Q4 2021 Sanofi SA Earnings Call

Speaker 1: The contribution of our other GBUs has also been critical. The core assets we prioritized in our general medicines business grew 5.6%, now amounting to 5.8 billion Euros together. And our consumer health business is catching up fast to close the gap with multiple

Our other Gpus has also been critical core assets, we prioritized in our general medicines business grew five 6% now amounting to $5 8 billion yours together.

Our consumer health business is catching up fast to close the gap with multi credit.

Speaker 1: Bottom line, we delivered an EPS of 6 euros and 56, growing at 15.5%, and continuing the strong trend was 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 GenMed core asset portfolios, as well as our discipline in spending.

Bottom line, we delivered an EPS of $6 56, growing at 15, 5% and continuing the strong trend since 2019, we have again improved our profitability with the PMI that now stands at $28 six at CER. This was driven by both improved gross profitability given the growing specialty care.

And Jim met coal asset portfolios as well as our disciplined <unk> spending.

Speaker 1: 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.

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.

Speaker 1: 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, ecology, and vaccines. They're a perfect fit with our strategic priorities as outlined at our Capital Markets Day in December 2019.

Moving to slide seven let me turn to our main transformation activities. This year, we announced six bolt on acquisitions that strengthen our growth areas in immunology oncology and vaccines.

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 beyond which adds a new generation checkpoint inhibitor to our clinical pipeline. We also intend to unlock the potential of digital data.

Speaker 1: We feel on the lookout for exciting business development opportunities. For example, our collaboration with Beyond, which has a new generation checkpoint inhibitor to our clinical pipeline.

Speaker 1: 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 OCHIN and Accenture to help us further accelerate our efforts in immunology and oncology.

And artificial intelligence in drug discovery and development. This is the rationale behind our partnerships with oaken and Accenture to help us further accelerate our efforts in immunology and oncology.

Speaker 1: 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 commitment.

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.

Speaker 1: We've continued to divest brands from our established portfolio and moved more than 50 countries to a distributor model.

Continued to divest brands from our established portfolio have moved more than 50 countries to a distributor model.

Speaker 1: The standalone model for consumer health is about 80% complete and we started an ambitious program to reduce the number of consumer healthcare brands.

Standalone model for consumer health is about 80% complete and we started an ambitious program to reduce the number of consumer healthcare brands.

Speaker 1: 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.

The next major milestone for us this year will be the planned IPO of Euro API, which could create the second biggest API player in the world.

Speaker 1: Now let's move to what is at the core of our play to in 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 beats.

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.

To give you a few highlights of what has been achieved over the past 12 months to advance our party assets in feet.

Speaker 1: feet industry benchmarks in our indeed productivity. We delivered seven positive pivotal readouts last year. The seven above marks a major scientific advancement in our effort to provide protection against RSV for all in...

Industry benchmarks in R&D productivity.

We delivered seven positive pivotal Readouts last year, the seven month marks a major scientific advancement in our effort to provide protection against RSV for all infants whereabouts to begin global submissions. One year ahead of our initial plan and were getting ready to launch for the 2023 RSV season.

Speaker 1: We're about to begin global submissions one year ahead of our initial plan, and we're getting ready to launch for the 2023 RSVC.

Speaker 1: Depicson has only begun to penetrate the large type 2 patient population in a topic and act?vie

Do you pick some has only begun to penetrate the large type two patient population in atopic derm and asthma last year for additional indications delivered positive results.

Speaker 1: Last year, four additional indications delivered positive results.

Speaker 1: The year was also marked by eight major approvals for dupexam, libtaia and sarclisa, as well as next bi-asign and pompe disease with strengthens or rare disease franchise.

The year was also marked by eight major approvals for to pick some lip south pizza as well as next design in Pompe disease with strengthens our rare disease franchise.

Speaker 1: Our R&D engine achieved a remarkable milestone this year, with 10 molecules entering the clinical pipeline from in-house research. It's something we have never achieved in the past.

Our R&D engine achieved remarkable milestone this year with 10 molecules entering the clinical pipeline from in House Research is something we have never achieved in the past.

Speaker 1: Our focus on three key therapeutic areas, immunology, oncology, and neurology is increasing. We're building an industry leading immunology pipeline and have put our Ox 40 ligand antibody and the Telemab on the list of our priority aspects.

Our focus on three key therapeutic areas immunology oncology and neurology is increasing we are building an industry, leading immunology pipeline and to put our ox 40 ligand antibody I'm going to tell them up on the list of our priority assets, which allocate additional funding to allow accelerated development of the program.

Speaker 1: 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 a topic, dermatitis.

Potential first in class and best in class treatment for a range of immune mediated diseases, starting with atopic dermatitis will debride nib as in phase two development as a potential treatment option trials in asthma and C. S. You are going to be open soon.

Speaker 1: Will's Arroutness is in phase two development as a potential oral treatment option. Trial is in asthma and CSU are going to be open soon.

Speaker 1: And College of Keeps Building with the Ames Phinesphan First Line Study and Mirror 5 already fully recruited. Significantly earlier than planned, giving the high interest in the study from the investigator community. In addition, we entered Broad Phase 2 programs for our engineered besting class in Salucon 2, SARS-245. And our firsting class, C-CAM 5 antibody trutonjugate, to explore and accelerate the development in areas of high and met needs.

In college it keeps building with am Sonesta in first line study and there are five already fully recruited significantly earlier than planned given the high interest in the study from the investigator community. In addition, we entered broad phase III programs for our engineered.

Best in class interleukin, two SAR 245, and our first in class <unk> five antibody drug conjugate to explore and accelerate the development in areas of high unmet need.

Speaker 1: In neurology, our scientists are continuing to build the body of data, sharing the impact of Tollybrutinib on human microglia, which supports the thesis that this brain-penetrant molecule modulates neuroinflammatory processes directly within the central nervous system.

In urology, our scientists are continuing to build the body of data showing the impact of totally bruton on human microglia, which supports the thesis that this brain penetrant molecule modulates neuro inflammatory processes directly within the central nervous system.

Speaker 1: We will share new and important data to actrants just coming up shortly. We also have started phase three developments of Polly Brutonib for the treatment of myocenia gravis, a chronic progressive neuromuscular disease that strikes more than 10,000 people each year in the US alone.

We will share new and important data to actions just coming up shortly we also have started phase III development of calibrating for the treatment of myasthenia gravis, a chronic progressive neuromuscular disease that strikes more than 10000 people each year in the U S alone.

Speaker 1: 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

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.

Speaker 1: This speaks volumes about our commitment to build an industry-leading, sustainable pipeline with a steady stream of new assets that can transform the practice of mentoring.

This speaks volumes about our commitment to build an industry, leading sustainable pipeline the steady stream of new assets that could transform the practice of medicine.

Speaker 1: 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.

2021 is also about 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.

Speaker 1: We shared with you the interim results of our first mRNA monovalent flu study and pivoted our platform to modify their mRNA in record time.

We shared with you the interim results of our first mrna monovalent clear study and pivoted our platform to modify the mrna.

In record time.

Speaker 1: 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 sale.

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 would you pick.

Speaker 1: Key growth drivers for special care would do pixel 53% up compared to the same quarter last year. And our special care pipeline has grown to 87 projects in phase one to three with 61 in our key therapeutic areas of oncology, immunology and neurology. So with that, let's start with special care and build over the.

53% up compared to the same quarter last year and our specialty care pipeline has grown to 87 projects in phase one to three with 61 key therapeutic areas of oncology immunology and neurology, so with that let's start with specialty cat and bill over to you.

Speaker 2: Thank you, Paul. It is indeed a very exciting milestone for specialty care to emerge as the largest business unit of Sonopi 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 patient lives. The fourth quarter proved to be another remarkable period of growth for our specialty care franchises with 3.5 billion euros in sales of 21.3%.

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 three 5 billion euros and sales up 21, 3%.

Speaker 2: As mentioned by Paul earlier, who picks in our truly transformative immunology mega brand, delivered once again a stellar quarter with more than 1.5 billion euros of sales and higher double digit growth across all regions. More about the brand performance in just a minute.

As mentioned by Paul earlier, two pixels are truly transformative immunology Mega brand delivered once again, a stellar quarter with more than one 5 billion euros of sales and higher double digit and high double digit growth across all regions more about the brand performance in just a minute.

Speaker 2: Double-digit growth of our oncology franchise in the quarter and for the full year was mainly driven by the continued launch execution of Sarklisa and Laptayo in their respective key markets. Looking ahead, we are on a trajectory to exceed one billion euro in sales in oncology this year, despite the continued decline of Jettana due to generic competition for the product in Europe .

Double digit growth of our oncology franchise in the quarter and for the full year was mainly driven by the continued launch execution of start closer in la Tayo and their respective key markets. Looking ahead, we are on a trajectory to exceed 1 billion euro and sales in oncology. This year. Despite the continued decline of gip Tana due to generic.

<unk> for the product in Europe .

Speaker 2: Our rare disease business reported exceptionally strong fourth quarter sales up 9.5% driven primarily by higher demand across the Pompeii, Gose and Bradbury, franchise.

Our rare disease business reported exceptionally strong fourth quarter sales up nine 5% driven primarily by higher demand across the Pompeii doshi and Bradbury franchises.

Speaker 2: Notably, our Pompeii franchise reached blockbuster status in 2021, totaling more than 1 billion Euro in global sales. We are making great progress in the US uptake of VIA's I'm, our recently launched Next Generation ERT for Pompeii.

Notably our pump a franchise reached blockbuster status in 2021 totaling more than 1 billion Euro and global sales, we are making great progress in the U S uptake of <unk>. Our recently launched next generation E. R. T for Pompe disease.

Speaker 2: We are actively working on establishing next design as the next standard of care and global markets.

We are actively working on establishing next design as the next standard of care in global markets. We.

Speaker 2: 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 approving Europe from the EMA. Where 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 Kebleeby, mainly due to additional launches in Europe and higher alcholic sales in the US.

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 disorder franchise sales grew two 7% when excluding lower industrial sales to sobey growth of the franchise in the fourth quarter was driven by <unk>, mainly due to additional launches in Europe and higher alcoholic sales in the U S.

Speaker 2: 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 to salismat. As a result, we expected 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 a bazoo and lentrada in the quarter. ces voids

Hi, fourth quarter sales of neurology, and immunology, where due to the performance of kept Zara, which grew mainly because of the continued global demand for IL six receptor blockers and a temporary shortage of a competitor product coastal doesn't map as a result, we expect the demand for <unk>, which is indicated for patients with rheumatoid arthritis to.

<unk> strong in the coming months strong growth at <unk> was partially offset by anticipated sales declines of our Boswell and let me try to in the quarter now.

Now moving to slide 13.

Speaker 2: Depixon delivered another year of outstanding performance in 2021 driven by consistent strong growth quarter after quarter in US and XUS markets. Last year alone, Depixon added 1.7 billion euros of incremental sales to the top line, making it Sonophe's number one growth drive.

<unk> delivered another year of outstanding performance in 2021, driven by consistent strong growth quarter after quarter and U S and ex U S markets last year alone. We pixel added $1 7 billion euros of incremental sales to the topline, making at Sanofi is number one growth driver.

Speaker 2: Annualizing now at more than 6 billion euros in sales, we continue to believe that we are just at the beginning of the journey for this mega-brick.

Annualized now with more than 6 billion euros in sales. We continue to believe that we are just at the beginning of the journey for this Mega brand.

Speaker 2: Over the last two years, the key contributors of consistent strong growth have been patient demand, the approval of new indications, and the expansion in the younger patient population.

Over the last two years. The key contributors are consistent strong growth had been patient demand the approval of new indications in the expansion into younger patient populations.

Speaker 2: 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.

Like to remind you that Q4 to Q1 growth is commonly impacted in the U S. Due to patient deductible reset however.

However, consistent strong underlying demand quarter over quarter has resulted in the pixel, becoming the number one newly prescribed biologic among among each specialist we call on including Dermatologists, Allergists, Pulmonologists and E N T.

Outside the U S. China continues to represent a major growth opportunity.

Speaker 2: With more than 30,000 adult patients treated to date, the launch is progressing strongly and according to our plans.

With more than 30000 adult patients treated to date the launch is progressing strongly and according to our plans.

Speaker 2: Depictions growth opportunity in China is bolstered by the early NRDL listing, which was just extended by the authorities in China to include the 200 milligram dose, improving our access to the adolescent patient population.

<unk> growth opportunity in China is bolstered by the early NR D. L listing, which was just extended by the authorities in China to include the 200 milligram dose improving our access to the adolescent patient population.

Speaker 2: 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.

In atopic dermatitis, specifically, we have been rapidly advancing our leadership as new entrants coming 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 E D.

Speaker 2: 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.

Recent U S approvals of competitive 80 treatment options have come with a significant delay and in some cases safety concerns which are reflected in their label.

Speaker 2: In line with our expectations, some new entrants have restricted indications of second line systemic therapies, which can mean use after depicts.

In line with our expectations, some new entrants have restricted indications of second line systemic therapies, which can mean use after depiction.

Speaker 2: We believe this further reinforces the PICs and best in disease clinical profile, balancing rapid and sustained efficacy with proven long-term efficacy. This strengthens our position as first-line therapies 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.

