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Sanofi SA
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Good morning, good afternoon and good evening to everyone. Thank you for joining us to review Sanofi's 2022 Second Quarter Results followed by a Q&A session. As usual, you can find the slides to this earnings call on the Investors page of our website at sanofi.com.
Moving to Slide 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 Document d'Enregistrement Universel for a description of these risk factors. With that, please advance to Slide 4. Our speakers on the call today are Paul Hudson, Chief Executive Officer; the Global Business Unit Heads, Bill Sibold, Thomas Triomphe, Olivier Charmeil and Julie van Ongevalle; and Jean-Baptiste de Chatillon, Chief Financial Officer. For the Q&A, you have two options to participate. Option one, click the raise hand icon at the bottom of your screen or option two, submit your questions by clicking the Q&A icon at the bottom of the screen. And with that, I'd like to turn the call over to Paul.
Well thank you Eva and thanks to everyone for joining. I'm truly delighted to share our outstanding financial results with you today and as always with me here in the room are the team members of the Executive Team to take you through our business and financial performance. We delivered sales rate at 8.1% continuing the strong performance we saw in Q1. Our growth in specialty care has accelerated to more than 21%. Dupixent posted nearly €2 billion in sales and it's still growing at a stellar rate above 40%. Our disease franchise is growing double-digits driven by legacy products and recent approvals. Continued growth in PPH, further recovery in travel and booster vaccines drive another strong quarter for our vaccines business. In general medicines the focus were on our core assets well it continues to pay up. Consumer healthcare delivered another quarter of above market sales growth and this speaks volumes about the speed at which our business is transforming into a truly agile, fast moving, and consumer centric organization.
Moving to Slide 7, let's take a moment to consider the immense potential of Dupixent. Five years into launch, this medicine continues to grow at a remarkable pace. And while we have already treated over 450,000 patients worldwide, we know it is certainly really starting at this point. The markets will be approved just to launch the underpenetrated within eligible population of around 7 million patients. This quarter alone we added 150,000 eligible patients thanks to approvals in the areas of high unmet needs such as pediatric asthma in Europe and eosinophilic esophagitis in the U.S. And let me mention here the approval received in the United States for the youngest children suffering from atopic dermatitis making Dupixent the first and only biologic medicine approved in all age groups from infancy to adulthood as a complete paradigm shift. The breadth and depth of the Dupixent label is setting aside this megabrand from all other medicines in this area.
On Slide 8 as we get close to the end of the first phase of our six-year strategic plan, let’s take a moment to highlight some of our achievements and future perspectives. We have delivered eight consecutive quarters of sales growth, more recently growth even accelerated to high single-digits. While it is probably at least a decade since such a performance was achieved but above all it is a proof point that our focus on winning assets combined with strong commercial execution is clearly paying off. At the same time our profitability improved and thanks to the efficiencies and savings made across the company, we are making these improvements sustainable by largely reinvesting in our growth drivers and our science and as a result we remain on track to reach our 30% BOI margin guidance this year as we had committed back in 2019. We are on a quest to modernize the company. This modernization included deep cultural transformation but also important structural changes. The recent unsuccessful spin out of EuroAPI is a major milestone and so was the implementation of our CHC standalone model.
Looking ahead, several key factors will be instrumental for our strategic execution. Clearly, Dupixent remains the number one driver of our growth story. It will help to manage the LoE of Aubagio in the U.S. in 2023, our last meaningful LoE in this decade, making Sanofi the pharma stock with the least expose to generic competition amongst our peer group. We'll continue to focus on our deep productivity through increased investment in breakthrough science and first and best in class assets. Our pipeline is maturing fast and we will have multiple chances for transformative launches in the upcoming years. In the short term, we'll focus on making nirsevimab a success story by achieving all protection from RSV starting next year. Following shortly after we strongly believe efanesoctocog alfa will have the potential to revolutionize treatment for hemophilia A patients. Our belief in tolebrutinib, our oral brain-penetrant BTK inhibitor to address the full spectrum of multiple sclerosis remains unwavering.
Based on compelling Phase 2B efficacy data, we launched the largest Phase 3 clinical program in MS, and more than 2000 patients are currently on tolebrutinib therapy with duration of treatment up to three years. We expect the first pivotal read out by the end of next year. It's disappointing that the FDA asked us to pause new patient enrollment in the U.S. without assessing the impact of our trial protocol revisions implemented back in May. Let me point out that all of the 150 patients enrolled into the Phase 3 program will treat implementation of the revised protocols in May and the partial clinical hold in the U.S. at the end of June. None have had any sign of drug induced liver injury. We received a written feedback from the FDA and are confident to address the FDA's request for additional information by the end of this quarter. Meanwhile, the studies continue in dozens of countries around the world.
Moving to Slide 9, let's take a closer look at our R&D transformation, marked by clear prioritization and long-term ambition to lead with innovation. This slide illustrates just a few examples of the significant shift in R&D productivity we've made over the past few years, such as accelerating the development of Dupixent across a wide range of Type 2 inflammatory diseases and building an industry leading immunology pipeline. I simply could not be prouder of the organization and the progress we have made over the past couple of years.
Moving to Slide 10, on our hemophilia pipeline. If you had the chance to follow ISTH where the pivotal data for efanesoctocog alfa was presented earlier this month, you will almost certainly agree efanesoctocog alfa is reaching levels of advocacy that have simply never been seen before. Now there is little reason, in my view, for patients that are using factors today beyond anything other than efanesoctocog alfa in the future. And Bill will talk a little more about this and the upcoming launch in a few minutes. And another fact that came apparent to me when I had the chance to engage with key opinion leaders at ISTH, beyond effect, innovative hemophilia treatments have to be truly once monthly or even less frequently. So let's not forget the potential for fitusiran. We look forward to presenting more data from the ongoing fitusiran program next year, based on its revised schedule of every other month.
Moving on to Slide 11, Nirsevimab, a team is working around the clock to make this first in class immunization solution available to protect all infants against RSV once approved. RSV was recently on the agenda of the General Meeting of the U.S. Advisory Committee on Immunization Practices ACIP and recognized as the most common cause of hospitalization in U.S. infants. With extra results of the pivotal trials Nirsevimab is positioned to play an essential role in achieving the greatly needed all infant protection against RSV.
Advancing to Slide 12, you remember that we accepted the challenge to run a COVID-19 efficacy study at a time where many people had already been infected or were starting to get vaccinated during the first campaigns. Yes, we're not the first, but we knew the recombinant protein platform was not built for speed. However, it allowed us to include a vaccine based on a variance into the Phase 3 study and to test for efficacy in an Omicron world. Results were published recently for our beta containing vaccine clearly underlining the strength of our science and other combinant platform. Why beta? Well, because it allows for a broad cross protection across a number of variants of concern. As we said many times, this is not a financial place for us. The profile of our recombinant booster vaccine makes it an interesting solution for payers given the efficacy and the safety. Whilst authorized, a recombinant booster could play a meaningful role.
