Sanofi SA

PAR:SAN

Earnings Call Analysis

Sanofi shows strong Q1 sales with promising outlook

Sanofi had an excellent start to 2024, reporting a 7% increase in sales driven by the success of new launches and the continued growth of Dupixent, which grew 25%, hitting sales of €2.8 billion in Q1 alone. Consumer Health saw 9% growth, driven in part by the acquisition of Qunol. Despite the loss of exclusivity for Aubagio and the lack of COVID-19 related sales impacting overall revenue, Sanofi remains confident in achieving €13 billion in sales for Dupixent this year. The company expects a strong commercial performance and EPS rebound in 2025.

Solid Sales Performance

Sanofi started 2024 on a strong note with a 7% increase in sales for the first quarter. This impressive growth was largely fueled by the company's ongoing portfolio transformation towards biopharma medicines. Key contributors included the standout performance of Dupixent, which saw a 25% increase in sales, and the new launches like Beyfortus, which soared by 150%. Excluding the impact of the Aubagio loss of exclusivity and the absence of COVID-19 vaccine sales, underlying growth was 12%, illustrating the potential of the company's new direction【4:0†source】.

Dupixent's Global Success

Dupixent continues to be a major success story for Sanofi, with sales surpassing EUR 2.8 billion in the first quarter alone. Globally, Dupixent's sales increased by 25%, driven by strong demand across various indications. Remarkably, sales outside the U.S. surged by 51%, highlighting significant growth in markets like Japan, China, and Germany. The company projects Dupixent to achieve around EUR 13 billion in sales for 2024, bolstered by multiple new indications expected to launch across major markets .

Challenges with Aubagio and Gross Margin Impact

The loss of exclusivity for Aubagio had a notable impact on Sanofi, contributing to a 2.6 percentage point decline in the gross margin, which stood at 73.5% for the quarter. The absence of COVID-19 vaccine sales further hit the gross margin. Additionally, a one-off inventory adjustment reflecting declining standard costs affected the quarter's performance【4:0†source】.

Focused Investment in R&D

Sanofi is strategically shifting resources towards advancing its pipeline, particularly in late-stage immunology and neurology projects. R&D expenses increased by 12% at constant exchange rates, in line with the company's ambition to invest more in its pipeline. This move is expected to yield promising advances and solidify Sanofi's position in these therapeutic areas【4:0†source】.

Upcoming Expectations and Guidance

Looking ahead to Q2 2024, Sanofi expects continued growth from Dupixent and new pharma launches, despite the ongoing impact of Aubagio's loss of exclusivity in Europe. Interestingly, no Beyfortus sales are expected in Q2 due to early deliveries in Q1 for Southern Hemisphere countries, with shipments to the Northern Hemisphere anticipated in the second half of the year. For the full year, Sanofi maintains its sales outlook for Dupixent at around EUR 13 billion, with the vaccine franchise forecasted to grow at a mid-single-digit rate. Planned divestments will reduce sales by about EUR 300 million【4:0†source】.

EPS and Cash Flow Considerations

Sanofi reported a 7.4% decline in EPS for Q1, partly due to a higher tax rate and lower business operating income. The cash flow outlook for 2024 will be influenced by lower business operating income and the phasing of rebate payments in the U.S. related to prior-year sales. Despite these challenges, Sanofi anticipates a low single-digit decline in business EPS at constant exchange rates for the full year【4:0†source】【4:1†source】.

Operational Efficiency and Cost Management

Operating expenses are expected to grow with an estimated EUR 700 million increase in R&D, while SG&A expenses are projected to remain stable. The implementation of the OECD Pillar 2 will increase the tax rate to around 21%. The company's strategic reallocation of resources towards high-potential areas and rigorous cost management reflects its commitment to sustaining operational efficiency【4:0†source】.

Pipeline Progress and Regulatory Milestones

Sanofi continues to make significant strides in its pipeline, especially in immunology and neurology. Key developments include promising Phase II data for Frexalimab in multiple sclerosis and positive advancements in atopic dermatitis with Amilitelimab. The company also reported substantial regulatory progress with Dupixent, positioning it for potential new indications and expanded market reach【4:1†source】【4:2†source】.

Earnings Call Transcript 2024-Q1

[Paul Hudson, executive]

Hello, everyone. It's Paul Hudson, the CEO of Sanofi. Welcome to the Q1 2024 conference call. You can find the slides of this call on the sanofi.com Investors page.

I'd like to remind you that the information presented in this call contains forward-looking statements which is subject to substantial risks and uncertainties that may cause actual results to differ materially. I encourage you to read the disclaimer in our presentation. In addition, I refer you to our Form 20-F on file with the SEC [Foreign Language] for a description of these risk factors.

I'm pleased to welcome our new CFO, François to the presentation, and François will be followed by Houman, our Head of R&D on the pipeline.

For Q&A, we have Brian, Olivier, Thomas and Julie to cover the global business units and Roy our GC. [Operator Instructions].

Let's turn to the business. We had an excellent start in 2024 with 7% sales growth, in line with our fast-moving portfolio transformation, our growth was driven by launches, including new and existing indications for Dupixent and this performance fully underpins our 2024 EPS guidance as CEO.

Dupixent continues to increase penetration in all approved indications, and we saw performance diversified further across all geographies, plus, of course, the usual U.S. insurance plans.

Pharma launches were led by Nexviazyme and Altuviiio with more details to come a little later. Launches also boosted the performance in Vaccines with Beyfortus making further progress including in countries in the southern hemisphere.

In Consumer Health, growth of 9% reflected the consolidation of the Qunol acquisition as well, of course, as organic growth. We're progressing the plan to separate this business as discussed in the past.

Overall, we're pleased with the ongoing portfolio transformation, which is becoming more visible, also in our cost lines with more resources going into the pipeline and less into SG&A. This is exactly the development we set out last year and when we announced the next chapter of our strategy.

Before moving on, I'd like to extend my thanks to all the Sanofi colleagues for their dedicated work and their commitment to patients, chasing the miracles of science to improve people's lives.

Dupixent continues to perform a strong demand-driven growth. Therein sales of more than EUR 2.8 billion in the first quarter. Sales of this unique medicine increased by 25% globally, fueled by the accelerated growth from indication expansions in the ex U.S. markets, where sales grew as much as 51%.

With now more than 850,000 patients worldwide, the strong contribution from countries like Japan, China and Germany highlights the tremendous growth potential for Dupixent across all indications and geographies.

In the U.S., sales exceeded EUR 2 billion in the quarter, up 17% and as we can see every year, U.S. growth reflects the impact from the customary dynamics of the annual reset of insurance plans. Almost 8 years into its initial U.S. launch in atopic dermatitis, this effect underscores the large size and rapid growth of Dupixent with the leadership positions in new prescriptions across all 5 approved indications.

As we look ahead to Q2, we remain very excited about the outlook for Dupixent's outstanding commercial success across all geographies, supported by regulatory progress towards launching multiple new indications in major markets. And with our strong Q1 performance, we're extremely confident in delivering our previously communicated objective of around EUR 13 billion in sales for the full year.

As one of the leading medicines in immunology respiratory is a core disease area for Dupixent, well ahead of any of the competing -- of any other competing biology medicine. Dupixent has established and maintained a distinct leadership position in new prescriptions amongst pulmonologists across asthma and chronic rhinosinusitis with nasal polyps in the U.S. We believe in the growing importance of pulmonologists in adopting biologics to treat respiratory diseases, but also confident that they're growing familiarity with Dupixent in type 2 inflammation will play a key role in the adoption of Dupixent as the potentially first advanced therapy in COPD in more than a decade if approved. We also continue to build a growing body of scientific evidence around Dupixent in addressing airway inflammation.