We believe this further reinforces depicts them best in disease clinical profile balancing rapid and sustained efficacy with proven long term efficacy. This strengthens our position as first line therapy and the growing market at the same time, we remain focused on delivering milestones for future growth, including the regulatory.

<unk> of <unk> in children younger than six years old and in eosinophil like esophagitis.

Speaker 2: In asthma, we received a positive CHMP opinion for dupixin in patients as young as six years old, with a final decision expected by the European Commission in the coming months.

In asthma, we received a positive <unk> opinion for <unk> in patients as young as six years old with a final decision expected by the European Commission in the coming months.

Speaker 2: We are also excited about the recent pivotal data readout in Praegonodularis, which I will discuss briefly on my next slide.

We're also excited about the recent pivotal data readouts and prego nodule areas, which I will discuss briefly on my next slide.

Speaker 2: On slide 14, the data points on the charts demonstrate impressively the consistent benefit that you pick in has shown across two phase three trials. Prime and prime two.

On slide 14, the data points on the charts demonstrate impressively the consistent benefit depicts and has shown across two phase III trials prime and prime too.

Speaker 2: These data confirmed 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.

These data confirmed 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.

Speaker 2: 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 depiction if approved.

Pivotal data readout is also confirming the potential benefit of targeting IL, four and IL 13, as the central drivers of type two inflammation in this specific disease, adding yet another indication for <unk> if approved.

Speaker 2: Importantly, data from the PRIME and PRIME 2 studies were consistent with the well-established safety profile I have depicted in already approved indications.

Importantly data from the Prime and Prime two studies were consistent with the well established safety profile I have depiction in already approved indications. We are very excited about the opportunity in prego nausea, laris given the high unmet need and lack of approved systemic therapies. We are on track to begin submissions to regulatory agencies and the <unk>.

Speaker 2: We are very excited about the opportunity in Prego 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.

First half of this year.

Speaker 2: 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 and specialty care, addressing underserved and sometimes under ultra rare diseases where there are fewer no approved treatment options available.

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 fewer no approved treatment options available.

Speaker 2: On the left side of the slide, we are eagerly expecting to obtain the FDA approval of cetimlamab with a PDUFA date tomorrow, February 5th. Cetimlamab has been developed as the first treatment for cold glutenin or CAD, and our plan is to begin launching the product in the U.S. through our existing rare blood disorders business operator.

On the left side of the slide we are eagerly expecting to obtain the FDA approval of the timber mab with the Paducah date Tomorrow February 5th So Timna Mab 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.

Speaker 2: A rollout of launches is planned for Japan later this year and in key European markets beginning in 2023.

A lot of launches is planned for Japan later, this year and in key European markets beginning in 2023.

Speaker 2: On the right side of the slide, the upcoming launch of Olipidase Alpha underscores our unwavering commitment to delivering innovative therapies for the rare disease patient community.

On the right side of the slide the upcoming launch of <unk> de Silva underscores our unwavering commitment to delivering innovative therapies for rare disease patient community.

Speaker 2: Once approved, Olipidase 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.

Once approved <unk> will be the first and only therapy for pediatric and adult patients living with non CNS manifestations of acid single myelination deficiency or a S. M. D. A rare disease that robs quality of life for patients and their families and also increases the risk of premature death.

Speaker 2: The clinical development program for lipidase has demonstrated positive results in two separate clinical trials, an adult and pediatric page.

The clinical development program for a lipid days has demonstrated positive results in two separate clinical trials.

<unk> in pediatric patients.

Speaker 2: Data from the ASCEND and Phase 2 ASCEND-PEDS trial evaluating a lipidase alpha served as the basis for regulatory filings.

Data from the ascend and phase II <unk> trial evaluating <unk> self served as the basis for regulatory filings.

Turning to slide 16.

F a.

Speaker 2: Our uniquely engineered Factor VIII has the potential to revolutionize factor treatment for hemophilia A patients, pending successful completion of our ongoing Phase III trial.

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.

Speaker 2: EFA is designed to maintain high factor levels for much longer than all currently marketed factor replacement therapies.

<unk> is designed to maintain high factor levels for much longer than all currently marketed factor replacement therapy.

Speaker 2: 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.

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.

Speaker 2: coupled with the low treatment burden of a once-weekly dose.

With the low treatment burden of a once weekly dose.

Speaker 2: Considering the winning combination of convenience with weekly dosing, therapeutic activity with unmatched factor levels, and a safety profile online with other factor therapies, FSA has the potential to become V factor therapy of choice, significantly improving quality of life for hemophilia, AAPA.

Considering the winning combination of convenience with weekly dosing therapeutic activity with unmatched factor levels and a safety profile in line with other factor therapy <unk> has the potential to become B factor therapy of choice significantly improving quality of life for hemophilia a patients.

Speaker 2: 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.

With the potential to capture a significant share of the global 5 billion dollar 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.

Speaker 2: We also believe that EFSA'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.

We also believe that efficacy 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.

Speaker 2: While we are still waiting to see the phase 3 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 vaccine.

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.

Speaker 3: Thank you, Bill. Q4 performance in vaccine generated significant sales of 2 billion euros, including a strong increase in flu sales in Europe , as well as growth reported by our PPH and travel.

Thank you Bill Q4, sometimes in the vaccine generated significant sales of 2 billion euros, including a strong increase in flu sales in Europe as well as growth reported by a P. P H in troubled franchisees.

Speaker 3: The lower GBU cells as of last year were mainly due to the U.S. influenza market. We have two factors combined. First, a low immunization rate due to the priority given to COVID-19 vaccination in November and December .

The lower GPU sales versus last year were mainly due to the U S influenza market with two factors combined.

Louis musician rate due to the priority given to COVID-19 vaccination in November and December .

Speaker 3: and second, a record pro-achievement in the third quarter, leading to a 55-45% split for the Q3-Q4 period.

And singing record part of cheap menu in the third quarter, leading to a 50, 545% split how they choose to reach $4 billion.

Speaker 3: The U.S. performance was partially offset by the strong Q4 demand in other geographies, especially Europe , where FUELDA was very successfully launched.

The U S performance was especially offset by the strong Q4 demand Universal Geography's, especially Europe , where if you will that was very successfully launched.

Speaker 3: The PPH franchise, recording a strong fourth quarter growth, despite lower birth rates around the world, mostly driven by Pentex's imperformance in China.

The BPH franchise recording a strong fourth quarter growth.

Tight lower birth rates around the world, mostly driven by pantex impediment in China.

Speaker 3: Finally, we are also pleased to see some recovery of the travel franchise, even though we are still far from the pre-pandemic level.

Finally, we are also pleased to see some recovery of the travel franchise, even though we are still far from the pre pandemic level.

Speaker 3: Of note, on a full year basis, despite the pandemic environment, all five vaccine franchises have demonstrated growth in 2021 compared to 2020, illustrating again the robustness of our vaccine business.

Of note on a full year basis, despite the pandemic environment. All five vaccines franchisees have demonstrated growth in 2021 compared to 2020 illustrating again, the robustness of our vaccines business.

Next slide please.

Speaker 3: On the next slide, let's look at our record flue performance in 2021, with a 6% growth over last year's record.

On the next slide let's look at a record throughput for months in 2021 with a 6% growth over last year's record.

Speaker 3: 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.

On the left chart you can see that the impact from the U S market complexion once more than compensated by the strong performance of Europe and rest of the world.

Speaker 3: Let me be very clear. The US sales reduction has nothing to do with our products performance. COVID-19 boosters were given the priority by retailers and at-calf providers, and as a result, a total number of US food doses injected this season decreased by 17%.

Let me be very clear the U S sales reduction has nothing to do with our products performance COVID-19, boosted like given the priority battery dangerous and as chemicals hydrous and as a result, the total number of U S. Food allergies injected V season decreased by 17%.

Speaker 3: Despite that challenging environment, Fluzone Idols continued to expand market share and gain 3.5 point share in the senior segment in the U.S.

Despite that challenging environment Fluzone Idose continued to expand market share and gain three five point of share in the senior segment in the U S.

Speaker 3: In Europe , the strong FUELDA launch execution in Germany enabled us to reach a spectacular 64% growth following the positive STICO recommendation.

In Europe , the strongest field announced execution in Germany, and enable us to reach the spectacular 64% growth following the positive <unk> recommendation.

Speaker 3: I'm glad to report that for the first season, three out of four German senior citizens have benefited from FULDAS Demonstrated Protection.

I'm glad to report that for the first season.

Out of four German senior citizens has benefited from if you will does demonstrate deep predictions beyond fuel.

Speaker 3: The right graph shows the continuous progress of our flu front.

The right graph shows the continuous progress of a few franchise.

Speaker 3: All incremental sales in 2021 were driven by our differentiated flu vaccines. Thanks to the proven ability to protect against cardiovascular events and against pneumonia hospitalization.

All incremental sales in 2021 were driven by our differentiated flu vaccines. Thanks have a proven ability to protect against cardiovascular events and against them when you're a stipulation.

Speaker 3: For the first time ever, our differentiated flu cells represented the majority of our annual sales, indicating that the importance of providing protection beyond flu resonates well with external stakeholders.

For the first time ever.

Differentiated through sales represented the majority of our annual sales, indicating that the importance of providing protection beyond flu resonates well with external stakeholders.

Speaker 3: I'm confident that our flu franchise will continue to grow in 2022 and that this year we'll see another record here. With that...

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 OTT.

Speaker 1: Thank you, Thomas. Moving to General Melton on slide 19, we are encouraged by our performance in the fourth quarter.

Thank you Thomas moving to General mentioned on Slide 19, we are encouraged by our performance in the fourth quarter.

Speaker 1: The execution of our strategy continues to deliver as planned, and the focus on our core assets has consistently generated positive results in recent quarters.

The execution of our strategy continues to deliver as planned and just focus on our core asset that has consistently generated positive results in recent quarters.

Speaker 1: In the first quarter, General Matin sales reached 3.4 billion euros, which included sales from industrial app.

The fourth quarter generally matching sales reached $3.

4 billion euros, which included sales from industrial Affairs I'll call. I said grew two 1% and were up as much as 4% when excluding the effect of pipeline sales tool that you have on in the U S, which ended at the end of 'twenty.

Speaker 4: Our core asset grew 2.1% and we're up as much as 4% when excluding the effect of premium sales to Regeneron in the U.S., which ended at the end of 2020.

Speaker 4: We drove double-digit growth for both Multac and Soliqua in the quarter, while Plavik 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. Praluan's sales...

We drove double digit growth for both <unk> and select wines a quarter.

Traffic growth of seven 5% was accelerated by just hung performance in China.

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.

And sales.

Speaker 4: increased by 36% excluding U.S. sales to Regeneron in the fourth quarter of 2020.

Increased by 36%, excluding U S sales to the fourth quarter of two of 'twenty.

Speaker 4: Outstanding growth of the brand was particularly due to its performance in Europe , where it was recently relaunched in Germany.

I would spending growth of that Brian was particularly due to its performance in Europe .

It was recently launched in Germany.

As highlighted during our previous earnings calls.

Speaker 4: Low enough sales were slightly down. This is mainly due to the high base for 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.

Moving now to sales were slightly down this is mainly due to the high base for comparison in the fourth quarter of two of 'twenty, which followed the introduction of the WH guidelines for the treatment of hospitalized COVID-19 patients as well as some supply limitations.

Speaker 4: Our leading transplant franchise was strengthened by the consolidation of our new product addition, Resiroc. Starting on November 9th, Resiroc added 20 million euros of sale in the quarter. I will provide more detail on this exciting launch on my next slide.

Our leading transplant fungicides were strengthened by the consolidation of our new product addition of Israel.

Switching on November 9th as you look at a 20 million euros of sales in the quarter.

I will provide more detail on this exciting launch on my next slide.

Speaker 4: In China, Sanofi participated in the VB program for insulin in November . We are very proud of the results in the Valenzuela insulin category with Lanthus and Tugeo.

In China Sanofi participated in the beta program for insulin in November we are very proud of the results in the balances all insulin category with launches and two zero.

Speaker 4: Sonneau C. was the only multinational company among the winners in category A, which is a product category that will receive most of the hospital volume allocation.

He was the only multinational company amongst the winners in category.

Which is a product categories that will receive most of the hospital volume of locations.

Speaker 4: Our Glargine franchise remains broadly stable in the quarter, supported by 2GEO. 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 2020.

Oh glad gene franchise remained broadly stable in the quarter supported by two zero and despite the price and inventory adjustments in China.

<unk> of the implementation of the insulin GDP, which is expected in the first half of 222.

Speaker 4: Sales and non-corathets were lower in the quarter in line with our expectations. The decline of 7.6% deflected the impact of product divatcher, which are key to ongoing strategic streamlining.

Sales of non core assets were lower in the quarter in line with our expectations. The decline of seven 6% reflected the impact of product by betcha.

Sure key to our ongoing strategy streamlining efforts, we are vigorously with reducing the number of small product families.

Speaker 4: We are vigorous with reducing the number of small products families with the objective to drive efficiencies and increase profitability.

The objective is to drive efficiencies and increased profitability.

