Sanofi SA

PAR:SAN

Earnings Call Transcript 2023-Q1

[Operator]

Good morning, good afternoon and good evening to everyone. Thank you for joining us to review Sanofi's First Quarter 2023 results followed by Q&A session. As usual, you can find the slides to this call on the Investors page on our website at sanofi.com.

Moving to Slide 3, I would like to remind you that information presented in this call contains forward-looking statements that involve known and unknown risks, uncertainties and other factors that may cause actual results to differ materially. I refer you to our Form 20-F document on file with the SEC and also our [indiscernible] for a description of these risk sector.

With that, please advance to Slide 4. Our speakers on the call today are Paul Hudson, Chief Executive Officer; Dietmar Berger, Global Head of R&D at Interim, the global business unit head, bill Sibold, Thomas Triomphe, Olivier Charmeil and Julie Ongevalle; and Jean-Baptiste de Chatillon, Chief Financial Officer.

[Operator Instructions] And with that, I'd like to turn the call over to Paul.

[Paul Hudson, CEO]

Well, thank you, Eva, and thanks for joining our call today. Together with members of the executive team, I'll take you through Sanofi's business and financial performance in the first quarter of 2023. We had a strong start to the year, reporting first quarter sales of EUR 10.2 billion, an increase of 5.5% and delivering double-digit growth across 3 out of our 4 businesses. Our Specialty Care business continued to grow strongly driven by Dupixent across all geographies, indications and demographics. We also saw good business momentum from launches in the rare disease franchises with nirsevimab, increasing its patient share in Pompe. The consistent performance in Specialty Care is expected to more than offset the decline of Avago following loss of exclusivity, which we expect to become more meaningful throughout the remainder of the year.

Vaccines reported a particularly strong quarter as we keep delivering on COVID-19 contracts in Europe. In addition, sales of travel and endemic vaccines continue to recover post pandemic. In General Medicines, we continue to execute on our strategy by investing in transplant and other growth assets, while rapidly divesting declining noncore products.

Our Gen Med core assets continued to grow, driven by solid demand. The Consumer Healthcare business delivered double-digit growth in the quarter across key franchises such as digestive wellness, allergy and cost of coal. Advancing to Slide 7, I'd like to highlight and provide some context around important achievements of the quarter.

We have just launched Altuviiio in the U.S., a best-in-class factor treatment for hemophilia A with the potential to set a new efficacy standard. The rollout is progressing well, and we continue to receive positive feedback from physicians and importantly, patient communities. Bill will touch more on this in his section.

For fitusiran, the Phase III results were published in the Lancet last month, scientific evidence is growing for fitusiran to become an important addition to the transforming landscape of hemophilia treatments with as few as subcutaneous injections per year. For Dupixent, we delivered Phase III pivotal study in COPD, achieving clinical outcomes never previously seen with the biologic.

Remember, in 2019, we outlined our bold approach with our direct to Phase III program, shaving years of standard clinical development time lines. And thanks to this, Dupixent is today positioned to be potentially the first approved biologic in the disease marked by a very high unmet need and with huge medical costs that could be offset.

COPD today is what atopic dermatitis was 6 or 7 years ago. No advanced therapies, no recent innovation, but was significant -- with a significant difference that that the patient population is already well identified. We are looking forward to sharing the data with the broader scientific community next month. Dietmar will provide more details in just a moment.

Switching gears and moving to another innovation. The acquisition of Provention Bio, which we expect to close today with TZL as its first-in-class therapy to change the course of type 1 diabetes. TZL is a great fit to our Gen Med business as it provides us with the opportunity to leverage our expertise in diabetes and the existing prescriber network, our strategic focus in immunology, coupled with our deep knowledge in identifying patients with rare diseases will be critical to the successful launch execution and effective use of patient screening programs.

With TZL, we are adding another potential blockbuster to our growing Genmed core asset portfolio. Now Slide 8. Coming back to our strategic framework and reminding you of how we continue to execute on our growth strategy as exemplified by the pipeline advances and launches in the first quarter. We are increasingly confident in our ability to fuel our next chapter of growth with innovative compounds and new launches from our pipeline.

Specifically, in immunology, we are aspiring for industry leadership with an outstanding portfolio of novel molecules. Our immunology assets cover a broad spectrum of inflammatory diseases in areas of high unmet medical need, supporting our ambition to achieve more than EUR 22 billion of sales by 2030, generating potential breakthroughs in COPD and acquiring TZL with 2 significant steps towards our goal of launching 3 to 5 products with EUR 2 billion to EUR 5 billion peak sales potential each in the second half of the decade.

Advancing to Slide 9, before I hand over to Dietmar for the R&D update, I want to highlight our upcoming investor events. On May 22, we will host an investor call in conjunction with ATF, where the full Dupixent COPD data will be presented for the first time. We will combine this occasion with a broader discussion of our growing pipeline in respiratory diseases -- in vaccines, Thomas and his leadership team will host an in-person event in London on June 29 to update you on the progress we're making and our ambition to double vaccine sales by 2030.

And finally, we also plan for an R&D Day in the second half of this year to provide a comprehensive overview of our early to mid-stage pipeline set to deliver on our ambition to transform the practice of medicine. Dietmar, over to you.

[Dietmar Berger, Global Head of R&D]

Thank you, Paul. Now starting on Slide 10, let me give you some additional insights into the recent progress we have made in advancing our innovative pipeline across core therapeutic areas. We are extremely proud of the progress we've made in immunology with the success of Dupixent and the leadership we have built in type 2 inflammatory diseases.

Huge potential remains on Slide 11 to transform the practice of medicine for patients suffering from diseases driven by Type 2 information. We are determined to expand our immunology portfolio beyond type 2 and to drive innovation by deploying disruptive technologies for the development of first and best-in-class medicines. On Slide 12, let me expand on Paul's earlier comments regarding the truly impressive results from BOREAS a randomized Phase III double-blind, placebo-controlled trial, evaluating the efficacy and safety of Dupixent in 939 adults who were current or former smokers aged 40 to 80 years with moderate to severe COPD.

All patients in the BOREAS trial had evidence of type 2 inflammation as measured by blood eosinophils of greater or equal to 300 cells per microliter. Importantly, they all were on triple center therapy and still had uncontrolled disease. This means they still experience exacerbations and each exacerbations may leave behind permanent irreversible lung damage.

During the 52-week treatment period, patients received DUPIXENT or placebo every 2 weeks added to their triple standard therapy. Double maintenance therapy was allowed if inhaled corticosteroids were contra indicated. Primary and all secondary endpoints of the study were met, validating the role type 2 inflammation plays in driving COPD in these patients. It also underscores Dupixent's unique profile. It is the first and only biologic to demonstrate clinically meaningful and statistically significant reduction in exacerbations compared to placebo.

Exacerbations were reduced by 30% and a rate of reduction not seen before with biologics in these patients that have exhausted all currently available treatment options. And it is the first and only biologic to show rapid and significant improvement of more than 80 milliliters in lung function compared to placebo. The data also showed significant improvement for life and respiratory symptoms with a safety profile consistent with findings in earlier studies.

COPD is an urgent and costly global health concern and a difficult-to-treat disease due to its heterogeneity. We are thrilled to share the full data with the medical community at the American Thoracic Society Conference next month, and we invite you to discuss with us the details of the clinical outcomes achieved with Dupixent in this patient population.

Now on Slide 13, I'd like to remind you that we are developing not 1 but 2 unique targeted therapies with the potential to build clear leadership in COPD. The mechanisms of action are different. And together, they are addressing more than 80% of the COPD population with the highest unmet medical need. This accounts for approximately 2 million patients in the G7 countries alone.

Itepekimab is the second biologic we're developing in COPD in collaboration with our partners at Regeneron. We are studying itepekimab across a spectrum of moderate to severe COPD because of the known effects of IL-33 on both type 2 and non-type 2 inflammation. This is supported by published data demonstrating that IL-33 levels in advanced COPD patients who are former smokers are elevated compared to healthy controls.