In the VESTIGE study, which was recently presented at the Quadruple AI Congress, Dupixent demonstrated reduced airway inflammation of mucus plugging in functional respiratory imaging in essence.

We have an ambition to potentially introduce a new standard of care with Dupixent in COPD for patients with type 2 inflammation. As you may recall, significant regulatory progress has been achieved with Dupixent's potential in COPD across key markets. We are preparing for a potential launch in the U.S. as early as late June if approved by the FDA and plan for additional potential approvals in Europe and China by the end of the year.

We're excited about the outlook for Dupixent's potential to become a breakthrough medicine for COPD, a leading cause of death worldwide. Dupixent is well positioned to potentially address the high unmet need in COPD with a strong clinical profile across 2 large Phase III studies and more than 7 years of real-world evidence of -- real-world evidence data on safety across 5 approved indications.

Dupixent addresses unmet medical need of a well-defined population of roughly 300,000 patients in the U.S. alone, whose disease is driven by type 2 inflammation and uncontrolled despite standard of care therapies. COPD is a historically difficult disease area and a heterogeneous disease with multiple development failures in the last decade.

Over time, many patients become resigned to their medical condition with an experienced team that has a track record of development and commercial excellence in respiratory, we plan a targeted approach to drive the awareness and identification of COPD with type 2 inflammation among patients and pulmonologists.

As we have seen with our launches across other major indications, the adoption of Dupixent as the first and only biologic in the COPD indication will require some time initially and the inflection of sales growth is most likely to come in 2025 after the U.S. launch.

We are confident that if approved, COPD will become the next major growth pillar for Dupixent. And together with our second potential blockbuster developed for COPD, itepekimab, we continue to expect peak sales of more than EUR 5 billion for both products combined.

Let's now move to the new launches as Q1 further demonstrates our ability to execute successful launches and bring new medicines to patients. This quarter, all our new launches including Beyfortus made up close to EUR 1 billion in sales or 9% of our total biopharma business.

Beyfortus continued its global rollout in the quarter with the launch in the Southern Hemisphere countries of all interim protection programs in some Australian states and Chile. As RSV is seasonal, Beyfortus will have a sales pattern like what many of you know from flu vaccines.

Nexviazyme grew strongly from new patients as well as patients converting from older medicines in the Pompe franchise. We're pleased with the overall growth in franchise sustainability.

Altuviiio is soon annualizing its launch. It has been -- it has seen continued strong uptake with most of the growth coming from other factor medicines done a lot of uptake and even some uptake from patients not on factor medicines. It showed us how innovation can help to revitalize hemophilia and grow Sanofi's total share.

Other launch medicines also did well in growth in absolute terms, including Sarclisa approved in multiple myeloma.

Taking a closer look at Beyfortus. What we're really focused on and proud of is the impact on improving public health and benefit of thousands of families. We've now real-world results from last year's implementation of broad immunization programs in the U.S., France and Spain with Beyfortus. The results are strikingly impressive.

You can see the dramatic reduction of hospitalizations by the numbers on this slide. These real-world results are either consistent or even better than those from the clinical trials. The U.S. CDC recently published our effectiveness data for Beyfortus at 90%, and in Europe, we have seen similar results for hospitalization reduction across France and Spain.

Overall, following the first season in the 3 launch countries where Beyfortus is used for all in from protection, this means that nearly 40,000 hospitalizations have already been avoided for families. This is the impact that matters most.

This also provides a perspective for Beyfortus global health benefit as we plan to launch in additional countries in H2. Together with AZ, we're working with the regulatory authorities and extending the manufacturing network to make Beyfortus more available for the upcoming season, as we're glad to see such enthusiastic demand.

We're confident that where we will meet anticipated customer demand and look forward to extending all in from protection programs in the upcoming Northern Hemisphere RSV season.

On my final slide, I wanted to highlight some progress on our ESG ambition exemplified by the work of our Global Health unit. Since its launch in 2021, the essential medicines from our GHC portfolio have supported close to 550,000 patients, suffering from noncommunicable diseases in 31 countries, with the objective to reach 2 million NCD patients by 2030.

An additional differentiator is the meaningful work done by our teams to help building sustainable health care systems through partnerships with the Ministries of Health, trainings of healthcare professionals and our impact investment fund focused on supporting exclusive start-ups and businesses.

I now have the great pleasure to hand over to François, our new CFO.

[François-Xavier Roger, executive]

Thank you, Paul. I'm pleased to have joined the team here at Sanofi earlier in April, and I'm looking forward to interacting with all of you in the future.

Sales were up 7% in the quarter, and as Paul mentioned, growth was driven by our ongoing portfolio transformation towards biopharma medicines with Dupixent sales up by 25% and the new launches, including Beyfortus, up by 150%.

Excluding the impact of Aubagio loss of exclusivity and COVID-19, growth was 12%. This analysis does not aim at removing all headwinds, but simply illustrates what the new Sanofi may look like in the future.

On gross margin at 73.5% was down by 2.6 percentage points, mainly due to Aubagio and due to the absence of COVID-19 vaccine sales this year. In addition, the quarter was impacted by a one-off inventory adjustment to reflect declining standard costs. R&D expenses increased by 12% at constant exchange rates in line with our ambition to invest more in our pipeline.

Resources are being deployed to advance late-stage immunology and neurology projects. SG&A increased by less than 3% below half of sales growth, illustrating our strategic reallocation of resources. Our business operating margin decreased to 27.2%, mainly due to the gross margin decline, the step-up in R&D expenses and an increase in the profit sharing with Regeneron.

As expected, EPS was down 7.4% in Q1, also partly impacted by a higher tax rate. Just one word on cash flow. It will be impacted in 2024 by our lower business operating income and by the phasing of rebate payments in the U.S. related to prior year sales.

Let me now give you some additional information on our coming quarter. In Q2 2024, we expect Dupixent and the new pharma launches to grow further while we continue to see the impact of the Aubagio loss of exclusivity in Europe. Of note, we don't expect any Beyfortus sales in Q2 due to early delivery in Q1 in some Southern Hemisphere countries, while shipments in Northern Hemisphere countries are not expected before the second half of 2024.

For the full year 2024 sales outlook, we expect Dupixent to reach around EUR 13 billion and the vaccine franchise to grow mid-single digit, with Beyfortus anticipated to reach blockbuster status. The Aubagio loss of exclusivity will continue to impact the top line, mainly in H1.

Finally, planned divestments will lower our sales by around EUR 300 million over the year. For the full year P&L, we expect our gross margin to decrease slightly due to Aubagio and the absence of COVID-19 sales on revenues this year.

OpEx is expected to grow with about EUR 700 million step-up in R&D, while SG&A expenses are expected to remain stable. Finally, our tax rate will increase to around 21% due to the implementation of the OECD Pillar 2.

We confirm our full year 2024 expectation of a low single-digit decline of our business EPS at constant exchange rates. Excluding the impact of the higher tax rate, the full year 2024 business EPS is expected to be roughly stable.

On foreign exchange, we see a negative currency impact to EPS of around 6% based on April 2024 average exchange rates. As a reminder, we continue to anticipate strong business EPS rebounds in 2025. And as we have mentioned earlier, in 2024, we are transforming the company for long-term value creation.

With that, I will now hand over to Houman.

[Houman Ashrafian, executive]

Thank you, François. We've seen substantial Phase II -- we've seen substantial positive pipeline progress already in Q1 where we continue to deliver a consistent news flow of clinically important data and scientific publications and congresses.

Frexalimab's encouraging Phase II data and multiples sclerosis was recently published in the New England Journal, but updated with data from the 48-week open-label extension, which we presented last week at the AAN conference supporting our commitment to MS patients.

In atopic dermatitis, we have the potential to further establish our leadership with amilitelimab, where we presented the Phase IIb data at AAD where largely sustained effective amilitelimab on atopic dermatitis symptoms, which demonstrated after 52 weeks of dosing.

