Ladies and gentlemen, thank you for standing by, and welcome back. We are now going to begin the virtual Sanofi Capital Markets Day 2021 portion of today's event. Following the initial presentation, we have planned for a five-minute break before the second section of the CMD event. You may remain connected to this Zoom link for all sessions. I would now like to turn the call over to Eva Schaefer-Jansen, Head of Sanofi Investor Relations. Eva, please go ahead.
Thank you, Natalie, and welcome. We are looking forward to spending the next couple of hours together with you and various members of the Sanofi leadership team to share and discuss the overall progress we are making in implementing our strategy in core parts of our business, as well as in transformation R&D. As usual, you can find the slides on the investors page of our website at sanofi.com. Moving to slide two, I would like to remind you that information presented in this call contain forward-looking statements that involve known and unknown risks, uncertainties, and other factors that may cause actual results to differ materially. I refer you to our Form 20-F document on file with the SEC, and also our document, for a description of these risk factors. Now, let me take you briefly through the agenda for today.
Paul Hudson, our Chief Executive Officer, will start with opening remarks, followed by Dietmar Berger, Head of Global Development and Chief Medical Officer, who will provide an update on the late-stage priority assets. Natalie Bickford, Chief People Officer, will then introduce us to the culture change here at Sanofi, which is imperative to deliver on our Play To Win strategy. Olivier Charmeil, Head of General Medicines, and Julie Van Ongevalle, Head of Consumer Healthcare, will then discuss the new strategic priorities of their respective businesses, followed by a Q&A session. With that, I'd like to turn the call over to Paul.
Well, thank you, Eva. Earlier today or just a few minutes ago, many of you participated in our Q4 earnings call. I thank every one of you for joining us and staying with us for the 2021 virtual Capital Markets Day. It's been a little bit over a year since we met at our 2019 Capital Markets Day, where we embarked on our Play To Win strategy. Today, we want to give you a snapshot of our progress. It has been an exciting journey for us, and I hope that you, at the end of today, will be as confident as we are in our amazing future at Sanofi. Let me start by saying that we are ahead of our six-year plan, the one that we shared with you in December 2019.
This is even more reassuring in the backdrop of the unprecedented times that we have been facing during the pandemic. Across the organization, our teams have been relentlessly executing on this plan. I want to take this opportunity to express my gratitude for all their hard work. Together, we continue to be entirely focused on achieving the targets which we have set out for 2022 and 2025. Our three core growth drivers have delivered in 2020. DUPIXENT, with EUR 3.5 billion of sales in 2020, has now reached blockbuster status in a quarter and continues to grow strongly. It is Sanofi's biggest contributor to sales growth. This is just the beginning for DUPIXENT's amazing growth trajectory. Later today, Brian Foard is going to share with you how he and his team are expanding around this mega brand in type 2 COPD, chronic sinusitis without NP, and other diseases.
While we are convinced of its sales potential of being greater than EUR 10 billion. Our vaccine franchise has generated EUR 6 billion in sales in 2020. Influenza was certainly the strong driver, but also the PPH portfolio grew double digits, over EUR 2 billion in annual sales. I'm extremely confident that we will continue on our mid to high single-digit growth ambition going forward. Our rich pipeline is getting significant momentum as we continue to follow the science, and we are only accelerating, demonstrated by 12 projects entering phase III in 2020 alone. John and his leadership team will share with you the progress on the R&D transformation. Looking at slide seven, you can see how it demonstrates our ability to execute on capital allocation.
Over the last 12 months or so, we engaged in multiple M&A and BD transactions, employing our capital to bolster the pipeline in existing priority areas, supported by the proceeds from the sale of our passive stake in Regeneron. What is driving us? Adding exciting science and first-in-class technologies to our pipeline. We're doing this in areas where we are strong from a capability perspective, where there is low marginal cost to commercialize, and where accretion can be reached even faster. Starting with Synthorx acquisition, adding THOR-707 that combines so well with other assets in our oncology pipeline. For the first time today, we'll speak about THOR-809 fitting perfectly into our immunology pipeline. This has the potential to address a wide variety of autoimmune diseases.
Moving on to Translate Bio, I think it's worth remembering that we've had a strong relationship dating back to 2018, and that relationship has all been about trying to make sure that we're also going to be heavily involved in messenger RNA. In June of last year, before we'd even had a readout in mRNA, we also knew that it was an opportunity for us to simply double down. We widened that collaboration. We took all of the targets, all the assets, tech transfers, so we could really make sure that we could participate fully in the future if mRNA becomes successful. As we know now, certainly in a pandemic, that's proven to be the case.
On Kymera and the IRAK4, you will also hear today it's a great fit with our immunology franchise, and we're getting ready to move the first molecule of that collaboration into the clinic this year. The Principia deal gave us full control of tolebrutinib, the brain penetrant BTKI, a potentially truly disease-modifying asset that we put into four phase III trials straight after PoC in the middle of a pandemic. We also picked up rilzabrutinib, another exquisitely selective BTKI. You'll hear more about this today. This is the path we want to continue on to add to the sustainable growth of this company. We are consistently seeking value-creating opportunities, and here we took decisive action to create a new European industry champion in API manufacturing. We've started with the carve-out activities, appointed a CEO, and we're on track towards a potential IPO in 2022.
