Good morning, good afternoon, and good evening to everyone. Thank you for joining us to review Sanofi's 2021 fourth quarter and full year results, 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 three, 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 advance to slide four. Our speakers on the call today are Paul Hudson, Chief Executive Officer, the Global Business Unit Head, Bill Sibold. Thomas Triomphe, Olivier Charmeil, and Julie Van Ongevalle, and Jean-Baptiste Chasseloup de Chatillon, Chief Financial Officer. For Q&A, you have two options to participate. Option one, click the raise hand icon at the bottom of your screen, or option two, submit your question by clicking Q&A icon at the bottom of the screen. With that I'd like to turn the call over to Paul. Well, thank you, Eva, and thanks to everyone for joining our call today. Delighted to be here and together with the members of the executive team to take you through the updates on our business and financial performance. You may have noticed that the visual change to our materials is more clear, it's more modern. I want to emphasize that as part of the transformation, simply nothing is off the table, including how parts of the business are named or indeed presented. Going forward, we'll be known as Sanofi across our businesses, and we continue to work to raise the standards of disease treatment and prevention. Let's start with full-year view. We delivered a 7.1% sales growth this year compared to 3.3% last year. Dupixent grew across all geographies, and Vaccines delivered another year of record influenza business with more than EUR 2.6 billion in sales. The contribution of our other GBUs has also been critical. The core assets we prioritize in our General Medicines business grew 5.6%, now amounting to EUR 5.8 billion together. Our consumer health business is catching up fast to close the gap with market growth. Bottom line, we delivered an EPS of EUR 6.56, growing at 15.5%, and continuing the strong trend we set since 2019. We have again improved our profitability with a BOI that now stands at 28.6 at CER. This is driven by both improved gross profitability, given the growing Specialty Care and Gen Med core asset portfolios, as well as our discipline in spending. At the same time, the way we have set our financial targets allows us to keep adding to our early-stage pipeline. I'll talk a little more about that in a few minutes. Moving to slide seven, let me turn to our main transformation activities this year. We announced six bolt-on acquisitions, which strengthen our growth areas in Immunology, Oncology, and Vaccines. They're a perfect fit with our strategic priorities as outlined at our Capital Markets Day in December 2019. We stay on the lookout for exciting business development opportunities. For example, our collaboration with BeiGene, which adds a new generation checkpoint inhibitor to our clinical pipeline. We also intend to unlock the potential of digital, data, and artificial intelligence in drug discovery and development. This is the rationale behind our partnerships with Owkin and Accentia to help us further accelerate our efforts in Immunology and Oncology. As we focus our efforts on building a sustainable pipeline, we're also taking action to reduce our complexity, again, fully in line with our 2019 commitments. We have continued to divest brands from our established portfolio and moved more than 50 countries to a distributor model. The standalone model for Consumer Healthcare is about 80% complete, and we started an ambitious program to reduce the number of Consumer Healthcare brands. The next major milestone for us this year will be the planned IPO of EUROAPI, which could create the second biggest API player in the world. Now let's move to what is at the core of our Play to Win strategy, developing breakthrough medicines and vaccines to improve people's lives. Let me give you a few highlights of what has been achieved over the past 12 months to advance our priority assets and beat industry benchmarks in R&D productivity. We delivered seven positive pivotal readouts last year. Nirsevimab marks a major scientific advancement in our effort to provide protection against RSV for all infants. We're about to begin global submissions one year ahead of our initial plan, and we're getting ready to launch for the 2023 RSV season. Dupixent has only begun to penetrate the large type two patient population in atopic derm and asthma. Last year, four additional indications delivered positive results. The year was also marked by eight major approvals for Dupixent, Libtayo, and Sarclisa, as well as Nexviazyme in Pompe disease, which strengthens our rare disease franchise. Our R&D engine achieved a remarkable milestone this year, with 10 molecules entering the clinical pipeline from in-house research, is something we have never achieved in the past. Our focus on three key therapeutic areas, Immunology, Oncology, Neurology, is increasing. We're building an industry-leading Immunology pipeline and have put our OX40-L igand antibody amlitelimab on the list of our priority assets, which allocates additional funding to allow accelerated development of the program. A potential first-in-class and best-in-class treatment for a range of immune-mediated diseases, starting with atopic dermatitis. Rilzabrutinib is in phase II development as a potential oral treatment option. Trials in asthma and CSU are going to be open soon. Oncology keeps building with the amcenestrant first line study, AMEERA-5 already fully recruited significantly earlier than planned, given the high interest in the study from the investigator community. In addition, we entered broad phase II programs for our engineered best-in-class interleukin-2 SAR245, and our first-in-class CEACAM5 antibody drug conjugate to explore and accelerate the development in areas of high unmet need. In Neurology, our scientists are continuing to build the body of data showing the impact of tolebrutinib on human microglia, which supports the thesis that this brain penetrant molecule modulates neuroinflammatory processes directly within the central nervous system. We will share new and important data at ACTRIMS just coming up shortly. We also have started phase III developments of tolebrutinib for the treatment of myasthenia gravis, a chronic progressive neuromuscular disease that strikes more than 10,000 people each year in the U.S. alone. Advancing to slide nine, I want to highlight how we have strengthened the early stages of our clinical pipeline by adding 36 projects in one year. This speaks volumes about our commitment to build an industry-leading sustainable pipeline with a steady stream of new assets that could transform the practice of medicine. 2021 has also marked the creation of our mRNA Center of Excellence to accelerate the development of the next generation of vaccines, with the ambition to deliver a minimum of six clinical candidates by 2025. We shared with you the interim results of our first mRNA monovalent flu study and pivoted our platform to modified mRNA in record time. As we transform and modernize the company for the long term, the teams also keep delivering robust performance and creating value in the short term. Our Q4 program is a good reflection of this. In fact, this quarter marks the first time that the Specialty Care business has led our business units by sales. Key growth drivers for Specialty Care with Dupixent 53% up compared to the same quarter last year, and our Specialty Care pipeline has grown to 87 projects in phase I to phase III, with 61 in our key therapeutic areas of Oncology, Immunology and Neurology. With that, let's start with Specialty Care. Bill, over to you. Thank you, Paul. It is indeed a very exciting milestone for Specialty Care to emerge as the largest business unit of Sanofi by sales in the last quarter. This milestone validates our commitment to execute on our business priorities and to be a leader in innovative medicines that change patients' lives. The fourth quarter proved to be another remarkable period of growth for our Specialty Care franchises, with EUR 3.5 billion in sales, up 21.3%. As mentioned by Paul earlier, Dupixent, our truly transformative Immunology mega brand, delivered once again a stellar quarter with more than EUR 1.5 billion of sales and high double-digit growth across all regions. More about the brand performance in just a minute. Double-digit growth of our Oncology franchise in the quarter and for the full year was mainly driven by the continued launch execution of Sarclisa and Libtayo in their respective key markets. Looking ahead, we are on a trajectory to exceed EUR 1 billion in sales in Oncology this year, despite the continued decline of Jevtana due to generic competition for the product in Europe. Our rare disease business reported exceptionally strong fourth quarter sales up 9.5%, driven primarily by higher demand across the Pompe, Gaucher, and Fabry franchises. Notably, our Pompe franchise reached blockbuster status in 2021, totaling more than EUR 1 billion in global sales. We are making great progress in the U.S. uptake of Nexviazyme, our recently launched next generation ERT for Pompe disease. We are actively working on establishing Nexviazyme as the next standard of care in global markets. We obtained marketing approval in Japan in November and have launched there. In addition, we look forward to a number of potential approvals in 2022 and continue to work toward approval in Europe from the EMA. Rare blood disorders franchise sales grew 2.7% when excluding lower industrial sales to Sobi. Growth of the franchise in the fourth quarter was driven by Cablivi, mainly due to additional launches in Europe and higher Alprolix sales in the U.S. High fourth quarter sales of Neurology and Immunology were due to the performance of Kevzara, which