Later, I will further talk about the data presented from these 2 pipeline projects. On the regulatory side, we've reached an impressive pace of approvals with 2 of them for Dupixent in multiple indications within different countries. FDA discussions regarding Dupixent's sBLA in COPD are ongoing under the priority review process, as Paul has mentioned.

As usual, it's always possible that the FDA could require additional information to complete the priority review of our submission to finalize labeling. As a reminder, there is currently no biologic treatment approved in COPD underlining our commitment to make Dupixent available to as many patients as possible as quickly as possible and supporting the ambitions for Dupixent that Paul has already outlined.

Amilitelimab, our nondepleting OX40 ligand monoclonal antibody, has shown potential best-in-class efficacy with a durable clinical response rate after 52 weeks from the STREAM AD Phase IIb study. The responder percentage is reflected in the IIGA 0/1 and the EASI-75 scores, which are both surrogate endpoints AD were maintained and still significant, in fact, following the withdrawal from the drug at week 24.

As you can see from the bar chart, at week 52 results on and off medicine are similar, which shows the persistence of response, suggesting the potential normalization of inflammatory T cell activity and potential effect on type 2 and non-type 2 biomarkers.

These important data support the viability of the 12-week extended dosing interval, which will improve the patient's treatment paradigm and potentially expand Sanofi's presence in AD and beyond has been interpreted by some to hint the potential disease-modifying activity. The opportunity of treating patients by treating this core central pathway with consistently good safety in both parts of the study signals that amilitelimab has the potential to reach much beyond AD and become pipeline and a problem.

The cleanest AE profile in this class may reflect the importance of nondepleting mechanism differentiating amilitelimab. The enrollment of all 4 studies Phase III studies is on track for the first regulatory submission expected in 2027.

Now switching to frexelimab, our CD40 ligand antibody high-efficacy nonlymphocyte depleting potential MS treatment also has a pipeline and a product potential with multiple indications under development. Most importantly, in relapsing remitting MS, the 48-week data from the Phase II open-label extension study has shown a sustained reduction of disease activity monitored by a mean number of gadolinium-positive type 1 lesions occurring appearing at each MRI.

As you can see on the bar chart, patients who have switched from the placebo arm to the frexelimab arm, both IV and subcu have shown an impressive decrease of use.

It's important to mention that nearly every patient on frexelimab IV had no new lesions presented at a near to 0 annualized relapse rate at 48 weeks. 87% of participants completed the extension and frexelimab once again proved to be well tolerated with an acceptable safety profile.

Phase III studies are relapsed on remitting MS and nrSPMS have initiated and the first regulatory submission is expected in 2027. Frexelimab has the potential to provide additional benefits to patients and extend Sanofi's presence in multiple sclerosis.

Switching gear now turning to rilzabrutinib, our oral BTKi, 1 of our 12 priority medicines. As you can see, we're developing this medicine in multiple indications such as in ITP and rare hematological diseases, but also in our main key therapeutic area immunology, including asthma and chronic spontaneous urticaria. We were pleased to announce earlier in the week the positive readout of the LUNA 3 Phase III study in ITP, a rare autoimmune bleeding disorder characterized by abnormally low levels of platelets, persistent and disabling fatigue and increased hemorrhage.

These results confirm the positive Phase II data with additional details to be presented at forthcoming medical meetings and a regulatory submission later this year.

Alongside this positive news, we also received more Phase II data in asthma. This time at the high dose, confirming the previous positive trends. We are very excited by the opportunity to present the data at the ATS conference next month. We can't wait to see that.

Positive data in the third indication CSU were presented in February at the AAAAI Annual Meeting with Phase III starting later this year. These datasets are important stepping stones of our R&D transformation journey, emphasizing our commitment to rare diseases and to unlocking the important potential for BTK inhibitors and also highlighting the value that our experience in immunology can bring to the development of a medicine that started its life in another company. Having recently reshaped our overall oncology strategy, we want to cover this in a little greater detail.

Our strategy is one of selectively investing in areas where we believe we have a chance to make a meaningful difference based on our expertise in immunology. Our aim is to focus on critical unmet medical need for patients benefiting from immune mechanisms and related mechanism of action, such as our NK cell engagers and using our technologies and platforms with the ABCs of the nanobody.

I would like to end this slide on the positive news for the cancer community, where we are pleased by the recent positive U.S. development supporting the use of minimal residual disease or MRD has clinical endpoint in myeloma, recognized by the FDA, this could potentially bring new effective treatments to patients earlier. We currently have Sarclisa, our CD38 with a best-in-class potential and approvals in more than 50 countries as an option in the relapse myeloma setting.

Last December, the readout of the [ Ixia ] study marked the fifth positive Phase III study and second positive in transplant eligible, newly diagnosed multiple myeloma patients, where 77% of patients received -- reached MRD negativity versus 67% in the comparator arm.

The Sarclisa group had a 60% higher chance of achieving these stage. Additionally, we had the IMROZ Phase III study which was positive, and we look forward to sharing in the Latin upcoming Medical Congress anticipated -- with anticipated submission in trial.

To end my part of the presentation on a positive note showing our long our ongoing commitment to deliver clinical data in the service of patients. I would like to highlight the upcoming Phase III and Phase II readouts as well as regulatory submissions occurring in '24 and '25. As you can see, news flow will increase and become busier as we move into '25, supported by the step-up in R&D investments that Francois just mentioned. I'm enthusiastic and impatient at the same time, as the news flow keeps on getting richer and better, thanks to the clinical study that we are constantly starting.

With this, I hand back to Paul.

[Paul Hudson, executive]

For sure, enthusiastic and impatient, I can confirm that.

[Paul Hudson, executive]

We'll now open the floor for questions. [Operator Instructions] Over to you.

[Eva Schaefer-Jansen, executive]

Yes. The first question will be from Peter Welford from Jefferies.

[Peter Welford, analyst]

Can we just start off with Dupixent and just thinking about the momentum we've seen, but equally then the more important new indications COPD. I guess, I just wanted if you can sort of square up some of the very positive commentary. I guess we heard on the potential for this indication, obviously, significant unmet medical need and that there also is some, perhaps word of caution does not get to ahead of ourselves.

I guess, we've done a lot of doctors seem to think that COPD patients, they already know whether they have type 2 information in many cases or not. So if you could talk about, from your point of view, what the challenges are here and why we shouldn't expect at least initially a potential bolus of patients given they currently have no other options available and potential challenges, I guess, what would you think about that?

And then if I could just ask a second question just quickly to François, you mentioned on the gross margin just with regards to a onetime adjustment. I would maybe just go into that in a little bit more detail? And is that very much onetime for the first quarter? And then perhaps if you could be possible quantify, it would help.

[Paul Hudson, executive]

Good, thank you. Brian, Dupixent, COPD.

[Brian Foard, executive]

Yes. Thank you so much for the question. Really, as we get ready for the launch in COPD, first and foremost, it all starts with the patients. And I think what we've seen with this brand is that by going into diseases that are driven by underlying type 2 inflammation, we've really opened up new treatment opportunities for these patients and really transform a lot of patients' lives, I think, as Paul mentioned, over 850,000 patients already on therapy.

Many of those actually happen to be asthma sufferers and are treated by the pulmonologist community. So as you can imagine, as we've spoken with pulmonologists, they're extremely excited about having potentially a new option to treat these patients that, quite frankly, are on the highest dose of therapy, and that's why I think to contextualize them, these patients are on the highest doses of therapy and still exacerbating.

So we have to contextualize that the right way. And then you saw our reductions in both the BOREAS and the NOTUS trials, how effective they were at actually adding reduction in exacerbation rates of 30% and 34%. So we're very positive about this. I think the challenge with this particular patient population is probably less about the patient population and more about the fact that whenever you bring a new therapy like this in more than 10 years, biologic ramp will take just a little bit of time.