In our Phase II study published in the Lancet in 2021, Itepekimab reduced COPD access orations by more than 40% in former smokers. And importantly, this effect was similar in patients with Type 2 and non-type 2 inflammation. We hope that Itepekimab may become the best-in-class and first-in-class IL-33 treatment option in COPD. The chart on the right side of the slide summarizes our expected time lines for data readouts and subsequent submissions to regulatory authorities in the U.S. and Europe.

Notice the second replicate Phase III trial for DUPIXENT COPD is about to finish recruitment and will read out next year. Itepekimab received FDA Fast Track designation in January 2023. And results of the pivotal trials, RIP1 and 2 are due sometime in 2025, and both trials are reading out concurrently.

Turning to Slide 14. We are also encouraged by recent results of some earlier-stage molecules in our immunology pipeline. We introduced these 2 highly innovative compounds at our immunology event in March last year. Firstly, SAAR 764, an antibody targeting both IL-13 and TSLP delivered Phase Ib results that will be shared very soon at the upcoming ATS conference as well.

The target selection was based on the rationale that blocking IL-13 potentially enhances the more modest impact of anti-TSLP blockade on lung function while anti-TSLP targeting provides the opportunity to treat a range of asthma subtypes, targeting IL-13 and TSLP in one molecule promises the potential of enhanced efficacy in a broad range of asthma patients with largely derisked mechanisms of action.

Based on the data we now have in-house, we are moving to Phase II in asthma in the coming months. We also have data in-house for SAR 566, our oral TNF alpha inhibitor, potentially addressing the largest therapeutic class game immunology. This inhibitor benefits from its unique molecular design. It binds the TNF trimer and then selectively inhibits TNFR1 signaling, but not TNFR2 signal. That is important because TNFR1 signaling is pro-inflammatory, while TNFR2 signaling is involved in tissue repair and regulatory T cell expansion.

The data set that we have generated so far is pointing to a drug profile that is both safe and efficacious. We plan to present the Phase Ib data in psoriasis at a conference later this year. We are now moving to Phase II in psoriasis and look forward to updating you on the potential target profile across a spectrum of inflammatory diseases in the future. Concluding my comments on the progress of the immunology pipeline, the table on Slide 15 illustrates how we position our industry-leading portfolio of novel molecules in the highly attractive and growing immunology market.

With 12 molecules across key inflammatory disease areas, we are laying the foundation today for our ambition to be the leader in immunology. Switching to neurology on Slide 16, let me focus on multiple sclerosis and how we are applying our expertise in understanding MS to develop new treatments. MS is a condition that often strikes early in life is debilitating and ever progressing with a very high burden to patients, families and payers.

Significant unmet need remains, most notably the smoldering neuro inflammation and progressive forms of MS. Starting with tolebrutinib, our brain penetrant and bioactive Bruton's tyrosine kinase inhibitor. Only tolebrutinib achieves CSF concentration, sufficient to modulate B lymphocytes and microglial cells. Data shared today at AAN 2023 showed tolebrutinib to be between 10 to 50x more potent than other BTKIs currently tested in MS. These data also show that tolebrutinib inhibits BTK at least 60x faster.

The combination of sub nanomolar potency, fast reaction rate and CNS exposure that exceeds the IC50 suggests a unique ability to engage CNS-resident microglia and lymphocytes, the cells that are thought to drive disability accumulation in MS. Our Phase II clinical data as well as available Phase II data of competitors have shown clear signs of efficacy. Recent evidence suggests that the rare liver injury cases observed are likely a class effect, which appears not to be linked to potency.

We have currently the broadest pivotal program in place to develop BTKI in MS with 3 or 4 studies recruited, and we expect first results in RMS either later this year or early next year. More importantly, tolebrutinib is the only BTK inhibitor that is currently tested in secondary progressive MS. The pivotal study is fully recruited, while recruitment in the PPMS study continues, mostly in major European countries.

Considering the advanced recruitment status of our pivotal studies, we are currently not largely impacted by the ongoing partial hold in the U.S. We are working on a risk mitigation strategy to allow for safe initiation of the drug, which we expect will be ultimately informed by the efficacy data and the overall risk benefit profile. Beyond BTK, the CD40 ligand pathway also plays a significant role in the regulation of both humoral and cell-mediated immunity and appears to be involved in the MS-related inflammatory process. inhibition of CD40, CD40 ligand in the periphery, upstream of T cell interactions with B-cells, dendritic cells and microglia prevents activation of these cells and may block the inflammation that drives MS progression.

Tracsalimab is a second-generation antibody against CD40-ligand and importantly, does not deplete B or T cells. We are excited to present our Phase II data of the randomized controlled study in RMS at an upcoming medical congress. Lastly, SAR'H20 is a first-in-class brain penetrant RIPK1 inhibitor. RIPK1 is a newly described pathway and different from apoptosis and necrosis.

It is activated in several neurodegenerative and neuroinflammatory conditions, including ALS, Alzheimer's and MS. SAR'H20 has demonstrated robust target engagement and CNS penetration at doses that were generally well tolerated in healthy volunteers and is currently in Phase II development in ALS. A Phase II study in patients with RMS has just started. Moving on to oncology. I'm delighted to see that the work we initiated in research in 2019 is now starting to be presented at important conferences such as AACR.

Today, I want to highlight the anti-CEACAM5 Topo 1 antibody drug conugate. You may remember that tusumitumab Ravtansen, the anti-C5 DM4 is currently studied in non-small cell lung cancer and other cancers where antitubulin agents have been proven to work. In colorectal cancer, the rate of CC5 expression is among the highest, around 90%. And the compound delivers a cytotoxic topoisomerase 1 inhibitor payload to the targeted cells.

The data recently generated in [indiscernible] models were just presented at AACR, showing a response rate of more than 50%. We're looking forward to moving this asset into the clinic later this year. And with this, I will hand the call over to Bill.

[William Sibold, EVP, Specialty Care and President, North America]

Thank you, Dietmar. Now looking at our performance in Specialty Care, we had a strong start to the year. As you can see on Slide 19, Specialty Care delivered another quarter of solid double-digit growth with sales of EUR 4.3 billion, representing approximately 42% of total Sanofi sales in Q1. I as mentioned by Paul earlier, Dupixent's stellar performance continues to be our core growth driver in 2023. Strong demand for Dupixent from launches in new indications across all geographies and drove sales growth in the quarter, adding EUR 700 million in sales when compared to Q1 last year.

We remain excited about our momentum in rare diseases, up 14.8%. Strong growth in the first quarter was driven by the launch execution of NexViazyme and Zempizyme, the steady increase in patient numbers across geographies as well as some positive phasing effects in the rest of world region. In oncology, Sarclisa continued its fast uptake in approved indications in Q1, capturing share in key markets and partially offsetting increased Jevtana competition as well as the deconsolidation of Libtayo.

As anticipated, multiple generic versions of Abagio have entered the U.S. market in the second half of March. We have previously communicated that generic competition is included in our plans, and we continue to expect a meaningful impact on our sales in the U.S. beginning in the second quarter.

Now on Slide 20, let's focus on Dupixent. Six years into Dupixent's U.S. launch in its first approved indication, this unique medicine delivered another outstanding performance with 40% growth globally. Sales of EUR 2.3 billion in the first quarter give us great confidence in our ambition to achieve the EUR 10 billion sales milestone for the year 2023.

At the same time, we keep making tremendous progress in achieving new development milestones, which will enable us to address new areas of high unmet need. Dietmar spoke about the progress in respiratory diseases such as COPD. In immuno-dermatology, we remain focused on pursuing growth opportunities by consistently expanding our leadership position. This is exemplified by the milestones achieved in CSU and where our filings for regulatory approval were accepted by the agencies in the U.S. and Japan in Q1 as well as the approval in AD and 6 months to 5-year-old children in Europe.