We will set up this company for success and plan to maintain our supply chain with EUROAPI while reducing the complexity within our own Sanofi industrial network. When we set out on our margin targets in 2019, I remember that many of you questioned our ability to be sufficiently disciplined to reach them. Well, we are well on our way with margin expansion and increased our BOI margin by 120 basis points in 2020. This evidence should leave you with absolutely no doubt that we will not only achieve the 30% target in 2022, but also reach the target of more than 32% in 2025. We announced today that DUPIXENT is expected to be accretive to BOI margin by the end of 2022. I suspect that is faster than many had assumed.
On slide 10, you can see a snapshot of the 2020 sales performance of our four global business units. We created them in 2019 for more autonomy and more accountability in our execution. Specialty Care and Vaccines are delivering healthy growth rates as we're freeing up resources across the group and investing behind our growth engines. A focus of our discussions today are the strategic choices we're making in our General Medicines and Consumer Healthcare businesses. In General Medicines, Olivier will explain through the importance of prioritizing core brands, key markets, and digitalization. Julie will give you her management perspective on how to bring Consumer Healthcare back to growth, the progress towards a standalone unit, and where we are importantly on the switches to OTC for Tamiflu and Cialis. What do we hope you'll take away from today?
That we set out to do everything we said we would do. Not everything is perfect. We don't pretend it to be the case, had our challenges. I'm really proud of the organization and delighted with the progress that we have made. We are delivering on the fundamentals, getting us in shape to do what we need to do. Many great things are happening internally every day that are simply not visible or appreciated outside. We want to take the opportunity to simply talk about some of them today. The longer term, 2023 onwards, this is about the pipeline. I would like to ask Dietmar to update you on the status of our late-stage priority assets. Dietmar, over to you.
Thank you, Paul. It's my pleasure to be here with all of you today. 2020 has been a year of true progress in our R&D portfolio transformation, and John will provide you with a full update later today. I want to share highlights on the development progress of our six priority assets. As you know, the COVID-19 pandemic has posed unprecedented challenges for all of us, and I'm proud of the agility and innovative approaches to secure the continuity of our many clinical development programs. I find it remarkable that we were able to enroll more than 4,000 new patients in clinical trials in 2020 while maintaining 98% of patients in our ongoing studies with timelines largely unaffected. Let us turn to the priority assets. Our success story of DUPIXENT continues as we were able to rapidly roll out our development plan in several new indications.
We initiated three new pivotal studies in 2020. Brian Foard will provide more details on our ambitions in new indications later today. We continue to remain excited about our fully owned SERD called amcenestrant, which is a potential best-in-class endocrine backbone in hormone receptor-positive breast cancer across treatment lines. We expect the pivotal data from our AMEERA-3 trial in 2nd-line and 3rd-line metastatic breast cancer later this year. We are also looking forward to sharing the compelling combination data from our AMEERA-1 trial, which led us to rapidly initiate our 1st-line pivotal trial in combination with palbociclib. On fitusiran, we have encouraging news to share. First, fitusiran received Fast Track designation from the FDA in December. Second, we resumed dosing in patients in our pivotal trial program in January, less than three months after we had initiated a voluntary pause.
More on the fitusiran program in just a minute. For BIVV001, we completed enrollment to meet the end of study criterion in our pivotal trial in December. The study includes a 52-week follow-up period, and due to the COVID-19 pandemic, we now plan to share top-line pivotal results in early 2022. Venglustat continues to be a highly attractive program for us. While we are disappointed by the results of the phase II trial in the GBA-associated Parkinson's disease population, biomarker data confirmed the mechanism of action of venglustat with both meaningful and predictable GL-1 reductions in plasma and the cerebrospinal fluid. More on the progress of venglustat development in a moment. As for nirsevimab and tolebrutinib, our phase III programs continue, and we remain confident in the planned submission dates of 2023 and 2024, respectively. On slide 13, a few more details on fitusiran.
We remain committed to improving therapy for patients suffering from hemophilia, to an innovative portfolio, including the first-in-class siRNA fitusiran, which has the potential to rebalance the deficient coagulation cascade without sacrificing efficacy for convenience. Later today, fitusiran's amended protocol and dosing will be presented to the scientific community in an oral presentation at the annual congress of the European Association for Haemophilia. While we cannot share all the data yet due to the conference embargo, what I can tell you is that the new protocol suggests a potentially stronger profile of fitusiran through a lower dose and extended treatment intervals. In the coming months, we will be engaging with health authorities to discuss the regulatory path forward. More to come on submission timelines following our alignment with the regulators.
Early feedback from investigators and the hemophilia community has been positive, and the vast majority of patients are continuing the trials at this point. On slide 14, I want to re-emphasize our conviction that venglustat has the potential to become a transformative medicine across multiple diseases. As a reminder, venglustat is a next generation oral, brain-penetrant glucosylceramide synthase, or GCS inhibitor, with clearer proof of concept data in Gaucher type 3 and Fabry diseases, and a potentially transformative effect in the treatment of polycystic kidney disease. While the recently completed MOVES-PD study demonstrates that effective GCS inhibition does not show benefit in Parkinson's, it's important to note that the underlying biology in Parkinson's disease is entirely different from rare lysosomal storage disorders or ADPKD.
Biomarker findings from the MOVES-PD confirm that venglustat exquisitely targets GCS and leads to consistent, predictable GL-1 reductions in both plasma and the CSF. This reaffirms our confidence in moving forward with venglustat in our three lysosomal storage disease indications, as well as in ADPKD, with even greater conviction in the safety profile of the asset. Due to COVID-19, we're now expecting pivotal data in ADPKD in the first half of 2022, which leaves the submission on track for 2022 as previously guided. With that, I hand back to Paul.