Even though there's a burden of disease there for the patients, they will take a bit of time to get these physicians used to using biologics. That said, the pulmonologist community does use biologics today. So we feel like we're in a good spot and preparing the marketplace really quite well. But excited about bringing it whenever it comes to the market.

[Paul Hudson, executive]

Thank you, Brian. Houman, anything to add?

[Houman Ashrafian, executive]

Yes. Hi, Peter, you asked a very specific question about the patient burden of disease and patient population. I just want to be clear about how we develop this molecule, both in BOREAS and NOTUS, we were very specific about our stratification strategy, we thought very deeply about the eos concentration in the blood and specifically the pheno.

We stuck to our knitting very specifically on what we saw in the Phase II and that reflected in an outstanding reduction in the exacerbations in our Phase III studies. I think it's really important to recognize the Sanofi goes forward. But our development strategy, is laser focused to enable launch in the highest unmet medical need population. And that's what we've done. So that's why we have confidence in the way this population launch will expand.

[Paul Hudson, executive]

Let me just add. I think, Brian, just on it, too. But remember -- and I have to give Regeneron some credit for really pioneering in AD with us back in the beginning, but they were strong on that. We had to really build out the education around these things. When you enter new areas you have to do the proper amount of education and work, make sure the right patients are identified and get supported. And that's why I think we've shared that we expect an inflection point in the business evolution more likely to be in 2025 because we have got work to do.

François?

[François-Xavier Roger, executive]

Yes. So the question on the inventory adjustment, it's a one-off essentially for the Q1. What happened is that our standard costs are moving down, which is actually a good news for the medium term. But we had to revalue as a consequence of that, our existing inventory to the lower standard cost and this is a one-off adjustment that we booked in Q1.

We don't expect to get much of it in Q2 and Q3 and for the balance of the year. And it was relatively sizable because it was close to half of the gross margin decline in Q1, so which means that we can expect that our gross margin should not see the same negative deviation versus last year as we progress further into the year.

[Eva Schaefer-Jansen, executive]

The next question is from Luisa Hector from Berenberg.

[Luisa Hector, analyst]

I wonder if we could just get an update on consumer factors that will determine your exit strategy and the timing and pros and cons of the different exit routes for maximizing shareholder value?

And then I wanted to ask on rilzabrutinib. So good data in ITP. Just how you think about that sales opportunity and also the asthma, so the Phase II positive for the high dose, I think, in asthma, any more color around the safety profile and how you can proceed in asthma. I think the next step was Phase IIb, but then any more color on the endpoints, trial design and that stepping stone to Phase III?

[Paul Hudson, executive]

Okay. Good. François CFC?

[François-Xavier Roger, executive]

Yes, Luisa, François speaking. So I'll take the question on consumer. As of now, we want to keep all options open. So which means, basically, you can consider that we can consider a potential spin-off, an IPO, probably partnering as well with private equity. So we keep all options open with one single idea, which is to maximize value creation for shareholders. So I don't want to comment on the pros and the cons of each of the options for the time being given that we are working on -- with a very open view for the time being. But we'll keep you posted as we progress further into the year. But don't be worried, this is about creating value for shareholders.

[Paul Hudson, executive]

Did you want a quick comment about where we're at in terms of technically being ready?

[Unknown Executive]

Sure. I mean, first, I can confirm that we're excited and that we're on track and to give maybe a little bit more color on the practical side, all our system cloning activities that had to happen successfully happened actually just last week and moreover, we're well advanced in determining the scope of all the transition service agreements, which are very important as well. And in the meantime, we continue to focus on our 3 strategic priorities as we execute our overarching mission to make self-care as simple as it should be. So we're well underway.

[Paul Hudson, executive]

Thank you, both. Good questions on rilzabrutinib. Houman -- I don't remember Brian, do you want to comment on potential value in ITP or Houman can either. But Houman, do you want to start off with...

[Houman Ashrafian, executive]

Let me start -- actually, Brian and I will tag team on this one. Luisa, thank you for the question. So let's -- you have 2 parts to your question. There was ITP and asthma tolerability. So I'll just hit this very directly. I think that there still is a major unmet medical need in ITP.

As you know, it's 50% of patients remain undercovered for care, particularly in terms of a lack of stability of platelet count, they also suffer very substantially from fatigue. Rilzabrutinib is something a great joy to me personally having treated these patients. The beauty of this treatment has a number of elements.

One is, it obviously prevents the production of B cells, hence the BTKi, the Bruton's tyrosine kinase inhibition, but also prevents phagocytosis of those platelets and reducing their platelet count. So mechanistically interesting compared to standard of care today, which undercovers 50% of patients, but also in some cases, required relatively extreme dietary modification.

Rilza offers real opportunity, point 1. Point two, you asked about tolerability. To date, what we've seen has been gratifying in terms of rilza's tolerability in every aspect. So that's pretty exciting. And then your question about asthma is super clear.

We presented our latest asthma data last year. As you know, we are excited by that data. The opportunity for rilza to become the first oral advanced asthmatic treatment is remarkable, but it has the potential to change the paradigm of how we treat asthma compared to what we have today. All I can say is that it is with very substantial pleasure that I will invite everyone on this call to come to the ATS meeting to see the outcomes of our rilza study, which we could not be more thrilled in sharing.

With that, to dimensionalize the market, I'm going to hand over to my friend, Brian.

[Brian Foard, executive]

So I think -- it's a really good question. I think as you saw on R&D Day, when we really started to talk about the 12 assets. This was one of those assets we talked about. So the slide I think that was presented earlier was really impressive to show that in 3 potential indications, CSU, ITP and then in asthma. This can be really differentiated versus the competition in each of those therapeutic areas.

Now specifically as it relates to ITP, and maybe I'll go a little bit broader and just say in rare blood space. We actually think that this could be potentially a blockbuster across both ITP and wAHA combined. But contextually speaking, I mean, if you think about the 2 of them, obviously, ITP will be a little bit bigger than what we see in wAHA just based on the size. I think there's about 50,000 patients we see as being eligible for ITP. So really excited about this differentiated profile and bringing it to patients as soon as possible.

[Paul Hudson, executive]

Thank you. I'll be in San Diego at ADS for the weekend between other meetings. So I'm looking forward to seeing the data presented, too.

[Eva Schaefer-Jansen, executive]

Next question from Graham Parry from BofA.

[Graham Parry, analyst]

So first one is just on tolebrutinib and just thinking about scenarios for the readout of the data there. Just given the low likely annualized relapse rate that you're going to see in the control arm, if you assume it's going to be similar to ibrutinib. Do you see that there's a thought process here that perhaps actually progression would be the better primary endpoint?

And is there a possibility here to change the statistical analysis plan for those relapsing studies to disease progression? And alternatively, in the event that you didn't see that you met the primary endpoint on the GEMINI studies and you do hit endpoints in the progressive trials.

Do you think that this could be something which should be priced higher in the market for that smaller overall MS patient population, but just as a progressive MS drug. So first on tolebrutinib.

Second one, Beyfortus supply. You said you can do -- make this a blockbuster this year. I think my understanding was that, that's sort of based on what you know you definitely have for supply, but you're working on increased supply. So perhaps could you sort of dimensionalize or quantify the upside here from bringing more supply on through the course of the year? I think if you just assumed you're able to satisfy the U.S. both cohort alone that would be EUR 1.5 billion-or-so. And you did talk about launching an additional market. So perhaps help us to dream a little about Beyfortus revenue for the year.

[Paul Hudson, executive]

Okay. We'll help you dream a little in a moment, Graham, but first that well, maybe there, too. Tolebrutinib. Houman?