Speaker 4: Moving now to slide 20. For the full year 2021, general matching sales reached 14.2 billion euros, which included sales from industrial affairs totaling 808 million euros. Importantly, our core assets were up 5.6%. This performance translates into growth of 7.6% when excluding the impact of private sales to virgin reginalde volume.

Moving now to slide 20.

Full year 221, Jennifer mentioned sales reached 14 2 billion euros, which included sales from industrial affairs totaling $8 8 million euros importantly, our core assets were up five 6%. This performance translate into growth of seven 6% when.

Excluding the impact of cognitive status diligent ammonia into the U S.

Speaker 4: Across our brands, Lovinox, Haluent, when excluding U.S. sales, Soliqua, and our established brands in the transplant business, Thymoglobulin and Mozobil, delivered double-digit growth in 2021.

Across our brands loving ox heartlands, when excluding U S sales siliqua I know I established brands in the tungsten business.

Globally and in most of your delivered double digit growth into 'twenty one.

Speaker 4: The performance of our core asset in 2021 reinforced our confidence to deliver on our ambition to grow our core asset mid-single-digit GAGA over the period of 2020-2021.

The performance of Opco assets into a 'twenty, one reinforce our confidence to deliver on our ambition to grow.

Mid single digit gagan over the period of two or 'twenty four 'twenty five.

Speaker 4: For 2022, we expect another year of strong performance of our core.

Both towards 'twenty, two we expect another year of strong performance of our core assets.

Speaker 4: Despite a high base of comparison in 2021 for Lovenox, we expect sales of Lovenox in 2022 to be close to the level of 2021.

Despite the high base of comparison into 'twenty, one for Lovenox, we expect sales of loving us into 'twenty two to be close to the level of $2 21.

Speaker 4: Our well-established transplant transcribe is expected to continue the growth path, strengthened by the launch execution on Regis.

Well established constant punch site is expected to continue to grow spot trying.

And by the launch execution of individual.

Speaker 4: Soliqua is also set to continue its growth trajectory, supported by differentiated clinical profile.

So equal is also set to continue its growth trajectory supported by differentiated clinical profile.

Speaker 4: leveraging the compelling stolemiq data. Stolequa is well-boiled for the competition with premix insulated key muscles.

Leveraging the compelling selling mix data siliqua is well poised for the competition with Pemex insulin in its key markets.

Speaker 4: We are also very excited by the anticipated approval of Soliqua in China later this year.

We are also very excited by the anticipated approval of suite equal in China later this year.

Speaker 4: In China, the winning position of our battle in insulin products, lances and Toujero in category A of

China is a winning position of our battle ensuing products can also send to zero in category eight of EVEP will enable us to deliver significantly higher volumes, but at lower pace wisdom.

Speaker 4: will enable us to deliver significant higher volumes but at lower price.

Speaker 4: With the pricing effect in mind, we expect our total gludge in sales to zero and not use, to decrease by around 30, 30% in 222 in time.

With the pricing effect in mind, we expect our total lodging sales to sue and notice to decrease by around 33 zero percent into 'twenty two in China.

Speaker 4: Looking ahead, we aim to establish Toujou as a battle in Srinath's choice in the large diabetes market in China and expect to make Toujou an important growth driver for our business in China in 2020.

Looking ahead, we aim to establish two zero at the basal insulin of choice in the large diabetes market in China and expect to make to show an important growth driver for <unk>.

<unk> in China into 'twenty, two and beyond.

Speaker 4: Our non-core asset performance in 2021 reflects the impact from the progress we are making with our portfolio streamlining.

Our noncore asset performance into 'twenty, one that reflects the impact from the progress we are making with our portfolio streamlining efforts.

Speaker 4: As discussed earlier, we continue to reduce the number of non-pathetic tail product families.

Discussed earlier, we continue to reduce the number of nonstrategic product families.

Speaker 4: In summary, our 221 achievements give us confidence in our ability to deliver on our commitment to stabilize sales by 225 as compared to the 222 base and to maintain general matching B.O.I. margin-acquitive for the group over the 222-25 period.

In summary, our 221 achievements give us confidence in our ability to deliver on our commitment to stabilize sales by 225, that's comparable.

Base and two main things and then I'll make some feel like margin accretive for the group over the two or 'twenty four 'twenty five.

Speaker 4: Now moving to Cadmons' slide to a 21, let's discuss the value proposition of this important transaction for Sanofi and our transplants business. The acquisition was completed in November and represent a strong fit with our strategy.

Now moving to Cat Mone on slide 21, let's discuss the value proposition of this important transaction for Sanofi and all transplant business. The acquisition was completed in November and represent a strong fit with our strategy.

Speaker 4: Cadmonds' key asset was approved in the U.S. last summer and receiving positive market feedback as highlighted on the slide. Resuroc has already reached 96% penetration in 80 key centers and more than 500 patients have been treated today.

Cat months key asset was approved in the U S last summer and receiving positive market feedback as highlighted on the slide.

Work has already reached 96% penetration in H T. He centers and more than 500 patients have been treated to date.

Speaker 4: As we share on our last earning calls, Resurote is the first in class treatment for adults and pediatric patients 12 years and older with chronic graft versus osd disease. We have failed at least to prior align the system, Xera.

As we shared on our last earning calls but as you look is a first in class treatment for adults and pediatric patients.

Yours and older with colleague half versus disease, who have failed at least two prior lines of systemic therapy.

Speaker 4: The prevalence is roughly 14,000 patients. In the US, we steroid being the current standard of care in front lines CGDHD-3.

The prevalence is roughly 14000 patients in the U S. We stay low it means a current standard of care in front line C. G H D treatments.

Speaker 4: We estimate that 5,000 to 7,000 patients in the US were treated with steroids, sprayed on their therapy, and a RICY additional treatment.

We estimate that 5000 to 7000 patients in the U S. We are treated with steroids, so you're on their therapy and require additional treatment.

Speaker 4: In the slightly more than four months in the US launch, Resurov generated the sales of 44 million euros, of which 20 million were consolidated by Sanofi, in the...

In Z slightly more than four months in the U S launch reservoir generated sales of 44 million euros of which 20 millions were consolidated by Sanofi since the acquisition.

Speaker 4: Going forward, we plan on accelerating the geographic expansion. We will continue to leverage our transplant expertise to maximize regular growth potential, capitalizing on our long-standing relationship with the transplant community.

Going forward, we plan on accelerating that geographic expansion, we will continue to leverage our transplant expertise to maximize our growth potential.

Utilizing our long standing relationship is the transplant community.

Speaker 4: In conclusion, we are excited about this innovative new core asset for Sanofi and confirm that the CADMUN acquisition will be slightly accretive in 2022. With that, I hand over.

In conclusion, we are excited about this innovative new Clos at Sanofi and confirms that the Penguin acquisition will be slightly accretive into 'twenty two.

Is that I hand over the call to Judy.

Speaker 5: Thank you, DG. It's been a year since we presented our strategic priorities with the goal to grow our priority brands of both market growth as early as 2022 in geography. I'm glad to report that today.

Thank you Eddie Yeah, it's been a year since we presented our strategic priorities with the goal to grow our priority brands and both market growth as early as 2022 and C geographies.

Glad to report that to date, we're ahead of that commitment indeed.

Speaker 5: Indeed, in 2020, we were losing share, and we were trending about five points below market

Indeed in 2020, we were losing share and we were trending about five points below market growth.

Speaker 5: 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 strength.

The latest market data shows that we have close this gap.

In November on a rolling 12 months, we're at par with the market. So this despite her absence and cough and cold and physical wellness categories in the U S and mainly driven by our priority categories and key geographies gaining share.

Speaker 5: These results show that the execution of our three strategic priorities to drive our business is starting to pay off.

These results show that the execution of our three strategic priorities to drive our business and starting to pay off.

Speaker 5: 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.

And our first priority of cutting and embracing complexity, we've been able to increasingly focus on our key brands and geography, thanks to our simplification efforts.

Speaker 5: We have divested and pruned 111 non-core brands, a reduction of 40% of our total number of brands, which represents less than a point and a half of our...

We have divested <unk> hundred 11, noncore brands, a reduction of 40% of our total number of brand, which represents less than a point and a half of our sales.

Speaker 5: We've also reduced our trademarks by 50%, our domain names by 30%, and our continuously working on simplifying our processes in ways.

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.

Speaker 5: At the same time, we have embraced the complexity of our multi-local brands by real-locating investments to brands with the biggest growth potential in market share games.

At the same time, we have embraced the complexity of our local brands are really indicating investment two brands with the biggest growth potential and market market share gains.

Speaker 5: On our second strategic priority, to become a true fast-moving consumer health service, the creation of our standalone is a-

On our second strategic priority to become a true fast moving consumer health care business.

The creation of our Standalone is a key enabler and we're on track.

Speaker 5: 80% of our legal entities are now lies. And we integrated key functions like industrial affairs, all kinds related functions and supply chain under one-

80% of our legal entities are now lives and we integrated key functions like industrial affairs, all science related functions and supply chain under one roof.

Speaker 5: The success of this is twofold. First, a significant increase in agility in reaction to market and consumer needs. Coffin-Cold is a good example where we were able to quickly size the opportunity of the market rebounding Q4, resulting in market share gain in October and November , including China. This is the first in four years.

The success of this is twofold first is significant increasing agility in reaction to market in consumer you got some call. It is a good example, where we were able to quickly find the opportunity of the market rebound in Q4.

<unk> and market share gains in October and November excluding China. This is the first in four years.

Speaker 5: 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 system.

In addition, as mentioned earlier it helps us to revisit our ways of working and adapt them to the specificities isn't fast moving consumer health care business for example in consumer engagement digital marketing.

Speaker 5: For example, in consumer engagement, digital marketing, or speed of innovation.

Speed of innovation.

Speaker 5: A big focus has also been to strengthen our brand equities and campaigns, beyond the pure signs and quality of our products, which we already...

Our big focus has also been to strengthen our brand equities and campaigns beyond the pure signs and quantity of our products, which we already delivered.

Speaker 5: On our third priority to build our digital and data edge, the creation of our standalone here again has given us the opportunity to revisit and build fundamentals with a strong focus on e-commerce, brand sites, key achieve specific CRM and third party management systems, and data driven AMP and OKS.

Our third priority to build our digital and data edge the creation of our Standalone here again is giving us the opportunity to revisit and built fundamentals, but a strong focus on e-commerce and site.

Specific CRM and third party management disciplined and data driven in P&L patient cells.

Speaker 5: Regarding our Rx-0-2C switches, both programs continue to progress despite the pandemic. The team is actively working on the project and we continue to execute critical studies in accelerated

Regarding our Rx to OTC switches, both programs continued to progress despite the pandemic.

Actively working on the project and we continue to execute critical studies and accelerated session for CLS 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 strong no erectile dysfunction Rx to OTC switch project has gotten this spring we are now waiting for you.

Speaker 5: For Seattle's in the U.S., we have completed the self-selection studies, and the results have been submitted to FDA, along with the protocol for an actual use.

Speaker 5: No erectile dysfunction, Rx2OTC switch project, has gone this far. We are now waiting for the FDA feedback in order to...

The feedback in order to proceed.

Speaker 5: For Tami-Soo, 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,

Tamiflu, we're evaluating the status of the current flu season to date your mining certain studies 10 program in the meantime, we've accelerated all studies that can be done without the presence of disease to keep pace.

And both programs, we should be able to share more next quarter.

Speaker 5: Turning to page 23, when looking at net sales performance, we have delivered 5.6% growth in

Turning to page 23, when looking at net sales performance, we have delivered five 6% growth in Q4.

Speaker 5: Our organic growth is even higher with 7% growth in Q4 when excluding the impact of divestment. These results...

Organic growth is even higher with 7% growth in Q4, when excluding the impact of the cycle.

These results are driven by three factors.

Speaker 5: First, the progress we've made on the execution of our strategic priorities, as mentioned earlier. Second, we benefited from the market rebound in categories like stock and code. And lastly, we also benefited from COVID vaccination, specifically in things...

First the progress we've made on the execution of our strategic priorities I've mentioned earlier.

Secondly, we benefited from the market rebound in categories like Southern cone and lastly, we also benefited from Covid destination, specifically thank you.

Speaker 5: We will continue to focus our efforts to further deliver our 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 more.

We'll continue to focus our efforts to further delivering on three strategic priorities that have proven to be working with the ambition to build a true fast moving consumer health care business and be at par with Michael.

Speaker 5: Let me wrap up by saying how much I am enjoying working with the team, driving the TG business back to growth. With that, I hand it back to you.

Let me wrap up by saying how much I am enjoying working with the team driving the teach business back to growth.

I hand, it over to Mike.

Speaker 4: Thank you, Julie. Let me start by highlighting some strong proof points for sanitary confirmation in 2021.

Thank you Julien.

Let me start by highlighting some key points for Sanofi Pro formation in 2021.

Speaker 6: We managed to increase full year growth margin by 120 bits to 71.3%. It improved run to the growing self-contribution of our Browns in Special Decay. On Hayoung.

Bruce.

We managed to increase full year gross margin by 120 bps to 71, 3%. This improvement is linked to the growing sales contribution of pro brands in specialty care.

On how youre marketing vaccine products.

Speaker 6: This 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 true.