So let me close on Slide 13 with the recent progress of our CSR strategy. We launched the Sanofi Global Health in April 2021 during the pandemic, and it is clearly picking up pace now. The model of Sanofi Global Health is simply unique. It is the first and only global initiative to provide the access to a broad portfolio of medicines in so many countries and across so many areas using its own brand. We presented our ESG emissions at a dedicated investment event earlier this month, and Sanofi Global Health was recognized as a flagship initiative by attendees, by those that were at event as well as by the leading ESG building agencies. To sum up, as you can see, our scientific and commercial agenda is moving at speed and so is our commitment to society. I'm very proud of all the progress made and with that, I hand over to Bill for his update on Specialty Care.
Well, thank you, Paul. Moving to Specialty Care I'm excited to discuss the stellar performance in Q2 where all franchises as you can see are growing. Sales exceeded €4 billion, making Specialty Care Sanofi’s biggest GBU in the quarter growing at almost 22%. This quarter the core driver of performance was once again Dupixent with its outstanding sales across geographies and approved indications, and the recent addition of EoE in the U.S. Rare disease emerged with double-digit growth in the quarter, driven primarily by continued patient accruals in addition to favorable phasing, which are typical for this business overall throughout the year. However, we do not change our longstanding trajectory of mid-single-digit growth for this attractive franchise. In oncology our launch momentum continues for Sarclisa as we look forward to the additional potential growth opportunity in first line based on the IMROZ pivotal data read out later this year.
Moving to Slide 16, let's take a closer look at Dupixent performance in Q2, where we see a meaningful step up in sales from Q1 2022 depicted on the graph on the left. With the growth rate almost 40% compared to Q2 2021, we see the published sales figure benefiting from continued increase in underlying demand and the stronger U.S. dollar. These effects together have added €720 million in incremental sales versus Q2 2021. As Paul highlighted already, in Q2 alone we added 150,000 eligible patients and expanded into GI with the approval of eosinophilic esophagitis, where Dupixent is the first and only medicine indicated to treats the disease. Additionally, progress has been made to address the need in the pediatric population, where the well-established safety profile of Dupixent is an important differentiator.
Turning to Slide 17, you can see we now have five positive pivotal trial readouts in the pediatric population, substantially increasing the number of eligible patients for Dupixent. This achievement is based on a robust and ever growing safety database across Type 2 inflammatory diseases where Sanofi and Regeneron continue to generate a compelling body of safety and efficacy evidence compared to new market entrants. We believe this further elevates Dupixent's profile to be the preferred treatment choice with physicians, payers, and patients.
Shifting focus to another leading franchise were blood disorders, we presented two late breakers on our priority assets EFA and fitusiran at the ISTH Conference earlier this month. While closely engaging with the members of the hemophilia community and specifically the physician experts in the field, we highlighted the strong scientific evidence for our innovative hemophilia treatments with their potential to raise the bar for both efficacy and treatment burden. We have highlighted the key data for EFA on this slide, looking first at the primary and key secondary endpoints. The primary endpoint was met as the median AVR was zero, with an interquartile range of zero to 1.04. Using a model based mean, the ABR was 0.71. These impressive data do not come as a surprise to investigators, but rather fulfilling the expectation to be a highly efficacious treatment.
The key secondary endpoint depicted on the right compared the intra patient ABR between prior FVIII prophylaxis and EFA prophylaxis. The mean ABR for the prior FVIII prophylaxis in the patients that participated in the pre study was 2.96. With EFA prophylaxis however, the mean ABR was 0.69, an impressive 77% decrease in the mean [Technical Difficulty] more than half of the number of infusions that they were doing on their prior prophylaxis. Ultimately EFA offers a significant decrease in patient treatment burden with strong levels of protection and lower mean ABR. Based on the data, we see EFA creating a new class. We believe this is a high efficacy class offering superior efficacy above any product that there has been in Hemophilia A and anything that we see in development, near normal factor levels for the majority of the week and true once weekly dosing. This new standard of possibility I would call it is just starting to be appreciated and opens up EFA to the €5 billion factor therapy segment which represents 70% of the overall Hemophilia A non-inhibitor market valued at €7.4 billion. With that I hand over to Thomas to update you on the vaccines business.
Thank you Bill. In Q2, we continue on our strong trajectory of Q1 and delivered 8.7% sales growth. As the COVID pandemic progresses, we see a recovery of the booster vaccines and travel franchises across all regions. Our PPH franchise also demonstrated good performance. We experienced limited impact from China regional lockdowns, so growth in the rest of the world and Europe, more than compensated for the expected decline in reported U.S. PPH sales that is due to the solid uptake of vaccines. As explained before, we do not report sales of vac series. We do really share profit in other operating costs. And the quarterly performance of meningitis and influenza franchises, including some phasing ailments in Q2.
On the next slide, I'd like to mention a significant milestone that took place in June. The U.S. Advisory Committee on Immunization Practices ACIP, made a very important recommendation to enhance protection of their senior citizens against influenza and its consequences. The committee reviewed large sets of data available for every influenza vaccine license in the U.S., and they recognized that a standard dose of flu vaccine was not optimal to protect seniors above 65 years of age. That recommendation for the elderly population was updated. It includes now Fluzone High-Dose and Flublok and the abundance of data showing the benefit of Fluzone High-Dose was especially highlighted. This important step on an influential immunization recommendation is key to raise the bar for influenza immunization in people above the age of 65. And I'm glad that more seniors in the future will benefit from protection beyond flu, against the severe consequences of influenza, such as pneumonia and cardiovascular events.
Now, as we're approaching the northern hemisphere [ph] of 2022 influenza seasons, some uncertainties regarding possible COVID-19 created disruptions [indiscernible] do remain. However, I also want to reiterate that we expect another year of record flu sales, thanks to our strategy to focus on high value vaccines that provide improved protection. With that I hand the call over to Olivier.
Thank you, Thomas. Moving now to General Medicine on Slide 21. The execution of our strategy continue to deliver with core asset growing 6% in Q2, where we continue to gain market share. Total GenMed sales decreased 4.1% to €6.6 billion also due to the impact of VAT divesture and the consolidation of EuroAPI third party sales. Adjusting for these GenMed sales decreased 1%. Sales of non-core assets were down 8.6% in the quarter and mainly reflected expected VBP related impact on Lantus and our legacy oncology portfolio in China. In the U.S. Lantus sales are affected by the overall erosion of the Basel insulin market. Second, product divestiture which are key to our ongoing strategic streamlining efforts. Excluding the impact of divestiture non-core assets were down 6.7%.