grew mainly because of the continued global demand for IL-6 receptor blockers and a temporary shortage of a competitor product, tocilizumab. As a result, we expect the demand for Kevzara, which is indicated for patients with rheumatoid arthritis, to remain strong in the coming months. Strong growth of Kevzara was partially offset by anticipated sales declines of Aubagio and Lemtrada in the quarter. Now moving to slide 13. Dupixent delivered another year of outstanding performance in 2021, driven by consistent strong growth quarter- after- quarter in U.S. and ex-U.S. markets. Last year alone, Dupixent added EUR 1.7 billion of incremental sales to the top line, making it Sanofi's number one growth driver. Annualizing now at more than EUR 6 billion in sales, we continue to believe that we are just at the beginning of the journey for this mega brand. Over the last two years, the key contributors of consistent strong growth have been patient demand, the approval of new indications, and the expansion into younger patient populations. I'd like to remind you that Q4 to Q1 growth is commonly impacted in the U.S. due to patient deductible reset. However, consistent strong underlying demand quarter-over-quarter has resulted in Dupixent becoming the number one newly prescribed biologic among each specialist we call on, including Dermatologists, Allergists, Pulmonologists, and ENTs. Outside the U.S., China continues to represent a major growth opportunity. With more than 30,000 adult patients treated to date, the launch is progressing strongly and according to our plans. Dupixent's growth opportunity in China is bolstered by the early NRDL listing, which was just extended by the authorities in China to include the 200-mg dose, improving our access to the adolescent patient population. In atopic dermatitis specifically, we have been rapidly advancing our leadership as new entrants come to the market in the U.S., Europe, and Japan. We believe competition can further raise awareness and help unlock our full market potential in AD. Recent U.S. approvals of competitive AD treatment options have come with a significant delay, and in some cases, safety concerns, which are reflected in their label. In line with our expectations, some new entrants have restricted indications as second-line systemic therapies, which can mean use after Dupixent. We believe this further reinforces Dupixent's best-in-disease clinical profile, balancing rapid and sustained efficacy with proven long-term efficacy. This strengthens our position as first-line therapy in the growing AD market. At the same time, we remain focused on delivering milestones for future growth, including the regulatory submissions of AD in children younger than six years old and in eosinophilic esophagitis. In asthma, we received a positive CHMP opinion for Dupixent in patients as young as six years old, with a final decision expected by the European Commission in the coming months. We are also excited about the recent pivotal data readouts in prurigo nodularis, which I will discuss briefly on my next slide. On slide 14, the data points on the charts demonstrate impressively the consistent benefit Dupixent has shown across two phase III trials, PRIME and PRIME2. These data confirms significant improvements in itch and the appearance of skin lesions in patients who are inadequately controlled with topical therapies or for whom those therapies were not advisable. The pivotal data readout is also confirming the potential benefit of targeting IL-4 and IL-13 as the central drivers of Type 2 inflammation in this specific disease, adding yet another indication for Dupixent if approved. Importantly, data from the PRIME and PRIME2 studies were consistent with the well-established safety profile of Dupixent in already approved indications. We are very excited about the opportunity in prurigo nodularis, given the high unmet need and lack of approved systemic therapies. We are on track to begin submissions to regulatory agencies in the first half of this year. Moving to slide 15, I'd like to highlight two of our launch opportunities in 2022. Both new products exemplify our commitment to bring innovative treatments to the market in Specialty Care, addressing underserved and sometimes under, ultra-rare diseases where there are few or no approved treatment options available. On the left side of the slide, we are eagerly expecting to obtain the FDA approval of sutimlimab with a PDUFA date tomorrow, February 5th. Sutimlimab has been developed as the first treatment for cold agglutinin, or CAD, and our plan is to begin launching the product in the U.S. through our existing rare blood disorders business operations. A rollout of launches is planned for Japan later this year and in key European markets beginning in 2023. On the right side of the slide, the upcoming launch of olipudase alfa underscores our unwavering commitment to delivering innovative therapies for the rare disease patient community. Once approved, olipudase alfa will be the first and only therapy for pediatric and adult patients living with non-CNS manifestations of acid sphingomyelinase deficiency or ASMD, a rare disease that robs quality of life for patients and their families and also increases the risk of premature death. The clinical development program for olipudase has demonstrated positive results in two separate clinical trials in adult and pediatric patients. Data from the ASCEND and phase II ASCEND-Peds trial evaluating olipudase alfa served as the basis for regulatory filings. Turning to slide 16. Efa, our uniquely engineered factor eight has the potential to revolutionize factor treatment for hemophilia A patients, pending successful completion of our ongoing phase III trial. Efa is designed to maintain high factor levels for much longer than all currently marketed factor replacement therapies. The product profile aims at providing sustained protection at near normal factor levels for most of the week, helping patients enjoy normal levels of physical activity, coupled with a low treatment burden of a once weekly dose. Considering the winning combination of convenience with weekly dosing, therapeutic activity with unmatched factor levels, and a safety profile in line with other factor therapies, Efa has the potential to become the factor therapy of choice, significantly improving quality of life for hemophilia A patients. With the potential to capture a significant share of the global $5 billion factor class market, we see high commercial opportunity for Sanofi territories, U.S. and Japan, addressing patients already on factor therapy and expect a rapid uptake once approved. We also believe that efa's profile would be competitive against non-factor treatments, unlocking additional opportunities by converting a portion of the non-factor patient population to safe factor treatment. While we are still waiting to see the phase III data, we are looking forward to sharing the pivotal results with you, which we expect at the end of Q1. With that, I hand over to Thomas to update you on the Vaccines business. Thank you, Bill. Q4 performance in Vaccines generated significant sales of EUR 2 billion, including a strong increase in flu sales in Europe, as well as growth reported by our PPH and travel franchises. The lower GBU sales versus last year were mainly due to the U.S. influenza market, where two factors combined. First, a low immunization rate due to the priority given to COVID-19 vaccination in November and December. Second, a record product shipment in the third quarter, leading to a 55.5% split for the Q3, Q4 period. The U.S. performance was partially offset by the strong Q4 demand in other geographies, especially Europe, where Efluelda was very successfully launched. The PPH franchise recording a strong fourth quarter growth despite lower birth rate around the world, mostly driven by Pentaxim performance in China. Finally, we are also pleased to see some recovery of the travel franchise, even though we are still far from the pre-pandemic level. Of note, on a full year basis, despite the pandemic environment, all five vaccines franchises have demonstrated growth in 2021 compared to 2020, illustrating again the robustness of our Vaccines business. Next slide, please. On the next slide, let's look at our record flu performance in 2021, with a 6% growth over last year's record. On the left chart, you can see that the impact from the U.S. market contraction was more than compensated by the strong performance of Europe and the rest of the world. Let me be very clear, the U.S. sales reduction has nothing to do with our product's performance. COVID-19 boosters were given the priority by retailers and as care providers, and as a result, the total number of U.S. flu doses injected this season decreased by 17%. Despite that challenging environment, Fluzone High-Dose continued to expand market share and gain 3.5 points share in the senior segment in the U.S. In Europe, the strongest Efluelda execution in Germany enabled us to reach a spectacular 64% growth following the positive STIKO recommendation. I'm glad to report that for the first season, three out of four German senior citizens have benefited from Efluelda's demonstrated protection beyond flu. The right graph shows the continuous progress of our flu franchise. All incremental sales in 2021 were driven by our differentiated flu vaccines, thanks to their proven ability to protect against cardiovascular events and against pneumonia hospitalization. For the first time ever, our differentiated flu sales represented the majority of our annual sales, indicating that the importance of providing protection beyond flu resonates well with external stakeholders. I'm confident that our flu franchise will continue to grow in 2022, and that this year we'll see another record year. With that, I hand over