The readout of positive 52-week data in EoE in the population of 1- to 11-year-old children at the beginning of the year was similarly promising. Now on my last slide, the U.S. approval of Altuviiio, in the first quarter marked an important clinical advancement for the entire hemophilia A community. With Altuviiio, we have now the opportunity to define a new standard of efficacy by providing hemophilia A patients with a normal to near normal range of Factor VIII levels for most of the week. Commercially available since late March, we are still in the very early weeks of the Altuviiio launch.

We are very encouraged by our early launch indicators, including initial patient switches from both factor and Hemlibra to Altuviiio as well as an enthusiastic response by the physician and patient community. The launch is following the typical process of securing reimbursement, including a permanent J code. As of mid-April, we had signed direct contracts with customers who account for greater than 90% of all hemophilia A purchases in the U.S. market.

Outside the U.S. significant progress has been made, including the positive top line results from the XTEND KID study. We expect approvals in Japan and Taiwan later this year as well as the submission in Europe. We are very excited about Altuviiio as an important future growth driver for Sanofi, building on our expertise in the projected greater than EUR 10 billion hemophilia A market.

Beyond Altuviiio, we are looking forward to pivotal Phase III results for fitusiran later this year. We are encouraged by the recent results from our small open-label extension study for fitusiran, which demonstrated good efficacy and safety in patients who were on treatment for up to 7 years. And to remind you, there were patients in this study that were on the new regimen for up to 2 years, which is the regimen studied in Phase III. With that, I hand over to Thomas.

[Thomas Triomphe, EVP, Vaccines]

Thank you, Bill. Vaccine sales in Q1 were up 15% due to strong travel and dynamic vaccine sales as they continue to recover and have now almost reached pre pandemic levels. In addition, sales in the other category, benefited from COVID-19 booster shipments, mostly to EU member states. By now, almost all existing COVID-19 countries supply arrangements have been fulfilled. In the PPH franchise, sales decreased 11%, following the discontinuation of the oral polio vaccine at the end of quarter 1 last year in addition to the favorable phasing of IPV.

In China, the vaccine sales grew in the quarter while Vaxelis in the U.S. continues to gain market share at the expense of Pentacel. If a reminder, we do not consolidate Vaxelis sales, though it is booked in the line share of profit and loss of associates and JV. As for Influenza, our Q1 sales were up 6%, benefiting from improved time to market in the Southern Hemisphere. As presently mentioned, the relevance of South mister flu to predict the broader dynamics for season is very limited.

With currently many moving parts influencing the flu market dynamic, we will be able to provide you with a flow outlook for the year at the Q2 earnings call. My second slide focuses on Beyfortus and our vaccine R&D engine. Across multiple studies on endpoints, with single dose of Beyfortus demonstrated consistent and high efficacy of around 80% against RSV lower risk track disease throughout the entire duration of the RSV season.

Unlike maternal immunization, Beyfortus is the first and only preventive options designed to protect all infants against RSV regardless of the amount of birth. In the U.S., we are progressing on multiple fronts. At the February ACIP meeting, we were encouraged by the committee's positive feedback on Beyfortus efficacy and safety. There was a clear desire to work on implementation for all infants in the 2023 season.

In parallel, we are working closely with the FDA to expedite the review. Outside the U.S. our interactions with health authorities and scientific societies to really demonstrate RSV being a public priority to them. In Canada, Beyfortus was just approved 6-month period of schedule. In Spain, the first Allinson regional program has been announced. And in France, Beyfortus has been recommended for all infants by the French nemology society.

Finally, with the HARMONY study, which measures the efficacy of Beyfortus against Rezospetalization in a real-world setting in 3 European countries, we continue to enrich the strong scientific evidence of this product. The HARMONY study results will be presented at the SP Congress as soon as May 12. Please don't miss this day to discover new outstanding hospitalization results.

Moving beyond Beyfortus, our vaccines R&D team is working on a broad range of programs on RSV tolerant, RSV older adult to mRNA flu normal conjugate and meningitis vaccines. We will present new data at our upcoming vaccines investors event. So I warmly invite you all to join, and I look forward to exchanging with you on June 29. With that, I'll hand the call over to Olivier.

[Olivier Charmeil, EVP, General Medicines]

Thank you, Thomas. General Meeting sales in the first quarter were EUR 3.3 billion. Our core assets grew 1.6%, driven by the double-digit growth of Praluent, Reza, Thymoglobulin and Soliqua. Lovenox sales decreased in the quarter due to biosimilar competition and a high base in Q1 2022.

Toujeo sales were up 4.4% with a strong performance in Europe and in the U.S. We remain committed to growing our core assets, mid-single-digit CAGR over the period of 2020 to 2025. We expect Lovenox sales will start to stabilize in the second half to '23. We aim to establish Toujeo as a Basel insulin of choice in China. So we wave 6, making it an important growth driver in 2023 and beyond.

Sales of noncore assets decreased 20.5% in Q1 mainly due to lower loan of sales and strategic product divestiture. The legacy oncology products were impacted by COVID driven overall slow start to the year in China.

The Euro API spinoff will annualize in April, and we expect for full year 2023 sales to decline low single digits versus last year. Now moving to Slide 25. Let me summarize the strategic rationale of the acquisition of Provention Bio that we just closed.

This field is the first and only disease-modifying treatment for the delay of Stage 3 type 1 diabetes in adults and children throughout starting from 8 years. [indiscernible] diabetes is a complex and substantial burden of disease on individual health care system alike. [indiscernible] is an innovative, first-in-class therapy with the potential to bring life-changing benefits to people at risk of developing Stage II type 1 diabetes, particularly to young people.

The median age of diagnosis of Type 1 diabetes is 12 to 14 years and life expectancy significantly impacted, reduced by up to 16 years. Less than 20% of adolescents with Type 1 diabetes achieve glycemic control. For the first time, we can disrupt the autoimmune attack delaying the need for insulin treatment for almost 3 years. This means Children can just be children without the burden of disease, for them, every day counts.

For the currently U.S. approved indication, delayed onset of Stage 3 type 1 diabetes when diagnosed at Stage 2, we see a big sales potential up to EUR 2 billion. The path to peak sales will take time. We will work with the respective systems to increase cleaning program that will help identify people at risk. In the second half of the year, we expect the readout of the PROTECT study, and if successful, could lead to a second indication in the early intervention population.

Now moving to Slide 26. The recently signed partnership with the Guyana Ministry of Health delivered through Gen Med is a proof point of our commitment to improve access to diabetes care in low and middle and countries. The health care searches in Ghana will be able to purchase affordable high-quality Sanofi analog insulin products while we collaborate in the deployment of diabetes management solution and HCP training program. Through our commitment, we are aiming to impact the lives of 1,900 people living with either type 1 or type 2 diabetes in low middle-income countries within the next 5 years. With that, I hand the call to Julie.

[Julie Van Ongevalle, EVP, Consumer Healthcare]

Thank you, Olivier. The OTC market continues to post sustained growth with the progressive conversions to historical growth levels. The growth is primarily driven by price due to the inflationary environment, along with positive volume contribution. The strong cough and cold category performance is the key growth driver of the market. In this environment, our absence in key cup and cold markets like the U.S. has impacted our growth versus market in recent months, yet our overall performance approximates out of the market.

Our success is mainly driven by 3 key levers: first, growth in key categories such as our digestive wellness, which delivered another quarter of outstanding growth and continues to outpace well ahead of market. Second, geo expansion. Our strategy to expand key brands into new geographies is contributing positive early results. As an example, [indiscernible] launched in the U.K. in February 2022 reached a #2 position in the category within just 9 months.

Building on that success, we launched in Germany in January of this year, and we look forward to seeing similar performance there. Third, launching new brands. With the recent approval of Cialis together in the U.K. We are entering the intimate wellness category, specifically a rectal dysfunction. Cialis together will launch in the second half of this year, bringing a new self-care solution for an estimated 8 million man in the U.K. suffering from erection difficulties.