Well, thank you, Dietmar, for that update. As I mentioned in the last CMD, not every molecule proved to be successful, but that is the natural risk you run, especially when aiming for first in class. I remain very confident, though, in the science, the unmet medical need, and the commercial opportunity for our priority assets. I think we have some real game changers in our late-stage development. I'm now going to hand over to Olivier and Julie, who will give you an update on their strategic priorities. The businesses they lead are a big part of our company that contribute to, amongst other things, helping us finance R&D, helping us to deliver breakthrough medicines. We will run General Medicines even more efficiently, being BOI accretive for the group.
On Consumer Healthcare, we're making good progress to make it standalone so that it can be more agile and get back to growth.
Thank you, Paul. I'm excited to talk to you about our new priorities in General Medicine. We are in the process of drastically changing our business model. As you will remember, in the past, Sanofi's mantra was "No small products, no small countries." Our market environment has evolved and requires a radically different approach. In a nutshell, what got us here will not take us there. We are now focusing on core assets and key markets. This will enable General Medicine to remain a significant contributor to Group BOI and will fund Sanofi's Specialty Care pipeline. As you can see from the chart on the left, Gen Med GBU sales have been declining consistently over the past years, mainly as a result of the loss of exclusivity of parts of our portfolio.
Most of the decline has been driven by price, while overall volumes have been stabilizing in recent years. In fact, cardiovascular and metabolic medicines remain critically important for chronic disease management among large populations, especially in emerging markets where healthcare reform policies are aiming at improved patient access and affordability. We believe that our core assets, which today in total represent 40% of General Medicines sales, have the potential to grow mid-single digit CAGR over the period of 2020- 2025. By 2025, we expect these core assets to grow to 60% of our sales base. Within key markets, we will deploy our innovative go-to-market model to unlock the full potential of these markets. We are progressing well with streamlining Sanofi's long tail of small products. At the same time, we are reshaping our industrial network to reduce our cost of goods and improve our gross margin.
Our commitment is to generate the same level of sales in 2025 as we did in 2020, thus stabilizing sales of General Medicines over time. This, however, excludes the sales of few API, which are expected to be deconsolidated in 2022. The overall resilience of our business makes us very confident in our ability to deliver significant upside to current 2025 consensus estimates, coupled with an accretive and stable BOI margin ratio throughout the 2020 to 2025 period. Moving now to the next slide and taking a closer look at our off-patent established product portfolio. We benefit from two important trends. First, the graphic on the left of the slide depicts that global volumes are stabilizing in recent years, following the meaningful impact from LOEs, such as Renvela, U.S., and Plavix, Japan in prior years.
Second, Lovenox and Plavix are standard of care treatments in treatment protocols, which offer the potential to capitalize on growth opportunity in China and emerging markets. The low molecular weight heparin market continue to grow, with Sanofi as the market leader. In addition, we expect label expansion for Lovenox into cancer-associated thrombosis later this year. Regarding Plavix, the antiplatelet market continues to grow in volume, especially in emerging markets, driven by an aging population, increasing incidents of coronary heart disease, and ischemic stroke. In China, where the penetration into the antiplatelet market is still relatively low. Our successful VBP strategy delivered 90%, nine, zero, volume growth in 2020. Going to next slide. In our core assets portfolio, we have four patented brands with meaningful differentiation potential. As discussed earlier, we intend to focus on selected markets with class expansion opportunities.
For example, Praluent is the only PCSK9 associated with a reduction in all-cause mortality and offering a once-monthly single injection in a pre-filled pen. The cholesterol-lowering market is currently expanding at high rates, driven by improved cardiovascular outcomes. We will particularly focus on China, where we launched Praluent in April and have already more than 5,000 patients treated. We intend to relaunch Praluent in Germany, which is the largest market in Europe. Now let's talk about MULTAQ. This is the only antiarrhythmic drug to reduce the risk of CV hospitalization for atrial fibrillation and the only drug currently actively promoted in the U.S. New data was recently published showing the CV benefit of controlling rhythm early in AFib patients. Moving now to diabetes. We will compete in selected markets across Europe and key emerging markets, continuing to drive market share expansion.
As mentioned, Toujeo, our leading next generation basal insulin, is expected to continue to grow, driven by new launches in attractive emerging markets such as China, Algeria, and Turkey. We expect further study readouts during this year in both type 1 diabetes and chronic kidney disease. Moving now to Soliqua. Our focus will be on large emerging markets, where approximately 70% of global premix use is located. In the U.S., we are shifting our promotional efforts to the post-OAD segments for patients with A1C levels above 9. Bottom line, we have four differentiated core assets with potential for our key markets. With that, let me now hand over to Alexandre de Germay, Global Head of Cardiovascular and Established Products Franchise, to share some more detail on our tactical approaches.
Thank you, Olivier. Hello, everyone, and very nice to be with you today. Moving to Slide 19. We have thoroughly analyzed our portfolio in the market where we compete. Resulting from this analysis, we plan to focus on 13 key markets with our core assets, which include the U.S., China, EU5, and select key emerging markets such as Brazil, Russia, and India. As you can see from the pie chart on the slide, these markets are expected to make up roughly three-quarters of our General Medicines sales in 2025. We will continue to adapt our operating model in the other markets. Our focus on key markets correlates with a significant amplification of digital-enabled customer interaction, so that we can address the needs of our customer in a more efficient as well as impactful way.