to Olivier. Thank you, Thomas. Moving to General Medicines on slide 19, we are encouraged by our performance in the fourth quarter. The execution of our strategy continued to deliver as planned, and the focus on our core asset has consistently generated positive results in recent quarters. In the fourth quarter, General Medicines sales reached EUR 3.4 billion, which included sales from industrial affairs. Our core asset grew 2.1% and were up as much as 4% when excluding the effect of Praluent sales to Regeneron in the U.S., which ended at the end of 2020. We drove double-digit growth for both Multaq and Soliqua in the quarter, while Plavix growth of 7.5% was accelerated by the strong performance in China, where the product is already included in the volume-based procurement program for the second year and generated growth of 28% in the period. We are very happy about the performance. Praluent sales increased by 36%, excluding U.S. sales to Regeneron in the fourth quarter of 2020. Outstanding growth of the brand was particularly due to its performance in Europe, where it was recently relaunched in Germany. As highlighted during the previous earnings calls, Lovenox sales were slightly down. This is mainly due to the high base of comparison in the fourth quarter of 2020, which followed the introduction of the WHO guidelines for the treatments of hospitalized COVID-19 patients, as well as some supply limitations. Our leading transplant franchise was strengthened by the consolidation of our new product addition, Rezurock. Starting on November 9th, Rezurock added EUR 20 million of sales in the quarter. I will provide more detail on this exciting launch on my next slide. In China, Sanofi participated in the VBP program for insulin in November. We are very proud of the results in the basal insulin category with Lantus and Toujeo. Sanofi was the only multinational company among the winners in category A, which is a product category that will receive most of the hospital volume allocations. Our glargine franchise remained broadly stable in the quarter, supported by Toujeo, and despite the price and inventory adjustment in China. In anticipation of the implementation of the insulin VBP, which is expected in the first half of 2022. Sales on non-core assets were lower in the quarter, in line with our expectations. The decline of 7.6% reflected the impact of product divestiture, which is key to our ongoing strategy streamlining efforts. We are vigorously reducing the number of small product families with the objective to drive efficiencies and increase profitability. Moving now to slide 20. For the full year 2021, General Medicines sales reached EUR 14.2 billion, which included sales from Industrial Affairs totaling EUR 808 million. Importantly, our core assets were up 5.6%. This performance translate into growth of 7.6% when excluding the impact of Tresiba sales to Regeneron in the U.S. Across our brands, Lovenox, Tresiba, when excluding U.S. sales, Soliqua, and our established brands in the transplant business, Thymoglobulin and Mozobil, delivered double-digit growth in 2021. The performance of our core asset in 2021 reinforces our confidence to deliver on our ambition to grow our core asset mid-single digit CAGR over the period of 2020-2025. For 2022, we expect another year of strong performance of our core asset. Despite the high base of comparison in 2021 for Lovenox, we expect sales of Lovenox in 2022 to be close to the level of 2021. Our well-established transplant franchise is expected to continue the growth path, strengthened by the launch execution on Rezurock. Soliqua is also set to continue its growth trajectory, supported by differentiated clinical profile. Leveraging the compelling SoliMix data, Soliqua is well poised for the competition with premixed insulin in its key markets. We are also very excited by the anticipated approval of Soliqua in China later this year. In China, the winning position of our basal insulin products, Lantus and Toujeo, in Category A of VBP, will enable us to deliver significantly higher volumes, but at lower price. With the pricing effect in mind, we expect our total glargine sales, Toujeo and Lantus, to decrease by around 33.0% in 2022 in China. Looking ahead, we aim to establish Toujeo as a basal insulin of choice in the large diabetes market in China, and expect to make Toujeo an important growth driver for our business in China in 2022 and beyond. Our non-core asset performance in 2021 reflects the impact from the progress we are making with our portfolio streamlining efforts. As discussed earlier, we continue to reduce the number of non-strategic tail product families. In summary, our 2021 achievements give us confidence in our ability to deliver on our commitment to stabilize sales by 2025 as compared to the 2020 base, and to maintain General Medicines BOI margin accretive for the group over the 2020-2025 period. Now moving to Kadmon on slide 21, let's discuss the value proposition of this important transaction for Sanofi and our transplant business. The acquisition was completed in November and represent a strong fit with our strategy. Kadmon's key asset was approved in the U.S. last summer and receiving positive market feedback, as highlighted on the slide. Rezurock has already reached 96% penetration in 80 key centers, and more than 500 patients have been treated to date. As we shared on our last earnings calls, Rezurock is a first-in-class treatment for adults and pediatric patients 12 years and older with chronic graft-versus-host disease who have failed at least two prior lines of systemic therapy. The prevalence is roughly 14,000 patients in the U.S., with steroid being the current standard of care in front line cGVHD treatment. We estimate that 5,000-7,000 patients in the U.S. who are treated with steroids fail on their therapy and require additional treatment. In the slightly more than four months in the U.S. launch, Rezurock generated sales of EUR 44 million, of which 20 million were consolidated by Sanofi since the acquisition. Going forward, we plan on accelerating the geographic expansion. We will continue to leverage our transplant expertise to maximize Rezurock growth potential, capitalizing on our long-standing relationship with the transplant community. In conclusion, we are excited about this innovative new core asset for Sanofi and confirm that the Kadmon acquisition will be slightly accretive in 2022. With that, I hand over the call to Julie. Thank you, Olivier. It's been a year since we presented our strategic priorities with the goal to grow our priority brands above market growth as early as 2022 in key geographies. I'm glad to report that today we're ahead of that commitment. Indeed, in 2020, we were losing share, and we were trending about five points below market growth. The latest market data shows that we have closed this gap. In November, on a rolling 12 months, we are at par with market growth. This despite our absence in cough and cold and physical wellness categories in the U.S., and mainly driven by our priority categories in key geographies gaining share. These results show that the execution of our three strategic priorities to drive our business is starting to pay off. On our first priority of cutting and embracing complexity, we've been able to increasingly focus on our key brands and geographies thanks to our simplification efforts. We have divested and pruned 111 non-core brands, a reduction of 40% of our total number of brands, which represents less than 1.5% of our sales. We've also reduced our trademarks by 50%, our domain names by 30%, and are continuously working on simplifying our processes and ways of working. At the same time, we have embraced the complexity of our multi-local brands by reallocating investment to brands with the biggest growth potential in market share gain. On our second strategic priority, to become a true fast-moving Consumer Healthcare business, the creation of our standalone is a key enabler, and we're on track. 80% of our legal entities are now live, and we integrated key functions like industrial affairs, all signs related functions, and supply chain under one roof. The success of this is twofold. First, a significant increase in agility in reaction to market and consumer needs. Cough and Cold is a good example where we were able to quickly size the opportunity of the market rebound in Q4, resulting in market share gain in October and November, excluding China. This is a first in four years. In addition, as mentioned earlier, this helps us to revisit our ways of working and adapt them to the specificities of a fast moving consumer healthcare business, for example, in consumer engagement, digital marketing, or speed of innovation. A big focus has also been to strengthen our brand equities and campaigns beyond the pure science and quality of our products, which we already deliver. On our third priority to build our digital and data edge, the creation of our standalone CHC again has given us the opportunity to revisit and build fundamentals with a strong focus on e-commerce, brand sites, CHC specific CRM and third-party management systems, and data-driven A&P and location tools. Regarding our Rx-to-OTC switches, both programs continue to progress despite the pandemic. The team is actively working on the projects, and we continue to execute critical studies in accelerated fashion. For Cialis in the U.S., we have completed the self-selection studies, and results have been submitted to FDA along with the protocol for an actual use trial. No erectile dysfunction Rx-to-OTC switch project has gone this far. We are now waiting for the FDA feedback in order to proceed. For Tamiflu, we're evaluating the status of the current flu season to determine if certain studies can progress. In the meantime, we have accelerated all studies