Moving to net sales. I'm proud to share that we have delivered our eighth consecutive quarter of growth. In Q1, we posted plus 11.2% growth versus prior year and actually 12.7% growth when excluding divestments. Most of our categories portfolios posted growth in Q1 with cough & cold Digestive wellness and allergy up double digits.

Q1 did benefit from higher stock and trade in the U.S. and Brazil ahead of the deployment of our new ERP system. Excluding this favorable phasing effect, our performance was in line with market, driven by price and to a lesser extent, by volume. I'd like to call out a few outstanding performances.

In Europe, our cough & cold category grew 44%, boosted by our fully integrated on high-def multichannel campaign, which I shared with you last quarter and was deployed in more than 35 countries. In allergy, our lesion brand in Japan is overperforming the market in a context of record allergy season. And this quarter, again, digestive wellness is our champion category with a strong growth trajectory and market share gain.

Today, I would like to specifically highlight Inter Germina, up 48.5% in Q1. One of our love brands that exemplifies how a 65-year-old brand can be nurtured for growth and impact people and communities worldwide. Let me explain how. Slide 29. Enterogermina was born in Italy and was originally focused on pediatic diarrhea relief post-antibiotic Qus. Its differentiated science with unique strains, formula and format has led to positive recognition from health care professionals and consumers.

With this solid foundation in 2020, we identified the opportunity to ride the wave of growing consumer interest in probiotics and good health expanding the brand beyond kids and recovery to include the entire family and address other Gohil locations like unhealthy diet stress or travel. And EnteraGamina today is present in 55 countries, became the #1 probiotic brand worldwide. Its sales has more than doubled versus 3 years ago, and it has delivered 7 consecutive quarters of market share gain in an accelerated category. Contributing to our ESG journey and [ Don Germany ] is also committed to fighting according to WHO, the second leading cause of death in children under 5 years old, which is childhood mortality from [ diarrhea ]. The brand has partnered with several NGOs to provide from water filters to education on good hygiene. The program has already reached 161,000 people, mainly children in 19 countries in 2022. Recently, [ Endel Germinar ] renewed its partnership with several NGOs such as [ Save the Children ] or the Hope Foundation, which I personally met in Vietnam 2 weeks ago, and our ambition is to extend our effort to 30 countries by 2025. And more importantly, make an impact on 1 million people.

With that, I'm handing it over to Jean-Baptiste, our CFO.

[Jean-Baptiste de Chatillon, EVP and CFO]

Thank you. Thank you very much, Julie. [indiscernible] recorded a healthy sales growth, 5.5% this quarter, including one-off payments we received from COVID-19 booster shipments. The gross margin increased 1.9 percentage points due to favorable product mix and was also supported by the euro API deconsolidation. SG&A was up mainly due to launch costs in Specialty Care as well as increased cost for the stand-alone structure in CHE. We also recorded a high level of capital gains due to product divestment, EUR 75 million more than in the same quarter last year. As a reminder, Dupixent still benefit from the step-up in repayment of upfront development costs. EPS grew 11.9% in the quarter, helped also by increased short-term interest rates on our cash.

On Slide 32, I want to take a moment to also look at the new CHC segment reporting. CHC sales were up 11%, also driven by higher stock in trade in advance of a change in ERP system in certain countries as just mentioned by Julie, and the gross margin increased plus 12% in good part due to price increases. Operating costs in CHC were up 10.2% this quarter, mainly driven by R&D cost saving versus last year on a higher stand-alone cost. So strong seasonality of consumer health drives a high level Q1 margin, even though it is lower than last year due to a lesser positive impact from divestments and higher cost due to the stand-alone ramp-up.

Moving to Slide 33. Earlier this month, we made a significant step towards simplifying our Beyfortus collaboration. As you may recall, under the initial agreement, Sanofi on [indiscernible] were sharing the U.S. economics 50-50. [indiscernible] had subsequently transferred its economic rights to [ Sobi ] under a separate agreement in 2019.

Starting Q2 2023, Sanofi will have full commercial control of Beyfortus in the U.S. and consolidate 100% of the economics in business operating income. More details are available on the accounting of the calibration that you can find in the financial appendix. On Slide 35, for full year 2023, we expect continued growth in Dupixent, the Obagi full impact starting from Q2 onwards, a low single-digit decline of Gen Med me, mainly driven by divestments on lower net price for launches.

For CHC, please keep in mind for full year that the sales in Q1 were positively affected by seasonality and higher stocking trade. On the P&L side, we expect the gross margin to improve on a full year basis due to growth of our remaining Specialty Care franchise despite [indiscernible] . As said previously, capital gains from divestments are expected to reach around EUR 600 million in 2023. In Q1, we recorded EUR 307 million. And for the moment, we expect that the majority of the remaining EUR 200 million will occur in Q3 and Q4.

Advancing to my final slide, Slide 36 based on the business outlook just described, we continue to expect full year 2023 business EPS to grow in the low single digits at constant exchange rate. On foreign exchange, we see a negative currency impact of minus 5.5% to minus 6.5% based on April 2023 average exchange rate. And now let's open the call for Q&A.

[Eva Schaefer-Jansen, Head, IR]

Can we have the first question?

[Operator]

[Operator Instructions] First question is from Luisa Hector from Berenberg.

[Luisa Hector, Berenberg]

I wondered whether you could update us on Bay Fortis and how price discussions are progressing around Europe. And then thank you for the detailed pipeline update today. It links well to my next question, which is -- if we look from next year, we see a very clear runway for your top line in terms of LOEs. And then we have the strong growth potential from the marketed assets and you highlight the impressive 10 billion milestone for Dupixent this year.

So if we bring that together with the fact that you have expanded your early-stage pipeline significantly, how much confidence do you have that these pipeline assets will be making a meaningful contribution to your top line at the end of the decade?

[Paul Hudson, CEO]

Okay, Luisa, thank you. Well, maybe I'll start with Thomas on Beyfortus.

[Thomas Triomphe, EVP, Vaccines]

Thank you, Lisa, and thank you for starting with Beyfortus. We are very excited about the coming launch of BT. So where do we stand now? We foresee a launch in 2023, both in North America and in Europe. And the large dynamics is very positive. As you have seen during February at the ACPI. I think the burden of disease is very well understood, and there is a clear signal from the committee to move forward for our Pollington program as soon as 2023.

Same thing. We've made great progress with recommendation in Europes. And as you've seen, there has been a couple of regional programs already announced for all infant protection in Spain. Now I think your question was leading more specifically to the pricing discussions. I think the burden of this is being well recognized. Our pricing policy has always been to have a product that is available for all infants.

And therefore, we've signaled from the get go, but we will go from innovative premium vaccines pricing. This is well understood, and I'm confident we're moving forward properly in this direction for 2023.

[Paul Hudson, CEO]

Thanks, Tom. I've been taking phone calls myself from health ministers and others. It's really getting quite exciting. So the broader question is, and to be honest, for me, it's a great question to start because if you look at Beyfortus and the excitement, the examine Bill shared on Altuviiio, this year alone, to first-in-class, best-in-class assets going to be in flight, last meaningful LOE of Azure.

And if you look carefully, I think demos shown also molecule TNF IL-13, TLCP to name just 2 really out of them because they come out of immunology. Our confidence in our ability to deliver these new assets to contribute significantly in the second half of the decade is really high, I mean really high. You know between fexalamabolt2 TSP or TNF and arm that we're going to be in a really strong shape about atesial.

And we say it internally, I'm happy to say it externally, by the end of this year, it's the new sort of steady-state Sanofi, all about launches, all about new data, all about the marketed first-in-class, best-in-class assets and really a new setup, and we build that confidence through this year. I think that's just very exciting.

Thank you, actually, for a nice question to start, which is how we feel is how things are coming together, and we feel like we're becoming a very, very different company and still delivering the financial performance with whatever else is going on and absorbing that LOE. So it's getting exciting for us.

[Operator]

Next question from Richard Vosser from JPMorgan.