On Slide 22, I'd like to focus now on the performance of all costs set in the second quarter. Similar to Q1, Lovenox sales decreased 10.9% in Q2, reflecting less COVID-19 related demand and also an increase in biosimilar competition. Toujeo sales were up 2.4% in Europe and the U.S. partially offset by the expected impact of the implementation of the VBP for insulin from May in China. Total glargine sales which include Toujeo and Lantus, were down 24% in China in Q2. A 2021 full year results, we expected that total glargine sales in China would decrease around 30% in 2022. I'm pleased to announce that as of today, we expect 30% not to be exceeded. In April, at ATD Congress, we presented positive results of InRange, a head-to-head study comparing Toujeo and degludec in Type 1 diabetes using timing range as a primary end point. These results will help us to close the gap in Type 1 diabetes versus degludec and could strengthen Toujeo's position in Type 2 diabetes.
We are particularly pleased with our Transplant franchise, which delivered a strong performance. Sales are driven by Rezurock as well as by the strong performance of Thymoglobulin. Rezurock has achieved a robust adoption with more than 1,000 patients treated since launch corresponding to around 25% of the current addressable market and demonstrating excellent persistency rates. Praluent sales grew 148% in Q2 driven by continued growth in Europe as well as the ramp-up in China where Praluent is included in the NRDL since the beginning of the year. Sales growth also profited from a gross-to-net true-up in the U.S. related to earlier periods. Excluding this effect, sales of Praluent grew close to 50%. Plavix delivered strong growth in China, with sales up 19.1%. This consistent strong performance in China confirmed the success of our participation in the VBP program and the recent successful renewal. Global Plavix sales were flat in second quarter due to the lower sales in Europe and the mandatory price cut in Japan beginning of April.
Advancing to Slide 23. We continue our efforts to provide access to insulin to those most in need and not only in developing countries but also in mature markets. Since the start of this month, uninsured people living with diabetes in the United States can obtain insulin such as Lantus, Toujeo, Admelog [ph] at U.S. $35 for the 30-day supply through our Valyou program. This is a significant step forward from our previous value offer of U.S. $99 for a month's supply. In 2021, the Valyou program was used more than 97,000 times, providing many people with diabetes in the U.S. the medications they need. With that, I hand the call over to Julie.
Thank you, Olivier. In Consumer Healthcare, we continue to execute on our three strategic priorities to deliver consistent growth. As you can see on this page, on a 12-month basis, we are growing above market for the third quarter in a row. It is rewarding to see that our team's hard work is delivering results while striding along towards our standalone structure, greatly contributing to our agility to capture market opportunities and respond to competition, and while also keeping simplifying our portfolio. We're now down to 140 brands from over 250 18-months ago. While we have to compensate for some top line losses in the short-term, the greater focus and the increased resource and budget allocations behind our priorities are clearly paying off.
Regarding the Cialis Rx-to-OTC switch, as you know, the FDA placed our actual use trial on clinical hold in May. Since then, I'm glad to report we had a very constructive meeting with the agency. And importantly, we received clarity from them on the path forward. We are very encouraged by that interaction and we'll continue our conversations with the FDA in the coming months with a goal to finalize our next steps. Trust our motivation to progress this project remains unchanged because Cialis switch can provide improved access to safe and effective medicine for this underserved condition. And from a business opportunity, the size of that opportunity remains unchanged.
On the next slide, moving now to Q2 performance, I'm very glad to report that despite the strong Q2 last year, we delivered over 9% sales growth. The like-for-like organic growth meaning excluding the impact of the product divestments in the same period is a double-digit growth of 10.5%. Pricing contributed to 3.5 percentage points of this growth. With the COVID-19 pandemic, the Omicron variants often causing symptoms that are very similar to strong cold symptoms, this quarter was marked by a cough and cold season that lasted longer than usual. We were able to respond quickly and get our key brands in store. And as a result, we grew almost 75%. Also, the Digestive Wellness, our biggest category, we maintained strong momentum reaching again almost double-digit growth. I'm very proud to observe the strength of our business with growth coming from all categories and all geographies. With that, I hand it over to our CFO, Jean-Baptiste.
Thank you. Thank you, Julie. As highlighted by my colleagues, we continue to deliver strong top line results derived from our key growth drivers across our businesses. Turning now to business EPS, I'm pleased to report a 16.7% growth at constant exchange rate. Let's look at the drivers of this great performance, even slightly accelerated when comparing to the 16.1% growth reported in Q1. As guided, the gross margin continues to improve versus last year now reaching 74.1%, thanks to favorable portfolio shift to Specialty Care products and efficiencies. SG&A is growing considerably less than sales on a lower effective tax rate of 19% creates additional support. I would like to highlight that R&D keeps growing at a significant pace due to our expanding pipeline and platform acquisitions, such as TBIO, Kadmon, Kiadis, and lately Amunix. Other operating income consists mainly of the original alliance balance this quarter.
Moving to Slide 28 and taking a year-to-date view, sales grew 8.4% versus H1 2021 and our BOI margin improved by 110 bps putting us on a clear trajectory to deliver on our 30% margin target in 2022. We increased our R&D investment by more than 13% in the first half of €3.1 billion from the development of our priority assets on our latest bolt-on acquisitions. A quick update on our savings program on Slide 31, we have reached the 2.5 billion the last six months, especially driven by operational excellence in the area of cost of sales, as shown by the nice improvement in gross margin during the year. This still includes around 200 million of pandemic-related savings that we said that will come back over time. So our ambition remains to achieve the underlying 2.5 billion by year-end. And you might wonder what did we do with this 2.5 billion savings. Well, turning to Slide 30, what I would like to highlight, again, is that all of the OPEX-related savings were reinvested. In fact, total cumulative OPEX grew by 500 million due to investments in R&D and selling costs. Most of the savings still to be generated in the second half are going to be allocated to key programs in R&D.
Let's now move to the outlook on Slide 32 with a very positive margin development in the first half. We still have a bit to go to the 30% target. On the top part of the graph, we are highlighting the drivers. The main contributor will be the Dupixent growth accretive to group BOI margin starting from this year, as pointed out before. Other contributing factors will be capital gains from planned divestitures, which we estimate to be around 350 million in the second half, meaning that the expected total amount of 600 million for the full year remains unchanged. The restructuring of the alliance around Libtayo that closed earlier this month will also have a positive effect, especially due to the accelerated reimbursement of the development balance associated with Regeneron and Sanofi's antibody collaboration.
As announced early June, Regeneron will increase from 10% to 20% the share of its profit that is paid to Sanofi to reimburse Sanofi funded development expenses. This will apply also retrospectively to Q2 and will start to be booked in Q3. On the other hand, there are also some negative drivers to keep in mind. We have guided for 2022 gross margin improvement to be weighted to the first half of 2022. In the second half, underlying improvements are expected to be offset by macroeconomic headwinds such as increased cost of energy, transportation, as well as labor costs. The VBP on insulins in China will also negatively affect the gross margin for that part of the business.