Our goal is to conduct 70% of our HCP interactions supported by digital platforms over the next three years, compared to only 30% in 2019. This is a bold move, and we are confident in achieving this target. Actually, it's already well underway. Three reasons why we are confident. First, our digital material provide relevant, trustworthy, and fresh content. We have received very positive feedback from our HCP customer, which has provided us with evidence of their acceptance and appreciation, especially during the pandemic. Second, we have recently built our digital infrastructure to include a large-scale content factory and have already reached a critical mass on e-permission of around 60% of our HCP target universe. With this, we are already generating positive interaction with a large volume of customer. Lastly, we aim to integrate our main digital channel in all our key markets by the end of this year.
This will enable us to further improve individualized customer experience and progress towards a mass best action powered by artificial intelligence. With that, back to you, Olivier.
Thanks, Alexandre. Moving to the next slide. You may remember that at the Capital Market Day in 2019, we announced our intention to streamline our tail products from around 300 branded product families down to 100 by 2025. We are making great progress and already reduced our mature portfolio to 180 product families by end of 2020, ahead of target. Clearly, reducing the complexity of our portfolio is a critical lever to free up resources and unlock value from our core brands. At the same time, we are optimizing the remaining assets, reducing the number of SKUs, and concentrating them in the top-decile plants. Reshaping our industrial network to achieve higher utilization rates and greater focus is expected to lead to cost of goods improvements and contribute to our objective of keeping the Gen Med BOI margin ratio stable during the next five years.
In summary, on my last slide, I hope we were able to convey some of the excitement around our decisive actions that will be fundamentally changing our overall business approach and go-to-market model inside General Medicines with core assets in key markets. In executing on our plan, the Genmed business is expected to be accretive to group BOI margin and a resilient contributor to group BOI. While it will require some time before stabilization of General Medicines sales will be achieved, I expect to be able to share initial successes of our strategic choice along the way. With that, I hand over to Julie.
Thank you, Olivier. I'm delighted to be here today to share with you my perspective on the role of CHC in Sanofi's transformational journey. I've only been with Sanofi for five months, and I'm convinced that there's a significant value to unlock in our CHC business. I also have with me Josephine Fubara, our Chief Science Officer for CHC, who comes with a wealth of expertise on switches. Starting on slide 23, as you know, over the past couple of years, our CHC business has been performing below market growth. Therefore, together with my team, as part of our Play To Win strategy, we have decided to focus on three pragmatic strategic priorities to unlock growth. First, we will address our legacy of a rather complex portfolio with over 250 brands. Our performance has been impacted yearly by product-related issues on many of our tail brands.
The good news is that we have a very well-diversified portfolio across countries and categories, with still untapped potential in both already strong global and local brands. We have the opportunity to build on these strong assets, embracing our complexity to unleash the potential of these brands. You will see here similarities with what Olivier shared on Genmed, divesting where it makes sense to free up resources to focus on what adds value. In other words, we will reduce the complexity of our portfolio, sorry, by swiftly divesting our tail brands, concretely reducing the number of brands we operate by roughly 60% in two years, from over 250 to about 100 brands. We will also optimize our go-to-market model. We will remain present in all the countries we are in today, but our model will be more tailored by geography.
At the same time, we are embracing our complexity by taking a more granular approach, not being only focused on the big categories and global brands, but focusing on attractive subcategories in key geographies based on consumer trends and our portfolio strength and opportunities, with the ambition to outperform the market as early as 2022 in these specific areas. In addition, as you are well aware, we have two major switches, Cialis and Tamiflu, which are expected to be key pillars of our future growth. Trust my team and I are putting significant efforts behind these opportunities, which should contribute to reaching above-market growth from 2024. Second key pillar of our future success is to change our mindset to become a holistic, consumer-centric brand-building business, a mouthful, but very important, to unleash that untapped potential of our brands, delivering consumer-driven innovation and bringing sustainability at the core.
Becoming a fully integrated standalone CHC business is a key enabler to move faster in this journey. Finally, obvious, digital, a key driver of this strategy. We're accelerating our digital journey by building a true data and digital edge, ranging from data-driven decision-making to accelerating e-commerce and developing digital health opportunities. My vision is really to make our business the best consumer business in the world and for the world. To achieve this, as of this year, as of now, my focus is on a flawless execution of our strategic priorities. Moving to the next slide, I want to give you an overview of the market potential. The global OTC market is a EUR 130 billion market, which is anticipated to grow 4.5% CAGR over the next five years. When including other channels such as e-commerce, this CAGR is predicted to go up to 5.6%.
As I shared on my previous slide, we are taking a more granular approach, looking at consumer and market trends. We will be focusing on a subset of the overall market to appropriately capture value and maximize our brands, be it local or global brands. As an example, instead of looking at the allergy, cough, and cold big category, we will focus on allergy, where we are already well-positioned and are getting ready to accelerate, as you will see on the next slide. These subcategories are a EUR 51 billion market, overall growing faster than the market, and that, again, is excluding e-commerce. To us, they represent today about one-third of our CHC business. As you can see on slide 25, indeed, we have a rich portfolio of strong global but mostly local brands in these fast-moving subcategories.