[Richard Vosser, JPMorgan]

Maybe on the oral anti-TNF, obviously, PSO is a very significant -- or has very significant competition. How do you see the target profile of the product? I mean anti-TNFs injectable have been superseded by other injectables, for IL-23 and IL-17s. So where do you think this fits? And can it be more efficacious than injectable anti-TNF?

And then second question, just one for Thomas, I think, on the flu market. I was intrigued by the moving parts and lots of. So what are the different moving parts that are different this year to other years on the flu market?

[Paul Hudson, CEO]

I'll maybe start with Thomas and the annual moving parts. So Thomas, over to you.

[Thomas Triomphe, EVP, Vaccines]

If flu season is a new season. Thanks for the question, Richard. As I was mentioning in the call, it's still a bit early a strong outlook for the coming Northern Hemisphere flu season due to the moving part. But let me give a bit more color and specificity -- sorry, about what I mean. I think from a tailwinds perspective, on one hand, I see positive momentum in terms of our own execution. When I look at first, the expansion of Efluelda in Europe, Efluelda, our best-in-class flu vaccine for seniors.

Second point there, the continuous switch that we see of standard dose flu vaccines from trivalent to quadrivalent formulations in sizable volume countries like China or Mexico. And third, positive momentum in terms of execution and the solid ongoing supply execution that I see in our factories. On the other hand, when I look at the headwinds for the first, we have all observed some vaccination fitting in North America.

In the U.S. flu vaccination coverage rate more specifically, remains for me the key note for the coming season. So because of this back-and-forth movements, if you wish, we will give you an outlook more at Q2, including at that time the expected Q3 versus Q4 split for influenza assets.

[Paul Hudson, CEO]

Thanks, Thomas. I mean let's be clear, we literally played a win on flu every year that are variables, there are every year but we'll be well prepared to take advantage of what the opportunities are, we will. Maybe Bill, some headlines on the oral T&F.

[William Sibold, EVP, Specialty Care and President, North America]

Yes. Well, Richard, thanks for the question. Look, as you know, TNS have been a mainstay in immunology now for 25 years and we're getting into that range anyways. And the one question people always have is, can you make it a pill? Well, that is -- was the objective, and that appears where we're headed towards. Talking about kind of where the indications, where do you go?

I mean, you know where the TNFs are. There's a broad group of indications. Clearly, with a program like this, if it becomes what we hope there would be a plan to go after a broad group of indications, which are, as I said, they're pretty well defined. So really excited about it. Stay tuned. We'll have a little bit more on this at an upcoming meeting in the future.

[Paul Hudson, CEO]

Yes. Thanks, Bill. I mean I think it's really interesting. I know a lot of companies have tried to make a small molecule type of the reasons Bill said. And of course, we think we cracked it, but it's a small study until we get the big data to forward to turn the data on the Congress later this year. I think what's really interesting is [indiscernible] on the competitive set. I mean there's -- if the efficacy and safety are right, you can compete with biologics. But remember, there's a big gap between, for example, in Surasis, [indiscernible] and biologics and [indiscernible] as a mega blockbuster by being effectively not as good as biologics. It's a step through on the way to something else. So it's a good option for a lot of patients.

So if you end up with an efficacy somewhere between the 2 and a good tolerability profile, you really go to before everything else. Let's also remind ourselves that I think there are 2 IL-17s and 2 more to launch, an IL-12/23 and everything else are doing very well, all targeting the same effectively the patient population. There is lots of opportunity because biologic eligible penetrations are so low.

I think it's 25% of those eligible in psoriasis. So there's an opportunity for everybody and for every patient to get what they need. Let's be clear. if we are ambitious for the product profile, if the profile delivers, it's a big deal. But of course, there's some way to go on that. But I think you appreciate. It's on its own uniquely in terms of what it can do.

So we're excited. Maybe we'll share data later the share we had at the Congress and feel we know immunology very well. And so we're in a good spot. Okay. I think another question maybe.

[Operator]

The next question is from Peter Verdult from Citi. Peter.

[Peter Verdult, Citi]

Peter Verdult, Citi. Two questions, please, maybe starting with Julie. It feels a little bit like Groundhog Day when we asked this question, but the Charlson Tamiflu Rx to OTC switch programs, just checking in to see whether there's been any progress made with the FDA in terms of getting these actually use those started? And then at a more high level, can you discuss the scope for BOI margin expansion at consumer with and without these OTC switches. And then a quick one for Paul, just a high level. Do we need to wait until the second Phase III COPD study before Sanofi, provide an update on peak Dupixent sales. And I think -- I read I'm asking this question, it sort of plays on to what your opening remarks. I mean you are free of LOEs for the rest of the decade after this year. You're offering more attractive growth versus your peers. So I'm just wondering are you now willing to move your sort of midterm targets to more revenue-based targets? Or will you be updating us on a margin basis going forward?

[Paul Hudson, CEO]

Okay. Peter, excellent questions. I think Julie, maybe we'll start with the update, U.S. Cialis and Tamiflu. And you did touch on it in the U.K. launch, but the U.K. launch is quite important for getting a sense of what the over-the-counter opportunity could be and the appetite to stop there.

[Julie Van Ongevalle, EVP, Consumer Healthcare]

We're obviously extremely happy to be able to launch in the U.K. in the coming months. On the U.S., I wish I had more to share if I had, I would. Basically, while we continue to work with the FDA on the OTC approval for Sales in the U.S., we're advancing on the execution of our strategy to live the clinical hold and including the generation of the necessary data that was requested.

So we're still moving. And same actually on time, we're still moving as well. There is no specific update on the time full switch and we continue to work with the FDA to gain the important feedback on our program. So progress, but no new news.

[Paul Hudson, CEO]

Okay. Thanks, Julie. So I think not a risk of repeating myself, but I think we continue to have very active and encouraging dialogue with the FDA. I mean it's been quite a journey, but we still maintain a lot of confidence in getting the -- and again, I think the U.K. experience will be a good bellwether to what the market opportunity could be of scale to the size of the U.S. So that's good. That's exciting. Your other question is into one. I mean we -- we -- the COPD data, I think, from what we've shared is extraordinary, and hopefully, we'll see you at ATS and the call will have right after that to go through in some detail.

It is game changing. We know that. Look, we've been signaling we signaled $10 billion back in the day in 2019, and there's people small we're going to annualize above that, and we're going to achieve more than that this year. We gave you a way point of GBP 13 billion, I think, plus COPD. And I think later this year, we really want to really sit down with everybody and go through the immunology pipeline broadly and really lay out the full data set on some of the assets that we've shared today and some yet to come. and help people understand what is the shape of our immunology piece? And then perhaps what Dupixent will play in that. But it's the overall that we're really very much interested in. As for the I think you said when we move to a top line story, I think you said that. I think we have to earn the right for that, to be honest.

I think if our science wins out like we would like this year, I think you'll probably tell us before we tell you that you think we have enough going on that's exciting. We -- that's our goal. We just never put a time line on it because we have so much to do. So we will keep doing the job and delivering the guidance until the scientific news flow accumulation is enough for you to all say, we think there's something special going on here.

I know it's been a long time coming for us, it feels like it's getting really close in terms of the scientific and news flow and credibility. So thanks for your question, Peter.

[Operator]

The next question is from Graham Parry from BofA.

[Graham Parry, BofA]

So firstly, just going back to CAPD. And could you just touch on the ability potentially to file in Beyfortus alone? So have you actually met regulators? And is it fair to characterize this as 1 trial with great results. And if you have a highly significant p-value, could that be enough to get it over the line on a single trial given large unmet medical need?

And then secondly, on the oral TNF, I just wanted to follow up on, I think it was Richard's question earlier. Just on target product profile, is best case here as good as an injectable TNF? Or are you thinking when you reference biologic-like efficacy, could we even see something in the IL-17 or IL-23 range, and it sounded to me correct me if I'm wrong, that your sort of best base case would be listed somewhere between Otezla and injectable TNF on efficacy?