[Houman Ashrafian, executive]

I'll start before Paul breaks out in to song. I'm going to -- thanks for the question, Graham, deeply thoughtful as always. So first part of the question was on scenarios. As you know, there's a bunch of scenarios. We have 2 relapsing remitting trials running GEMINI 1 and 2. We've got HERCULES and PERSEUS.

I think going into all the presentation of those scenarios itself are challenging. But let me just be -- let me just dimensionalize this across those indications. Firstly, in terms of relapse and remitting, you make an excellent point about previous failures, particularly in comparison to [indiscernible]. Let me just remind everybody very briefly on this call that in terms of penetration across the CSF by a physical property and actually some of the biological properties we've seen with tolebrutinib, these are outclassed in some cases, by 2 log orders, any of the other molecules in this case.

Ibrutinib's primary biological capability is very substantial. Second point, I'll remind you when we talk about mechanism is compared to some of our competitors out there, patients who come off standard of care and go on to tolebrutinib have a continuing reduction in the neurofilament light.

These 2 parameters make us optimistic about the -- yet cautious in the role of tolebrutinib, both in relapsing and progressive, so it's point one. Point two, in terms of your specific question, which you asked about endpoints. Of course, you're right that in 2024, ARR is currently the endpoint of choice.

However, most of the community and most of the physicians that are looking after these patients will point you to the fact that actually composite confirmed disability progression is much more important to the patients. And indeed, many of the endpoints that are currently being used, use a relapsed independent progression rate.

So the short answer to this question is, we'll see where we get with GEMINI 1 and 2, but I would strongly suggest that the regulator and the patients care deeply about disease progression, and we are well powered to address that question. On the progressive disease, we're very substantially hopeful because of the data we've discussed before. And of course, there is no Aubagio comparator arm in that population. I think that provides you with a nice wrap up of tolebrutinib, I'm going to hand over to Brian on the other topic.

[Brian Foard, executive]

Yes, I think the question on price is really the question on value, I think, more than anything else. It starts with there's no more differentiated program, I think, in MS for sure than this tolebrutinib program. So we'll see what the scenarios are. It's hard to guess today what the final scenarios will likely be, and we'll determine the value based upon that, and we'll comment on price probably at that particular point, but not now.

[Paul Hudson, executive]

Thank you, Brian. Thomas, Beyfortus supply?

[Thomas Triomphe, executive]

Exciting to speak. So where we are on Beyfortus. First of all, you've seen the strong performance in Q1. I start by reminding on that point, with a significant amount of sales above EUR 180 million just in Q1. I'm mentioning that to highlight the fact that it covers not only NH23, 24 last shipment for Northern Hemisphere, but also the first shipment of Southern Hemisphere with 2 Southern Hemisphere countries where we have started. So that's the first part.

As you have seen also, we mentioned through François, that we will not expect sales of Beyfortus in Q2, has nothing to do with supply, simply related to the fact that we were able to actually ship the South Hemisphere supply in Q1 and not in Q2. And of course, the rest of the sales for this year will come with Northern Hemisphere in Q3 and Q4. Now as per the heart of your question on supply. We have full speed, both AstraZeneca and us are working on extending our industrial network as we have mentioned before, together. We are adding not -- we've already added, of course, packaging lines, we're adding filling lines as we have discussed altogether.

And as we speak today, we are, every single day, filling new Beyfortus syringes for the coming season. We're going full speed as we discussed also. Of course, while we are currently manufacturing and filling doses, it will then depend as to the release of this product as per the speed of approval on these 2 filling lines by the regulators, notably, U.S. FDA and EMA, especially.

So we believe that with all the elements we're putting together with our partner, we'll be able to have this supply release in due time for the coming Northern Hemisphere which is why we are very confident in our ability to reach blockbuster status. To be more specific beyond that will be what we will discuss together at the Q2 earnings call when we'll have more news from our supply perspective, and this insurance and regulators.

[Paul Hudson, executive]

Yes. And thanks, Tom. And I think everybody, AstraZeneca, ourselves, everybody is doing the very best because the demand is so significant and Q2 is a much better moment to give you much more facts as we have them, frankly.

[Eva Schaefer-Jansen, executive]

Next question from Tim Anderson from Wolfe.

[Brian Tsang, analyst]

This is Brian on for Tim. Just 2 quick ones from us. After the EPS reset in 2024, you talked about a strong rebound in 2025. Consensus has growth being around 15% in 2025. Any comment even if only directionally on that figure? I know you might not say anything right now, but anything you might want to call out, such as uncertain variables that might jump out. And then a second question on OX40.

You've said previously that this might be your most important pipeline drug similar to Dupixent, but you capture full economics. Just want to ask how derisked do you think this asset is at this point in terms of how Phase III trials might read out? And whether you can confirm that there might potentially be earlier readout potentially in 2025?

[Paul Hudson, executive]

Okay. Thanks, Brian, asking for a friend. I would say, François, any comment? I mean, to be clear, I don't want to put you on the spot, but we just had strong rebound. So is there any other color you can give?

[François-Xavier Roger, executive]

No, Brian, what I can tell you, I don't want to quantify the EPS rebound but we are very confident about it. I think we have the building blocks, starting with the growth profile that we have today. And if we -- you put aside already, even you can see it in the first quarter of 2024 some of the exceptional items, the negative ones like Aubagio and the comparison base for COVID-19 sales, for example, we are already on a very strong platform in terms of growth today and which gives you a fair illustration of where we can be in 2025. But I think it's too early to quantify it today. And I would not like to give a guidance for 2025 at this point in time.

[Paul Hudson, executive]

Thank you, Houman, OX40 ligand?

[Houman Ashrafian, executive]

Yes. Let me respond to this very briefly. I presented the data earlier. Super excited by the data, 3 points, rather this is a biologic, which has been on a large number of patients, it's likely to be extremely safe, particularly compared to anything else that's out there. It's highly well tolerated. The dosing interval, extremely interesting.

And importantly, off-drug disease suppression is important. So there are only 3 comments to make on this. One is, you said how optimistic are we, very optimistic. But we're optimistic because it may also have the opportunity, and this has been echoed by external commentators to have the potential to reduce atopic march and the progression of disease particularly in those with earlier atopic disease, point one.

So number one is we are bullish for that reason. Number two is, mechanistically, it's kind of interesting, right, because it addresses both TH2 as well as TH17, TH22 pathways, which impact on our broad ethnic sort of populations. So number two is, it derisked from that perspective.

And number three is clearly, we're taking it forward in a multiplicity of indications, some of which we'll read out this year. So the quick answer to your question is we're driving the studies as hard as we can. We've got 4 Phase IIIs in flight, we'll drive them to completion in an orderly manner as possible. And we -- bear in mind as a biologic, feel optimistic that we have been able to quantify its risks and benefits.

[Eva Schaefer-Jansen, executive]

Next question from Emily Field from Barclays.

[Emily Field, analyst]

The first is just piggybacking off of the earlier Dupixent launch and COPD answer. The contrasting thought between the biologic ramp is going to take some time, but that pulmonologists are very familiar with Dupixent, obviously. As we're thinking about this launch is this one that is going to require a great deal of incremental promotional spend?

And then on Altuviiio, you mentioned taking share from therapies other than [ alate ]. Are you seeing more share take from HEMLIBRA as that did decline in U.S. in the quarter? And then big focus of their call yesterday was on the potential competitive threat from [ MIMIC ]? Are you seeing that as a potential threat to Altuviiio or do you see that more as posing a threat to bispecifics?

[Paul Hudson, executive]

Okay. Brian, over to you, COPD ramp. And I think the challenge is if pulmonologists know Dupixent already, why should it take some other and what will be the cost of doing it?