When looking at our leading brands, we are currently ranked number three in allergy, number one in general pain, and number three in body pain globally. You will likely recognize Allegra, one of our most successful Rx-to-OTC switches, which along with Xyzal, have driven the growth of the business in the U.S., making Sanofi a preferred switch partner in the industry. Doliprane is a local love brand and the leader in the pain market in France with around 60% market share and a brand awareness as high as Coca-Cola at 99%. We have more love brands such as Icy Hot, America's number one topical pain relief brand, or Dorflex in Brazil, number one pain relief brand. Moving to slide 26, I wanted to share with you the example of the mental wellness market, or more specifically, sleep, which is a subcategory within Nutritionals.
As a consequence of the COVID pandemic, is anticipated to grow in line with the market over the next five years and obviously faster than the market when we include e-commerce. Based on these consumer trends, and even if it's not been one of our key priorities in the past, we have decided to focus on mental wellness, and we already have some high-performing local brands which we want to accelerate. In the U.S., we have Unisom, already one of the leaders in OTC sleep and growing faster than the OTC sleep category. We're now entering the largest and fastest-growing sleep segment, which is natural with the launch this year. Another one of our very well-known sleep brands, this time in Europe, is Novanight. In December, we launched a new campaign in France with immediate double-digit impact on growth, +20% growth versus the market at +12%.
Honestly, the more time I spend on our brands, the more I see the opportunity to grow them into true love brands, strengthening consumer engagement through insights, data, and leveraging digital. Our strategic priorities are all about unleashing the potential of our numerous brands, and as a result, unlocking growth. Now on slide 27, the creation of our standalone business is an important enabler to our strategy execution, and we're progressing well. The design and planning phases are complete. We expect to have operationalized the majority of our CHC legal entities by the end of 2021, and the relevant social processes are on schedule. Being standalone means that we will have a fully dedicated organization, making us more agile, competitive to unleash the potential of our brands and deliver on our switches.
With that, let me hand it over to Josephine to give you an update on where we are with our two Rx-to-OTC switches.
Thank you, Julie. Hello, everyone. It is my pleasure to be here with you today. On slide 28, as mentioned by Julie, Sanofi has a successful history in switches with Allegra and Xyzal. Allegra is the fifth-largest Rx-to-OTC switch of the last 20 years, and we have a very experienced switch team who between them have worked on every U.S. switch over the last 10 years. With a total of EUR 1 billion in sales potential, not only do we believe that Sanofi's Rx-to-OTC switch pipeline is the largest in the industry so far, but more importantly, we intend to provide broad access with these switches and thereby help millions of consumers. Tamiflu and Cialis, which we believe will be first in class, will have a significant impact on self-care in the U.S. and empower consumers to take ownership of their health and improve the quality of their lives.
OTC Cialis has the potential to allow more sufferers to obtain treatment with a safe, effective and reliable product without the access burden. While OTC Tamiflu has the potential to reduce the burden on healthcare systems due to influenza office visits and hospitalizations, particularly in situations like we're currently in today with the COVID-19 pandemic. Inherent with being first in class, these are not easy switches, and the planning gets further complicated in the pandemic environment, particularly for Tamiflu. However, we are in continued discussions with the regulators to ensure that these timelines can be maintained. Both programs are fully underway with 16 studies initiated or completed in 2020, and half of them been converted to virtual studies. We are currently on track with the case studies we need to do to meet the targeted launch dates.
One of those critical studies is the actual use trial, which measures whether test subjects can appropriately use the product according to the labeling without medical supervision under a simulated OTC environment. We believe no other manufacturer has reached the actual use trial phase in the U.S. for an OTC switch of an erectile dysfunction medication. We believe we will be the first to do so. The first patient in is planned for the actual use trial for Cialis this year and in 2022 for Tamiflu. With that, I hand it back to Julie for some concluding remarks.
Thank you, Josephine. On slide 29, just to summarize, we are committed to delivering best-in-market growth from 2024 with the potential addition of EUR 1 billion to the top line from the two switches. As early as 2022, we plan to have our priority brands in selected geographies growing above market, including the U.S. and China, the two largest CHC markets in the world. Our model is a true consumer-centric model designed to unlock the value and supported by consumer insights, data, digital, e-commerce, sustainability, and excellence in execution. Our standalone structure will allow us to be more agile, applying fast-moving consumer goods standards while leveraging Sanofi's expertise and capabilities where more efficient. Thank you. With that, I'm handing it over to Paul.
Thanks to Julie and Olivier and Josephine and Alexandre. I hope you get a sense of the major transformation ongoing on those two businesses and how our prioritized portfolio will enable us to continue to drive growth and innovation. We also talked at 2019 Capital Markets Day that as part of the Play To Win, we need to reinvent the way we work. It is my pleasure to introduce our new Chief People Officer, Natalie Bickford, to talk about how she's going to ensure that we have the culture change that is simply so imperative to deliver on our strategy. Natalie?
Thank you, Paul. I have to say it isn't common for a Chief People Officer to be invited to take part in a Capital Markets Day. I am delighted to be here and to share with you what we're committing to achieve with our people in service of our patients. Let me start by sharing a quick overview of my past professional experience, because indeed, like most of the new members of the ExCom, I haven't joined Sanofi directly from the pharma industry. Many years ago, I was a U.K. HR director for AstraZeneca. Indeed, worked alongside a young Paul Hudson. I've spent the majority of my career in highly consumer-focused businesses like Kingfisher, Sodexo, and Merlin Entertainments, which are low margin, high budget organizations where you have to place your bets and ruthlessly focus your efforts.