[Paul Hudson, CEO]

Okay. Well, I'll let you start, Dietmar, with COPD.

[Dietmar Berger, Global Head of R&D]

Yes, sure. No, the -- thanks for the question, Graham. You've heard already that the barriers data is really unprecedented, right? We've spoken to opinion leaders about we've spoken to trialists about it. They call it a landmark in COPD treatment, and they actually urge us, right, to move this forward. as quickly as possible.

So we are obviously having the discussion with the FDA. The early interactions have been encouraging, but we're not going to go beyond that at this point in time. But really, this is a highly, highly interesting data set, and we're trying to bring it to patients as quickly as possible.

[Paul Hudson, CEO]

I mean it is incredible. It's a landmark, agreed. I like that would be [indiscernible] . And so we really -- we would hope on behalf of patients to make progress, but we take nothing for granted, of course. Bill, I think the second part of the question was around position.

[William Sibold, EVP, Specialty Care and President, North America]

Your product profile. Yes. Look, Graham, again, a first study small study, big program ahead of us potentially. I think, as Paul laid out, he said, if it were like biologics like efficacy, yes, that -- if you can have that exact level or in the range regardless of the biologic if it's TNF, that is certainly a winner, but there are lots of steps between there as well that give a lot of flexibility for how this asset can ultimately be positioned.

So I think as we're looking through it, it's going to be driven by the data driven by the studies. But we think that just given what we think we have, we've got a big range of potential outcomes that make the target product profile extremely, extremely attractive to the market.

[Paul Hudson, CEO]

Thanks, Paul. I mean, we'll go through the data later this year. But I think this is what's fascinating. Just to couple that back to Peter's question, maybe Luis' question just a little bit. This is what's so special. I think about the year, we accumulate the science. We pick really smart positioning, particularly of the data this year, where it can help patients with TZL inflight, Altuviiio, Beyfortus.

And I just want to be clear, in case everybody misunderstands, we will do all this and deliver our guidance. That's what we do. There'll be -- I think, earn credibility that we don't miss numbers whilst we reinvent the company. And that's nonnegotiable internally. So I just want to be really strict with me and you that you should expect that deliverable at the same time as hopefully changing the practice of medicine in some of these areas. And that's why it's so exciting in 2023.

[Operator]

Next question from Seamus Fernandez from Guggenheim.

[Unidentified Speaker]

This is Colleen on for Seamus -- on flu, are there any updates to how you feel positioning following some of the competitor updates we've seen? And are you still on track for the mRNA flu candidate to enter Phase III this fall? And are quadrivalent targeting HA sufficing, or could we see a next-gen construct enter the clinic sometime this year? And separately, with the vaccine event this June provide meaningful updates on the path forward and plan for the 21 valent new cockhaul?

[Paul Hudson, CEO]

Okay. you come at it pretty strong there. I was expecting a lowball from shameless, but okay. And Thomas, maybe we will give it to you.

[Thomas Triomphe, EVP, Vaccines]

So different questions already to flu. I get that part. So on the first part of the question, for the coming flu environment. That's pretty much what we were saying before. We believe we have definitely the right assets. You know that [indiscernible] called in Europe. He's doing very well. We want to make sure that we keep our strategy of changing the standard of care in the 65 plus. That's extremely important. And that journey is ongoing in North America and in Europe, as you know very well. Execution is strong. Now we need to see where is the U.S. VCR.

The second part of your question was much more related to the future of Flu, mRNA flu, where are we? You've seen that some others have disclosed some results that are not convincing in terms of really challenging the standard of care. So as you alluded to, I think, in your question, you have part of the answer in the fact that we are going to have a vaccine event on June 29.

And our goal, as I was sharing in the call before, is really to show you a significant amount of data. It will include both RSV both Beyfortus and the RSV tolerant clinical data. It will include MR and flu. It will include you are leading to it. Our [indiscernible] conjugate 21,000 program as well as our meningitis vaccine program, which people may not have realized, but we're going to have also some data to share there.

So it's going to be a very complete review of our portfolio. So I really come and see the deficit there. We feel very strong in terms of the progress we have made on R&D in the vaccine space, and we really want to share that with you. That will include [indiscernible] and that will include PCB 21.

[Paul Hudson, CEO]

Thank you, Tom. That's June 29.

[Thomas Triomphe, EVP, Vaccines]

June 29, indeed, in London, physical presence is much better because you can ask all the questions and more.

[Paul Hudson, CEO]

I take it upon, Thomas. Okay. So next question, please.

[Operator]

Next question from Jo Walton from Credit Suisse.

[Jo Walton, Credit Suisse]

We've talked a lot about R&D, and I do have one R&D question, but I'd like to go back to the outlook for the new commercial products. It's very difficult for us to assess how quickly we might see the uptake of something like Bay Fortis or even Altuviiio because we have to think that some of the sales will presumably come from Eloctate. But the consensus at the moment, the company provided consensus for this year is around EUR 130 million for Altuviiio rising to EUR 370 million next year. And for Beyfortus, 170 this year rising to EUR 480 next year. I'm just wondering if you feel that together, we've got the sort of the cadence of that right appreciating that these will be very big products. There'll be a lot of focus on the speed at which you'll be able to do that ramp. And my second question is about the RIP kinase.

So you're talking about those. You've now got at least 3 different RIP kinase drugs entering the clinic. Can you tell us what's different about them? Is there -- are you able to tweak them so that one is uniquely suitable for ALS and one is uniquely suitable for other conditions? Why do you need so many of them?

[Paul Hudson, CEO]

Okay. Thanks, Joe. Well, then maybe there's 2 components to right. We're not going to comment on consensus for sure. We work hard to positively do a good job, but we can't comment on those numbers. Maybe, Thomas, a sort of feel for what you could expect from shape of curve if not numbers themselves.

[Thomas Triomphe, EVP, Vaccines]

So definitely not specific numbers, but a few things as alluded to for the first question, I think, which was on [indiscernible] , in terms of the qualitative part, clearly, we are all lined up to be ready to launch in 2023 in North America and in Europe. And so when it comes to North America, it's all about registration and it's CIP mean incoming as well as the inclusion of the product into VFC.

You remember that the inclusion to the VFC is an important part for the curve definition of the U.S. program, feeling strong in Europe with what we've seen in terms of recommendation. Now you know very well that having said that, for both North America and Europe, we are talking about changing national immunization calendar. And you also know that for -- like for every vaccines, even though it's a not antibody, it's used vaccines appreciated rego-vaccines and it goes very well on that pathway.

So as for any vaccine that is being launched, there is a progressive uptake just because you're in preventive measures and we can in practice, practice after practice which takes a bit of time. But again, feeling confident about moving forward on the trajectory of the launch, North America and Europe.

[Paul Hudson, CEO]

Yes. Thanks, Tom. We're obviously well prepared. There's a great deal of interest, fair to say. I think some of the interest, of course, is around the fact that it's quite unique that it would -- the value proposition is almost in the very first season. I think that's why we're seeing this level of assignment that is a bit different.

[Thomas Triomphe, EVP, Vaccines]

It's unique, and I really invite you to go at the SP European pediatric infectious disease to sit Congress in May because, again, we need to remember that this is the #1 cause of hospitalization in new bonds in those geographies. And you're going to see a first significant data set in terms of efficacy against hospitalization for those newborn. So interesting data that you need really to have a look at, which is promising when it comes to the one.

[Paul Hudson, CEO]

Yes, but I think that's why it is difficult to be precise. And I think my cost question is quite important because there's a real appetite, but there's still some unknowns. So we just -- the guidelines on one hand, there's also a shortage of pediatric ICU in general in that time, in that seasonal time. So we will see...

[Thomas Triomphe, EVP, Vaccines]

And as you said, from [indiscernible] , we can solve this.

[Paul Hudson, CEO]

Well, I think that's an exciting thing. It's really about organization. Bill, Altuviiio?