[Brian Foard, executive]

Yes, I think there's a couple of things in there. And so I think just as we said before, as you bring in a new therapy like this, any patient population, you've got to educate the patient population. You've got to educate the physicians. There's a lot to be done there to where it's not just to come in and take share game. It's going to be one of those things where it's biopenetration. We've seen this very well in atopic dermatitis. As you see in AD, here we are, we're nearly 8 years in and the biopenetration rate is 11%.

So it takes time, it takes effort. The good news about cost, and I think the expense is, if you think about it, we're very efficiently set up because we're already set up across the alliance actually deeply in the pulmonologist offices across all countries.

So from an OpEx standpoint, there will be a lot of efficiencies there because this will be our second indication in the same offices. So we, of course, will spend to support this launch. It's absolutely a critical launch to reach as many patients as possible, but we certainly see some efficiency there and the way in which we're set up.

[Paul Hudson, executive]

Thank you. Altuviiio share any business coming from nonfactor and a comment on [ MIMIC ]?

[Brian Foard, executive]

Yes. A couple of things there. I think it always goes back to the patient and the unmet medical need. So if you think about this patient population, it's all about efficacy at the end of the day. And previously, where you speak about HEMLIBRA, that was more of a convenience play than anything else. While effective, it was more of a convenience play, the first subcutaneous product. So I'll break it into 2 pieces.

Altuviiio is doing exceptionally well. We couldn't be more pleased with the launch progress because, again, the physician and the patient population really understood that for a single dose, you can actually have near normal factor levels for an entire week. And that's really changing the game in the offices.

Now where are we primarily taking business from? We always said we primarily take it from factors because we believe all patients that are on factors should be moved to Altuviiio. And the factor marketplace is about 60% of the marketplace still today, 60% to 65% of the marketplace. So that is primarily where we're taking business.

2/3 of our switches are coming from competitives, 1/3 is coming from Eloctate, again, a factor that should be switched. Now as it specifically relates to HEMLIBRA, and then we'll talk about the competitor that's coming, I definitely think HEMLIBRA should be more nervous about the competitor than us for sure.

But we're taking about 10% -- about 10% of our business is actually coming from HEMLIBRA. It wasn't what we anticipated necessarily, but again, I think it goes back to the efficacy side of things. So again, we couldn't be more pleased with the progress so far. A lot of our physicians more than 80% of the physicians have prescribed and we'll reiterate that they continue to increase their prescribing moving forward. So again, we're off to, again, a really good start as we hit almost the first year mark for Altuviiio.

[Paul Hudson, executive]

Thank you, Brian. And of course, as we watch the market evolve, you're right, I think we took more patients from HEMLIBRA than expected and probably because they're trying to chase efficacy down to the once a week, which meant once a week convenience was roughly the same.

I think when HEMLIBRA set the bar and we're trying to find some new convenience standard. And I think monthly or perhaps even 8 weekly with reducing, I think that could be a new level 2. So the market is clearly going convenience versus efficacy in the trade. So I think we're going to be well positioned.

[Eva Schaefer-Jansen, executive]

Next question from Emmanuel Papadakis from Deutsche bank.

[Emmanuel Papadakis, analyst]

Maybe a question on cash flow, first of all, please. François, you mentioned some caution on the outlook for this year. I think you mentioned some onetime adjustments for prior year rebating. Perhaps you could give us a bit of color maybe in absolute sense, cash flow last year was around EUR 11 billion, free cash flow was above EUR 8 billion. So what should we be thinking of for this year?

And you did have some rather outsized restructuring costs in Q1 over EUR 700 million. So where is that likely to land for the full year? And what proportion of that is cash and a lot of working capital outflow in Q1, which drove a negative cash from operations, which is also rather unusual. So comments around those would be very helpful. And then a quick one on Tzield, flat again, a few quarters in a row, still confident on blockbuster potential? If so, what gets us there? What are the time lines?

[Paul Hudson, executive]

So François, you do that and then maybe, I don't know, Olivier want to comment on Tzield?

[François-Xavier Roger, executive]

Let me start. On the cash flow, so it is essentially the fact that the decrease already in Q1 is essentially coming from the lower gross to net in Lantus. As you know, we are booking lower, but we have to pay from a cash flow point of view, to rebate on a higher base, at least in Q1, we will have a little bit of an impact as well in Q2 and Q3.

This has impacted our cash flow significantly in Q1, and there will be a little bit of it the next 2 quarters. Obviously, this will remain for the full year. So I just wanted to flag the fact that this is kind of a one-off that will impact our cash flow for the full year.

I don't want to quantify it because there are other moving parts, but this is a fairly significant one-off impact. On the restructuring costs, it's essentially linked to many of the projects that we have already announced part of it is actually obviously hitting France, as you know, because it's in the public domain as well. It's not necessarily a cash item that will be significant in 2024. It will spread over the next 2 years, partly, but some of it could potentially impact the end of 2024.

[Paul Hudson, executive]

Thank you. Olivier comments on Tzield?

[Olivier Charmeil, executive]

Comment on Tzield. So we see a positive evolution and a slight acceleration growth in terms of screening and in terms of infusion rates, Q1 versus Q4 where we have higher infusion in Q1, we have more -- we have higher infusion in pediatric patients, which is for us a good signal, which means that we are progressing. Infusion have accelerated, driven by more field force execution and better coordination along the patient journey.

Payers coverage is good. It's not a barrier to utilization. We said from the beginning that it would be a slow burn. We are shaping a market that didn't exist. There was no screening because there was no treatment. We know that it will take some time, but we think that it's worth the effort. It's about creating the awareness and making sure that both awareness at the patient level, at the family level but also with HCP is developed. We are very encouraged by the consensus guidelines that are being developed a white paper from ADA as that was recently developed, and there are a lot of activities in the congress of ATTD with GRF making and aligning a lot of medical society towards guidelines. So overall, it's going to be a slow burn, but we are confident that in the future, it will continue to progress. We think that it's worth continuing to invest, and this is reinforced by our exchange with KOL and clinicians that really gives us confidence that with Tzield we have the first and only disease-modifying therapy in type 1 diabetes.

[Paul Hudson, executive]

Maybe I could add as well, Olivier, that we said it, we knew full well when we made the transaction. There's a reason why some of these small companies sell a great medicine is because they just can't do this type of work over this many years.

If I could add anything, the quarterly transitions are less -- of less interest at the moment, the screening numbers are where we're heading. And we will, in '26, '27, '28, this medicine is going to be a big deal contributing to the company, would do the hard yards. And I'm not sure you mentioned, Olivier, but there was no competition for a decade. So we don't need to rush this. We can do this properly.

In fact, we're the next competitor with the CD40 ligand. So in time invested, in building proper screening, infusion capacity where necessary, doing these things. We've all been on this journey before, it was on with hep C, it was only with Remicade. You just do the to work properly, and we'll get the benefits a few years from now because there's nothing to displace us. And that, of course, will set us up in the community for the CD40 ligand. So we're actually really pleased with how guidelines and other things are falling quickly into that.

[Eva Schaefer-Jansen, executive]

Next question from Seamus Fernandez from Guggenheim.

[Seamus Fernandez, analyst]

So I just wanted to clarify the tolerability comments around rilzabrutinib. Just to confirm, it says safety consistent with prior results on the slide. Just wanted to confirm that, that is consistent with the lack of an LFT or liver signal, as previously stated as well as maybe confirmation to some degree that the MS population that the BTK signal and the MS population may actually be population-specific?

And just a quick second question. Paul, just wanted to get a sense for how you're thinking about business development from here. I guess, with the incremental investment in R&D, and the robust kind of pipeline dynamics heading forward. I wanted to get a better sense of how you're thinking about business development going forward in terms of perhaps areas that you're most focused on, building out or if there is kind of a profitability or stage of development, later stage that's more interesting versus early stage?

[Paul Hudson, executive]

Thank you, Seamus. Houman, tolerability, rilza; and some also comments about MS and the populations creating different responses.