More recently, I've been keen to get back to the pharmaceutical industry, and I felt a strong emotional engagement to Sanofi's purpose, and in particular to the strategy laid out by Paul. I've spent the last five months listening and learning and thinking about the role that HR needs to play to support the delivery of the Play To Win strategy over the next five years. Some of my first impressions are that we've had a somewhat inward-looking culture with too much corporate treacle, overly bureaucratic, and complex in its ways of operating. What I've also found is that our leaders show a huge amount of energy and enthusiasm to deliver the Play To Win strategy. They're taking accountability and are getting actively involved in evolving our culture.
Having our most senior leaders on site is critical, but to really move things, we need to engage the entire workforce in delivering culture change. Culture can be a difficult and somewhat vague concept to grasp. We've identified four Play To Win behaviors as proxies for the new culture that we need to live and breathe. By applying these behaviors to every decision that we make and every action that we take, real change will come. On slide 31, these behaviors are to stretch, which means taking calculated risks, pushing ourselves out of our comfort zone, and ruthlessly prioritizing our work. To take action, which means focusing on outcomes rather than activity, and delivering against our priorities.
To act for our patients and customers, meaning freeing up budgets to develop our pipeline, making sure that whatever we do, we see a really clear link to how this is going to deliver better outcomes for patients. Finally, think Sanofi First, which means always prioritizing the total company over our own interests or those of our direct team or our direct business area. On slide 32, let me give you a brief oversight of our new Sanofi people strategy, again, built to underpin the Play To Win. We want as a company to focus and deliver in four priority areas. Our first pillar is Healthy Organization. Here, we want to create a lean and adaptive organization with clear clarity of accountability. In 2021, we will successfully land the new Consumer Healthcare, Gen Med, and EUROAPI organizations.
We will anticipate and acquire future skill needs with a clear focus on digital capability. We must also develop a world-class talent pipeline to feed succession to key roles to ensure our future success. Our second pillar is purposeful experience. More than ever today, we are in a war for talent. To attract and keep the best people, we need to create a highly compelling work experience and give a real fundamental sense of purpose. Not enough people outside of Sanofi appreciate the amazing career opportunities we can and do provide. This year, you will see us deliver a new highly proprietary and compelling employee value proposition. Our third pillar is winning culture. We must anchor the Play to Win behaviors that I've just highlighted across the business to ensure that we leave our old ways of working behind us and embrace the new culture we need.
In 2021, so this year, we will build the Play To Win behaviors into all of our people journeys, from recruitment through performance management, learning, reward, and talent management. The fourth and final pillar, which is particularly close to my heart, is diversity edge. We've already made strong progress on gender at a group level, but now we need to broaden our lens to cover all strands of diversity. The business and societal advantages that come from driving diversity of the workforce and an inclusive environment are really significant. We're also highly committed to drive our relationships with the diverse communities that we serve, including better reflecting our communities in clinical trials, driving supplier diversity, and involving all our leaders in relevant local community projects.
This month, we'll launch our new Sanofi D&I strategy with clear deliverables around building representative leadership, creating a work environment where we can all bring our best selves, and engaging with our diverse communities. In a nutshell, there's a lot of work to do, but I have a clear focus on our required culture evolution and our wider people priorities. We're not starting from scratch at all. We're building on solid foundations. The trick now is to be highly focused on these deliverables that will tangibly drive our company performance. More than anything, this is a super exciting time to be part of the Sanofi story. With that, back to you, Eva.
Thank you, Natalie. We're now moving to our Q&A session, and we will now remind you how you can ask a question. You have two questions to participate in the Q&A. Option one, if you would like to ask a question, please click the raise hand icon at the bottom of your screen. You will be notified when your line is open to ask your question. Option two, you may submit your question by clicking the Q&A icon at the bottom of the screen, and your question will be read by our panelists. We will take the first question from Simon Mather at Exane. Simon, please go ahead.
Good afternoon, everybody, and thank you for taking my questions. The first question, Paul, is really just maybe some guidance on General Medicines. Obviously, you want to keep revenues flat between now and 2025, and you delivered EUR 14.7 billion in 2020. If you look at consensus estimates, they are significantly below this number. On top of this, consensus expectations for your margin are also significantly below.
I was wondering if you'd help square the circle in terms of what base we should use for 2020. Appreciate you have the value- accretive API coming up, so that's one aspect, but help there would be very welcome. The second question, and maybe this is a bit premature, but just moving on to Consumer Health, and you've outlined your growth aspirations and the fact for it to be a standalone by the end of 2022. I'm just wondering, beyond 2022, how we should think about the division and whether or not Sanofi still believe they are the best holders for that asset, especially given the strong growth profile that they'll be entering in past 2022. Thank you.
Thank you, Simon. I'll let Olivier comment on the base and the things, but just my own observations coming in. When you look at our Gen Med business, this isn't a carryover established products business. This has got some real growth-driving opportunities in it and an opportunity to be more efficient. Plus, I think Sanofi is pretty unique in its ability to work in some of these markets and deliver with the sort of entrepreneurship. You may say, "Well, doesn't everybody say that?" I would say how the company was created and its legacy touched on by Olivier, no country too small, no medicine too small. I think we have more ability to extract more value than most, which is what made us dig deeper.