He is also the result of efficiency measures and manufacturing, which typically require a longer lead time, because they become accretive to margin on those starting to come through.

Speaker 6: But as I said before, we are committed to continuing this trend of growth margin improvement.

As I've said before we are committed to continuing this trend of gross margin improvement.

Speaker 6: Second, we managed our opex in 2021 effectively and without disrupting the strong growth momentum. We successfully controlled the increase in opex and managing them to grow slower than sales, which was possible as a result of our rigorous prioritization.

So we manage our opex in 2021 effectively and without disrupting the strong growth momentum, we successfully controlled the increase in opex and managing them to grow slower than sales, which was possible as a result of a rigorous prioritization.

Speaker 6: As before, we reinvested the vast majority of efficiencies generated during the year.

As before we reinvested the vast majority of efficiencies generated during the year.

Speaker 6: 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.

Finally, let me briefly comment on another proof point to call. It transformation that hooked him when I took on the CFO role in 2018, the company employed around one of the little type size and employees worldwide.

Speaker 6: With the ongoing transformation towards a more giant organization, we are now in a new phase with approximately 96,000 globally.

The ongoing transformation towards a more joined organization.

And the new phase with approximately 96000 globally.

Speaker 6: 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 methods.

Continue to change our ways of working we are embracing digital change to mining our portfolio on collaborating with partners in geographies to balance of reducing costs, while improving access grow mid teens for this pass.

Speaker 6: 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% 1.5% lower headcount as compared to 2018, and would include the successful IPO of EuroAPI on the existing platform.

We expect to win the year with a conclusion from 90000, reflecting a more efficient organization. This would represent a 15% one five lower head count as compared to 2018 on would include the successful IPO of your API on existing claims.

Speaker 6: On slide 26, turning now to the full P&L for the fourth quarter, company sales increased 4.1% at TR, driven by excellent growth of depictment on other specialty care franchises, as well as consumer.

On slide 26, turning now to the Huk email for the fourth quarter company sales increased four 1% a tier driven by excellent growth of Davidson.

So it's a different size as well as consumer health.

Speaker 6: Disnet operating income grew 6.99% at CR

Business operating income grew six 9% at CER.

Speaker 6: benefiting from improvements at gross market level, which were driven by the favorable profitable shift to specialty care products on efficiencies within industrial.

Benefiting from improvements at gross margin level, which was driven by good favorable portfolio sheets has been simply geopolitics on efficiencies within industrial activities in the fourth quarter. We again saw an increase compared to last year with the margin improving 240 basis points.

Speaker 6: In the fourth quarter, we again saw an increase compared to last year, with the margin improving 240%.

Speaker 6: Business EPS grew 9.8% at ER, benefiting from a slightly lower tax rate of 20%.

This EPS grew $9 eight person that she aren't benefiting from a slightly lower tax rate of 21 five.

Speaker 6: Turning to slide 27, we have achieved around 2.4 billion of cumulative savings, of which 2.1 were accrued through OPEX efficiencies as depicted by the bright purple boxes shown on the

Turning to slide 27, we have achieved $2 4 billion of cumulative savings of which $2. One were accrued through opex efficiencies as depicted by the bright purple boxes, one of your slides.

Speaker 6: In addition, we realized an incremental $300 million in COGS reductions over the last two years.

Addition, we realized an incremental 200 millions in Cogs reductions over the last two years.

Speaker 6: Specifically, we achieved our target of 500 million savings in R&D due to prioritization of specialty care and the deepening liabilities on tarot restorer. In addition, last being efficiencies were generated by consolidating function across sites, including our trials logistic.

D. G. We achieved our target of 500 million savings in R&D due to prioritization of specialty care on the diabetes and cardiovascular.

Listen lasting efficiencies were generated by consolidating things across sites, including all trials logistic.

Speaker 6: Reducing cycle time through advances in data and digital coupled with more agile governance.

Reducing cycle times I've been Susan but on digital coupled with more a joint governance.

Okay.

Speaker 6: GenMed has been successful in reducing the complexity of its business, focusing on key markets, on employing a digitally enabled go-to-market.

<unk> has been successful in reducing the complexity because the business focusing on key markets unemployment digitally enabled go to market model.

Speaker 6: GNA, across all areas of FANUCI, contributed 500 million of savings over the last two years, driven by smart spending initiatives, real estate efficiencies, a preferred supplier model and digitalization. In summary, we remain on track to achieve our target of 2.5 billion savings by end of 2020.

G&A across all areas of Sanofi contributed $500 million of savings or is it.

Last two years, driven by smart spending initiatives real estate efficiencies the preferred supplier model on digitalization in summary, we remain on track to achieve our target of $2 5 billion sitting by end of 2022.

Speaker 6: Most of this year's savings are again earmarked to be reallocated to fund our growth drivers on key programs in our industry.

Most of the sourcing, Oregon earmarked to be reallocated to fund our growth drivers and key programs in R&D.

Speaker 6: 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 on change in working capital. Given the strong improvement in free cash flow in recent years, we were able to achieve our 2019 Capital Market Day objective of a free cash flow increase of around 50% one year ahead of schedule.

Moving to slide 28.

Briefly comment on a truly increase free cash flow in fact, we've doubled free cash flow since 2000 Eighteen's were focused on improved business performance on change in working capital.

Given the strong improvement in free cash flow in recent years, we were able to achieve our 2019 capital market day objective of freakish screen freeze up around 50%.

One you're ahead of schedule.

Speaker 6: 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.

On slide 29, we maintain our objective to continue Synopsys annual dividend policy, which is reflected in the fact that the company has consistently increased dividend payments for the past 27 years.

Speaker 6: As a result of Sanofi's performance in 2021, we announced that the Board has proposed a dividend of €3.33, since a growing dividend remains an important element of our capital allocation, but it shrinks behind our organic investment on business development in our priority areas.

As a result.

Some of its performance in 2021, we announced that the board has proposed a dividend of three year olds 33 cents, a growing dividend remains an important element of our capital allocation, but as folks behind our organic investment on business development.

Priorities.

Speaker 6: On slide 30, we provide an outlook highlighting expected business dynamics across sales on ex-

On slide 13, we provided an outlook I think expected business dynamics across sales on expenses.

Speaker 6: 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 Dupuytzen, recall flu season, and maintained business momentum for the core products of consumer health on GDP.

Because you know the left part of the slide you can see expected drivers of sales of course are would you be used including the continuation of strong growth from Davidson recalled flu season on maintaining business momentum for the core products of consumer health environment.

Speaker 6: As communicated before, we expect consumer health priority brands to grow above market in key geographies, resulting in growth for the entire business, but only progressively nearing market.

As communicated before we expect consumer.

Alrighty bones to grow above market in key geographies, resulting in growth for the entire business with only progressively nearing market rates.

Speaker 6: At the same time, we also foresee overall TBU cells in the neck to stabilize.

At the same time, we also of course, the overall GPU sales.

To stabilize.

Speaker 6: Your API third-party sales are currently consolidated in this business. Upon the planned, your API IPO, genomic sales will be reduced by that amount going forward.

European Light switch 40 sales are currently consolidated in this business.

One's a planned European IPO and Mitch sales would be reduced my exact amounts going forward.

Speaker 6: the right part of the slide, we expect gross margin to continue to improve due to product mix inefficiencies. Our end expenses are expected to continue to go in line with our strategy. As we keep streamlining our GenMed on THC business, we expect to generate around 500 million in capital gains throughout 2020.

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 ultimate on THC business, we expect to generate around $500 million in capital gains throughout 2022.

Speaker 6: We estimate that our 2022 ETR, effective tax rate, to be around 19%, 1.9%, given the evolution of our product on geographic mix. This estimate is based, of course, on current tax legislation.

We estimate that our 2022 ETR effective tax rate to be around 19% 1 million evens evolution of our product and geographic mix. This estimate is based of course on current tax legislation.

Speaker 6: So on my final slide, slide 31, we expect Full Year 2022 Business CPS to grow in the loadable digits at CER.

So on my final slide Slide 21, we expect full year 'twenty, two 2022 business EPS to grow in the low double digits at CER.

Speaker 6: On our way to achieve our 2022 financial targets, we also guide to a BOI margin of 30% for the year.

No way to achieve our 2022 financial targets, we're also going to be Oi margin of 30% for the year.

Speaker 6: On foreign exchange, we see a positive currency impact of 2% to 3% based on January average exchange rate.

For instance, we see a positive currency impact of 2% to 3% based on generally average exchange rates.

Speaker 6: With 9.3 EPS growth in 2020 and 15.5 EPS growth at TR in 2021, we are on track for a third year of double-digit or near double-digit EPS growth. I hand now the call back to Paul.

Nine three deals close in 2020 and $15 five EPS growth next year in 2021, we are on track for third year of double digit or near double digit EPS growth.

I don't know who to call back to Paul.

Speaker 1: We'll thank Shibby. We expect 2022 to be another busy year with important issues in milestones for our priority molecules and other pipeline programs.

Well, thanks, JB and we expect 2022 to be another busy year with important.

Excuse me milestones for our party molecules and other pipeline programs.

Speaker 1: We're looking forward to the results of four pivotal studies, including Amsinestron in second and third line metastatic breast cancer, as well as the phase three results of Resinostoctococcalpha in haemophilia. The readout of Dupixent in chronic cold-induced urticaria may add another dermatological indication, addressing a population of 25,000 patients in the US alone.

Going forward to the results of four pivotal studies in getting them. Some are strong in second and third line metastatic breast cancer as well as the phase III results. So that's an instructor alpha and hemophilia readout.

The readout of <unk> in chronic cold and used to the carrier may add another dermatological indications addressing a population of 25000 patients in the U S alone.

Speaker 1: We also anticipate making further important pivotal trial decisions, especially in oncology and vaccines.

We also anticipate making further important pivotal trial decisions.

Especially in oncology.

Vaccines.

Speaker 1: Moving to 534 and to ESG, you may remember that our social impact strategy was approved by the sanitary board a little more than a year ago.

Moving to slide 34 into ESG you in May remember that our social impact strategy was approved by the Senate you bought a little more than a year ago.

Speaker 1: renewed contract with society is fully aligned and embedded with our business strategy and ambitions, we make good progress across all our four pillars.

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.

Speaker 1: Today I would like to highlight some achievements in the area of affordable access. The mission of the Sanofi Global Health Unit 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.

I would like to highlight some achievements in the area of affordable access the mission of the Sanofi Global Health unit. We created last year is to increase access to essential medicines in some of the world's poorest countries.

The era of malaria TB Noncommunicable diseases, we have increased both the number of patients reached and the number of countries. In addition, Sanofi is committed to helping 1000 patients living with rare diseases.

Speaker 1: 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 disease.

No access to treatment, we donated again more than 100000 vials in 2021.

<unk> on a 30 year humanitarian commitment to patients suffering from rare diseases, such as Fabry Gaucher Pompe diseases moving.

Speaker 1: 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.

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.

Speaker 1: This quarter, we wanted to put the focus on access. We're proud to announce the 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.

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 Noncommunicable diseases, together, we will leverage digital health and a community based approach to improve disease awareness diagnosis and management of diabetes.

And hypertension and strong collaboration with health system partners.

Speaker 1: The public health burden of NTDs is staggering, with 35 million deaths globally, of which 28 million occur in low- to middle-income countries every year.

The public health burden of empty DS is staggering with 35 million deaths globally.

Which $28 million in low to middle income countries every year.

Speaker 1: This project will contribute to strengthening health systems as they build towards universal health coverage and sustainable development goals.

This project will contribute to strengthening health systems as they build towards universal health coverage and sustainable development goals.

Speaker 1: 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 taller root and data presented at the Actreams and will organize a virtual event around this. Invites will be sent out shortly. We also plan for an update on our immunology pipeline, including due pickstint in late March. As part of this update, we will revise upward our peak sales potential for this month.

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 taller breeding of data presented at <unk> and we will organize a virtual event around mis invites will be sent out shortly.

For an update on our immunology pipeline, including do pixel in late March.

As part of this update we will revise upward our peak sales potential for this medicine.

Speaker 1: We are currently finalising our plans for an event focused on ESG that we hope could take place in the June July . Time for it.

We are currently finalizing our plans for an event focused on ESG that we hope can take place in the June July timeframe.

Speaker 7: 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 each so we can call up a number of the questions.

Well, let's open the call now for Q&A. Thank you now open the call to your questions. We would like to ask a question.

Can call up a number.

Speaker 7: 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 questions. 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.

You have two options to participate click through rates and I can at the bottom of your screen because I didn't know decided when your line is open to ask a question at that time, please make sure your microphone.

Microphone or option to submit your question by clicking the Q&A I come up a bunch of my screen on your question, we do read out.

Tim and I have a quick question.

Speaker 8: Yes, the first question comes from Vimal Kapadia from Bernstein. Vimal?

Yes. The first question comes from female companion from Bernstein Nemo.

Speaker 9: Oh, great. Thank you very much for taking my questions. I'm Michael Pardish from Bernstein. So first, can I just ask on the U.S. flu business, you know, declined year on year. Thomas, you flagged a 17 percent market contraction in volume.

Oh, great. Thank you very much for taking my questions are about commodities and budgeting. So first can I just ask on the U S flu business.