that can be done without the presence of disease to keep the pace. On both programs, we should be able to share more next quarter. Turning to page 23, when looking at net sales performance, we have delivered 5.6% growth in Q4. Our organic growth is even higher with 7% growth in Q4 when excluding the impact of divestments. These results are driven by three factors. First, the progress we've made on the execution of our strategic priorities, as mentioned earlier. Secondly, we benefited from the market rebound in categories like Cough and Cold. Lastly, we also benefited from COVID vaccinations, specifically in pain care. We will continue to focus our efforts to further deliver on our three strategic priorities that have proven to be working with the ambition to build a true fast moving Consumer Healthcare business and be at par with market. Let me wrap up by saying how much I am enjoying working with the team, driving this CHC business back to growth. With that, I hand it over to our CFO, Jean-Baptiste. Thank you, Julie. Let me start by highlighting some strong proof points for Sanofi transformation in 2021. First, we managed to increase full-year gross margin by 120 basis points to 71.3%. This improvement is linked to the growing sales contribution of our brands in Specialty Care on higher-margin Vaccines products. It is also the result of efficiency measures in manufacturing, which typically require a longer lead time before they become accretive to margin and are now starting to come through. As I said before, we are committed to continuing this trend of gross margin improvement. Second, we manage our OpEx in 2021 effectively and without disrupting the strong growth momentum. We successfully controlled the increase in OpEx on managing them to grow slower than sales, which was possible as a result of our rigorous prioritization. As before, we reinvested the vast majority of efficiencies generated during the year. Finally, let me briefly comment on another proof point of our transformation, headcount. When I took on the CFO role in 2018, the company employed around 105,000 employees worldwide. With the ongoing transformation towards a more agile organization, we are now in a new phase with approximately 96,000 globally, and we continue to change our ways of working. We are embracing digital change, streamlining our portfolio, and collaborating with partners in geographies to balance a reduced infrastructure while improving access to our medicines. On this path, we expect to end the year with a headcount closer to 90,000, reflecting a more efficient organization. This would represent a 15% lower headcount as compared to 2018 and would include the successful IPO of EUROAPI per existing plans. On slide 26, turning now to the full P&L for the fourth quarter, company sales increased 4.1% at CER, driven by excellent growth of Dupixent in other Specialty Care franchises as well as Consumer Healthcare. The business operating income grew 6.9% at CER, benefiting from improvements at gross margin level, which were driven by the favorable portfolio shift to Specialty Care products and efficiencies within Industrial Affairs. In the fourth quarter, we again saw an increase compared to last year, with the margin improving 240 basis points. Business EPS grew 9.8% at CER, benefiting from a slightly lower tax rate of 20.5%. Turning to slide 27, we have achieved around EUR 2.4 billion of cumulative savings, of which EUR 2.1 billion were accrued through OpEx efficiencies, as depicted by the bright purple boxes shown on this slide. In addition, we realized an incremental EUR 300 million in COGS reductions over the last two years. Specifically, we achieved our target of EUR 500 million savings in R&D due to prioritization of Specialty Care on exiting diabetes and cardiovascular. In addition, lasting efficiencies were generated by consolidating function across sites, improving our trials logistic, reducing cycle times through advances in data and digital, coupled with more agile governance. Gen Med has been successful in reducing the complexity of its business, focusing on key markets on employing a digitally enabled go-to-market model. G&A across all areas of Sanofi contributed EUR 500 million of savings over the last two years, driven by smart spending initiatives, real estate efficiencies, a preferred supplier model on digitalization. In summary, we remain on track to achieve our target of EUR 2.5 billion savings by end of 2022. Most of this year's savings are again earmarked to be reallocated to fund our growth drivers and key programs in R&D. Moving to slide 28, let me briefly comment on our strongly increased free cash flow. In fact, we doubled free cash flow since 2018 through a focus on improved business performance and change in working capital. Given the strong improvement in free cash flow in recent years, we were able to achieve our 2019 Capital Markets Day objective of a free cash flow increase of around 50% one year ahead of schedule. On slide 29, we maintain our objective to continue Sanofi's annual dividend policy, which is reflected in the fact that the company has consistently increased its dividend payments for the past 27 years. As a result of Sanofi's performance in 2021, we announced that the board has proposed a dividend of EUR 3.33. A growing dividend remains an important element of our capital allocation, but it ranks behind our organic investments in business development in our priorities. On slide 30, we provide an outlook highlighting expected business dynamics across sales and expenses. Focusing on the left part of the slide, you can see expected drivers of sales across our GBUs, including the continuation of strong growth from Dupixent, record flu season, and maintained business momentum for the core products of Consumer Healthcare and General Medicines. As communicated before, we expect Consumer Healthcare priority brands to grow above market in key geographies, resulting in growth for the entire business, but only progressively nearing market rates. At the same time, we also foresee overall GBU sales in General Medicines to stabilize. The EUROAPI third-party sales are currently consolidated in this business, and upon the planned EUROAPI IPO, General Medicines sales will be reduced by that amount going forward. On the right part of the slide, we expect gross margin to continue to improve due to product mix and efficiencies. R&D expenses are expected to continue to grow in line with our strategy. As we keep streamlining our General Medicines and CHC business, we expect to generate around EUR 500 million in capital gains throughout 2022. We estimate that our 2022 ETR, effective tax rate, to be around 19%, given the evolution of our product and geographic mix. This estimate is based, of course, on current tax legislation. On my final slide 31, we expect full year 2022 business EPS to grow in the low double digits at CER. On our way to achieve our 2022 financial targets, we also guide to a BOI margin of 30% for the year. On foreign exchange, we see a positive currency impact of 2%-3% based on January average exchange rate. With 9.3% EPS growth in 2020 and 15.5% EPS growth at CER in 2021, we are on track for a third year of double-digit or near double-digit EPS growth. I now hand the call back to Paul. Well, thanks, JB. We expect 2022 to be another busy year with important development, excuse me, milestones for our priority molecules and other pipeline programs. We're looking forward to the results of four pivotal studies, including amcenestrant in second and third line metastatic breast cancer, as well as the phase III results of efanesoctocog alfa in hemophilia. The readout of Dupixent in chronic cold-induced urticaria may add another dermatological indication, addressing a population of 25,000 patients in the U.S. alone. We also anticipate making further important pivotal trial decisions, especially in Oncology and Vaccines. Moving to slide 34 into ESG, you may remember that our social impact strategy was approved by the Sanofi board little more than a year ago. Our renewed contract with society is fully aligned and embedded with our business strategy and ambitions. We make good progress across all our four pillars. Today, I would like to highlight some achievements in the area of affordable access. The mission of the Sanofi Global Health we created last year is to increase access to essential medicines in some of the world's poorest countries. In the area of malaria, TB, and non-communicable diseases, we have increased both the number of patients reached and the number of countries. In addition, Sanofi is committed to helping 1,000 patients living with rare diseases who have no access to treatment. We donated again more than 100,000 vials in 2021. This builds on a 30-year humanitarian commitment to patients suffering from rare diseases such as Fabry, Gaucher, and Pompe diseases. Moving to slide 35, as we look into the 2022 calendar, we will update you every quarter on our new initiatives happening across the four pillars of our ESG strategy. This quarter, we wanted to put the focus on access. We're proud to announce a partnership with Medtronic LABS and the launch of a multi-country, multi-year collaboration in the field of non-communicable diseases. Together, we will leverage digital health and a community-based approach to improve disease awareness, diagnosis, and management of diabetes and hypertension in strong collaboration with health system partners. The public health burden of NCDs is staggering, with 35 million deaths globally, of which 28 million occur in low to middle income countries every year. This project will contribute to strengthening health systems as they build towards universal health coverage and sustainable development goals. On my final slide, let me touch on some planned events in the first