Regarding H2 sales expectations, Specialty Care and CHC will continue on their respective growth trajectories with more moderate credits. GenMed growth will be more pronounced towards the end of the year, and we continue to expect another record year of sales with a split 60-40 between Q3 and Q4 due to our excellent time to market. So getting to the last slide on the full year 2022 guidance. We are upgrading our expectations on EPS growth to around 15% at constant exchange rate and foresee a positive currency impact of 7.5% -- 8.5% based on July actual rates.
To wrap it up, eight quarters of growth, another quarter with double-digit EPS growth; sound execution along the plan we laid out; important achievements were made during the quarter; EuroAPI shares were listed in May and the stock is performing nicely; three more approvals received for Dupixent covering all age groups in AD now in the U.S.; efanesoctocog alfa was submitted in the rest the second priority asset to be filed following Nirsevimab in the EU in February. With the transformation progressing, we remain on track to achieve our 30% BOI target on double-digit EPS growth in 2022. Let's open the call now for Q&A.
Thanks Jean-Baptiste. [Operator Instructions]. So we will now take the first question.
Yes, the first question will be from Wimal Kapadia from Bernstein. Wimal?
Great, thank you very much for taking my questions. Wimal Kapadia from Bernstein. So first, can I just ask on margins, please. So Jean-Baptiste, you talked about the renegotiation of resulting in a faster payback for Dupi development. I mean this seems like quite a smart move because the 10% of profit is quite meaningful on our methods of a few hundred million euro next year. So my question really is what impact this is going to have on margins in 2H 2023 and then the 2025 target, how should we really think about this change in the context of the greater than 32% target in 2025, is it fair to assume now you'll be comfortably ahead of this target because of this and you can really potentially expand margins next year as well through the patent [ph]? That's my first question.
My second question is just on tolebrutinib. It seems like you've recruited the majority of patients required. So my question really is, do you need to actually add more patients on the study or do you have enough to file regardless of the clinical hold being lifted? And then just in terms of commercial implications as a result, it's quite a competitive market, so has the safety signal really changed your thoughts on the commercial potential?
Is this the one question we asked people. [Multiple Speakers]. Thank you so much as always to kicking it off. Thank you also for the compliment on the construction of the deal with Regeneron. I think it worked out very well for both parties. JB, so where do you stand, is it in the numbers, I think people want to know.
Yes. Thank you, Wimal. Effectively, we're glad to have the simplification of our work with our partner. This amount of R&D we invested initially was due to be paid on a very long period of time, and this acceleration is quite meaningful and will effectively impact positively our P&L in 2023, 2024, 2025 and it's really nice. You also know that we look at the royalties out of the sales, the global sales which will come on top of that. So the question is, is that going to expand our margin or change our targets. No, Wimal, as I said several times, every opportunity we see to increase or improve our P&L or increase our margin, we are reinvesting in R&D. That's where we are. That's what we want to do. That's -- we are here for that to go for innovation and invest in our long-term growth by really being true to this commitment of investing in science.
Thank you. Well said. John Reed, tolebrutinib, will we have enough patients to file?
Yes. We're quite far along with the relapse and remitting studies -- 1 and 2 and the secondary progressive. The primary progressive, we're still enrolling there. We've got more than 2,000 patients currently on study and we continue to enroll around the globe with the exception of the United States and a couple of other countries. So we feel like we'll still have the recruitments completed by the end of this year. So we haven't changed our time lines at this point.
Just to contextualize these, we're -- we were cruising along quite well, and we're about 2,000 patients into the studies. And then in April, we experienced what appeared to be a couple of cases of hospital drug-induced liver injury, and that prompted us to make changes to the protocol in May that removed underlying risk factors for injury because these patients all -- for the most -- the majority of them had what looked like underlying conditions that could have been contributors. And we also increased the frequency of monitoring to every two weeks as opposed to every month. And we're quite confident that, that would then reduce the risk that these sorts of events might be seen again in the future and are proceeding accordingly. We've enrolled it close to 200 patients so far. They're all doing well. And the patients that we had on study for -- who had been now on therapy for quite some months are doing fine. So we're quite confident we'll get through this. We've got a checklist from the FDA of things that they are asking for in terms of information, and we're checking off that checklist and help add back to them by the end of September and move forward.
Thanks, John very clear. Bill, profile, where we stand?
Yes. Look, we see this still being the best-in-disease product for the reasons that we've said from the beginning. It's a brain-penetrant BTK, which we think is really important. We know that from the long-term study, the extension that we have self -- 88% of patients that remain on therapy. 85% of patient’s relapse-free at 72 weeks and then 85% reduction in gangrene [ph] enhancing lesions. That's still a profile which is great, and we expect it to be a multibillion euro blockbuster.
Well said, Bill. Okay, next question.
The next question will be from Jo Walton from Credit Suisse. Jo?
Thank you. My question, I have one on Dupi and one -- just a general one on U.S. healthcare reform and anything that you'd like to tell us about your perception of what seems to be likely to happen in the U.S. But my question on Dupi is whether you can give us any help on sales by indication, you talk a lot about the atopic dermatitis penetration, but you don't tell us so much about the asthma penetration, so just so that we can see as we go forward, where you could get particular growth? And if I could just adds to that, is there any region or indication where you're getting to a level that governments are now thinking, well, this is such a large drug I can do with the [Technical Difficulty] so is there any concern that you're now getting to that sort of level with higher price erosion likely? Thank you.
Thanks, Jo. Good to see you, at least from a distance at ISTH. I was hoping for an philosophical [ph] question, but okay. Dupi, Bill, why don't you take that, sales by indication and the penetration in another indication?
Yes. Thanks, Jo. We won't break it out by indication. As we've said all along, AD, it's been the first. It's the market that's -- the indication that's the least mature based upon us being the first product there. And there's still plenty of growth and we're still about that 9% penetration rate in the U.S. So we still see that as being the biggest indication.
Now as you looked at asthma, it's about 19% biologics penetration. As we said in the past, we think that can go up to about 30% or 40%. We've reported on previous calls, from a respiratory perspective, we are the leading asset in respiratory, bar none. And I think just to provide the perspective, we hear this quarter every now and then a question about a competitor getting an indication. And I think you have to look at what we presented in the call here and what Paul talked about, just with what we have approved this quarter, it's an additional 150,000 patient opportunity. And that is just a sampling of the additional age groups we're going into, an additional indication. So there is plenty of room for this to continue to grow.
Now growth clearly gets attention, but this is a product with demonstrated efficacy that we haven't found anyone in the world who's pushed back on the benefit of what this product has to offer. So with additional competition, etcetera, with additional indications, there will always be additional pricing discussions, but we've planned from the beginning for this to be a multi-indication, multi-country product. So we feel that we've handled it extremely well, and we don't expect anything above any kind of pricing erosion that would be typical in the space.