Declined year on year talked about you you flagged a 17% market contraction in volumes. So could you just provide a bit more color on your expectations for the volume value mix for the U S. In 'twenty, two and what was the level of coverage in 'twenty, one was that actually below historical pre COVID-19 levels and if so should we be should we be getting a nice bounce in coverage in <unk>.

Speaker 9: Could you just provide a bit more color on your expectations for the volume value mix for the US in 2022? 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 US?

22 specific to the U S. And then my second question is just on the all the ox 40.

Speaker 9: And then my second question is just on the, the ox 40.

Speaker 9: had some data last year for the Oxfordgy Programme, which is now a priority asset. It is curious how you are thinking about targeting the Oxfordgy versus Oxfordgy ligand. And then I'd love to hear, you know, how you think about the duration of effect. I just give him looking at Amdyn's drive, looked right at compelling on that front. Have you seen anything from your own asset suggesting a similar efficacy profile with time? Thank you.

<unk> had some data last year for the Ox 40 program, which is now a priority asset I'm just curious how you're thinking about targeting the ox 40 vessels 40 ligand and then I'd love to hear how you think about the duration of effect just given looking at amgen's drug looked about a compelling on that front have you seen anything from your own asset, suggesting a similar efficacy.

File with time, thank you.

Speaker 1: Thank you, Vimal. Great questions. Toma, flu coverage, read across the 22.

Thank you for your mom, great questions, Tom or flu coverage read across for 'twenty two.

Speaker 3: Thank you very much, Vimal. Indeed, you understood very well that the US flu situation in 2021 was a very specific US situation with minus 17 on the overall volume for the US.

Thank you very much indeed, you understood very well with the U S flu situation in 2021 and it was a very specific situation with.

With minus 17 on the overall volume for the U S.

Speaker 3: And what that means is that it was lower than 2019, very specific to the US 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 booster.

And 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. Our specifications you know very well that there was a lot of confusion with different age indications being licenses in time and a lot of discussion on the boosters.

Speaker 3: So 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 US vaccine coverage below 2019, that gives room for growth. So we are very confident about 2022.

So 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. Vaccines provide rich below 2019 that gives us room for growth. So we are very confident about 2022.

Speaker 3: We expect to see both volume and value increase in the US versus this year. To give you an example, and I think it's a good illustration of what could happen in the US for flu in 2022.

We expect to see both volume and value increase in the U S.

This year to give you an example, and I think it's a good illustration of that.

What could happen in the U S for flu in 2022.

Speaker 3: I think everybody has understood that there needs to be some fixes on the U.S. flu coverage and CMS has very interestingly decided to increase.

I think everybody has understood that it does need to be some fixes on the U S who coverage and CMS as they are interesting and decided to increase the flu vaccine administration fee from $17 to $30 per dose for the season and H 2022 in the U S. So I think there's going to be a strong.

Speaker 3: the flu vaccine administration fee from $17 to $30 per dose for the season NH 2022 in the US. So 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. And that's why we're expecting a record flu season overall for Sanofi Pasteur and indeed an increase of flu in the US in 22 versus 21.

The CDC understanding as well as stronger potential to make sure that 2022 is very different from <unk> and that's why we're expecting a record flu season overall for Sanofi Pasteur and indeed, an increase of a few years in the U S. In 'twenty two 'twenty one.

Speaker 10: Thank you. Thank you, Toma. Great to hear from us today for your vaccines.

Thank you. Thank you tell them that great to hear from Sanofi vaccines.

Speaker 1: 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.

John Reed Ox 40, like and I think the question from BMO is about duration and.

Efficacy in some maybe you have some thoughts on tolerability as well yeah. I think it was about <unk> 40 of the receptor versus ox 40 that ligand and we prefer the ligand because it is induced on azure presenting cell. So it's quantity in the body is less whereas ox 40 years.

Speaker 11: Yeah, I think it was about OX40 the receptor versus OX40 the ligand, and we prefer the ligand because it is induced on angiopresenting cells, so its quantity in the body is less, whereas OX40 is...

Speaker 11: is more heavily expressed on a constituent basis and can mean that you're going to have to dose higher to neutralize it. But more importantly, I think.

Is more heavily expressed on a consistent basis and can.

Meaning that you're going to have to dose higher to neutralize it but more importantly, I think.

Speaker 11: then that is the fundamental difference in the mechanisms of our molecule amlitelemab coming from the Kymab acquisition versus the Kirin antibody that Amgen

And that is the fundamental difference in the mechanisms of our molecule ammo, telling my upcoming from the <unk> acquisition versus the current antibody that Amgen has.

Speaker 11: accessed. The Karin slash 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.

Access.

The care and slides for Amgen antibody is a depleting molecule that actually kills the cells that express at 40, whereas we have a non depleting antibody that modulate talks forties pathway.

Speaker 11: uh... the downside of the pleading is that uh... both effector

The downside of depleting is that both effector T cells, which are contributing to the auto immunity, but also regulatory T cells that we need for suppressing auto immunity Express arch 40, so over time you'd have the risk of depleting those necessary regulatory T cells.

Speaker 11: t cells which are you know contributing to the autoimmunity but also regulatory t cells that we need for suppressing autoimmunity express ox forty so over time you'd have the risk of depleting those necessary regulatory t cells with a depleting mechanism uh... so i we we feel that in terms of long-term safety and durability of the effects that uh... a non-depleting antibody targeting the ligand is really a superior way to go thank you John couldn't agree more

Pleading mechanism.

So we feel that in terms of long term safety and durability of the effects that are non depleting antibody targeting the ligand is really a superior way to go.

Thank you John couldn't agree more.

Next question.

Speaker 8: The next question will come from Richard Bosser at J.P. Morgan. Richard.

The next question will come from Richard Buster at JP Morgan Richard.

Speaker 12: Thanks very much for taking my question. Two questions, please. First one, just on flu as well.

Thanks, very much for taking my question two questions the.

First one just on flu.

Speaker 12: Just 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 ? And then 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.

Well just a.

Could you talk about your manufacturing capacity and supply and how that will develop and and that demand you might see a for high days feeling in Germany and in.

In Europe , and then 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.

Speaker 1: First of all, I'll compliment Tom and the team on what they've done with the Hydas launch and particularly this year and remotely and incredibly in Germany. So the question is supply and beyond.

<unk>.

First of all complement Tom and the team and what they've done with the hydro launch and particularly this year in remotely and incredibly in Germany. So the question is supply and beyond.

Speaker 3: Thanks Richard, definitely no concern at all on US or non-US flu supply. We are very confident, you know very well that last year we added a new flu building in Swiftwater. You know also that we are further investing into additional.

Thanks, Richard definitely no concern at all on the U S Oh non U S through supply.

We are very confident you know very well that last year, we've added a new building in swiftwater, you'll notice, though that we are further investing into additional Susan idose and teach in for the mid to long term, a really kind of a blend so where are you moving forward on that and feeling very confident and setback for video of course as every single year, we are always risk.

Speaker 3: for the mid to long term with the Canada plant. So 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'll take that moment at the Q2 call to make a little bit of an update on supply and phasing for Q3.

In the northern hemisphere season, and the NFL.

And at the end of the Q2 call usually takes estimate at the Q2 call to make at either be definite date on Saturday and phasing for Q3 Q4, when it comes to demand as you violated the Sanofi vaccines team had done very strongly.

Speaker 3: 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. So 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.

In Germany, we expect these to further grow there is room to grow in Germany. When it comes to other markets in Europe , we are going to introduce in 'twenty. Two in a couple of new markets in Europe , but you know very well when it comes to vaccines and flew introduction, it's about adding pressure on show recommendation, it's about having reimbursement so.

Just a few countries in Europe little bit you said until we have the right reimbursement in place and then we will put out or something.

Speaker 1: Thank you, Toma. The consumer question, I think I got where you're heading. Richard, I think the thing for us, we go back to what we said, Capital Market State December 2019. We thought we could grow faster than we were growing. We thought we could carbon increase agility, accelerate growth, make better choices, prioritize leveragey, comma.

Thank you thank you tomer.

The consumer question.

You know I think I got where you're heading.

The thing for us we'd get back to what we said capital markets Day December 2019.

We thought we could grow faster than we were growing we thought we could carbon increased agility accelerate growth make better choices prioritize leverage e-commerce .

Speaker 1: and run fast all the way to the switches and I think Judy 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 19 and we're very happy with how things are performing.

And run fast all the way to the switches and I think.

Judy and the team have done an incredible job frankly in 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 19, and we're very happy with how things are performing.

Okay next question.

Speaker 8: The next question will be from Luisa Hector at Barenberg, Luisa.

The next question will be from Luisa Hector at Vandenberg Lisa.

Speaker 13: Hello. Thank you for taking my question. 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.

And I. Thank you for taking my question.

And possibly if the JV that you mentioned head count reduction I just wondered if you can give us an update on your M. P. I spend time engaging actions.

Speaker 13: And then 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 a Baggio generics arrives? Thank you.

And no no effect on gross margin I'd say clearly right.

Hi, good progression.

Very hard on this and it's paying off can you guide us to buy the kit.

Think about a continued improvement.

We're trying to trying to train when Pasha of generics and nice thank you.

Okay. Thank you Luisa.

Speaker 1: So JB, you always get the fun ones. So maybe those are your API questions. It was partly related to headcount. You may want to go a tiny bit broader. And then, of course, goes.

JP you always get the fun months so maybe.

Does your API question that it was partly related to head count and you may want to tiny bit broader and then of course gross margin. Let me go from them yes.

Speaker 6: Yeah, so effectively we turned it 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. And so the IPO is announced for H1 2022. We are on course to do this. So yeah, as planned, we're looking forward to make it happen in H1.

Yeah.

Turning to transform with the new business model operating in a in some countries commercially, but if we're able to.

These activities.

Activity, which.

Which is going to be a leader.

These fields. So J P. Originals for 2022, we are on course to.

To do this so yeah as planned the results.

We're looking forward to to make it up in the next one.

Speaker 14: on the growth margin. Yeah, effectively, we delivered on 21. We are guiding again on improvement on the midterm. I won't

On the gross margin.

Typically we delivered in 'twenty, one we are guiding a gain on the improvements.

Term.

I won't.

Speaker 14: make a gross margin guidance multi-year. But is there something which is a strong element you have to keep in mind?

Our gross margin guidance.

But is there something which is a strong elements you have to keep in mind is that on our maintenance. It depicts and we are going to have quite a transformative journey in terms of Cogs, which should really help us.

Speaker 14: is that on our main asset, Dupiccent, we are going to have quite a transformative journey in terms of COGS, 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 COGS improvement.

To neutralize any price originally we could have because we are looking at implementing a new a new manufacturing processes that will deliver strongly in terms of our Cogs improvement.

Speaker 1: Thank you. And Louise, you didn't ask me, but I'm glad you asked the questions because...

Thank you and I know you didn't ask but I.

Me, 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 30 60 programs in our early development.

Speaker 1: You know, there's a huge amount of work, you know, while we're advancing the pipeline to 30, 60 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, the right size in 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 in a consumer business.

The six acquisitions I think well just kept my standard discussion a little bit occasionally as the fundamental work that's going into reshaping the company the right.

Right sizing the company of course, more importantly, you know when having an IPO in the first half of this year at the same time, we are carving in our consumer business and on all these things, we're outperforming whilst doing them, whilst delivering on the science and the overall financial performance and the commitments, we make to the street for 'twenty two so.

Speaker 1: and on all these things we're outperforming whilst doing them, whilst delivering on the science and the overall financial performance and the commitments we made to the street for 2022. So, you know, we really feel like, you know, the level and scale of transformation that's happening is perhaps not fully understood and it's okay, but it's extensive.

We really feel like you know the level and scale of transformation that happening is perhaps not fully understood and its okay, but its extensive so maybe next question.

Speaker 8: Yes, next question will come from Simon, Simon Metzler at Exane, Simon.

Yes next question will come from Simon Simon and my friend at Exane climate.

Yeah.

Speaker 15: Hi guys, thank you for taking my questions. I'm loving the new branding by the way. The first question is actually for JB. You've given guidance for 19% tax rate for 2022. If you look at consensus and LTAs, it's something 30 places point higher.

Hi, guys Yeah. Thank you for taking my questions on that.

The new branding by the way.

And the first question it sounds like a JV, you've given guidance for 19% tax rate for 2022, if you look at consensus and Lcs.

But in fact, it's quite high just wondering if you can potentially comment on the sustainability of this tax rate or how we should maybe revisit all of our expectations.

Speaker 15: Wondering if you can potentially comment on the sustainability of this tax rate or how we should maybe, you know, revisit our expectations there.

Speaker 15: And then the second one, it's just on the PIXEN. Thank you for the updated timeframes with respect to guidance.

And then the second one is just on the picks and thank you for your time claims with respect to your guidance.

Speaker 15: I mean, I think it's clear you blow everything out of the water in terms of safety and efficacy in atopic lymphitis. And I 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 Tazepatide in severe asthma and feedback that you may be getting from.

I mean, I think there's clearly blow everything off the water incentives or anything.

Anything you see in a practice.

Appreciate it it's early days, but maybe could you comment on any impact that you're seeing.