half of this year. As mentioned, we expect to have further tolebrutinib data presented at ACTRIMS, and we'll organize a virtual event around this. Invites will be sent out shortly. We also plan for an update on our Immunology pipeline, including Dupixent in late March. As part of this update, we will revise upward our peak sales potential for this medicine. We are currently finalizing our plans for an event focused on ESG that we hope could take place in the June, July timeframe. Well, let's open the call now for Q&A. Thank you. We will now open the call to your questions. We would like to ask you to limit your questions to one each so we can call up a number of the participants. You have two options to participate. Click the Raise Hand icon at the bottom of your screen. You will be notified when your line is open to ask your question. At that time, please make sure you unmute your microphone. Or option two, submit your question by clicking the Q&A icon at the bottom of your screen, and your question will be read out. Can we now have the first question? Yes. The first question comes from Wimal Kapadia from Bernstein. Wimal? Oh, great. Thank you very much for taking my questions. Vimal Kapadia from Bernstein. First, can I just ask on the U.S. flu business, you know, declined year-on-year. Thomas, you flagged a 17% market contraction in volumes. Could you just provide a bit more color on your expectations for the volume value mix for the U.S. in 2022? And what was the level of coverage in 2021? Was that actually below historical pre-COVID levels? And if so, should we be getting a nice bounce in coverage in 2022, specific to the U.S.? Then my second question is just on the OX40. I know we had some data last year for the OX40 program from, you know, which is now a priority asset. Just curious how you're thinking about targeting the OX40 versus the OX40 ligand. I'd love to hear, you know, how you think about the duration of effect, which is given looking at Amgen's drug looked rather compelling on that front. Have you seen anything from your own asset suggesting a similar efficacy profile with time? Thank you. Thank you, Vimal. Great questions. Thomas, flu coverage read across for 2022. Thank you very much, Wimal. Indeed, you understood very well that the U.S. flu situation in 2021 was a very specific U.S. situation with -17% on the overall volume for the U.S. What that means that it was lower than 2019. Very specific to the U.S. again, as you've seen from the other markets, and completely linked to the COVID-19 specifications. You know very well that there was a lot of confusion with different age indications being licensed at the same time and a lot of discussions on the boosters. Definitely we don't see that as a play moving forward for 2022, because of course, if you end up being in 2021 with the U.S. vaccine coverage below 2019, that gives room for growth. We are very confident about 2022. We expect to see both volume and value increase in the U.S. versus this year. To give you an example, I think it's a good illustration of what could happen in the U.S. for flu in 2022. I think everybody has understood that there's needed to be some fixes on the U.S. flu coverage. CMS has very interestingly decided to increase the flu vaccine administration fee from $17- $30 per dose for the season in 2022 in the U.S. I think there's going to be a strong CDC understanding as well as strong retailer preparation to make sure that 2022 is very different from 2021. That's why we're expecting a record flu season overall for Sanofi Pasteur and indeed an increase of flu in the U.S. in 2022 versus 2021. Thank you. Thank you, Thomas. Great to hear from Sanofi Pasteur. John Reed, OX40 ligand. I think the question from Vimal is about duration and efficacy, and maybe you have some thoughts on tolerability as well. Yeah. I think it was about OX40, the receptor, versus OX40, the ligand. We prefer the ligand because it is induced on antigen-presenting cells, so its quantity in the body is less, whereas OX40 is more heavily expressed on a constitutive basis and can, you know, mean that you're gonna have to dose higher to neutralize it. More importantly, I think, than that is the fundamental difference in the mechanisms of our molecule, amlitelimab, coming from the Kadmon acquisition versus the Kyowa Kirin antibody that Amgen has accessed. The Kyowa Kirin/Amgen antibody is a depleting molecule that actually kills the cells that express OX40, whereas we have a non-depleting antibody that modulates OX40's pathway. The downside of depleting is that both effector T cells, which are, you know, contributing to the autoimmunity, but also regulatory T cells that we need for suppressing autoimmunity, express OX40. Over time, you'd have the risk of depleting those necessary regulatory T cells with a depleting mechanism. We feel that in terms of long-term safety and durability of the effects that a non-depleting antibody targeting the ligand is really a superior way to go. Thank you, John. Couldn't agree more. Next question. The next question will come from Richard Vosser at J.P. Morgan. Richard? Thanks very much for taking my question. Two questions, please. First one, just on flu as well. Could you talk about your manufacturing capacity and supply and how that will develop and the demand that you might see for high dose beyond Germany in Europe? Second question, there's clearly been quite a lot of interest for consumer assets early on this year. Does that lead you to change or accelerate any of your plans for the consumer business going forward? Thanks very much. Thanks, Richard. First of all, I'll compliment Tom and the team on what they've done with the high dose launch, and particularly this year and remotely and incredibly in Germany. The question is supply and beyond. Thanks, Richard. Definitely no concern at all on U.S. or non-U.S. flu supply. We are very confident. You know very well that last year we've added a new flu building in Swiftwater. You know also that we are further investing into additional Fluzone High-Dose antigen for the mid- to long-term with the Canada plant. Really moving forward on that and feeling very confident on supply for this year. Of course, as every single year, we are always receiving the Northern Hemisphere season at the end of February, and at the end of the Q2 call, usually we take that moment at the Q2 call to make a little bit of an update on supply and phasing for Q3, Q4. When it comes to demand, as you've highlighted, the Sanofi vaccines team have done very strongly this year in Germany. We expect this to further grow. There is room to grow in Germany. When it comes to other markets in Europe, we are going to introduce in 2022 in a couple of new markets in Europe, but you know very well when it comes to vaccines and flu introduction, it's about having preferential recommendation, it's about having reimbursement. We'll start new countries in Europe little by little until we have the right reimbursement in place, and then we will provide the supply. Thank you, Thomas. The consumer question, you know, I think I got where you're heading, Richard. I think, the thing for us, we go back to what we said Capital Markets Day, December 2019. We thought we could grow faster than we were growing. We thought we could carve in, increase agility, accelerate growth, make better choices, prioritize, leverage e-commerce, and run fast all the way to the switches. I think, Julie and the team have done an incredible job, frankly, on doing that, and we're really delighted with the progress we made. We know a lot happens outside with other companies and different things, but we know the choices that we made back in 2019, and we're very happy with how things are performing. Okay. Next question. The next question will be from Luisa Hector at Berenberg. Luisa? Hello. Thank you for taking my questions. Possibly for JB, but you mentioned the headcount reduction. I just wondered if you can give us an update on the EUROAPI spin, timing, gating items. Also on gross margin, so clearly, very good progression, so you're working very hard on this and it's paying off. Can you guide us to whether to think about a continued improvement through 2023 when Aubagio Generics arrives? Thank you. Okay. Thank you, Luisa. JB, you always get the fun ones, so maybe, there's a EUROAPI question. It was partly related to headcount. You may wanna go a tiny bit broader and then, of course, gross margin and where we go from there. In the journey to transform, we have the new business model operating in some countries commercially, but we have also this API activity which is going to be a leader in its field. IPO is announced for H1 2022. We are on course to do this. As planned, Luisa, we're looking forward to make it happen in H1. On the gross margin, effectively, we delivered on 2021. We are guiding again on improvement. On the midterm, I won't make a gross margin guidance multi-year, but there's something which is a strong element you have to keep in mind, is that on our main asset, Dupixent, we are going to have quite a transformative journey in terms of costs, which should really help us at least to neutralize any price erosion we could have, because we are looking at implementing new manufacturing processes that will deliver strongly in terms of cost improvement. That's a clear piece. Thank you. Luisa, you didn't ask, but I'm glad you asked the questions because you know, there's a huge amount of work. You know, while we're advancing the pipeline, 36 new programs in early development, the six acquisitions, I think what does get missed out of our discussion a little bit occasionally is the fundamental work that's going into reshaping the company. They're right sizing the company, of course, but more importantly, you know, we're having an IPO in the first half of this year. At