[Houman Ashrafian, executive]

Yes. So Seamus, thanks for the question, both thoughtful. The first one brief and to the point, I can confirm that we are pleased with liver tolerability profile of rilzabrutinib thus far and are confident taking it forward. As you said, point two tolebrutinib, you very thoughtfully have called out the fact that multiple sclerosis appears to be a distinct indication with the BTKis.

There may be interaction between the BTKi and the underlying biology in MS, which pretty set people to a liver signal, I think that's, as you were referring to, reasonable hypothesis, we have data supporting it and reflects clinical experience. I think both of these points are well made.

[Paul Hudson, executive]

Thank you. On the BD, I guess, to M&A point, we guided to the sort of EUR 2 billion to EUR 5 billion range in bolt-ons, that's sort of standard, I think. We did commit after Q3 last year that we would hold R&D through '24 and '25 round about EUR 7.7 billion. So we don't want to regale away from that. I don't think that's appropriate. Of course, we will get some failures in there, which will free up some capacity or some delayed starts, so different things, which will mean that capacity will open up for us perhaps into '25 and '26.

And then, of course, most of the big studies start to graduate as the pipeline comes along and that gives us the sort of automatic bandwidth. I think to maintain that, you might see more of our effort and energy on the bolt-ons, either in the early phases where this bigger spend comes later and we can absorb that without missing a commitment or indeed in the late stages where the R&D commitment ongoing is minimal, and we can hold the line on what we've said and perhaps bring in a later-stage asset.

We have a good balance sheet. We have to leverage that. But I think the discipline around working within the envelope on our R&D budget is to be maintained. Should I throw the normal CEO disclaimer in, we remain opportunistic and everything else. Of course, but we've given guidance to you, we'd like to honor it for us and for you and make sure we get it done. And if we find some opportunities to reallocate, that's perhaps our biggest thing, we'll take it.

But demonstrating the discipline post Q3 last year is the number one priority because don't forget we're having enough assets in-house to, we believe, to grow EPS, of course, and to do what we need to do and to go all the way through the LOE of Dupixent whenever that comes. But the discipline is what will be judged on, I think, over the next couple of years at least. So that's as much as I can share with you.

[Eva Schaefer-Jansen, executive]

Next question from Jo Walton from UBS.

[Jo Walton, analyst]

Two quick questions then, please. On Altuviiio, I wonder, is there any evidence of moderate patients rather than severe patients beginning to try prophylaxis given that this is now an ability to get to a normal level of factor clotting, on Beyfortus, could you give us an idea of what the next countries would be?

So you've obviously got potentially more demand than supply. What's the sort of order of countries that we should be thinking of as you roll out because you said you would be rolling out some more this year. If I can just finally say, is there any read across from the failure in frexelimab [indiscernible] to any of the other indications or should we see that as completely isolated?

[Paul Hudson, executive]

Good, Jo. Good questions. Brian, Altuviiio use moving into [indiscernible].

[Brian Foard, executive]

Yes. I think I mean the way we think about the marketplace is actually, again, all these patients are on therapies. So it's -- when we talk about the switches, again, these patients are identified really early in their life and then they're on some type of therapy.

So from a moderate standpoint, we don't think about it that way. Actually, we think about it as what type of therapy are you on? And what types of efficacy levels are you looking for or convenience levels are you looking for?

And that's why, again, we're really bullish because of what we've seen from a switch standpoint the marketplace is really responding to the profile that we're bringing, which is better efficacy near normal factor levels over a weekly period with a 1 dose type of therapy. So we're seeing switches of all patient types, no matter the types of therapy that they're on.

[Paul Hudson, executive]

Thank you. I do think Altuviiio is going to surprise everybody. I have to say all the feedback and a bit in the conferences, I think that near normal thing Jo mentioned is the goal. Thomas, I'm not sure whether you're prepared to share a list of countries in what order, but maybe you could give some regional input?

[Thomas Triomphe, executive]

Yes. And I can say a little bit of flavor of how we are doing it and why we saying so much more. So rightfully, as you said, Jo, of course, we are going to make sure that we have ample supply for the 3 geographies where we had significant uptake last year. You know very well about Spain, the U.S. and France. Moving forward, we've already doing South Hemisphere ongoing season, open Chile and a couple of regions in Australia.

Moving forward for Northern Hemisphere 2024, I expect more European countries to pick up. What happens, and that's very important to remember, each time we introduce a new immunization, it's always -- there is always a very specific national process for first setting up the right to recommendations through the recommending body, then high setup and then we launch into the right national immunization schedule, which is why I cannot give you specific European countries right now because I need to leave it to the recommending bodies to make sure that we have those votes and we proceed for NH 2024.

In addition to this geography in Europe, you know very well, but we just got the registration of Beyfortus in Japan in Q1, 2024. And you should expect a little bit of Japan and China sales in the private setup, I would say, not national immunization program for 2024 in order to prepare for larger volumes in the coming years, that's for the following season.

[Paul Hudson, executive]

[indiscernible] Jo's comment on frexelimab is well placed?

[Houman Ashrafian, executive]

Thanks, Paul. Thanks, Jo. Great question. Just to be super clear, we've always positioned frexelimab, primarily on MS in T1D medication, and it's clearly demonstrated as chops in MS in great detail and is progressing in T1D. It is incumbent on us as a patient-centric organization for us to be thoughtful about the broadest possible patient benefit we can bring with our drugs.

In my own clinical practice, I treated a bunch of patients with Sjogren's and they are definitely an unmet medical need we initiated some experimental medicine study to see whether we could signal seek in those indications. I don't see the Sjogren's readout as anything other than failure in a signal-seeking study, and we remain confident about frexelimab in the bigger latter indications.

[Paul Hudson, executive]

Yes. I think you're right, the type 1 diabetes and MS, where I think you said it already, but just the risk of repeating it. Where we have a pipeline in a product, we will go and explore some adjacent areas where we think there's some pathway or some biological reason why there might be an impact. And you should expect more of that from us in like early pox, left and right the pipeline on the product drugs because we need to do that.

I think we really need to do that. And of course, everybody's tried Sjogren's because it's difficult to crack. And we can't blow any bunches if we can do something.

[Eva Schaefer-Jansen, executive]

Next question from David Risinger from Leerink.

[David Risinger, analyst]

Yes. So I just have one question, and maybe you could comment in some detail, please? So the company has accelerating I&I Phase II readouts in 2025. Could you discuss the key cards that will be turning over for the candidates with the biggest commercial potential?

[Paul Hudson, executive]

Okay, David, thank you. So I think Houman will start with you on -- we've already put them into 2 buckets, frankly. So we -- I don't know how much more we need to add. But for the readouts that you're excited about, for example, Houman for I&I for 2025, specifically is what you asked.

[Houman Ashrafian, executive]

Yes, specifically. It's like choosing between one's favorite children for our readouts in 2025, but I'll give it a go. So firstly, it's our big letter. I mean you asked for the answers in some detail, and I will try and provide them with thoughtful detail.

So our Phase IIs reading out, as you've seen there, amilitelimab in a variety of disorders, particularly hidradenitis suppurativa and alopecia. Number one, as I said, with a nondepleting OX40 ligand inhibitor, we hit the type inflammation, but also take on a bunch of other mechanisms.

OX40 is often regarded to the checkpoint and a new checkpoint. And I'm excited about its alopecia areata and hidradenitis suppurativa which have very diverse clinical indications. Obviously, we have an all RIPK1 with a rolling of colitis. We think that's interesting. The biology is well precedented.

So number one, I think the amilitelimab constellation of therapeutic opportunities is interesting. I think the IRAK degrader is super interesting. It's mechanistically unique where we with our partner have played both in atopic dermatitis as an oral therapy, but also in hidradenitis suppurativa again.

