in, we'll take the first question, which I think was in mRNA. It was the next question heading towards amcenestrant? I can't -- it was hard for me to tell. But maybe, Thomas, you like to talk about where we're at monovalent, quadrivalent mRNA.

[Thomas Triomphe, Executive VP & Head of Sanofi Pasteur]

Yes. Thank you, Graham. Indeed, as you noticed, we started our first flu mRNA trial, a monovalent trial, as you mentioned, a few weeks ago. We're going to get the data pretty soon. And the goal is you need to learn, as you remember, that's our second mRNA trial after the COVID-19 one. So it's starting through mRNA. We want to compete aggressively, which is why we have set up the center of excellence, extremely important for us. But indeed moving forward, and we'll build up on this in Q4 during the investors event. We are going to move forward a broader platform switching to quadrivalent flu moving forward.

[Unknown Executive]

So the next question will be from Mark Purcell at Morgan Stanley. Mark?

[Mark Douglas Purcell, Equity Analyst]

First one on amcenestrant, AMEERA-3. If you do not see superiority in terms of efficacy, are the data fileable? And then some of your competitors are going a little bit broader in adjuvant. So I just wonder what your options are there relative to the AI intolerant patient group. So that's the first question, if I may. And then the second question, just going back to rilza and starting Phase II trials in asthma, CSU and AD. Could you sort of help us understand the approach here in terms of a combination approach versus a sequential approach? That will be useful as we sort of think about the broader franchise longer term.

[Paul Hudson, CEO & Director]

Okay. John -- thanks, Mark, and John comments on amcenestrant and potential for superiority or not and filing strategy. And then maybe on the combination approaches in rilza, I'm not sure there's much we can share on that at the moment, but maybe tackling amcenestrant first.

[John C. Reed]

Yes. So on amcenestrant, as you can imagine, if the AMEERA-3 study should not show superiority but should show a very strong profile, perhaps numerically better than fulvestrant, which is one of the standard of care agents that we believe the investigators are turning to a lot in this population. It will really be a discussion with the regulators. So that's going to be, I think, how we would see that playing out. So I can't really give you a definitive answer. It will really be dependent on the regulatory discussion. In terms of the adjuvant, I mean, there are a number of ways to tackle the adjuvant space and that we see different companies try to do it different ways. We're compelled to focus initially on the higher-risk patients that are more likely to have relapses. That obviously can give you answers quicker and -- but it should be a more robust test. The study that we designed in the aromatase inhibitor-intolerant, that concept really emerged from the collaborative work we've done with these cooperative groups, which are the leaders in the field around how to do adjuvant studies and one of the patient populations with the greatest unmet need. And so it's through combining our best thinking with theirs that we came up with this study as our initial entry. But that won't be the only adjuvant study we'll do. We're planning others as well. We're currently working those plans up. But we feel that the study we've outlined AMEERA-6 is a great place to start. And I would say -- so far, the feedback from regulators as we've presented our plans there has been very positive, requesting essentially no changes in the design, et cetera. And what was that...

[Paul Hudson, CEO & Director]

The rilza combinations in asthma and other illnesses, I said that maybe it's a bit too early, but you may have a view.

[John C. Reed]

Yes. I think probably too early to really pontificate about what might be a future combination therapy. Let's see what rilza monotherapy does, the strong rationale to believe that as a monotherapy, it could make a tangible difference in diseases like asthma based on the centrality of BTK and in the immunobiology and the cellular signaling mechanisms that are believed to be prominent. So let's get that done first, and then we can think about where we go from there.

[Paul Hudson, CEO & Director]

Thanks, John. I mean there is -- depending on how the profile evolves, there is an add-on opportunity clearly in some of those illnesses and that's not uncommon in treating asthma, for example, but we'll see what we get to. Next question.

[Unknown Executive]

The next question is from Laura Sutcliffe at UBS. Laura?

[Laura Sutcliffe, Equity Research Analyst]

First question is on [ insulin ], please. Is the approved [Audio Gap] glargine in the U.S. built into your internal expectations for the year? Or should we be thinking about the downside there? And then second question is on amcenestrant. I was just wondering if you could talk about the drug-drug interactions you see between amcenestrant and CDK4/6? I remember ASCO, your AMEERA-1 poster revealed the dose-dependent decrease in palbo exposure. So just wondering if you've learned anything more there and how that's impacted your decision-making across the program at this point?