Yes, thanks, Bill. I mean the health economic data that supports Dupi and beyond every indication is absolutely incredible. So the unmet need is massive. So okay. Jo, the other question I think was around the U.S. and reconciliation. So maybe just take a step back for a second. So we've come a long way from HR3 to the current reconciliation package that's on the table. Remind you, it's not done yet, right. You probably are even more aware of some of the technical processes that we have to go through in the U.S. or at least this type of Bill has to go through. We've not even got to the Bill back there, yet for those that understand how the technical opportunity there. Either which way, it's not good for patients, it's not good for affordability for patients, not good for innovation in general. Let's be clear about that. And I think we all know that. I had the opportunity to sit down with close to nine senators in one-on-ones last week to get our heads around it. So I'm putting my energy into it and everybody is trying to help remind people that it's not where it needs to be. It is not doing what it's supposed to do in terms of helping patients through innovation and affordability, I mentioned.
As for us, as a company, of course, we have a little less exposure in the United States in general than many of our peers. And then if you -- because our portfolio is a little diverse, you see different levels of technical exposure. And I think in general, we would say that we -- that it's one of those things that we just have to take. Of course, we have not much choice. We'll find out what it says next week. Not good for patients. Not good for innovation, frankly, but we'll find a way, as always. So thank you Jo.
The next question will be from Graham Parry from BofA. Graham?
Great, thanks for taking my questions. So firstly on efanesoctocog. I think, Paul, you said and the physicians on your call said no reason for a factor patient not to switch. The only reason perhaps that there could be so if they can't get reimbursement for it. So could you just help us understand your pricing and access strategy that you're thinking about efanesoctocog which you had towards launch? And then on tolebrutinib, I think, John, you just said a couple of cases of drug-induced liver injury. It sounds like a very low incidence. Is it fair to assume the incidents here that you're seeing in the trial is below the evobrutinib Phase 3 trials where around 26% of patients saw raised liver enzymes and 11% discontinued due to liver enzyme elevations. So in short, do you still see tolebrutinib as potentially differentiated on liver profile versus evobrutinib? Thank you.
Okay. Graham, thank you. We'll come to John in a moment. As for efanesoctocog alfa, and we look forward to sharing the brand name with you when it's approved, it's an interesting one, right. We haven't got to sharing price yet, but you jump in if you want to comment, but the efficacy is so good. My own time at ISTH will really reinforce that. The important thing to remember is what worked against us with [indiscernible] sale uptake works for us with efanesoctocog because patients, if they want to move in this market, they will move. And so they'll get switched, they get initiated. The momentum is patients wanting as normal life as possible. And so we are very excited about what we'll do with this meds. Bill, do you want to add anything?
No, I think that's right. I think a couple of things there, favorable as well, as what we've seen globally is still a recognition for innovation. And clearly, when you looked in the hemophilia space, don't see anything in the real immediate term that looks to be as innovative as EFA. Now if the market becomes a purely efficacy-driven market, there's really only one choice because there's really only one product that has ever gotten you close to near normal for the majority of the week. So we have high expectations, we're excited about it. We believe that there will be a path to reimburse for it, and we believe that patients will want to -- and they will seek out a higher efficacy option.
Thank you, Bill. John Reed, how about liver enzymes?
Yes, Graham, you're correct there. The frequency which we've seen these possible cases of drug-induced liver injury has been very few patients, a fraction of a percent, whereas with evo, they've had double-digit numbers of percentages of patients that have had to go off study because of liver transaminase increases. So we still believe that we have the strongest safety profile. And the other thing is that these cases always occur within the first couple of months of treatment. So the monitoring is important to do potentially in the beginning of the therapy. But after patients have been on therapy for a couple of months, if they haven't had one of these issues, they're going to be buying, it looks like. As I said, we have 2,000-plus patients still on study and up to this point, all well. So we think we've got a good plan for going forward with reducing the problem, and we'll work through getting this resolved with the FDA as expeditiously as possible.
Sorry, the line just cut there. Did you say a few percent versus double-digit for evobrutinib, sorry I just wanted to clarify that?
It's at a fraction of 1% that's what he said. [Multiple Speakers]. We have taken a few questions on it. Honestly, I mean, let's be really clear. I think we made the right changes to the protocol. We feel very good about that was to find information to the regulator, and it's really basically just the U.S. And then we're heading to get this corrected with the plans come off hold in Q4. That's what we're working towards. Okay, next question.
Yes, next question will be from Richard Vosser from J.P. Morgan. Richard?
Hi, thanks for taking my questions. Perhaps switching topics maybe to vaccines, first of all and the flu supply. Maybe you could give us some context on the amount of Fluzone High Dose we should anticipate in the -- in Europe and U.S. this season. Do you have enough capacity for say 60 million doses this year? And then a couple of questions or one question, sorry, on consumer. Perhaps you could give us some context on how you see the market growth for branded products going forward in Q3 and Q4, and are you thinking people will downtrade as we see the economic crisis may be worsening a bit, and if I can be cheeky, Tamiflu wasn't mentioned with Cialis, so just what's going on with Tamiflu? Thanks very much.
Okay, good. Thank you. Maybe I can go to Julie in a moment, but Thomas, Fluzone High Dose volumes.
Yes. So overall, we're in a very good spot from a flu supply perspective. Clearly, supply is not going to be any problem as it's not been a problem for the past two years. And you know very well that we built capacity a few years ago to feel very confident. And it comes at the time, as I mentioned, during the position of the ACIP recommendation. So that's why we feel strong about delivering a record flu year this year, which comes on top of significant growth over the past few years as you know very well. So it's not a small feat. And I expect, therefore, a good Fluzone High Dose delivery both in Europe and in the U.S. So we are in shape and of course, that can be seen, this good level of supply by the indication of the fact that when you look at the timing, we expect roughly even it's a bit early to be visiting about 60% of the flu second half of the year to be in Q3 versus 40% of it being in Q4, which reflects the quality of the supply we're getting.
Thanks, Thomas. It's great work actually by the vaccine team -- season. So Julie, are people going from branded -- will people go from branded to generics with the pressure on people's pocket expenses and maybe a quick comment on Tamiflu?
Thank you, Richard, for your question. So first of all what we've seen in healthcare is that share of private labels have been relatively stable in the past two years. However, with increased inflation pressure and economic downturn, we are very conscious that consumers will have to make choices more than in the past. But we -- again, we've seen that in our area consumers and patients make the least compromises. And again, health is definitely most important. And efficacy and very strong -- is a very strong loyalty driver even -- again, even more so in healthcare. As a result, the quality and the value of our brands is what really makes a difference. And that's what we're bringing forward, and here I'm very confident. On Tamiflu, nothing has changed from the last quarter is that we are waiting for the flu season to be able to start the new testing. So no news on Tamiflu so far.
Yes. And thank you. Thank you, Julie. [Indiscernible] in the pharmacy. Okay, next question.
The next question will be from David Risinger from Leerink.
Yes, thanks very much. Can you hear me?
Yes.