[William Sibold, EVP, Specialty Care and President, North America]

Yes. Thanks, Joe. So Altuviiio, our first-in-class high sustained Factor VIII ,a replacement therapy. We are really, really excited about that. Just to kind of go back a little bit to some of the comments made in the opening remarks. The switches that we're seeing, and it's going to be a switch product, right? People are going to be coming to it.

We think, initially, it's going to be from the other factor products. However, what we're seeing in the early switch data is we're getting HEMLIBRA patients as well. Eloctate will absolutely be impacted as it should as all factors should because this is, we believe, just a far better product offering and potentially a new level of efficacy. So early feedback is very strong from the community. Physicians are excited. Patients are excited and they are depending on the practice, thinking about how to switch patients, either as patients are coming into their visits. Some are a little bit more proactive than that.

We're still really early but incredibly encouraged. And just as we think about the sizes of the markets here, the hemophilia A noninhibitor markets in about that $8 billion range, and we expect it to grow to over $10 billion. And of that $8 million, about $5 million of that is factor.

So if you think of -- and that's on a global scale, and about 50% of that is U.S. related. So you think of those -- that opportunity with a product like this, and we see a very significant opportunity with Altuviiio.

[Paul Hudson, CEO]

Dietmar. RIP Kinase?

SPEAKER01

Yes. RIP Kinase, thanks for paying attention to our portfolio really closely, right? The RIP Kinase is an important pathway in an important inflammation pathway. It's involved in neurodegeneration, neuroinflammation also other types of inflammatory diseases. It's different from necrosis or apoptosis. We feel it's an important pathway to explore both from a research perspective and from a clinical perspective.

And at this point, we have 2 RIP Kinase inhibitors in the clinic, not 3, 2. We've spoken during this call about SAR'120, right, which is the one that we're testing in ALS in amyotrophic lateral sclerosis and also in MS. We have a different molecule, SAR'122 in immunology that you're also testing in different immunological indications.

And obviously, we need 2 molecules because you require different pharmacological properties in these different types of diseases, for example, when it comes to brain penetrants, et cetera, et cetera. So I hope that answers the question.

Yes. Thank you, Doetmar. And Joe, thank you, right? Great to get a question about 2 launches in our pipeline. That's how we sort of like it.

[Operator]

Next question from David Risinger from sibling.

[David Risinger, sibling]

So congrats on the progress, and thank you for the pipeline commentary and plans for additional pipeline updates this year. I have 2 questions. First, with respect to the tolebrutinib liver tox concerns, I'm sure the company must be frustrated that the FDA hasn't lifted the partial clinical hold after receiving the additional data, is there any additional color you can provide about what concerns persist for the FDA? And what that may mean for the potential approvability of the drug? And then with respect to the PCV2 update on June 29. Obviously, you have the adult Phase II data in hand, but should we expect infant data as well?

[Paul Hudson, CEO]

Okay. Maybe Torud, FDA Pocola, Tipo?

Geoffrey Porges (Analysts)

Yes. Thanks for the question. So the FDA partial hold is still in place. But let me first say, it really only affects recruitment into the PERC study, only into the per study in the U.S., the other trials that we have, 3 out of 4 trials that we have in MS are fully recruited. And we're working to address the issues raised by the FDA, right?

We continue to work closely with them. What they're looking for, obviously, is further understanding of the patient population, working closely to do that. We have our program ongoing with regards to a safe initiation of the drug with regards to really close monitoring. We have not seen any new cases of liver toxicity in the same way since we introduced that level of monitoring, which is important to understand, obviously, FDA is looking for more data on that.

And FDA is also looking eventually then for benefit risk information, which we will have at the time when we will read out the study. In addition, what's important to understand is we just presented that data, and I also talked about it during the presentation here, that tolebrutinib is potent drug. It acts fast. At the same time, we have these data about drug in drug-induced liver injury and really rare cases of that drug-induced liver injury across different BTK inhibitor, which seems to really underline it appears that this drug-induced liver injury is more of a class effect and is not linked to potency.

That's important also as -- we are the only company at this point that has studies in the progressive setting and especially in the SPMS setting where no other treatment for these patients is available at this point in time. So we are really confident about the potential of tolebrutinib and really looking forward to work with FDA on the future of tolebrutinib in these patients.

[Paul Hudson, CEO]

Yes. I think it's worth adding is that of course, that when you see partial hold, you automatically assume studies are stopped and milestones are missed. As Dietmar said, just not the case. Three studies probably enrolled and will be event-driven. So unlike pretty much everybody else, we're enrolled and the [indiscernible] study, the primary progress us still recruiting excess, as you said.

So our program is pretty much exactly where we needed to be. So I think there's -- we always [indiscernible] the question about partial, what's more important probably is that before we get the readouts is that we have fully understood with the FDA how to initiate a BTKI because that's going to be important. And as you said, after the change of protocol no new cases.

So it's quite clear that there are ways of doing monitoring. And then as you add the weight of evidence, particularly SPMS, secondary progressive disease, which nobody has studied. It's worth us, I think, taking our time with the regulator to reach the very best outcome in anticipation of the results. Our time lines did not change, did not change at all. I think that's really important for everybody in there. So we're optimistic, and we really think of the other data that keeps a massing around how potent and effective this could be. And we now know that, that appears to be unrelated to safety. That really starts to get very compelling. Thomas, pre CB21.

[Thomas Triomphe, EVP, Vaccines]

Shorter response, David, is yes, 75% or more actually market is in pediatric. So we wouldn't want you to come in London on June 29 and be disappointed by not seeing pediatric data for PB21. So . yes. Yes.

[Operator]

Okay. Next question is from Gary Steventon from x

[Unidentified Analyst]

So first, just a follow-up on tolebrutinib. You mentioned earlier, you see the observed liver tox as a class of effect. So can you just talk to how you view perhaps the predictability and management of those events? And maybe any views you have on whether you think or have feedback that there may be any perceived impact on uptake or perception from neurologists? That's the first question.

And then secondly, one on Tsao and the prevention deal, please. So you flagged the up to GBP 2 billion of sales potential. So could you just help us understand how you split that between the opportunity and delaying the onset of Stage II type 1 versus the Protex opportunity big potential market, but screening and awareness are more challenging. So just any color on how you've addressed those points in that figure would also be helpful, too.

[Paul Hudson, CEO]

Rocko, I'll come to Olivier in a moment, and I think we've covered tab perhaps a little bit back and forth, but it's not uncommon for monitoring initiation in MS, right? I think there's many drugs that have had that -- what matters is that you have great efficacy data and that it's worth monitoring.

And so we know that's early monitoring at the early stage. That's what we're working through. As Dietmar said, there's been no new cases. So -- it would -- it's quite an interesting time for tolebrutinib because we look forward to the data. That's going to be the next most important thing. And then we'll share with you how we hope to approach the monitoring. But frankly, if the efficacy data is what we hope the monitoring is really not a barrier to uptake.

Olivier, any news on T Ziel and where you see that.

[Olivier Charmeil, EVP, General Medicines]

So we are thrilled to bring on board TCL within Gen Med. We, of course, as you know, have been working in the last few months on a co-promotion agreement, and we have been impressed by the reception after myself to many key opinion leaders and the feedback is very positive. We have always been very clear that for the first indication, the delay onset of Stage II for patients that are in Stage 2. We have always been very clear that it's going to be a slow burn is going to be about a progressive screening.

But what is amazing is that in the last few months, and we have seen that in the U.S. but also in other parts of the world and specifically in Europe. It's clear that there was no incentive to screen and young kids or young adolescents because there was no medicine. And we see a lot of traction now in the -- and momentum around screening. So this will take some time on our hand, we are going to focus for first, of course, not on general population, but we are going to focus on the first degree relative where the rebalance is 10x that in general population.

So for us today is a great day, and the deal has just been closed. Regarding the second indication, which is a PROTECT study we made our offer based on the first indication. So any good news on PROTECT would be, of course, an upside. Of course, with regard to PROTECT, it's about the delay in -- it's about early intervention for people that have been identified as having Type 1 diabetes. So the population is much more well defined. In the , we are talking about 60,000 to 65,000 new incidents and new patients are getting type 1 diabetes. And of course, we would like to get a share of that part.