To get the sales back to where they were and to help you guys understand that that estimation on decline is just too easy given where we think we can actually go and beat that. That's a really important fundamental piece of understanding, and perhaps a misunderstanding I had before I came in, and I'm much clearer now that I see it. Olivier?
General Medicines base is EUR 14.7. This includes EUR 500 million of API that will go with the EUROAPI project. Of course, I'm projecting ourselves in the next two or three years, how we are going to get there. It's of course through focus on core assets and key countries, where we are going to allocate significant portion of our resources. It's also about making sure that we stabilize the de-growth of our non-core assets. It's really growth on the core assets through volume growth and of course, stabilizing as much as we can the non-core assets.
There's truly great work being done already. Again, just to remind everybody that we were challenged a lot by yourselves, Simon and others, around sort of opening the black box about Gen Med business. You can get a sense of why you shouldn't just make an assumption bucketing such an important piece. You'll see at the time as we share the progress made, that's why we think we can beat what you guys have in models and why we will update you regularly on that. The other question was on creating a more valuable business, and are we still going to be the best owner? I think our entire effort is standalone, increased agility, provide focus, give Julie and the team the wind at their back to go and get growing fast in the market.
I think the switches are such a big opportunity, and particularly at a time in our evolution after an Aubagio patent expiry, where our focus is single-mindedly on growth and preparing for switches. We are not thinking about anything else. We hope to create something incredibly valuable here inside the organization. Next question.
The next question is from Luisa Hector at Berenberg. Luisa, please go ahead. No? Okay.
Hi, can you hear me?
Yes, we can, Luisa.
Thank you. Thanks for taking my questions. On vaccines, you're reinforcing your target of the growth to 2025. I just wondered whether you have a wider spread on that number to factor in potential mRNA vaccine disruption. Maybe with that in mind, you could comment on your mRNA flu vaccine program. Should we see that as an extension of your differentiated offering in flu vaccine? Is there any color you can provide? Presumably, this would have to be single dose to be competitive. Do you think regulators will require head-to-head studies and non-inferiority or superiority endpoints? Maybe if I could just ask a quick one back on the relative profitability of General Medicines versus Specialty Care today and how you see that in 2025. Thank you.
Okay, Luisa, thank you for those questions. We'll come back, I think, to JB on what we have shared or not shared around relative profitability. We'll come to Thomas on the evolution of the business, mRNA. Look, Thomas, it's a question that's being asked all over the place. Maybe you can give a perspective on timelines and potential areas of disruption and areas where we don't anticipate disruption, then our own role in influenza.
Definitely. In turn, yes. Thank you, Luisa. In terms of mRNA disruption, as mentioned before, definitely we see mRNA as a very interesting technology. That's why we started with the Translate Bio partnership in 2018, extended it in 2020. Where we see the potential is definitely in getting to new territories, especially in viral diseases. We start, as mentioned before, by phase I in flu. Now where is it going to land on the influenza? It's very early to say. We need to have the data first, and we're not there yet. I need to watch there. Sorry about that. We are in phase I right now. As you mentioned, I think it's very important, I can give you my perspective on how do I see mRNA.
I think it's very important to have in mind first, that when you look at mRNA for flu, it will be very different when you look at the development of a vaccine in a pandemic situation, like it is today for COVID-19. When we are looking into it, when the development of a field where there is already a standard of care, for flu, for example. I'm alluding to the second part of your question, what will it mean? In flu, there is already a standard of care in terms of efficacy and in terms of safety. What we will want to see is that with mRNA, especially flu mRNA, are we able in one single shot, thermostable with rapid logistic all over the world, where it's required every single year to provide a shot that has the same level of safety than standard seasonal flu.
I remind you that the safety is highly proven and very strong, and the same level of efficacy, and I remind you that different flu vaccines have seen double-digit increased efficacy when compared to standard dose flu vaccine. There's a lot we need to see. It's still extremely exciting, that's why we're getting there, but there's a lot of things we need to see. That's going to take a few years. It will ask phase I, phase II, phase III when it comes to seasonal flu. It will ask for comparison, as you mentioned. It will probably require multi-year check because you want to see not only one year, but two years, that it's successful. Of course, when you look at the portfolio we have in flu and the partnership we have with mRNA in Translate Bio, that's an interesting opportunity.
Beyond flu, and I think that's why it's very interesting, there's a lot of viral targets where mRNA vaccine development could be super exciting. We have seen some targets that have been started by the competition. We are, of course, in the middle of defining exactly where we want to go. We have not communicated on that path, for obvious reasons, but it's extremely exciting to look at how fast we can go into phase I trials in the coming years on some viral vaccine targets. The earlier part of your question was more about the, I would say, target of growth for the Vaccines GBU. I won't say much more on the specifics, even though you're probably interested, but we are really looking at mid to high single-digit growth from 2018 to 2025. That was our commitment.
I think it's very important to highlight that it's based not on one single pillar. We are not a flu vaccine company. We're a multi-vaccine company. It's based on flu pillars. It's based on pediatric combination pillar. It's based on the coming launch of RSV nirsevimab. We have a lot of pillars that will fuel that growth. We'll take it year by year, we have this mid to high single-digit ambition for six years and for every year.
Thanks, Thomas. Luisa, it doesn't change. Our commitment as stated doesn't change, and we'll participate in the next wave of innovation. We don't think it's an easy ride for us either, by the way, of mRNA and influenza, and et cetera. We'll be there, and we know how to do it. Jean-Baptiste, maybe something on relative profitability?