Great. So congrats on the performance. I have questions on tolebrutinib and amcenestrant. So with regard to tolebrutinib, have you already enrolled enough U.S. patients in order to be able to deliver a sufficient U.S. regulatory filing, and what is your current estimation for timing for top line Phase 3 results from your global RMS studies? And then regarding amcenestrant, is there an opportunity to pursue a more targeted approach with ESR1 mutant patients with greater likelihood of generating compelling efficacy results? Thank you very much.
Okay. David, thank you. I think we've touched already a little bit on the tolebrutinib question on enrollment for but John, do you have anything extra to add?
I just said we -- the RMS studies, we expect will read out the end of next year. And then the progressive studies would be the following year, which is pretty much on par with what we had originally forecasted. At this point, we are -- it is a global trial. It is actually our new series of trials, and this is the largest campaign that's ever been orchestrated for an MS drug. So it is global. We do feel like we have the U.S. sufficiently covered. And I forget, what was the other...
Yes, amcenestrant, do you think we need to look at an ESR mutation to show greater efficacy or should we just focus on the adjuvant setting where the opportunity is?
Right. Well, actually, you'll be obviously the ESR mutant versus wild-type data at ESMO in terms of what we show in the late line setting. But in terms of the -- where we really have always felt the sweet spot to this mechanism in the adjuvant space, we're quite comfortable with the profile there, where there's a very small percentage of mutations in that setting and most patients still have wild-type receptor. And -- but we're active events, both wild-type and mutant receptor. So we sort of have our bases covered, I would say.
Okay. Thanks, John. Next question please.
Yes. The next question will be from Mark Purcell from Morgan Stanley.
Great, thank you. Thank you very much for taking my questions. I have two. The first one on R&D investment, how should we think about the level of investment in R&D going forward over the medium term and how should we think about investment discipline here, I mean, Sanofi has now got so many new platforms to choose from delivering new medicines through the government [ph] engine so a nice problem to have, but at 15% of sales in terms of an R&D margin, is a nice offset potentially with gross margin, but it would be interesting to understand your level of ambition there in terms of increasing investment and future innovation? And then the second question was on CEACAM5 ADC. Can you help us understand your ambitions beyond lung cancer as the understanding of ADCs, I guess, is changing quite a bit at the moment and what the key data points are to watch out for over the next 12 months in lung cancer?
Okay. Thanks, Mark. So John, I think back to you actually for that. Maybe you'd like to make a comment JB on R&D investment levels.
Yes. So there's no magic number on maybe by the way you would consider consumer health within the equation because it is in consumer. This is R&D driven. Our vision is clear, it is to increase within respect of our guidance is to increase as much as we can to spend on R&D. That's what we are doing. I know that sometimes it's -- I see the instances that some are not believing us that we -- when we said we would add about 0.5 billion this year in our P&L, that's what we are doing, and you see it in Q2. It's a clear proof point of our decisiveness in terms of being true to this commitment. So I think I repeat the magic number, but the direction is clear.
Thank you. Thanks, JB. John, CEACAM5 ADC beyond one?
Yes. So we are pursuing that molecule for other CEACAM5 positive tumors, gastric, breast, etcetera. Still collecting data in those contexts. And then, of course, in lung, we're also in Phase 2 studies in frontline and coupled with pembro and exploring whether we can move into the frontline setting with that. I thought the question was more broad about modalities in general. And if that's the case then, indeed, we have quite substantially expanded and modernized our drug discovery infrastructure with new modalities, some of that organic, a lot of it through bolt-on acquisitions. But our ability to support those from a CMC manufacturing, I feel we're quite confident we've been able to leverage our capabilities, for example, in microbial production of insulin to support the Synthorx platform, synthetic biology, which is the COWARK [ph] platform to support the mRNA [ph] platform to support the antibody platform where, again, we use microbial species and all that’s really been able to just kind of modify what we had available at our Frankfurt site there. And then the other biologics platforms that we've been able to adapt to what we've had there. And then we're really leveraging a lot of capabilities in vaccines for some of the others, for example, the AAV platform, making viruses, live [ph] viruses for vaccine to something our colleagues there have known how to do for years, and we're actually doing our GMP production in the vaccines facility there and leveraging that. And of course, the commitment to the mRNA platform that the vaccines colleagues made will plug right into that for the therapeutics as well.
Yes. Thanks, John. Let me try and connect those changes together actually because it's really an interesting question. To JB's point, our priority is to deliver our financial guidance increments. And we work really hard to reallocate R&D within that. So let's just be really clear because that's the goal within what we've committed. And outside of that, the platform piece, we made a decision with John and the team to take a platform base, one of the reasons why we have 13 shots on goal in immunology, more than half in antibodies. So we get a really efficient entry to have a shot at least proof of concept and beyond. And I think we knew that was probably going to be our best way. The real magic when we start to convert the platforms. And that's why as we bring our [indiscernible] in say on top of antibodies it starts to help us get to that two little piece. So there is individual platform opportunity and volume at scale as we get into our stride, I think we're not far off. Then there's a convergence of the platforms that bring a lot of opportunities. And we work really hard as a team, the people on this table and beyond, to make sure that we can redistribute -- deliver guidance and redistribute to R&D. That's the job, and that's the final job. Okay, next question.
The next question will be from Keyur Parekh from Goldman Sachs.
Hi, thank you for taking my questions. John, if I could just confirm your answer to David’s earlier question, are you confident that you have enough U.S. patients given the extra patients you are recruiting on the tolebrutinib program kind of elsewhere around the world for it to be okay from an FDA perspective? Secondly, kind of just looking at the consumer health business, clearly, kind of demonstrating very strong execution and continued growth. But your guidance assumes kind of much more deceleration in growth towards the second half of the year. Just wondering, beyond tougher comps, is there anything else you are seeing from an end market perspective that is driving or should we think of it as classic Sanofi conservatism on this guidance over here? Thank you.
I didn't quite get the second question, but someone is going to repeat it to me. On the first question, John, I'm not sure there's much more to add on the tolebrutinib piece. I can understand everybody's level of interest. Let's just fast recap, right. We have adjusted the protocol, we were in good shape. We get the questions. We get the partial hold. We know what we need to do to come off it. We have to get that done. We come off it in Q4, and we get on with it. So if there's anything more to add to that, any point.
The word partial, I think, is very important because it means all the patients who had already been enrolled and we're 60 days plus past the overall study, including in the United States. So all those patients continue to be followed and until the outcome of the study. So I think just remember that. Also, we didn't reemphasize here, but it probably merits that the liver injury cases we saw were reversible. Nobody went to transplant. Nobody died. I mean they were picked up by a routine monitoring. So we feel like if we can address this, we've got to just give the FDA their checklist of things that they want as additional returns.
JB, are you being conservative?
Okay. Are you having a go at me. I have more insight than you have, and we don't see meeting outside that you can see. So it's very transparent -- we gave for the second half of the year. And we're raising our guidance. That summarized it, and so we're conservative, yes.
Okay, next question please.