the same time, we're carving out a consumer business. On all these things, we're outperforming while doing them, while delivering on the science and the overall financial performance and the commitments we made to the Street for 2022. You know, we really feel like, you know, the level and scale of transformation that are happening is perhaps not fully understood, and it's okay, but it's extensive. Maybe next question. Yes, next question will come from Simon. Simon Mather at Exane. Simon? Hi, guys. Yeah, thank you for taking my questions. Loving the new branding, by the way. The first question is actually for JB. You know, you've given guidance for 19% tax rate for 2022. If you look at consensus and out years, it's some 230 basis points higher. Just wondering if you can potentially comment on the sustainability of this tax rate or how we should maybe, you know, revisit our expectations there. The second one is just on Dupixent. Thank you for the updated timeframes with respect to guidance. I mean, I think it's clear you blow everything out of the water in terms of safety and efficacy in atopic dermatitis. Appreciate it's early days, but maybe could you comment on any impact that you're seeing or that you expect to see with the recent launch of tezepelumab in severe asthma and feedback that you may be getting from physicians? Thank you. Okay. Well, thank you for the kind words on the branding. You know, for those that haven't followed it closely, you know, it is the original font from our birth in 1973. It's also an opportunity for us to be a little bit more disruptive and unify the company as well at the same time. I'm glad that it's recognized. I think it's more dynamic, frankly, and reflective for the comments I made earlier, how much the transformation is happening here. From that high energy question to tax, Jean-Baptiste. To you. Thanks. Thank you very much. Yeah. It's a nice trend on our effective tax rate, 200 basis points. Effectively, as I said in my previous speech, it's really something which is dependent on further changes in the tax legislation. We have structural good trends, and let's say that the underlying tax rate is like between 19%-20%. As we speak, I don't know what will be the full impact of Pillar Two or changes of taxation in some other regions like the U.S. A good trend, with a big chunk of it linked to our business and tax rate in France also, which is going positively. That could be disturbed in the midterm by other changes in other regions. Thank you, JB. Thanks also, Simon, for the compliments on Dupixent, which is, you know, a frankly incredible performance, and led by Bill and the team. Bill, comments about new entrants and early signals. Yeah. Well, thank you for the question. You know, none of the new entrants are a surprise, for one thing. We've been planning on these. We've been waiting, in some cases, extended waits for the JAKs as they were almost a year delayed. While it's new competition in the U.S., you know, we've had these competitors that have already launched in Germany and on their way in Japan as well. We're certainly used to them. I think the one thing that they do is they really reinforce our best-in-disease clinical profile that we have. You know, just go back to the biology. Targeting IL-4 and IL-13, that is fundamental to Type 2 inflammation, and no other product has been able to show the profile that we have in any of the Type 2 diseases, and, you know, clearly starting with atopic dermatitis, where we are the leader now. Asthma as well, you know, the profile, again, we think is the top, the best profile that is in asthma, and we're, you know, seeing really very promising signs all around the world of our ability to compete and win in the asthma space. Just one comment. You know, as we have competition come into the atopic dermatitis market, it actually helps to serve to grow the market, grow awareness of atopic dermatitis, et cetera. As we've had competitors launch in other countries, as I said, Germany and Japan, we have seen market expansion. That's what we expect. That's part of our aspiration to have a, you know, 25%-30% advanced therapy penetration in atopic dermatitis over time. That's one of the contributors. You know, the one thing that's clear is that we are on top, we remain on top, and we believe being best in disease, we will stay on top. Sorry, can I? Apologies to interrupt. Yeah, I think I said tezepelumab. I've got it on my brain. I meant tezepelumab in the U.S. Is there any early feedback you could share? Yeah. No, there's really nothing that we're seeing. It's still very early. Yeah. You know, we're staying with the trends that we've seen. Yeah. Just to add a kind of point to Bill's, which is, you know, I think the assumption is always it's a zero-sum game. You know, say with the JAKs, for example, the baggage, and you know with the IL-13s, it's half the answer, missing the IL-4. You know, and you know that most of these mechanisms have failed in at least one of the indications that Dupixent is already approved. Tezepelumab would probably be in that box too. I think it failed in AD, if I remember correctly. Yes, correct. We're on one hand, we're the only medicine that will play in every indication. On the other hand, as Bill said, and I think it gets missed every time, a little bit of competition to help drive up penetration of advanced therapies is absolutely essential. Bill's comments about Germany should not be underestimated because you know we obviously will carry the education of these disease areas, but it's good that others want to come in and try and do that too. In growing markets where you're the market leader, it's a very healthy place for us to be on behalf of patients. Okay, next question, please. Next question will be from Graham Parry at Bank of America. Graham? Great. Thanks for taking my questions. Congratulations on getting an hour into the call without an AMEERA-3 question, but I'm afraid we're gonna break that. Just wondering, have you accrued all events now, and in data lock? We still look for Q1 readout on that study. The elacestrant results, I think have led to some concern in the market that oral SERDs only show benefit in ESR1 mutated patients, who are obviously more rare in the front line setting. I think that's leading some pessimism around, you know, the potential in front line. Perhaps if you could just address that point. Then secondly, a question on M&A. You've done a lot of smaller pipeline deals of late. Obviously biotech valuations have fallen somewhat at the moment. With the weakness that you're seeing in biotech prices, are you seeing more value and opportunity perhaps to build out further in Oncology where I think you've highlighted is still a key target? Thank you. Thank you, Graham. I didn't hear the first part of your question. It's an AMEERA-3 question. Thank you for raising it. I'm gonna toss it to John. John, I don't know if you heard it. It was, you know, the competition showed more efficacy, I think, in ESR1 mutation, and what's the read-through for us? Where are we on database lock and reporting out in Q1? Right. Okay, Graham. No, thank you. In terms of the activity of our SERD on wild type versus mutant estrogen receptor, we're fully active on both. Whereas the competitor molecule is better on the mutant than on the wild type, so that's not at all a liability for us. It is one of the differentiators of our molecule and one of the many factors that we think gives it a best in class profile along with the pristine tolerability. You know, we expect to have the data this quarter with respect to AMEERA-3 and the late-line metastatic breast cancer. I'm also pleased to report we're fully enrolled now in the frontline study in combination with the CDK 4/6 inhibitor, and that the first of our adjuvant studies is now open for enrollment. We're making good progress across the spectrum from early to late line in each of these indications where we think amcenestrant has a strong value proposition for women with hormone receptor-positive breast cancers. Thank you, John. Categorically, Graham, results in Q1. Okay, JB, M&A? Yeah. Well, thanks for the question, but I do think that our M&A activity is not related to the peak and trough of the valuation of biotechs. It's much more dependent on the leadership of our R&D team and on John scouting for the right asset, which is really fitting with our strategy, really fitting with our TAs. No specific impact from the current level of valuation. It will be up and down. We are still on for bolt-on acquisitions, of course. Great. Thank you. Next question, please. Next question will be from Tim Anderson at Wolfe. Tim, your question please. Thank you. A couple of questions. Going back to oral SERDs, we'll be getting two readouts this year from two similarly designed trials later-line for us, your trial and then Roche's trial. Both companies claim best-in-class. Do you think these upcoming datasets will help prove which company is right and which company is wrong in making that claim, or would that not become clearer until we get additional trial readouts, such as in the first-line setting? Second, we'd love to get your thoughts on Lilly's lebrikizumab. They're saying they think that will have a profile that's very competitive to Dupixent. They talk about differentiation in ocular side effects. I'm wondering what your thoughts are on them as a competitor. They do know the derm space well because of Taltz. Thank you. Okay. A few good things in that. John, given Roche's data and our impending data, do you think we'll be able to declare a winning profile this year? No, it's a good question. I'm not sure that these late line settings are, you know, the best place to really differentiate on efficacy. Where we do feel confident that we'll be able to perhaps differentiate is on the safety