[Paul Hudson, CEO & Director]

So maybe a good chance to bring in Olivier to talk about glargine in U.S.

[Olivier Charmeil, Executive Vice President of General Medicines]

Yes. So Laura, thank you for your question. So there is no surprise for us. This is something that we had built in our plan. And when I shared the profile of the sales for General Medicine at the beginning of the year at the CMD on February 5, this is something that we have incorporated. For 2020, we see relatively minimal impact for 2022. I remind you that assembly will have a 1-year exclusivity. So we view that as another competitor on top of Abasaglar in a space where, of course, they have a very significant rebate. Of course, Toujeo is not impacted, so everything is built in our plan.

[Paul Hudson, CEO & Director]

Thank you. John, amcenestrant and drug-drug interactions?

[John C. Reed]

Yes. We don't believe it's an issue. We know that our SERD has a mild to moderate SIP induction. But palbo is -- the label improves its use with moderate SIP inducers. Palbo also, because of its toxicity profile, often has to be down-dosed and about 1/3 of patients at least, they have to skip doses or reduce doses because of trying to titrate the side effect profile of the drug. So we feel that we're well within a comfort zone there at the 200-milligram dose. We also know that we're well above the level needed to fully saturate estrogen receptors, as we get that done and doses less than 150 milligrams. So we feel that we're in good shape there, and I think that would be validated by the Phase I data that we presented at ASCO just a couple of months ago, with showing a strong overall response rate and a clinical benefit rate that leads us to be even more confident that this combo can go forward. The frontline setting in which we're testing the combo, I would say, incidentally, those studies are enrolling very well. The investor-related community is quite enthusiastic, so we hope to get that fully rolled ahead of schedule.

[Paul Hudson, CEO & Director]

Thanks, John. Next question.

[Unknown Executive]

The next question is from Peter Welford at Jefferies. Peter?

[Peter James Welford]

So firstly, just sticking on amcenestrant for a minute. Just thinking about the question about the superiority. I'm curious if you had a chance to see -- I think it was the VERONICA study that was presented from Roche, which was a failed study. But curious on your view on the PFS rates we were seeing in that study around sort of 2 to 3 months. Is that representative of what you believe the control arm, I guess, the patients who don't get amcenestrant could achieve? Or is it something we should be thinking about that makes your control patients perhaps different to what was reported in that study. Secondly then, just on Dupixent. Obviously, a good result in CSU and other trials coming. I guess, could you help us think about what are the triggers in terms of your original framework you set out for that EUR 10 billion aim? What are the triggers to potentially revise that? CSU obviously, a big indication now looks positive. What else do we have to see for the balance to get that to potentially look conservative?

[Paul Hudson, CEO & Director]

Thank you, Peter. John will come to you really on amcenestrant or rather specifically on Roche trial failure, which I'm not -- I don't have at my fingertips, you may have a view. On Dupi, I think we laid it all out pretty clearly in December '19. First thing we said EUR 10 billion plus, and I think the plus gets forgotten sometimes, and it shouldn't. Secondly, the major patient population that was not included was COPD. And we're delighted with CSU, the scale of the population that comes into play on CSU is equivalent to those that we're currently treating with Dupixent. And so you have to understand that's an event ultimately for this medicine. And then beyond that, COPD, I mean, Bill can give you some more stats, but it is -- there are over 700,000 patients, we think, roughly that are biologic eligible. So Bill, do you want to touch on that also as an additional trigger that goes beyond the 10-plus that's sort of been communicated?