I think there was a question on consumer and on how we see the remainder of the year. I think what's important -- so first of all, thank you for saying what you said because, yes, not so long ago, we were losing share for a while. And it's really since Q4 last year that we've been catching up on a 12-month rolling basis. Looking ahead, after this fifth I think, strong quarter, we expect the market to experience a more normalized growth because we have to keep in mind that we had a high market overall, and we did to a higher 2021 comparison. But we still have the ambition to continue to grow in line or slightly ahead of the market. I hope that answers your question.
Yeah, thank you. Well said. Okay, where are we.
Yes. Next question Tim Anderson from Wolfe.
Thank you. A couple of questions on Dupixent, and it's really on China. In China, there's at least one local lab product moving into Phase 3. And in certain categories, we've seen fast follower products kind of cause headaches for multinationals. So I'm wondering how much China is in your €13 billion forecast for Dupixent and just in general, how are you viewing local market competitors that you see potentially emerging nearer term? And then second question on tolebrutinib. Just back on LFT elevations, I know the frequency was lower, any of those Grade 3 or Grade 4, and have any other countries besides the U.S. put the drug on clinical hold?
Okay. Well, that I am going to throw to you Bill -- in China, I think at this point we've answered all the tolebrutinib questions. I understand, as we get more information, we'll share with you as we get into Q3, but getting off the whole is a priority, we'll update you. So anything to add on China, and China’s part of the -- 13 billion and/or the fast follow-up to market?
It is. It certainly is long. I think what we've also said is that we expect it to be a blockbuster in its own right in China. So the opportunity there, we think, is still a very significant. We're just at the beginning. Just like we are everywhere else in the world, we're at the beginning in China. We've seen some really great uptake, additional indications that we've been successful with, and positive data readouts that’s really with some -- another asthma trial there. So yes, we think that within China, any follower is going to have to, first of all, compete against the product, which has kind of opened up the AD market in China. We expect that -- we have high hopes that there will be a recognition of the IP that exists within China. And we think that the expertise that we brought to the market will be recognized. And as we get more information on it, we're not even certain if anything will come at this point. But we -- as I said, it's baked into our 1 billion-plus forecast that we have in the way point of 13 billion that Paul said.
Yes. Maybe I think started really well, I mean really well.
Unprecedented start really for a biologic.
Maybe I can we should share timeline launches in China we'll get in a moment and it's a rocket ship. And then even after the lockdown, we haven't had a chance to comment about it today. But patients coming literally spread back out and getting to see the dermatologists. And so it bodes well, bodes really well. Okay, next question please.
Yes, the next question will be from Laura Sutcliffe from UBS.
Hi, thank you for taking my questions. I have a question on rilzabrutinib, please. Could you just talk to the commercial potential for that in ITP, given that we've seen a molecule terminated in this space elsewhere today, albeit not an oral, even though there was no negative data? And secondly, could you maybe just tell us why you've discontinued dupilumab in peanut allergy? Thanks.
Okay. Well, John, I'll come to you on peanut allergy. And Bill, maybe just a general comment about dose overall approach and then maybe I think you answer…?
Yes. Thanks for the question. So look, let me start with ITP. There's about 25,000 chronic ITP adults in the U.S. that are eligible for the second line plus treatments after steroids. So again, coming fresh off of ISTH and hearing from the physicians, there was a lot of enthusiasm about rilza in the ITP space. They clearly see there's an unmet need there. And they like to be a fast onset of action and durable effect that took place. So we'll continue wait for the data, so to speak. But we see that as a nice potential. And also with rilza we've got a broad development plan. We're also looking at it in AD, looking at it in asthma, looking at it in IgG 4 way etcetera. So this is one of those products that we think is so fundamental, the biology that it gets us into a lot of spaces. Obviously, you've seen the BTKI and the effect in MS with tolebrutinib but we think rilza allows us to go to other places as well. So quite promising in ITP specifically strong data, fast onset of action, durable effect.
Okay, thanks Bill. John, any comment on peanut allergy?
Well, I can tell you that it's really difficult to do good clinical trials in that space. We did do some Phase 2 kind of exploratory work. Just decided it was not ranking as high on our strategic priorities. There's other places we could invest in. And so we kind of just let it stay there for now.
Okay, thank you. Okay, next question please.
Next question is from Gary Steventon from Exane.
Yes. Sorry. It is Simon actually, my apologies. Two questions not on tolebrutinib, thank you. Firstly, a follow-up on the margin question, if you could. I mean you're able to consistently deliver with the strong results despite your commitment to meaningfully increase your investment in R&D. I'm thinking just taking into account your prior commentary around meaningful Dupixent gross margin step up from 24, the Regeneron renegotiation you've just talked about earlier and your focus on high-margin offerings. I mean the question is really, when do you think you may be able to quantify more than -- in the more than 32% operating targets for 2025? And just a quick follow-on, can you quantify the remaining R&D spend that has to be repaid by Regeneron? And the second question is I was wondering if you could be willing to share your latest views on the [indiscernible] litigation liabilities with the first trial on firm early next year. I mean I appreciate it has become somewhat a defense attorney celebrity per se. I'm just wondering if you could tend to share your thoughts on your exposure in light of his remarks that Zantac could potentially draw from that? Thank you.
Okay. Simon, thank you. So let's start with JB and then get to Julie.
Yes. Sorry, Simon. I'll have just to repeat the same message. We will increase our R&D spend as much as we can if we have room to do it because you see our portfolio. You see a need for innovation, and we want to stand by this commitment. On the total impact, as an indication, I can tell you that we will not have finished to have this accelerated repayment to equally practice at least through 2026. So yes, it's a very significant amount of R&D that we will see coming back through the acceleration of the development balance. That's great. That means that we can invest in more innovation.
Thank you. Julie, do you make some comments on Zantac?
Sure. So first, I want to remind that Sanofi voluntarily withdrew the OTC Zantac from the market in 2019 and Zantac OTC products containing ranitidine remain off the market. Both the FDA and Sanofi have conducted investigations into levels of NDMA in ranitidine products. The FDA has stated that although NDMA may cause harm in large amounts, the NDMA levels that the FDA found in Zantac ranitidine from preliminary test barely exceeds the amounts found in common foods. Therefore, we at Sanofi believe strongly in our defenses. Sanofi contends that the plaintiff will be unable to prove that Zantac causes any type of cancer. Basically, the science does simply not support the plaintiff’s claims. So we're confident.
Okay. Bill, do you want to add anything?
I think Julie covered it well. There's no reliable evidence whatsoever that Zantac causes cancer. The amounts are stuff that's found in a lot of common foods, and we feel very strongly about our defenses. And also we acted responsibly -- more than responsibly at all times.
Okay, thank you. Next question.
Yes, next question will be from Simon Baker from Redburn.