[Paul Hudson, CEO]

Thank you, Olivier. And I think you said it. But to be clear, there's really nothing coming to compete in the class or in this patient population. But before us, maybe at some point in our future, we'll see, but at least this decade, which gives us time to do the work to make sure that we get those patients and need it. So it's exciting -- it's exciting. And the another question maybe?

[Operator]

Yes. Next question from Emily Field from Barclays.

[Emily Field, Barclays]

Maybe I'll just ask a quick one on financials. I was noting the slight improvement in gross margin that's expected for the year inside of the Aubagio LOE, I mean I believe consensus had been modeling for a little bit of compression. So maybe just any details on the driver of that? Is that just operating leverage from the growth of Dupixent or some of the new manufacturing process? Any color you could give would be great.

[Paul Hudson, CEO]

Okay. Thank you, JB, maybe you want to comment?

[Jean-Baptiste de Chatillon, EVP and CFO]

Yes. Thank you for the question. As I explained, there are some on pushes on June 23. And we are launching, we have a very good start in the year. But you're right. Of course, the growth of Dupixent will, of course, help grow profitability and take us to a nice place in spite of the LOE of [indiscernible] that will kick in from Q2 onwards. So nice situation. On the gross margin, it's mainly linked to this balance, which goes in the right direction. We are pursuing all our efforts to be able to finance more R&D. So efficiencies are still being delivered by all departments in the company.

[Operator]

Next question is from Peter Welford from Jefferies. Peter,.

[Peter Welford, Jefferies]

And just 2 quick ones. Firstly, just on the oral TNF again. Obviously, one of the indications where we are seeing OTNF still be used and actually not facing the same competition is HS, where I think you've also got some other programs looking at as well. I'm curious, I guess, why necessarily the focus on psoriasis, which is a pretty competitive market and I guess not some other potential statements as there are where perhaps less competition about the more amenable there for you to be an early entrant.

And then just going back to the vaccines event again. I just wonder if you can just outline with regards to the 21 valent PCV vaccine, will we get data where you look at as usual, as often with its early stage these data sets, it's highly extrapolatable to the commercial setting. And how you just talk about then the strains you're particularly looking at. How should we compare this to some of the other vaccines in development well that have higher valencies than past '21? I know you take advantage you're looking to get there.

[Paul Hudson, CEO]

Okay. Thomas, vaccine event on June 29.

[Thomas Triomphe, EVP, Vaccines]

I see we are starting to raise some interest, which is good news. When it comes to PCB 21 our goal, to be very clear, is to -- because you're leading Peter, to the competitive space. Our goal here is to be the first pediatric registered and used more conjugate vaccines with more than 20 balances. And that's why we want to share with you at this event our Phase II data. Of course, it will include the strains, the results of those, our position and what are the next steps. So we really believe that it's going to be a competitive asset. Of course, we keep monitoring the environment. We know very well the world of players where are they going and what are their present cons. And we'd be happy to elaborate more together on June 29 numbers.

[Paul Hudson, CEO]

And Peter, then back to your original question on -- or the first part of the question, [indiscernible] TNF. I just think -- I think you said why do we start with psoriasis. I think -- just 2 things, one auto maybe another discompoint. There is the biologic penetration of these incredibly distressing illnesses is still less than 30%. So even if there are 6, 7, 8 biologics, patients need something else or patients may not want to go to injectable, whatever it may be. That's why all of these medicines tend to do pretty well, some do better than others.

When we embarked on the program with the oral TNF, one of the reasons we chose psoriasis is because from a proof of mechanism, we can move really quickly. If you start with an RA study, it takes longer. And so we wanted to see quickly whether we could be in the biologic ballpark and have the right safety in patients where it would be explicit and not even patient reported. So we're -- that's why we started there.

But I think what it tells you -- I should tell you, I'm trying to remember the exact word on the slide that we start in psoriasis. I think that's how we say it, because our ambition and we'll update you as we go forward, is to go beyond it. Of course, our profile has to deliver. We have to feel confident. But I think you have to imagine, Peter, that if the profile holds together through a succession of TNF currently treated diseases, we should go there.

So we -- give us a bit of time, and it's a good opportunity, I think, at an event in the second half of the year for us to update you very specifically about what that could mean. So first question, it's an important question, but hopefully, it's just the beginning. Eva, where are we near the end?

[Eva Schaefer-Jansen, Head, IR]

So we're near the end, but we have a question that came in online from Florence Cespedes on 2 questions. The first one is on Zantac. Could we have a quick update on the cases and the arbitration with BI? And the second one is on the ILRTSLP. Why are you confident to show benefit with this product when RostanIF13 in 2017 with lebrikizumab.

[Paul Hudson, CEO]

Okay. Well, I would love to take the second part of that question. But Roy, maybe you have to take the first part of the first question on Zantac.

Question

Richard Parkes (Analysts)

Those anti cases, you've seen the MDL ruling on Zantac, which we're very pleased with. And of course, we agree with. There are a number of cases now in state courts, where there are less cases here and there. We are not a defendant in all of those cases that are scheduled this year. I guess, will be up next year. We're encouraged by the decision in Dabur and hope that everything ends up that way, which is where we [indiscernible] very strongly. On the arbitration, as you know, we have been expecting the outcome of this for a while now.

We do believe it's going to come out in the coming weeks. What's more important is that given the strength of our case as proven by the overwhelming scientific evidence, we feel that regardless of the outcome of the arbitration, the potential exposure for Sanofi is manageable in the usual course of business, and it's not going to be something that will impact our delivery of our strategy or the pipeline is that you have today.

[Paul Hudson, CEO]

Thanks, Roy. So regardless of the outcome of arbitration, we feel that it's absorbable in the normal course of business. I think an important point for everybody because as these things are, we get an announcement we put it out. I'd like people to anchor to what we've said today. So Roy, thank you very much for sharing that. It's, I guess, a nice last question, 13 TSLP. We -- I think the comment was about another medicine that had not done so well, I can't remember, maybe it was an IL-13.

We know IL-13s worked quite well in AD quite well, better with an IL-4. We know they don't work so well in asthma. We know reciprocally TSLP works quite well in asthma, but doesn't really work in AD. So one of the benefits of this nanobody excellence that we have is potentially creating a unique moment for almost potentially a synergistic effect, and we'll see.

And we just look to ourselves to say, as I said earlier, there's room for many biologics in these diseases, number one. But number two, we set a high bar on our profile. And if we land it, then it's really compelling. I think maybe the difference to this to some other diseases is we know both those pathways have drugs that are approved for different diseases.

So we know that the risk is a lot less, technically as long as our nanobody can really deliver. And if there is a synergistic benefit, then we're really in a good spot. It's is, right? But if we're there, then there's a high degree of confidence. So we will see, and we will share data upcoming one, Steve.

[Dietmar Berger, Global Head of R&D]

We share data at ATS, right? As we said during the presentation, we have the data in-house, right? We're moving into Phase II -- and on top of what Paul has said, which I absolutely agree to write these are de-risked pathways where we have data in -- with the individual molecules. We have data in-house, and those data give us a lot of confidence.

[Paul Hudson, CEO]

Dietmar, wow, I love it. Good place to finish. So maybe just -- I know people will be dropping off and have other places to be. But just while I can say it, back to Louise's question, we did -- it's an important year for us. Scientific news flow is building really credible interesting first-in-class, best-in-class science, 2 best-in-class, first-in-class launches the last LOE behind us by the end of the year and still putting together without wavering commitment to deliver guidance. So it's a good moment to reflect on how far we've come and proud of the team and the work done. But if you're looking at us carefully, I think you can feel the difference in how we're moving. So I look forward to rushing quickly through '23 and show people what we're capable of. So thanks, everybody, for connecting.