[William J. Sibold]

Yes, absolutely, Paul. And as I said in my remarks, COPD isn't included. And look, that's a really exciting opportunity for us. And we have 2 assets that are actually there. And sometimes I think we forget that we've got Dupixent, which will be addressing the type 2 COPD population. And then we have itepekimab which is our anti-IL-33 again, in partnership with Regeneron, which will have more of a non-type 2 COPD focus, but also some -- a little bit of type 2. And to give you the idea of the scale, if you look at the type 2 disease, we think it's over 300,000 patients. And that's really, really firmly where Dupi can play. If you add in that non-type 2 former smokers, it's over 350,000 patients. So between the 2 products, we get a really, really meaningful piece almost 700,000 additional patient potential in an area where there are no other therapies that are available biologics, that is. We know some of the IL-5s are taking a look at it. They've had mixed results. They'd be focused solely in the type 2 space. But this looks like a great opportunity for us. Just to remind you, we'll have Dupi pivotal data expected in '23 and itepekimab in 2024. So we've got a lot to look forward to there. Just a comment, if you allow me to talk about the greater than EUR 10 billion as well. There is so much potential in the indications that we have and what we've just talked about. What we've really done, we have an obsessive focus on execution, and we have created a real global playbook for how we roll out each of these indications in each market around the world. And what you're seeing in each of the markets that we're launching is similar uptake like we saw in the U.S., which is just really, really strong. And I think it all goes back again to the profile of the product. It's the best product in each of the indications that we're in, and that's going to help us get to the greater than EUR 10 billion and with the addition of something like a COPD. So I'll leave it there.

[Paul Hudson, CEO & Director]

Yes. Well said, Bill, and this -- I've seen a lot of global executions. This is really a top class what the team have done, and it bodes very well for the launches that follow, because it's not easy to do, but you're starting to see the world come online now to Dupixent. John, I don't know whether you had a comment on Roche's failed study.

[John C. Reed]

I guess just to remind that the standard of care has been evolving in hormone receptor positive breast cancer, and the context in which we'll be testing amcenestrant, in which we are testing is in a largely -- a post CDK4/6 inhibitor world. There just aren't any data yet on anti-hormonal agents as monotherapies in this post CDK4/6 inhibitor class of patients or there just aren't very many data. Ours will be probably the first randomized assessment, randomized clinical trial assessment of endocrine therapies in that context. So it will be -- I think setting a strong foundation for how to think about using molecules like amcenestrant, the oral SERD class in that setting. We're -- we don't -- we can't predict what the PFS will be, but I would just say that we are in an event-driven study and the study has not reached enough events yet. So we cautiously interpret that as a good sign, but we'll see how things settle out when the data emerge, but it looks like we're trending to PFS as more in the 4 to 6 months kind of window right now based on how the events are coming in.

[Paul Hudson, CEO & Director]

Okay. Thank you, John. Next question.

[Unknown Executive]

For the next question, we have Seamus Fernandez at Guggenheim. Seamus?

[Seamus Christopher Fernandez, Senior Analyst of Global Pharmaceuticals]

So just a couple of quick questions. I wanted to just ask quickly as it relates to AMEERA-3, just trying to get a better understanding of, if you feel this trial is -- warrants the amount of attention that is being afforded it by The Street, it seems like this is a small potential indication. Just wanted to get a better sense of if this should be viewed as altering the opportunity for amcenestrant and if the trial should show an equivalent result. And then separately, as we think about the MS opportunity, obviously, this is an area of great enthusiasm when you presented the initial data, hoping that we might see some follow-up data at a medical meeting in that same population where we see longer-term data. Is that something that we could see either later this year or perhaps early next year to validate that strong early signal that we saw?

[Paul Hudson, CEO & Director]

Thanks, Seamus. I'll give you my view, I guess, on AMEERA-3, which is I think there's a convergence of things that make this interesting. Of course, for us, it's a stepping stone in restoring our credibility in science. So I think it gets a disproportionate amount of attention for that, because we have a lot of readouts coming over the next sort of 12, 24 months. And I think we -- obviously, everybody would like us to stay positive, not least for patients. Secondly, whilst I don't think the -- if you like, the business opportunity is significant. It is the first step on a journey. We will learn a ton and we will understand. We put everything on the table. We're doing all the studies. We've not hesitated because we approach things differently. And then, of course, I think the conversation is juiced somewhat by the fact that the competition, we believe, have inferior molecules, but really creating the debate and creating the level of interest. And of course, our data comes early, and I think everybody will be trying to find an angle on that. Just to remind you, we're going all in and pushing right across. We're very confident in the science behind our molecule. We think it will be the winner. This will be an important stepping stone but not the defining moment. But we are and remain optimistic. The second question was on the SHP2, I think? Did I hear that right? Sorry, did I mishear it?