Thank you very much for taking my question. Two if I may, one on vaccines and one on consumer. And also just a quick clarification on Fluzone flu record year, Thomas. Is that record year in terms of just value or volume and value? And the main question on vaccines, as you indicated that you have data for the COVID booster against Omicron Ba1. I just wondered this is still fairly early stage if you have any data against Ba4 and Ba5? And then on consumer, Julie, I wonder if you could give us a little color on the regional split of pricing. You said it was 3.5% overall. If you could give us any color on that, that would be very handy? Also, some of the moving parts within what was a very impressive performance on the gross margins, well, I'm assuming the pulls and pushes on that if you could give us some color, that would be very helpful. Thank you.
Okay. Thank you Simon. So Thomas, then record, we see split between value and volume, of course, and you heard it was added in Ba4 and 5 with David [ph].
Thanks for the question, Simon. It's been a while since we stopped talking about volume. So what we're really looking is how do we contemplate value. So each time we are talking about record full year, it's about sales. And especially, as we know very well, we pivoted from standard dose to vaccines a few years ago to deliver differentiated flu vaccines that provide protection beyond flu endpoint itself. So we're really -- and the market is totally recognizing the value of those products. And therefore, each time we're talking about a record value in sales. Your second question is about COVID-19, very early data is showing against Ba4, Ba5, early read, but shows exactly what we have seen against Ba1, Ba2. So I'm confident that the booster we will be providing to the market, if approved, has the ability to be a booster of use and of choice, as discussed before by Paul during his presentation. So we believe it's a good opportunity for public decision makers.
Thank you, Thomas. Julie, I'm not sure how you normally break price down publicly, if you choose not to share it's okay by region.
I don't think we usually share it. What I can say is that the majority of our portfolio, we can impact pricing. And that we obviously do it based on the actual raw material cost, the competitive behavior by region as well as the consumer elasticity, and all regions have increased prices.
Thank you. And JB, gross margin.
Yes. Well, the margin of -- in terms of gross margin is part of the business that we can reprice but the headwinds, it's maintaining quite well. We see that across the board on the regions. In terms of overall stability of the margin, of course, we cannot read through our current sectorial publication, the effective level of margin of -- that will be externalized more next year.
Okay. Thank you. Next question.
Yes, the next question will be from Seamus Fernandez from Guggenheim.
Yeah, thanks. Can you just -- hoping you guys could update us on Amlitelimab and the progress towards hopefully entering registrational trials. Maybe you can just talk a little bit about the differentiation that you see on that product as well. I know it's core to the continued attempts towards dominance in the immunology space. So love to hear your thoughts along those lines and when we might see data. I believe the first quarter of next year was the target, but I didn't know if we might see advancement into a pivotal sooner than that? Thanks.
Okay. Thanks, Seamus. John, why do we have the winner with…
Yes, let me maybe do the differentiation first and then cover where we are with aspiration to accelerate. On the differentiation of -- as you know, we're targeting the ligand, whereas others that are targeting the receptor. And there -- a reason to believe that could be better from the standpoint that the ligand is prevalent at lower levels and you have less problem really covering the full target and getting good target exposure, we believe. But more importantly, probably is that Amlitelimab is a non-depleting antibody. It doesn't kill the cells that express the ligand, whereas the competitor molecule that binds a receptor actually kills the cells. And we think over the long run, because it's a depleting antibody, that's going to be disadvantageous because among the cells that express that OX40 receptor are regulatory T cells, the immunosuppressant cells that you need for immune homoeostasis. We also think because that is a depleting antibody that activates complement another mechanism that that's probably why the computing molecule has shown evidence of infusion types of reactions with febrile episodes and other sorts of evidence of inflammatory responses in the first couple of injections. Of course, we don't have anything like that with Amlitelimab.
In terms of the acceleration, we are very much working directly with all the health authorities around the world to explore what is possible. We're still trying to work out the best path forward for meeting all the regulatory requirements not only around demonstrating efficacy but also the safety database that will be required, etcetera. We want to make sure that the study population does represent the diversity of patients that struggle with atopic dermatitis both in terms of what therapies they've experienced as well as, of course, the D&I types of issues around representation. So we're really working with the authorities to figure out how quickly can we deliver high-quality data. We will have more to tell you as those discussions and plans unfold.
Okay. So I think -- thanks, John. I think just mechanistically we have the advantage. I think we want to get there as soon as we can. You know we're ambitious. We told you that. We're looking for all the opportunities to do that and when we can confirm that we will do that. But it's going to be really important to make sure everybody else finds the full benefit of what this medicine can do and have the opportunity to be with the team until -- last week, and it's starting to get really exciting. So I really appreciate the question, Seamus. We have time for one more.
The last one will be from Peter Verdult from Citi.
Yes, thanks. Peter Verdult from Citi, two questions, just for Paul first. It's been three years since the play-to-win strategy was laid out. You're obviously continue to be very keen to highlight the absence of LoEs post Aubagio. So the question is when might we get revised midterm targets and are they likely to put it towards top line growth aspirations rather than staying focused on BOI and margins and free cash flow? And then second, very quickly for John on the pipe, IRAK4, is this asset still viable in light of the recent data we saw highlighting a QTC signal? Thank you.
Excellent questions. So some reflections maybe in three years. I think it's incredible the speed of the transformation company -- incredible and do incredible things. So obviously, we're ahead of where I'd hoped in the weeks leading that to join in. I think we have to earn the right to move to that sort of top line through. We have to deliver the science. We have to deliver the guidance. And we said back in 2019, we would earn the credibility from delivering exactly what we said we would do. And so we doubt that's nonnegotiable for us. And we think we're building quite a high degree of trust on that. Maybe there'll come a moment where we get to look further ahead is, of course, you'd expect that and to be bold about what that looks like for us because, of course, investments in R&D, that's an important consideration over the long term. But I do think we have to earn it. We're not quite at that point yet. And when we're ready to share that with you, we'll do.
As for IRAK4, it's really fascinating. We took a little bit on rilzabrutinib earlier. In biologic dominated marketplaces, there are rooms to beautifully put together orals. It's been a holy grail for most companies and most diseases. It's a needle to thread. You have to remember that the goal is not always to be as good as a biologic than to be a relevant medicine on the journey perhaps to a biologic. And so we know what you have to look like to be a successful oral and according to slightly earlier in diseases it's something like some of the oral in psoriasis. You have to think in those terms. So we remain enthusiastic about the IRAK4 methods, and we're working with the teams on making sure that we -- because we're careful and judicious about where we spend our R&D dollars, that we think we would have a profile that could be meaningful share-wise in the market. And so stay with us on that.
I'm glad you asked about it because as we build out our immunology leadership across the entire industry, we've got some really intimate shots of different mechanisms, patient populations, different methods of delivery. So yes, thanks Peter for that.
That's a good way to maybe to bring it to an end, if that's okay. Thanks to the team. Thanks to everything that people are doing. And thanks to everybody that is tuned in. We're doing exactly what we would say we would do and a little bit more, and we look forward to reconnecting with you in Q3 and in between. Thank you very much.