Expect to see with the recent launches because I decided in severe asthma and feedback you're getting from.

From a physician thank you.

Speaker 1: Okay, well thank you for the kind words on the branding. For those that haven't followed it closely, it is the original font from our birth in 1973 and it's also an opportunity for us to be a little bit more disruptive and unify the company as well at the same time. So I'm glad that it's recognised. I think it's more dynamic, frankly, and reflective of the comments I made earlier.

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 fund from all our bus and 1973.

And it's also.

An opportunity for us to be a little bit more disruptive and unify the company as well at the same time, so I'm glad that it's recognized I think its more dynamic frankly and reflective of the comments I made earlier, how much of the transformation.

Speaker 1: is happening here. And from that high energy question to tax, John-Baptiste, to you.

Happening here and from that high energy a question to tax Jamba T cell to you.

Speaker 14: Thank you very much. It's a nice trend on our effective tax rate.

Thank you very much yeah, it's a it's a nice trend on our effective tax rate a 200 bps better effectively as I said in my in my previous speech, it's really.

Speaker 14: But 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...

Something which is dependent on for further changes in the tax legislation, we have a structural good trends on let's say that the underlying tax rate is likely between the 19 and 20, but.

Speaker 14: And let's say that the underlying tax rate is like between 19 and 20, but as we speak, I don't know what will be the full impact of Pillar 2 or changes of taxation in some other regions like the US.

But as we speak I don't know what will be the full impact of pillar two of changes Oh for.

Taxation in a in some other regions like the U S. So yeah, a good trend with a chunk is a big chunk of it leads to our business on tax rates in France, also which is a growing positively.

Speaker 14: Yeah, a good friend with.

Speaker 14: There's a big chunk of it linked to our business on tax rates in France also, which is going positively, but that could be disturbed in the midterm by other changes in other regions.

But that could be disturbed in the midterm by other changes there.

The regions.

Speaker 1: Thank you JB. Thanks also Sam for the compliments on Dupixent which is you know frankly incredible performance and led by Bill and the team. So Bill comments about new entrants and early signatures.

Thank you JP and thanks also for the compliments on to pick some which as you know.

Frankly, an incredible performance.

Led by Bill and the teams are bill comments about new entrants in early signals.

Speaker 2: 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 JACs, because they were almost a year delayed.

Yeah, well thank you for the question.

Now none of the new entrants or a surprise for one thing we've been planning on these we've been waiting in some cases extended waits for the Jacksons they were almost a year delay and while it's new competition in the U S. We've had these are competitors that have already launched in Germany and.

Speaker 2: And while it's new competition in the U.S., you know, we've had these competitors that have already launched in Germany and underway in Japan as well. So we're certainly used to them. And 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.

On the way in Japan as well, so we're certainly our use of them.

And 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.

Speaker 2: Targeting aisle 4 and aisle 13, that is fundamental to type 2 inflammation and no other product has been able to

Targeting IL four and IL 13 that is fundamental to type two inflammation and no. Other product has been able to show the profile that we have in any of the type two diseases and clearly starting with atopic dermatitis, where we are the leader now asthma as well.

Speaker 2: the profile that we have in any of the type two diseases and clearly starting with atopic dermatitis where we are the leader now. Asthma as well, the profile again we think is the top, the best profile that is in asthma and we're seeing really very promising signs all around the world of our ability to compete and win in the asthma space.

Now the profile again, we think is the top the best profile that is in asthma, and we're seeing really a 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.

Speaker 2: Just one comment, you know, as we have competition come into the atopic dermatitis market.

Speaker 2: It actually helps to serve to grow the market, grow awareness of atopic dermatitis, et cetera. And, you know, as we've had competitors launch in other countries, as I said, Germany and Japan, we have seen market expansion. So that's what we expect. That's part of our aspiration to have a, you know, 25 to 30 percent advanced therapy penetration in atopic dermatitis over time. That's one of the contributors. But, 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.

It actually helps to serve to grow the market grow awareness of atopic dermatitis et cetera, and I as we've had competitors launch in other countries as I said, Germany, and Japan, we have seen market expansion. So that's what we expect that's part of our aspiration to have a.

25% to 30% advanced therapy penetration in atopic dermatitis overtime, that's one of the contributors, but the one thing that's clear is that we are on top we remain on top and we I believe being best in disease, we will stay on top.

Speaker 2: So, sorry, can I get apologies to interrupt? Yeah, I think I said to the other side, I've got it on my brain. I meant to tell them I've been in the US. Is there any early feedback you could share? Yeah, no, there's really nothing that we're seeing. It's still very early. Yeah, we're staying with the trends that we've seen.

Sorry can I can I apologize to interrupt yeah, I think I said cause appetite Oh, my Brian and I have to tell them not been met.

In the U S is there any early feedback you can share.

No there's really nothing that we're seeing it's still very early.

We're staying we're staying.

With the trends that we've seen.

Speaker 1: Yeah, just to add a 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 Jacks for example, the baggage and you know with the 13s it's half the answer missing the 4. So, you know, and you know that most of these mechanisms have failed in at least one of the indications that Doopey's already approved. And Telly would probably be in that box too, I think it's...

To add to kind of put to those which as you know.

The the assumption is always just a zero sum game, you know say with the Jacks for example.

Baggage and you know with the 13th Softy I'm missing the full so.

You know that most of these mechanisms have failed in at least one of the indications that Duke is already approved.

And tells you would probably be in that box too I think it can get built in a day, if I remember correctly. So so where on one hand, we're the only medicine that will play in every indication on the other hand as.

Speaker 1: So on one hand, we're the only medicine that will play in every indication. On the other hand.

Speaker 1: 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. And Bill's comments about Germany should not be underestimated because, you know,

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 and Bill's comments about Germany should not be underestimated because.

No.

Obviously, we'll carry the education of these disease areas, but it's good that others want to come in and try and do that too and in growing markets, where you're the market leader, it's a very healthy place for us to be on behalf of patients.

Speaker 1: will carry the education of these disease areas, but it's good that others want to come in and try and do that too. And 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.

Speaker 8: Next question will be from Graham Perry at Bank of America. Graham?

Next question will be from Graham Parry of Bank of America grams.

Speaker 16: Great, thanks for taking my questions, so congratulations on getting an hour into the call without in a mirror three questions, I'm afraid I'm going to

Great. Thanks for taking my questions.

Congratulations on getting an average to call it out in a matter of three questions I'm afraid I'm going to kind of break that out.

I'm wondering have you accrued all events and then data lock and say we slowed for Q1.

Speaker 16: a readout on that study. And the L-acestrin results I think have led to some concern in the market that oral SIRDS only show benefit in ESR1 mutated patients who are obviously more rare in the frontline setting and I think that's leading to some pessimism around, you know, the potential in frontline. So perhaps if you could just address that point.

Readout on that study and the <unk> results I think has led to some concern in the market that oral says any shade benefit you saw one you take patients who are obviously more rare in the frontline stretching and that thing that's eating some pessimism around you know the potential and in frontline say, obviously, if you could just address that point.

Speaker 16: And then secondly, a question on M&A, you've done a lot of smaller pipeline deals of late.

And then secondly, a question on M&A, you've done a lot of smaller pipeline deals of late and obviously biotech valuations have fallen somewhat to the mainland and so really 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 and it's still a key target. Thank you.

Speaker 16: Obviously, biotech valuations have fallen somewhat at the moment, so 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.

Speaker 1: Thank you, Graham. I didn't hear the first part of your question. So, oh, right. It's an Omera 3 question. Thank you for raising it. So I'm going to toss it to John . John , I don't know if you heard it. It was the competition showed more efficacy, I think, in ESR.

Thank you Graham I didn't hear the first part of your question. So Oh right. That's an amira three question.

Thank you for raising it so I'm gonna toss it to John John No. What you heard it was.

You know.

The competition.

Should more efficacy I think than you saw.

Speaker 11: mutation and so what's the read across for us and where are we on database lock and reporting in q1 right right okay Graham no thank you in terms of the activity of our third on wild type versus mutant estrogen receptor

Mutation and so what's the read across for Us and where are we on database locked and we're putting out in Q1 right right. Okay. Graeme though thank you in terms of the activity of our surge on wild type versus mutant estrogen receptor.

Speaker 11: We're fully active on both, whereas the competitive molecule is better on the mutant than on the wild type, so that's not at all a liability for us.

We're fully active on both whereas the competitor molecule is better on the mutants and on the wild type. So that's not at all a liability for us and.

Speaker 11: So 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. So, you know, we're...

So 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 the pristine tolerability.

You know, where we expect to have the data this quarter with respect to a mere three in 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 four six inhibitor and that are at first of our adjuvant studies is now open.

Speaker 11: We expect to have the data this quarter, with respect to MIRA 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 CDK4-6 inhibitor, and that first of our adjuvant studies is now open for enrollment.

For enrollment so we're making good progress across the spectrum from early to late line in each of these indications, where we think our amps veteran has a strong value proposition for women with hormone receptor positive breast cancers.

Speaker 11: So we're making good progress across the spectrum from early to late line in each of these indications where we think ampsinesterin has a strong value proposition for women with hormone receptor positive breast cancer.

Speaker 1: Thank you, John . So categorically, Graham results in Q1.

John .

Categorically.

Our results in Q1.

Speaker 14: OK, 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 biotech.

Okay, <unk> M&A yeah.

Well, thanks for the question, but I.

I do think that Oh, M&A activity is not related to the peak and trough the valuation of biotech is much more dependent on the on the leadership of our R&D team and our Undrawn AR.

Speaker 1: 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, so no specific impact from the current level of valuation. It will be a pound down, but we are still on for bolt-on acquisitions, of course. Great, thank you. Next question.

Accounting for the rights.

Right, which is really a fitting.

Fitting with our strategy really fitting with our Tas.

So no specific impact from our from the timetable of valuation.

The Oh come down.

But we are still on for bolt on acquisitions of course, great. Thank you.

Our next question.

Next question will be from Tim Anderson that Doyle.

Tim.

Your question please.

Speaker 17: Thank you. A couple of questions. So going back to oral SIRDS, we'll be getting two readouts this year from two similarly designed trials later in line for us. Your trial and then Roche's trial, both companies claim best in class. Do you think these upcoming data sets would 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?

Thank you.

Couple of questions.

Going back to or all Serge.

We'll be getting two readouts. This year from two similarly designed trials later line, perhaps your trial and then Mashes trial, both companies claim best in class do you think these upcoming datasets.

Prove which company is ranked much company is wrong, making that claim or that not become clearer until we get additional trial readouts such as in the first line setting and then second I would love to get your thoughts on Lilly's Levered Kaiser Mab, they're saying they think that will have a profile that is.

Speaker 17: such as in the first line setting. And then second, I would love to get your thoughts on Lilly's Lebritizumab. They're saying they think that will have a profile that's very competitive to duplex scent. They talk about differentiation in ocular side effects.

Very competitive to do fix them.

Talk about differentiation and ocular side effects.

Speaker 17: And I'm wondering what your thoughts are on them as a competitor as they do know the dermis space well because of TALS. Thank you.

And I'm wondering what your thoughts are on them as a competitor they do notice the terms baseball because Charles Thank you.

Speaker 1: 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?

Okay. A few good things in that John given roche's data and our pending data do you think we'll be able to declare a.

Winning profile this year.

Speaker 11: No, it's a good question. I'm not sure that these late line settings are.

It's a it's a it's a good question I'm not sure that these late line settings are.

Speaker 11: 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, where so far, you know, Amsterdam has really been delivering a best in class profile, whereas.

The best place to really differentiate on efficacy.

Where we do feel confident we'll be able to perhaps differentiate is on the safety and tolerability profile, where we're so far you know.

And so that trend 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. So.

Speaker 11: Molecules from others, including Roche, have been showing safety signals around cardiac issues and, in some cases, vision issues.

Speaker 11: I think that's probably the best answer I can give you for now. I would probably be looking to how the tolerability profiles hold up in these early lines as opposed to hinging a lot on the efficacy profile given.

That's probably the best answer I can give you for now I would probably be looking to you know how the tolerability profiles holdup in these early lines.

Those two hinging a lot on.

I missed on the efficacy profile given.

Speaker 11: you know the uh... a lot of the uh... heterogeneity in these patient populations you've seen the late line and therefore the difficulty to really do cross trial comparisons in a in an apples to apples way

You know the there's a lot of the heterogeneity in these patient populations you seen of late line and therefore, the difficulty to really do cross trial comparisons in a in an apples to apples way.

Speaker 10: Thanks, John . I reiterate to everybody, we haven't seen the data. We are optimistic that we're in a good spot.

Thanks, John 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.

Speaker 1: and we look forward to getting it. You all know I think it's a small indication if we are successful so in terms of value perspective it's not as important although it may bring benefit to those that need it let's be frank.

Symptoms of value perspective, it's not as important although it may bring benefit to those who need it let's be Frank but from a confidence perspective, we know it's important to everybody.

Speaker 1: but from a confidence perspective we know it's important to everybody.

Speaker 1: So, when we have the data, you'll be soon after us in terms of knowing, as I do think.

So when we have the data you'll be soon after us in terms of knowing I do think whereas in most of the areas I've worked in Tolerability inevitably plays a part, particularly this is we've moved earlier lines and Jonathan touched on it.