tolerability profile, where so far, you know, amcenestrant has really been delivering a best in class profile, whereas molecules from others, including Roche, have been showing safety signals around cardiac issues and in some cases vision issues. You know, I think that's probably the best answer I can give you for now. I would probably be really looking to, you know, how the tolerability profiles hold up in these early lines as opposed to hinging a lot on this on the efficacy profile, given, you know, the, a lot of the, heterogeneity in these patient populations you see in the late line, and therefore the difficulty to really do cross-trial comparisons in a, in an apples to apples way. Thanks, John. I reiterate to everybody, we haven't seen the data. We are optimistic that we're in a good spot, and we look forward to getting it. You all know, I think, it's a small indication if we are successful. In terms of value perspective, it's not as important, although it may bring benefit to those that need it, let's be frank. From a confidence perspective, we know it's important to everybody. When we have the data, you'll be soon after us in terms of knowing. As for, I do think, whereas in most of the areas I've worked, intolerability inevitably plays a part, particularly this, as we move earlier lines, and John touched on it, tolerability will be a key differentiator. If I understand correctly, the competitor you referenced at a lower dose continues to have cardiotox challenges. You know that we think those things are gonna be very, very important over the longer term. Bill, IL-13s, Lilly is saying that they have a winning profile. Yeah. Well, thanks for the question. You know, as Paul said, I think earlier on, with the IL-13, it's incomplete. It's missing the IL-4. We think starting with the biology, it's not the complete biology. When you take a look at their results, and let's remember, these are phase IIb results. They're still waiting on their later results. You know, there's nothing that really stands out from our perspective. Efficacy looks fine. The conjunctivitis looks similar to Dupixent. You know, I think some of the big differences is that we're six years ahead at that point by the time they launch. We are a mega blockbuster. We've become the standard of care. I think for somebody to come in with something that isn't so much to offer, you know, I think that is regardless of your experience in a therapeutic area, it's not therapeutic experience in atopic dermatitis. You know, as we said, it's part of the story, IL-13, certainly not the full. We've got the best profile. Yeah. Thanks, Bill. Thank you. Oh, was there a follow on? Thank you. That's it. Okay, thanks. Yeah, for mine, it's great that they have experience with Taltz. I have a lot of experience with Cosentyx, and nobody's got the experience like we have in AD. I'm telling you what the team has done with Dupixent is incredible. We never underestimate competition, particularly well-organized ones. It starts with the biology, like Bill said, and if you have got half the answer, you have a long row to hoe. I'm sure they'll make some progress. Let's go all the way back to the fundamental, which is additional weight in the market to help educate and improve penetration is welcome. If we have the best profile, which we believe we do, then we will disproportionately benefit from that, you know, we look forward to the meeting in March, where we'll update you more deeply about our forecast and indeed our Immunology pipeline in general. Next question, Evan? Yes. Next question comes from Marc Purcell at Morgan Stanley. Matthew, if you have a question. Thank you. Thanks, Bill Sibold. Thanks, everyone. Two questions. Firstly, on the Dupixent, could you give us an update in terms of where you are in terms of advanced therapy penetration rates in AD versus the 25%-30% you just gave, and also some idea of an indication split? Ahead of the twenty-ninth of March, just to sort of get us in the mood, perhaps if you could help us understand sort of where you believe in the future a U.S., ex-U.S. split could be. Obviously, ex-U.S. growing 80% from a lower base than the U.S., but where eventually do you feel ex-U.S., U.S. split could be? The second one on THOR-707 or SAR444245, the IL-2, phase III go-no-go decision is coming up in the second half of this year. I wonder if you could help us understand which indications and lines of therapy those decisions will be made on, if it's monotherapy or combination therapy, and what are the gating decisions when making that hurdle into phase III. Okay. Thank you, Matthew Weston. Bill, I think the question is, where are we now, and what is the penetration? How does it evolve towards that 20%-30% you're talking about? Yeah. Thanks for the question. We've got a, you know, still a long way to go. Just to give you a sense in U.S. adult AD at 7.9%. When I say the finish line's looking at, you know, 25%-30%, which is a little bit. It's in the range of psoriasis, maybe a little bit higher. We've got a long way to go. Just reinforcing what Paul and we've said along the way, new competitors in the marketplace help to accelerate that. Regarding U.S., ex-U.S., you know, we have seen kind of similar patterns in every market that we've launched in the world following the U.S. from a growth perspective. We continue to see that. We expect that. We're not gonna comment on what we think the ultimate geographic distribution will be or indication split. Yeah. Thanks, Bill. You know, I think as well, you know, Europe always takes an extra time to get through the reimbursement cycles. The rest of world takes some time to get through the reimbursement cycles. It always starts slower, then it always gets more interesting, and then everybody always starts to ask questions about it. Now, Bill, we don't need to share the relative proportions, but the fact that the rest of the world will just get stronger and stronger in terms of its contribution because the medicine is so good. I think Bill mentioned China earlier. That is quite 30,000 patients in just months. I think that starts to help you understand where we might be heading. John, SAR444245 or formerly known as THOR-707, in likely indication split and thoughts on, I think it was combos. Yes, you know, thanks for the question. Maybe before I jump into SAR444245, though, since you brought up the Immunology event coming in March, we're really looking forward to not only talking about Dupixent but also the broader portfolio. You know, we've grown from just six molecules in development for Immunology to now 17. You'll be, you know, hearing about our biologics that include amlitelimab, the OX40 ligand, itepekimab, the IL-33 antibody in development for COPD, our engineered interleukin-2. On the other flip side of the story, THOR-809, that stimulates regulatory T cells instead of effector T cells, our bispecific multi-specific nanobodies that do nifty things like neutralizing both TNF and IL-23 in a single molecule, a new concept for inflammatory bowel disease, CD40 ligand, et cetera, as well as our oral small molecule portfolio of rilzabrutinib, a unique BTK inhibitor, our RIPK1 inhibitor, our oral TNF inhibitor, and the IRAK4 degrader. That portfolio for Immunology has really blossomed, and we look forward to talking more about that in March. Now, the SAR444245, we have a large platform study underway in lung, head and neck, GI, skin and lymphoma. Like most companies, we sort of started with the obvious to do combinations with PD-1, and we're pursuing that. This year, we will be embarking on novel combos with other kinds of mechanisms. I would note, for example, that we have three T-cell engagers now in development. We have our first NK cell engager went into development. We have our universal allogeneic NK cell platform. There's a lot to think about as combination opportunities with SAR444245 across a range of solid tumors and hematologic malignancies. This will be a rich year for generating those early data signals. We're eagerly anticipating what we might be able to do with this best-in-class engineered version of interleukin-2. Thanks. Thanks, John. I do think we were talking about it actually quite recently, the number of signals that we're gonna get across the pipeline, but particularly in Oncology, is gonna be quite interesting this year. While we know they're only early for some of you, but we would like to be an emerging player in Oncology. There'll be nice moments for us to make some decisions about which way to go, and we're optimistic. Next question, please. Yeah, next question would be from Emmanuel Papadakis at Deutsche Bank. Emmanuel? Thank you for taking the question. Perhaps I could go with one on efanesoctocog. Just your expectations or your ambitions, perhaps, for the upcoming pivotal data. I think you said you're hoping to show above near normal expression, above 40% factor VIII 4 days. What sort of figures would you be hoping to be showing at seven days? And what kind of share implications do you think that could have relative to what Eloctate has at present? Indeed, if you could give us some color on where you think Eloctate is presently, that would be helpful as well. And then perhaps the second question on the SHP2, right, is given the decision to progress the combination to phase II with Amgen. Just wondering if you've seen any data to provide confidence on synergy for that combination, given the pretty clear lack of SHP2 monotherapy activity, and the timing of that potentially either phase I or data from the ongoing phase II being presented to us at a scientific conference. That'd be helpful. Thank you. Thank you, Emmanuel. John will come to you in a moment, but Bill, I don't know if you have any comment. Actually, John may have two as well on efanesoctocog. I don't think we've declared what our