[Seamus Christopher Fernandez, Senior Analyst of Global Pharmaceuticals]

Yes, can you hear me still?

[Paul Hudson, CEO & Director]

Yes, sorry. Could you repeat the question on tolebrutinib?

[Seamus Christopher Fernandez, Senior Analyst of Global Pharmaceuticals]

Yes. It was if we might see some additional data.

[Paul Hudson, CEO & Director]

Right.

[Seamus Christopher Fernandez, Senior Analyst of Global Pharmaceuticals]

And with that same patient population, perhaps either at a meeting later this year or perhaps like at AAN next year or something like that?

[Paul Hudson, CEO & Director]

Yes. I don't -- Bill, why don't you comment on our plans for sharing data if you have them at your fingertips?

[William J. Sibold]

Yes, I've done a little bit here. I mean we're -- there isn't so much that's going to read out additionally from the trial. We have ECTRIMS, which is going to be in October in 2021, and we'll be presenting some additional information. We -- at EAN in June, we presented the effective BTK on modulating microglia driven neuroinflammation and MS progression. That's a recent presentation we had for it. So we -- the focus has been in getting all of our studies up and running. We've moved extremely fast, and I think we've really set the pace for all of the BTK. Some -- as you know, when we started this thing, there wasn't so much talk about BTK and now everyone is adding their BTK to try to catch up. We believe that this is the best in disease potential profile across the full spectrum of MS. Brain penetrants is really, really important. And brain penetrance is important, but achieving a pharmacologically relevant brain penetrant level is the most important thing. Otherwise, you're just not going to see that effect. And that's why we think it works across the broad spectrum of MS. So stay tuned for data. Everything is progressing very well, and the community is really excited and we are as excited as we were the day we first mentioned it.

[Paul Hudson, CEO & Director]

Yes. Thanks, Bill. And we mentioned -- I think I mentioned it from the 95% of the patients in the open-label extension are what, over a year, I guess in -- and those stepped out were because of nondrug-related events. So it's quite interesting. That's a good leading indicator and Bill just touched on the pharmacologically relevant crossing of the blood-brain barrier. As always, when you're trying to [ beat that ] great data, everybody's just trying to find a way to come around the edges. But the proof of the pudding will be in the data, and we're way out in front. And you know we recruited the studies pretty fast and in the pandemic. So I think that's pretty exciting what is around the corner.

[Unknown Executive]

The next question is from Luisa Hector at Berenberg. Luisa?

[Luisa Caroline Hector, Co]

So maybe just one question on your announcement of the investment into the mRNA Center of Excellence. I just wondered if you could split that EUR 400 million in terms of CapEx, R&D spend. And as I understand it, it is budget neutral, so I just wonder whether other -- can you specify particular plans that have been scaled down to allow for this investment?

[Paul Hudson, CEO & Director]

Luisa, thanks so much. Thomas?

[Thomas Triomphe, Executive VP & Head of Sanofi Pasteur]

Luisa, so indeed, as mentioned, it's about EUR 400 million investment annually to accelerate the end-to-end R&D of the next generation of vaccines. As you mentioned, it's going to be fully financed through resource reallocation. How do we do that? We made a number of changes in our preclinical and early clinical programs. We don't disclose those targets, really. And we are clearly focusing on really a potential that we see for the future, and that's why we're pushing forth by 2025.

[Paul Hudson, CEO & Director]

Yes. Thank you. And we have towards the end of the year an Investor Day where we'll try and share a bit more detail around that. J-B, I don't think we split the CapEx, OpEx.

[Jean-Baptiste Chasseloup de Chatillon]

It's mainly here.

[Paul Hudson, CEO & Director]

It's many -- it's -- I think it says a lot about this organization. We know how to do vaccines, and we've done extraordinarily well. But we're not naive. And if we see an opportunity, we'll go after it. Now actually, when you start looking at the landscape, it's really about pivoting in a select number of areas. It's not right across the board. It's about going and getting stuck in pretty fast, because there's -- the distance to catch up is actually manageable. So it was a question of whether we had the courage to pick our areas and double down. And I think we're seeing that right across the company, frankly, but we're seeing it in mRNA too. And I think it says a lot about the leadership in vaccines that we're not -- with our head buried in the sand. Okay. Next question.