Speaker 1: Whereas in most of the areas I've worked in tolerability inevitably plays a part, particularly this, as we move earlier lines and Jonathan touched on.

Speaker 1: Tolerability tolerability will be a key differentiator and if I'm understand correctly the competitor you reference at a lower dose

Liberty Tolerability will be a key differentiator and as time understand correctly. The competitor you reference at a lower dose.

Speaker 1: continues to have cardiotoxic challenges. So, you know, that, we think those things are gonna be very, very important over the longer term. Bill, IL-13s, Lily is saying that they have a winning profile.

<unk> continues to have cardio tox challenges. So you know that we think those things are going to be very very important over the longer term.

Bill I'll say teens Lilly is saying that they have a winning profile.

Speaker 2: 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. So we think starting with the biology, it's not the complete biology.

Yeah, well thanks for the question.

<unk> said I think earlier on with the IL 13, it's incomplete it's missing the IL four so we think starting with the biology, it's not the complete biology.

Speaker 2: So when you take a look at their results, and let's remember these are phase two B results. They're still waiting on their later results. You know, there's nothing that really stands out from our perspective. Efficacy, you know, looks fine. The conjunctivitis looks similar to Dupixent.

So when you take a look at their results and let's let's remember these are phase two b results, they're still waiting on their later results.

Yeah, there's nothing that really stands out from our perspective, our efficacy looks it looks fine.

The conjunctivitis looks similar to a depiction.

Speaker 2: uh... you know i think some of the big differences are that uh... we're six years ahead at that point for the time they launch uh... we are you know a mega blockbuster uh... we become the standard of care so i think for somebody to come in with something that isn't so much to offer you know i think that that is regardless of your experience in a therapeutic area uh... it's not therapeutic experience in uh... atopic dermatitis so you know as we said it's a it's part of the story aisle thirteen certainly not the full we've got the best profile

Yeah, I think some of the big differences are is that we're six years ahead at that point by the time. They launch a we are you know a mega blockbuster we'd become the standard of care. So I think for somebody to come in with something that isn't so much to offer.

Think that that is regardless of your experience in a therapeutic area, it's not therapeutic experience and atopic dermatitis. So you know as we said it's a it's part of the story IL 13, certainly not the full we've got the best profile.

Yeah, I think so.

So it was a follow on.

Speaker 1: Thank you. OK, thanks. Yeah, it's great that they have experience with TALS. I have a lot of experience with Consentex. And nobody's got the experience that we have in AD.

Okay.

Yeah.

It's great to have experience with <unk>.

I have a lot of experience with Concentrix.

And Nobody's got the experience like we have in a day.

Speaker 1: And I'm telling you, what the team has done with Dupixent is incredible. We never underestimate competition, particularly well-organized ones.

And I'm, telling you what the team has done with due pixel was incredible we never underestimate competition, particularly well organized ones, but just started apology like Bill said, if you got half the answer you have a long road to hoe I'm sure they'll make some progress, but let's go all the way back to the fundamental which is additional.

Speaker 1: But it starts with the biology, like Bill said. And if you have got half the answer, you have a long road to hoe. I'm sure they'll make some progress. But let's go all the way back to the fundamental.

Speaker 1: additional weight in the market to help educate and improve penetration is welcome. And if we have the best profile, which we believe we do, then we will disproportionately benefit from that. So, you know, we look forward to the meeting in March.

Weight.

In the market to help educate and improved penetration is welcome and if we have the best profile, which we believe we do then we will disproportionately benefit from that so.

We look forward to the meeting in March where we'll update you in more deeply about our forecast and indeed, our immunology pipeline in general.

Speaker 1: where we'll update you more deeply about our forecast and indeed our immunology pipeline in general.

Next question.

Speaker 8: Yes, next question comes from Mark Purcell at the Morgan Stanley . Mark, if

Yes next question comes from Mark Purcell at Morgan Stanley markets.

Speaker 18: Thank you. Thanks for everyone. Two questions. Firstly, on the depiction, could you give us an update in terms of where you are in terms of advance?

Thank you.

Alright, thanks for everyone two.

Two questions firstly on the depiction and could you give us an update in terms of where you are in terms of an advanced.

Speaker 18: therapy penetration rates in AD versus the 25 to 30 percent you just gave, and also some idea of an indication split. But ahead of the 29th of March, just to sort of get us in the mood.

Therapy penetration rates in AG versus the 25% to 30% you just gave and also somebody tariff and indication split.

But ahead of the 29th of March just to sort of get us in the mood.

Speaker 18: Perhaps you could help us understand where you believe in the future a US-ex-US split could be. Obviously, ex-US growing 80% from a lower base than the US, but where eventually do you feel ex-US-US split could be?

Perhaps you could help us understand sort of where you believe in the future of U S. Ex U S, but could be obviously ex U S drilling 80% from a lower base in the U S. But wherever eventually do show ex U S. You expect could be and then the second one so 700, having a solid 245, if the oil to a phase III go no go decisions coming up in the <unk>.

Speaker 18: And then the second one on 707 or 245, the IL-2.

Speaker 18: phase three going to go decisions coming up in the second half this year.

Speaker 18: I wonder if you could help us understand which indications and lines of therapy those decisions be made on, if it's monotherapy or combination therapy, and what are the gating decisions when making that hurdle into phase three?

Second half of this year I Wonder if you could help us understand which indications and lines of therapy. Those decisions would be made on if it's monotherapy or combination therapy and walked through the gating decisions when making that how to enter phase III.

Okay and chemo.

Speaker 2: Bill, I think the question is where are we now and what is the penetration, how has it evolved towards that 20 to 30 percent you're talking about? Yeah, so 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 it's 7.9 percent, and when I say the finish line is looking at, you know, 25, 30 percent.

Yeah.

Bill I think the question is where are we now and what is the penetration how does it evolve towards that 20% to 30% you're talking about yeah. So thanks for the question. We've got a still a long way to go just to give you a sense in the U S. Adult 80 at seven 9% and when I say the finish.

Lines looking at you know 25% to 30%.

Speaker 2: which is a little bit in the range of psoriasis, maybe a little bit higher. We've got a long way to go. So just reinforcing what Paul and I said along the way, new competitors in the marketplace help to accelerate that.

Which is a little bit it's sort of in the range of psoriasis, maybe a little bit higher and we've got a long way to go so just reinforcing what Paul and we set along the way new competitors in the marketplace help to accelerate that rigor.

Speaker 2: Regarding USXUS, you know, we have seen kind of similar patterns in every market that we've launched in the world following the US from a growth perspective. We continue to see that, we expect that. We're not going to comment on what we think the ultimate geographic distribution will be or indicate.

Regarding our U S ex U S.

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 continued to see that we expect that we're not going to comment on what we think the ultimate geographic distribution will be or indications play yep.

Speaker 1: But I think as well, as Europe always takes some, and the rest of the world takes some time to get through the reimbursement cycles. And so it always starts slower, then it always gets more interesting, and then everybody always starts to ask questions about it. And then 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 a...

But I think as well.

As Europe always take some.

The festival will take some time to get through the reimbursement cycles and so.

It always starts so that it always gets more interesting and then everybody who was supposed to ask questions about it than we thought we don't need to share.

The relative proportions, but.

The fact that the rest of world will just get stronger and stronger in terms of its contribution because the medicine. So good and I think Bill mentioned, China really that is quite a 30000 patients.

Speaker 1: in just months, I think start to help you understand where we might be heading.

In just months I think starts to help you understand where we might be heading.

Speaker 1: John , SAR245 or formerly known as SAR707, likely indication split and thoughts on, I think it was combos.

John saw 245 or four my name is still 707.

Likely indication split.

Thoughts on I think it was combos.

Speaker 11: Yes, thanks for the question. Maybe before I jump in this R245 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.

Yes. Thanks for the question, maybe before I jump in the SAR 245, though since you brought up the immunology event coming in March were really looking forward to not only talking about do pixel, but also the broader portfolio.

Growing from just six molecules in development for immunology 2017, and so you'll be hearing about our biologics that include M. With telematics. The ox 40 ligand, Egypt packing Mab the IL 33 antibody in development for COPD.

Speaker 11: And so you'll be hearing about our biologics that include amlitelimab, the OX40 ligand, etopecumab, the IL-33 antibody in development for COPD, our engineered interleukin-2. On the other flip side of the story, Thor809 that stimulates regulatory T-cells instead of effector T-cells.

Our engineered interleukin two on the other flip side of the story for Ori don't mind that stimulates regulatory T cells, instead of effector T cells or by specific multi civic man of bodies that do with nifty things like neutralizing both TNF and IL 23 in a single molecule that a new concept for inflammatory bowel disease.

Speaker 11: are by specific multi-civic nanobodies that do nifty things like neutralizing both TNF and IL-23 in a single molecule, the new concept for inflammatory bowel disease, CD40 ligand, et cetera, as well as our oral small molecule portfolio of Rilsabrutinib, a unique BTK inhibitor, our RIP kinase inhibitor, our oral TNF inhibitor, and the IRAC4 degrader. So that portfolio for immunology has really blossomed, and we look forward to talking more about that in March. Thank you.

C D 40, ligand et cetera, as well as our oral small molecule portfolio of reels ibrutinib, a unique PTK inhibitor or rip kinase inhibitor or oral TNF inhibitor and the Iraq for Degrader. So that portfolio for immunology has really blossomed and we look forward to talking more about that in March.

Speaker 11: Now the SAR245, we have a large platform study underway in lung, head and neck, GI, skin, and lymphoma.

Now the SAR 245, we have a large platform study underway in lung head and neck Gi skin and lymphoma.

Speaker 11: And like most companies, we sort of started with the obvious, to do combinations with PD-1, and we're pursuing that. But this year we will be embarking on novel combos with other kinds of mechanisms.

And like most companies, we sort of started with the obvious to do combinations with PD, one and we're pursuing that but 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 engages now in development we.

Speaker 11: I would note, for example, that we have three T cell engagers now in development.

Speaker 11: We have our first NK cell engager went into development.

We have our first NK cell engagement went into development, we have our universal allogeneic NK cell platform. So there's a lot to think about as combination opportunities with our two for five.

Speaker 11: We have our universal allogeneic NK cell platform.

Speaker 11: So there's a lot to think about as combination opportunities with SAR 245.

Speaker 11: 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.

Across a range of solid tumors and hematologic malignancies. This.

This will be a rich year for generating those early data signals are where we're eagerly anticipating what we might be able to do with this this best in class engineered version of interleukin two.

Speaker 8: Thanks, thanks, John . I do think, and 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, next question, please. Yeah, next question would be from Emmanuel Kodakis at Deutsche Bank. Emmanuel.

Things things John I do think we're talking.

But 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 for them, but we would like to be an emerging play.

They are an oncology that'd be nice moments for us to make some decisions about which way to go.

We're optimistic.

Next next question. Please yes.

Next question would be from Illinois, but I guess at Deutsche Bank.

Speaker 19: Thank you for taking the question. Perhaps I could kick off with one on Evanescence Octocog.

Thank you for taking the question.

I'm sorry, one quick one on Coke.

Speaker 19: 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 percent factor at four days. What sort of figures would you be hoping to be showing in seven days and what kind of?

Just your expectations what are your ambitions, perhaps for the upcoming pivotal nature. I think you said you hope you shave.

Above the normal expression of about 40% factor in four days, what sort of factors would you be hoping to see.

Shutting in seven days and what kind of.

Speaker 19: share implications do you think that could have relative to what Elokta has at present? Indeed, if you could give us some colour on where you think Elokta is presently, that would be helpful as well. And then perhaps a second question on the Ship 2K rise given the decision to progress the combination to Phase 2 with Amgen. Just wondering if you've seen any data to provide confidence on synergy for that combination given

Sure implications, you think that could have relative to what they locked as president. Indeed, if you could give us some color on why you think luxury is presently that would be helpful as well.

Second question on the shift to Kay rise given the decision to progress combinations phase two with Amgen.

Just wondering if you've seen any dates on confidence on synergy for that combination given.

Speaker 19: the pretty clear lack of SHIP-2 monotherapy activity and the timing of that potentially.

<unk> pretty clear lack of ship to monotherapy activity.

On the timing that potentially.

Speaker 19: either phase one or based from the ongoing phase two being presented to us at a scientific conference. That would be helpful. Thank you. Thank you.

The phase one or phase from the ongoing phase two being presented to us at a scientific conference that'd be helpful. Thank you.

Thank you Emmanuel.

Speaker 1: I'll come to you in a moment, but Bill, I don't know if you have any comment, or actually John may have too as well on FNS-OCTACOG, I don't think we've declared what our expectation is, but certainly our profile.

It's John I'll come to in a moment, but bill do you have any comment on what you're telling them they have to as well and that's in a soft economy.

We've declared what our expectation is but.

Suddenly all profile.

Speaker 20: going to be best in class and built on a common. Yeah, I think that's right. I think if you take a look at what we showed in the phase two, which showed that, you know.

It's going to be best in class I don't Wanna comment, Yes, I think that's right I think if you take a look at what we showed in the phase two which showed that.

Oh, perhaps a week.