And then 2 others, just to call out, as you asked what our favorites were. The oral TNFR1 signaling inhibitor has the potential to be a truly disruptive therapy for patients with inflammatory disease as it will capture potentially the value of classical TNF treatment but with a differentiated side effect profile not affecting TNFR2.

And the second one I wanted to call out is, obviously, Lunsekimig, our very special molecule in asthma. The reason it's special is because it seeks to augment durability but also raise efficacy healing. And the way it does so is to take 2 modular targets both of which are precedented mechanisms in asthma put them together.

So what we do is learn from the ecosystem and with the excellence of our platforms to enhance what we know from the ecosystem. Before I jump off the pedestal, I also want to [indiscernible] because it would be remiss of me to talk about our pharma agents and not talk about the RSV products that are reading out in Phase II next year. We remain as excited about vaccines as we do as our pharma products.

[Paul Hudson, executive]

So Houman, it's nice it took you a while to David's question. Did you mention OX40 ligand in HS?

[Houman Ashrafian, executive]

I didn't mention, nor did I mention TL1A or some of the other...

[Paul Hudson, executive]

TL1A will be up there, too. So it's going to be busy. It's going to be busy, but this is what we've been trying to get the company to this point. We don't know if they will work, of course, but we do know that we would rather have the readouts.

[Eva Schaefer-Jansen, executive]

The next question from Gary Steventon from Exane.

[Gary Steventon, analyst]

Just firstly, on the outlook. Given the top line momentum, could you frame maybe the level of flexibility you have in the R&D and launch plan and hence, the likelihood that any outperformance could drop through to earnings? I mean, it wasn't that long ago, you outlined the acceleration.

So I assume that any near-term investment opportunities that you wanted to accelerate, you perhaps have done already? And then secondly, just on the theme of the consumer separation. -- perhaps, François, it's your first earnings call as CFO, I ask your thoughts on what might be on your list in the scenario where Sanofi was to receive a significant cash inflow. So really just your thoughts on appetite for larger volume or larger value of M&A, larger buybacks or willingness to operate with net cash for a period of time?

[Paul Hudson, executive]

François, do you want to take a stab at those?

[François-Xavier Roger, executive]

Yes. I can. On the R&D flexibility, I mean this is good news if we can generate additional resources. I think that we will need to decide in due time on each and every single case on their merits. If we have good cases for good return on investment on R&D, I think we will not hesitate to do it.

But that being said, I mean, we should not discount the fact that we let some of it flow to the bottom line. And I think that it's extremely important that one that we reward our shareholders in an attractive way, which is the reason why I'm coming back to what I said earlier as well on our total confidence on the significant rebound in EPS, for example, in 2025.

I think on capital allocation, I think that we have a very clear policy. So first of all, we want to invest in our business, both organically and inorganically as well. I think Paul touched on it earlier, and we need to be very disciplined on that, so which is -- which means that we are rather thinking today of bolt-on cases within the EUR 2 billion to EUR 5 billion.

Clearly, with a view to get some return and generate value for shareholders as well. Paul said it, we don't want to discount either larger opportunities if they themselves and these are attractive, obviously. In terms of capital allocation, we don't want to discount share buybacks. That's a possibility, especially in the context of the separation of CHC. So this is part of the option that we keep on reviewing. Let us work further into the year to decide exactly on which route we get. But we heard the message that there is an appetite as well from shareholders to get some share of the cash that we could generate from that transaction.

[Eva Schaefer-Jansen, executive]

The last 1 will be from Peter Verdult from Citi.

[Peter Verdult, analyst]

Peter Verdult from Citi. Two questions, please. I think everyone on the call realizes in your comments portray that pipeline perception is the missing piece of the puzzle to get the shares flying again and above 100. So with that in mind, I've got 2 follow-up questions for Houman, please, on rilza and tolebrutinib.

I totally get you can't disclose too much ahead of data presentation, but Houman, can I push you as best I can to give us a sense of how competitive you think that rilza dataset in ITP is from an efficacy safety perspective to incumbent molecules such as Promacta, especially given Promacta is facing generic risks and I'm going to try to push as best I can without getting you to disclose the data?

And then on tole ahead of the late summer Phase III readouts, just how you're thinking about the relative opportunity across readouts remitting and progressive because on relapse remitting the KOL feedback we're receiving and the data that's being presented at ACTRIMS and ECTRIMS seems to be showing a waning effect for both evo and tole over time as it relates to gadolinium lesion reduction.

So the message we're getting is be wary of a positive result in relapsed remitting, progressive is clearly where the biggest unmet need is. But we don't yet have any randomized Phase II data we can sort of bank on. So is it just the brain penetration angle and the NFL data that you spoke about earlier, Houman, and what gives you confidence in the progressive trials or would you bring any other points to the table?

[Houman Ashrafian, executive]

Okay. Thank you so much for those questions. As always, deeply thoughtful, let me just take rilza very quickly. I think the existing standard of care leave -- they've been incredibly important medicines by the way. I don't want any level of people not to appreciate how important they've been to the treatment of ITP.

But they don't get to the heart of the disorder, as I said, mechanistically, suppression of the B cells and the reduction of Fc-gamma-based macrophage platelet destruction has been really important and just building up a number of platelets doesn't ameliorate the severe fatigue, et cetera.

So I really do think rilza is a deeply important new add to that space. And as Brian beautifully said, beyond ITP, its future role potentially in rare blood is really very significant. And the tolerability profile is -- as you said, I can't disclose, but to my mind, very pleasing. So the ITP answer, bullish on rilza.

On tolebrutinib from time to time, I find it frustrating that people try and change the goal post. And let me be super clear, I think in progressive disease, there is almost nothing out there of any significant value in secondary progressive MS. It's a horrible disorder with ventricular dilatation and substantially unmet medical need.

Today, many of those patients are either undertreated or labeled as a different condition in order to access therapy, right? So for progressive disease, I think the risk benefit should the tolebrutinib readout play to our favor is unequivocal. And I'm prepared to be confident that if there is efficacy with the level of safety we've now seen with monitoring that in progressive disease, there is significant value over here.

With respect to relapsing/remitting when my frustration comes in, to take at this stage in GEMINI's development to argue that even if the molecule works in a Phase III and passes the goal post that we now have another discussion about whether this is going to be sustained. I think difficult question to answer.

My view is, in a few months, we will see the results of GEMINI 1 and 2. I think that the regulatory path is really well established, both with respect to ARR, but also with respect to disability. This isn't something we've invented. And I think the owners will be on us and the regulator to get this through and benefit patients with relapsing disease, if we hit ARR and/or disability. I think as simple as that.

[Paul Hudson, executive]

Yes. Thank you, I mean we -- I'm with you, I think rilza is a really competitive profile irrespective of Promacta and its challenges with diet and everything else. I think we -- I think once we get beyond as well to asthma and to CSU, I think you took in advanced orals in these spaces -- and I think the question is the right question about earlier was asked about tolerability. If you can thread that needle, which I believe we can, you really unlock huge patient potential, that's why we put it in Q4.

On tole, I think Houman summed it up beautifully. Let's not forget that an advanced oral with potentially disease-modifying could be the profile. And it's -- there's a real space for it. So I think that if we can get it done the right way and we'll get the study soon enough, so it's sort of not even worth speculating anymore.

I think if we take progression in any form, even if we have to have conversations with regulators about what is sort of understood and what is not, actually, it's very hard to resist something that could do that. We will find out, we'll see how the data result is.

So thanks, everyone, for your time today. We've had an excellent start in 2024. Sales advanced by 7%, growth was driven by launches, including new indications for Dupixent. Our transformation is gathering pace, and I thought that a bit today who joined the call that questions weighted towards the future and what we're trying to do.

If you have any follow-up questions, feel free to contact the IR team, they never rest. And have a great rest of your day. Thank you.