[Unknown Executive]

We'll take the final questions from Keyur Parekh at Goldman Sachs.

[Keyur Parekh, Equity Analyst]

My apologies if these questions have been asked already, but 2 please, if I may. First one on China and insulin VBP. Our understanding is that yesterday, there was a meeting held by the National Health Care started his question around table with all the key insulin players to discuss the plan and the feedback for potential in VBP. I was wondering if there are any insights that you're able to share on -- from this perspective, what your base case expectation today is and how we should think about the timing and the impact of this? That's question number one. And then secondly, relative to EUROAPI. Just wondering, J-B, if you can provide us with some incremental details from a time line perspective of kind of when we should expect this company to be stand-alone? And what the plan is from your perspective on separating this from Sanofi and potentially raising some capital out of it?

[Paul Hudson, CEO & Director]

Thanks, Keyur. Olivier, VBP China?

[Olivier Charmeil, Executive Vice President of General Medicines]

Keyur, thank you for your question. You understand that I'm not going to comment on working meeting with the authorities. But we -- when we share our assumption at the Capital Markets Day at the beginning of the year, we incorporated, of course, the impact of VBP or VBP-like scenarios. And so for us, there is no surprise. The exact mechanism, the scope, the timing is not known, and we feel very confident, given our track record in managing VBP in our ability now to grow volume. We have been able on Plavix to grow the volume, the first year about more than 90%, 9-0. And we continue to grow volume at the second year, and you saw that in the quarter. So for us, nothing unexpected, really in line with what I shared with you at the beginning of the year.

[Paul Hudson, CEO & Director]

Thanks, Olivier. J-B, EUROAPI.

[Jean-Baptiste Chasseloup de Chatillon]

Yes. Thank you, Keyur, for this question. It reminds us that we are effectively driving the transformation of Sanofi on multiple fronts. We are setting up consumer health as a stand-alone unit. We are transforming our commercial footprint with distributors versus subsidiaries in many regions, so it's many fronts. And EUROAPI is one of them, and it's fully on track. We said in December '19 that we would be aiming to deliver in H1 2022. We are there. Carve out is happening as planned. And the financials are also as planned. The activity is improving strongly since we manage it as a stand-alone unit, and it's getting ready for this IPO in H1 2022. We are expecting it to have a very small accretive impact on Sanofi. I remind you, we don't do it mainly as a financial play, but we do it really to drive this deep simplification we do across the board, as we also execute on our commitments on divestment of the long tail of products, both in Gen Med and in Consumer Health. So we are really executing transformation on multiple fronts. Thank you very much.

[Paul Hudson, CEO & Director]

Yes. Thanks, J-B, and thanks for the question here. Just on that last point about the simplification of the company. It's like when we -- I think you touched on it, J-B, some of the divestments. You should expect to see us do things like that, because there's a lot of things that we have levers to pull to simplify our business, to make us more agile and more productive and that's a real opportunities for us. So you should expect more of that, delighted with the progress made in EUROAPI says a little bit about the transformation that's ongoing and how creative we can be to create value.Maybe just before we just close the call down, delighted with the financials for Q2. Very pleased with how we're doing. Whilst I recognize everybody else had a low Q2 last year and the comps are relevant, I think our underlying growth is something that's more resilient than perhaps gets picked up and you'll see that evolve over the rest of the year. I think we've raised guidance, so you know we're confident in the financials. Dupi, well ahead of where any of you, I think, would have expected, and we're delighted with the progress. And we've added CSU, which I think was a major step, frankly, in terms of addressable patient populations in terms of the data at least. And our science moves on. And of course, you've asked about AMEERA, you're asking about rilza, you're asking -- these are the right things between the fall and into the first part of next year, there's readouts, publications and data. And that's what we're about. And that's sort of the piece that we're all excited about getting to on top of merely financials, although they take a lot of hard work, too. So thank you to everybody for your attention today. The transformation continues at Sanofi, and we look forward to connecting with you over the coming weeks and months.

[Eva Schaefer-Jansen]

Thank you, Paul, and thank you, everyone, for joining us today.