Speaker 20: four days where you're at essentially a near normal level. And by the end of the week, it tapers off to

Four days, where a year at a essentially a near normal level and by the end of the week it tapers off to in the 10% I believe yeah, but still quite a check out even at the end of the week. Yeah. I mean this is just.

Speaker 20: I believe yeah, but still quite a strong protection even at the end of the week Yeah, I mean this you just look on the slide that that I showed You know, no one's even close to that and

Look on the slide that our that I showed you.

No one's even close to that and no one's even close to that with a once a week. So this we consider a really transformative and hemophilia a space you know.

Speaker 20: So this we consider really transformative in the hemophilia age.

Speaker 20: You know, when you think about patients, kids who want to have an active life.

When you think about Ah patients kids, who want to have an active lifestyle.

Speaker 20: And if you can give them something they've never seen before, then maybe for, you know, just a brief moment, normal.

And if you can give them something they've never seen before then maybe for just a brief moment normal.

Speaker 20: 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.

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. So we're really excited and that's what we expect to see that interfaces are three weeks, we hope that it set a pretty high bar.

Speaker 10: and being active and so forth so you know we're really excited that's what and we expect to see that uh... uh... interface uh... three weeks we hope you know that uh... it's a pretty high bar uh... that i've offered a high bar for the market i think overall so uh... now uh... they didn't want to come on that one but uh... you know this is really something which is different no one's been able to offer this before so i think now we're here in patient communities really excited yeah and uh... it's uh... that people to receive them i think uh...

Set a high bar for us at a high bar for the market I think overall so stay.

Stay tuned more to come on that one but this.

This is really something which is different no one's been able to offer this before so I think now we're hearing patient community is really excited yeah I know.

It's a Philadelphia about Silversea, Bill and I think the.

Speaker 1: The real question is, could it go even longer, depending on which the patient's longer term? I mean, it gets very exciting for an esophthalmic organ. Our confidence is building. And as you know, the gene therapy, at least this generation, doesn't seem to be definitive. And of course,

And the real question is can they go even longer depending on which are the patients longer term I mean, it gets pretty exciting.

And it's up to talk and our confidence is building and as you know is gene therapy.

At least this generation doesn't seem to be you know.

No definitive.

And of course, some libre come.

Speaker 1: 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. And of course, half the market's been impacted, like Bill said, so it's quite interesting.

It comes more towards the weekly or biweekly itself.

Then then the opportunities, perhaps even bigger than we thought when we started on this journey I'll be honest and of course half the market dependent.

Speaker 1: John , maybe ship to K-RAS.

Interesting for us.

John maybe a ship to K Ras.

Speaker 11: Yeah, so you know, the reason that we're pursuing that combination is because in preclinical studies where we and others tried different combinations of

Yeah. So you know the reason that we're pursuing that combination is because in preclinical studies, where we and others tried different combinations.

Of ship to with various other signal transaction blocking molecules that was always consistently the place where we saw the best the best combination from efficacy so the most synergy.

Speaker 11: various other signal transaction blocking molecules. That was always consistently the place where we saw the best combination from efficacy, so the most synergy. And again, this is not just Sanofi data, but it's Marati data, it's Amgen data, et cetera. So 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...

And again this is not just with L. P data, but its Marathi data as Amgen data etcetera. So we think that if theres a combination were shipped to can shine. This is it and we're doing the studies. This year. It's another one of these where there's.

Speaker 11: The signals will be the important determinant of what kind of trajectory we can take with that mechanism.

This signals will be the important determinant of what kind of trajectory, we can take with that mechanism.

Speaker 1: So that's the rationale, and the data will ultimately speak for themselves, and we'll be gathering it this year. Thanks, John . And maybe I might just thank you for the bit of research you did on Resiroc. I find it really interesting how physicians...

So that's the rationale and the data will ultimately speak for themselves and we'll be gathering it this year.

Thanks, John and maybe just thank you for the research you did on reservoir component really interesting.

Speaker 1: We're really thinking, confident already, and thinking about moving to earlier lines. I mean, of course, it's just a.

Physicians.

We're really thinking continent already I'm thinking about moving to earlier lines. I mean of course is just to survive, but but it was very insightful and we enjoyed reading that so thank you for that work you were concerned congratulations on the strong launch, but thank you very much.

Speaker 1: 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. Thank you very much. Means a lot. OK.

Means a lot.

Okay.

Yep.

Okay.

Yeah.

Speaker 8: Yes, last question would be from Matthew Weston at Credit Suisse, Matthew.

Yes last question will be from Matthew Weston at Credit Suisse Matthew.

Yeah.

Speaker 13: It's Joe here, I'm sorry. I had two questions. On Doopie, I wonder, you've given us the 8% penetration in the US adult market in AD.

It said, it's Jim here I'm sorry.

Yes, I have two questions J P. I wonder you've given us the 8% penetration in the U S market in AG.

Speaker 21: perhaps half of the sales potential comes from other indications, so 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. And I noted that you're going to update your sales projections.

Perhaps half of the sales potential comes from other indications. So 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 based is beyond atrophic.

I just I noticed that you didn't update I'll say, you'll sales projections.

Speaker 21: But that's before you have the COPD data. I thought you were waiting for that before you gave us an update. And my second question would be on IFA. So I would have assumed that if somebody was interested in efficacy.

But before you have the C O P. D paycheck I saw you're waiting for that before you gave US an update on my second question, which they own them Aesop.

So I would have assumed that if somebody is interested in efficacy.

Speaker 21: but not so concerned on safety, they may already have moved from a factor to a non-factor. So 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? And what makes you so confident that people won't think that the different pharmacodynamics of this factor?

But not so concerned safety. They may already have latest refractory to a known factor. So safety is likely to be a very important part in making the decision for these patients to move on so you'll need product how much safety data what do you have at the time of submission and launch and what makes you so confident that people want.

Things are different the pharmacodynamics of the factor.

Speaker 21: could impact on the safety characteristics of the product.

The impact from the safety characteristics of the product.

Speaker 20: Okay, well, there's quite a lot in there. Joe, you always keep me guessing. Sometimes you can't connect, and then you appear as Matthew Weston. But either which way, I'm glad that we got to the questions. Do you see in other indications penetration, Bill? Yeah, so, you know, if you look, Joe, in as...

Okay, Ms Karla and that keeps me guessing sometimes you can't connect and then you pair with Matthew Weston, so, but either which way I'm glad that we got we got to the questions.

D C a.

In other indications penetration well, yeah. So you know.

Yeah, if you look at Joe and asthma.

Speaker 20: uh... at about nineteen percent by a lot of penetration

We're at about 19% biologics penetration okay. So that's the starting point and then as you've heard from a.

Speaker 20: And then, as you've heard from a per-specialty perspective, we're leading in each.

For specialty perspective, we're leading in each of the each of the specialists with depiction.

Speaker 20: And the other the other indications You know

And the other the other indications are.

<unk>.

Speaker 20: It depends again on the bio 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 they're 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

Sure.

It depends again on the bio penetration there pretty low we're seeing we're starting with a brand new indications so to speak with a nasal polyps were the only player there.

Still working on the epic a little but it appears as though we're having good strong penetration there won't give a number at this time.

Guarding the second question was on.

Speaker 1: Well, there's one about why aren't we waiting for the COPD data and I'm sure I'm happy to answer, but then we move to a safety and efficacy trade-off on FNS Octocog, which maybe get to with John . So, Joe, we can't win.

Well, there's one about my only waiting for the COPD data and how much time have you know answer, but then the remove trial the safety and efficacy tradeoff on that front or something to come yeah, I'm trying to get to with John .

John .

So Joe we can't win if we if we wait you say why are you waiting and if we if we don't wait to say why we don't wait.

Speaker 1: If we wait, you say, why are you waiting? And if we don't wait, you say, why have you not waited? So we're sort of betwixt and between. I think because the COPD data is in 23, I think we all know that.

Where sort of betwixt and between I think because of the COPD data is in 'twenty three.

I think we all felt.

Speaker 1: 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.

A good time to take stock.

It would be towards the end of Q1.

Using a deeper immunology catch up that we think that's worth doing and of course.

Speaker 1: we won't be able to declare a new peak without referencing, that it's like, it'll be different with COPD if the data reads out. How we frame that, we're very early in the thinking, so we stay loose on that until we get there, but 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...

We wouldn't be able to declare a new peak without referencing that.

It's slightly 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 stay loose on that until we get there, but I just don't think given the run rate and the prescriptions that we can we can ask people to wait a full year or more on June two two under.

What the peak could be.

Speaker 11: John , I don't know if you've got it all on the safety-efficacy trade-off on what data we'll have. Yeah, I'm a little, I'd say I'm a little surprised by the question because the safety of this next-generation Factor VIII is...

I didn't really get it all on the safety efficacy tradeoff on what data we will have yeah, I'm I'm, a little I'm, sorry, I'm, a little surprised by the question because the safety of this next generation factor eight is its pristine. We there there have been no safety signals, where you don't have any reason really to leave there would be any.

Speaker 11: There have been no safety signals. We don't have any reason, really, to believe there would be any.

Speaker 11: Um, you could almost say, you know, to some extent.

You could almost say you know to some extent.

Speaker 11: That way was paved with products like eloctate, which fuses an FC region onto Factor VIII, and here there are some additional embellishments with the so-called Xtend technology, but that had also been de-risked with other molecules that had been taken in the clinic, including an approved product. So the components of the molecule have all been de-risked, and we've not seen any.

That way it was paved with products like <unk> blockade, which fuzes an FC region on two factor read and hear there is some additional embellishments with a so called extend technology, but that it also been derisked with other molecules that have been taking the clinic, including an approved product. So the components of the molecule of all.

Been derisked and we've not seen any safety liabilities on the other hand, if you think about alternatives are they do have some safety historical safety baggage. So I really think on a safety standpoint again, we come out best in class and John just just to add to that.

Speaker 11: safety liabilities on the other hand if you think about alternatives uh... they do have some safety uh... historical safety baggage

Speaker 11: So I really think on a safety standpoint, again, we come out best in class. Yeah, and John , just to add to that.

Speaker 2: I think clearly from an efficacy perspective, we win.

I think clearly from an efficacy perspective, we went into.

Speaker 20: I mean, no one's, if you look at the comparison where emethizumab is, if you try to estimate where it is, it's nowhere near normal.

No ones. If you look at the comparison, where I'm a schism that as if he tried to estimate where it is it's nowhere near normal.

It's nowhere near normal.

Speaker 2: factor level. So, you know, we're really confident that we win on the on the safety for, you know, just redefine the safety bar. And then if, you know, you're looking at a weekly dose.

Factor level. So you know, we're really confident that we went on the on the safety for you know just redefined the safety bar and then if you're.

You know you're looking at a weekly.

Speaker 1: that's pretty convenient as well. So I think across both parameters, we're in really good shape. Yeah, thank you. When I joined the company, a lot of people asked questions like, did the company not understand Hemlibra was coming when we got into FITUS around in 001?

Dose.

That's pretty convenient as well so you know I think the cross both the parameters. We're in we're in really good shape. Yeah. Thank you you know when I joined the company a lot of people ask questions like did the company not understand him Libra was coming when we got into for two surrounding areas are one.

Speaker 1: Half the people responsible for home-lever work for us now. John Reed, thanks. But 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 one to two weeks in the case of the non-factor.

Half the people responsible for them Libre workflows math, John Reid, Thanks, but one thing we did was that these.

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 or actually a every one to two weeks.

In the case of the non factor.

Speaker 1: 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 that position in the first place, and it's what we'll do when we launch with EFFA, which is not that far away. So thank you for those questions. Thank you to everybody for the energy and the contribution. Delighted, by the way, as always,

As Bill said, you know set a new standard I think the competition needs to be slightly more concerned that the patients.

Much more likely to change its what got them that position in the first place first place and it's what we'll do when we launch with Axa, which is not that far away. So so thank you for those questions.

Thank you to everybody for the energy and the contribution.

I'm delighted by the way as always.

Speaker 1: It's starting to transition more towards science and the transformation of the company, a little less just on the basic financials which

Starting to transition more towards science and and the transformation of the company a little less just on the basic financials, which every day. We are responsible for doesn't even think that we're not but we think in terms of value creation and the right to bring a pipeline for them surprise you is.

Speaker 1: every day we're responsible for it, don't even think that we're not, but 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 feel that you're not part of it. But I think as we look back, I like to particularly at full year, we get to look at the distance traveled just in 12 months. I think it feels like we've come an awful long way.

It's very very important.

Nothing is off the table, we've reshaped the company real time, you may not see it and put it you don't you know part of it but I think as we look back I like to particularly at full year. You know we get to look at the distance travel just in 12 months I think it feels like we've come an awful long way and while we got some news flow up ahead of us and we hope it's all positive.

Speaker 1: And 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 last year, sorry, at the beginning of last year.

We will keep moving forward finding signals and advancing 36 programs that were not.

Moving last year, sorry at the beginning of last year to move last year and.

Speaker 1: and 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. So thank you to everybody on the team. Thank you to Ayaan, thanks to everybody on the team.

And 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. So I think everybody in the team. Thank you Tycho and thanks, everybody on the phone.

Thank you very much you may now disconnect.

Yes.

Yes.