expectation is, but you know, certainly our profile is gonna be best in class. So Bill do You want to comment? Yeah, I think that's right. I think if you take a look at what we showed in the phase II, which showed that, you know, over half the week, four days where you're at essentially a near normal level, and by the end of the week, it tapers off to in the 10%, I believe. Yeah, still quite. It's still robust. Quite strong protection even at the end of the week. Yeah. I mean, you just look on the slide that I showed, you know, no one's even close to that, and no one's even close to that with a once weekly. This we consider really transformative in the hemophilia A space. You know, when you think about patients, kids who wanna have an active lifestyle, and if you can give them something they've never seen before, then maybe for, you know, just a brief moment, normal, and you do that for the better part of the week, you know, you begin to think about giving them a little bit more of their life back and being active and so forth. You know, we're really excited. That's what we expect to see that in our phase III, at least we hope. You know, that's it set a pretty high bar. Set a high bar for us, set a high bar for the market, I think, overall. You know, stay tuned. More to come on that one. You know, this is really something which is different. No one's been able to offer this before, so I think, you know, we're hearing patient communities really excited. I know it's. I've heard that feedback too obviously, Bill, and I think the real question is could it go even longer depending on the patient's longer-term? I mean, it gets very exciting for efanesoctocog and our confidence is building. As you know, the gene therapy. At least this generation doesn't seem to be, you know, definitive. Of course, Hemlibra comes more towards the weekly or bi-weekly itself, you know, then the opportunity is perhaps even bigger than we thought when we started on this journey, I'll be honest. Of course, half the market is still impacted, like Bill said, so quite interesting for us. John, maybe SHP2, KRAS. Yeah. You know, the reason that we're pursuing that combination is because in preclinical studies where we and others tried different combinations of SHP2 with various other signal transduction blocking molecules, that was always consistently the place where we saw the best combination from efficacy, so the most synergy. Again, this is not just Sanofi data, but it's Mirati data, it's Amgen data, et cetera. We think that if there's a combination where SHP2 can shine, this is it, and we're doing the studies this year. It's another one of these where the signals will be the important determinant of what kind of trajectory we can take with that mechanism. That's the rationale, and the data will ultimately speak for themselves, and we'll be gathering it this year. Thanks, John. Maybe, Emmanuel, I just thank you for the bit of research you did on Rezurock. I found it really interesting how physicians were really thinking confident already and thinking about moving to earlier lines. I mean, of course, it's just a survey, but it was very insightful, and we enjoyed reading that. So thank you for that work. You're welcome, sir, and congratulations on the strong launch. Great. Thank you very much. It means a lot. Okay, Emma. Felix, last question, right? Yes. Last question would be from Matthew Weston at Credit Suisse. Matthew. It's Jo here. I'm sorry. Yes. I have two questions. On Dupixent, I wonder, you've given us the 8% penetration in the U.S. adult market in AD. Perhaps half of the sales potential comes from other indications. I wonder if you could just tell us how successful you've been in penetrating things like asthma so that we can see how broad the appeal of this is beyond atopic dermatitis. I noted that you're going to update your sales projections, but that's before you have the COPD data. I thought you were waiting for that before you gave us an update. My second question would be on Efa. I would have assumed that if somebody was interested in efficacy but not so concerned on safety, they may already have moved from a factor to a non-factor. Safety is likely to be a very important part in making the decision for these patients to move on to your new product. How much safety data will you have at the time of submission and of launch? What makes you so confident that people won't think that the different pharmacodynamics of this factor could impact on the safety characteristics of the product? Okay. Well, there's quite a lot in there. Jo, you always keep me guessing. Sometimes I can't connect, and then you appear as Matthew Weston. Either way, I'm glad that we got to the questions. Dupixent and other indications, penetration, Bill? Yeah. You know, if you look, Jo, in asthma, we're at about 19% biologics penetration. Okay. That's the starting point. Then, as you've heard from a specialty perspective, we're leading in each of the specialties with Dupixent. The other indications, you know, look, it depends, again, on the biologic penetration. You know, they're pretty low. We're starting with, you know, a brand-new indication, so to speak, with nasal polyps. We're the only player there. Still working on the epi a little, but it appears as though we're having good, strong penetration there. Won't give a number at this time. Regarding the second question was, Well, there's one about why are we waiting for the COPD data, which I'm happy to answer, but then we move to a safety and efficacy trade-off on efanesoctocog w hich we may get to with John. Jo, we can't win. If we wait, you say, "Why are you waiting?" And if we don't wait, you say, "Why have you not waited?" I'm we're sort of betwixt in between. I think because the COPD data is in 2023, I think we all felt that a good time to take stock would be towards the end of Q1 and using a deeper Immunology catch-up, that we think that's worth doing. Of course, we won't be able to declare a new peak without referencing, you know, that it's like, you know, it'll be different with COPD if the data reads out. How we frame that when we're very early in the thinking, so we stay loose on that until we get there. I just don't think, given the run rate and the prescriptions, that we could ask people to wait a full year or more actually to understand what the peak could be. John, I don't know if you got it all on the safety efficacy trade-off and what data we'll have for- I'm a little surprised by the question because the safety of this next generation factor VIII is pristine. There have been no safety signals. We don't have any reason really to believe there would be any. You could almost say, to some extent, that way was paved with products like Eloctate, which fuses an Fc region onto factor VIII. Here there are some additional embellishments with the so-called XTEN technology, but that had also been de-risked with other molecules that have been taken to clinic, including an approved product. The components of the molecule have all been de-risked, and we've not seen any safety liabilities. On the other hand, if you think about alternatives, they do have some historical safety baggage. I really think on a safety standpoint, again, we come out best in class. Yeah, John, just to add to that, you know, I think clearly from an efficacy perspective, we win, too. I mean, no one's. If you look at the comparison where emicizumab is, if you try to, you know, estimate where it is, it's nowhere near normal, right? It's nowhere near normal factor levels. You know, we're really confident that we win on the safety for you know, just redefine the safety bar. If you know, you're looking at a weekly dose, that's pretty convenient as well. You know, I think across both parameters, we're in really good shape. Yeah. Thank you. You know, when I joined the company, a lot of people asked questions like, "Did the company not understand Hemlibra was coming when we got into fitusiran in 001?" Half the people responsible for Hemlibra work for us now. John Reed, thanks. One thing we did learn was that these patients are dynamic and they will move fast if they see a better choice to be made, particularly if you're not a true monthly, you're actually every one to two weeks, in the case of the non-factor. As Bill said, you know, set a new standard. I think the competition need to be slightly more concerned that the patients are much more likely to change. It's what got them their position in the first place, and it's what we'll do when we launch with Efa, which is not that far away. Thank you for those questions. Thank you to everybody for the energy and the contribution. I'm delighted by the way, as always, we're starting to transition more towards science and the transformation of the company, a little less just on the basic financials, which every day we're responsible for. Don't even think that we're not. We think in terms of value creation and in the right to bring our pipeline forward and surprise you is very, very important. Nothing's off the table. We're shaping the company real time. You may not see it, and pity you don't, you're not part of it. I think as we look back, I like to, particularly at the full year, you know, we get to look at the distance traveled just in 12 months. I think it feels like we've come an awful long way. While we've got some news flow up ahead of us, and we hope it's all positive, you know, we will keep moving forward, finding signals and advancing 36 programs that were not moving at the beginning of last year, that moved last year. 10 first in human for the first time in the company's history. The penny should be dropping that our ability to pivot on science is really in full flight. Thank you to everybody on the team. Thank you to Eva. Thanks to everybody on the call. Thank you very much. You may now disconnect.