Yes. Luisa, I think you're asking exactly the right question. I think you know very much what is the answer, but let me give more color with what we heard from Olivier today. Yes, Genmed is a very accretive business, it's a buy play, we've seen it today. Not only we want to keep it stable over time in terms of size, we want also to maintain, and that's what we are looking at, this accretion over time. What's going to happen relatively to Specialty Care is just that Genmed will stay where it is. Why? We bring progressively Specialty Care at a higher level, which will help, of course, the global Sanofi. You have the first proof point with what's happening on DUPIXENT. Of course, progressively, it will also happen with other products.
Right now, Specialty Care is where we are investing. The R&D effort is increasing on that area. It will be a slow motion, but it will go in the right direction.
Thank you, J.B.
Okay. The next question is from Peter Welford at Jefferies. Peter?
Hi, yes. Thanks for taking my question. I've got a question on consumer, and actually just
Peter?
Peter?
I think we lost you. We may go to the next question.
Sorry, there you go. I'm here. Sorry, I think you cut me off. I'm sorry. Right. Sorry about that. Let's go again. Question on consumer. Just curious here with regards to the Rx2OTC switches here. Obviously, Cialis is entering use trials sooner than Tamiflu, but Tamiflu potentially launching before that. Is that just related to the complexities, obviously, the ED market and flu, or is it something else we should read into what's required here? I guess for Paul, or maybe also for Julie, just with regards to how important potentially bolt-ons are in your consumer strategy. You didn't mention the potential need to bulk up any of your franchises. I guess from Paul's perspective, is this a division where there is capital allocated to be able to do that? Should it be deemed the best to reach growth?
Sorry, just coming back then to JB. Just trying to understand, maybe you could give us some clarity, how many years forward should we think about GenMed still being accretive? I appreciate you don't want to give the margins, but can you give us an idea, for how much longer GenMed is accretive potentially to Sanofi? If you like, the crossover, I guess, is the question. Just to Thomas, sorry, just back on the mRNA. Is there a phase I guess immunogenicity or biomarker type read that can give us a quick yes/no to, is this as good as your vaccine, or do we need multi-year studies to know?
Okay, Peter. I'm glad you didn't get cut off. You got quite a fistful of questions.
Sorry.
That's all right. No worries. Josephine, maybe you just want to share just some flavor around the switch timelines. I think what we've tried to say is that, and I think you touched on it, the complexity and the journey is one thing, and of course, COVID is another. We feel confident in and around those guidelines given, and we've reached with Cialis, as was outlined, first patient in an actual use study will be this year. Nobody's ever even made it that far. We're doing things that have never been done before, which also increases certainty over time. Josephine, maybe you want to add something.
Thank you, Paul. That's a really great answer to the question as well. Like you said, right, we are advancing the programs. We have been able to conduct a number of case studies in 2020 that actually continue to progress us towards the actual use trial for Cialis in 2021, which we're confident that we're going to be able to meet. For Tamiflu, we are going into actual use trial in 2022. The only reason you see a difference in both timings is just because of the timings from when we started both programs and where we are, right, with the pandemic situation. Again, like I said, we remain confident in our ability to conduct these actual use trials and progress these programs to the expected launch date as communicated.
Thanks, Josephine. The next question was really about bolt-ons and whether you'd buy things for CHC. I think what we've tried to say is that we think we have enough organically to make the progress when we have the switches. I think where Julie's challenged me is around whether we can add other capabilities in around digital, Thomas, looking at China and other areas where we can accelerate our performance. We really have to think about being accretive. I think ultimately, buying to bulk up would not be where we wanted to go. As you've seen, I think some of the clarity that Julie's brought is actually slimming down to grow faster based on better choices. I think we would look to capabilities and different things.
No. Again, I 100%, obviously agree with what you said, that's exactly what we're trying to do. We're always looking at ways to grow our business, be it organically and inorganically. Our Play to Win strategy is not dependent on M&A to deliver the growth ambitions that we have. That being said, we're of course constantly evaluating opportunities to provide greater scale, be it in geographies or to add onto our subcategories that we're focusing on. As well as Paul said, accelerating our digital journey.
Thank you. J.B., Gen Med accretion, what is your outlook?
Well, Peter, it will be very long. This business is incredibly resilient. I love it, by the way. 2025, but after. There's no patent cliff, there's very little happening there, but with a very active management, we will keep it accretive for the long time.
Thanks, J.B. He loves all our businesses equally, just point that out. Thomas, mRNA phase I sort of proof of concept, any first feedback from you?
I'm afraid there's not going to be a phase I miracle read in vaccines. There is a litany of vaccine development, even for well-known targets that have failed in phase II or phase III, be it non-mRNA, mRNA would be the same. No. Long story short is no phase I, phase II, phase III will be required. Obviously, you want to see if you have neutralizing antibodies. If you don't, it's game over. If you have, it doesn't mean it's going to work. You need to check the ability of those to indeed protect. All three phases will still be required. I don't think it's really changing that part.
Thomas, maybe I could ask a supplementary on behalf of Peter, which is, where has mRNA not hit a home run in the development so far?
There are a few products indeed in the story of mRNA where it's not always been successful. Indeed in the past, there has been some publication, for example, on the pandemic flu mRNA trial that was not impressive at all. You also have noticed probably that, and it's public information, that Merck has given back the rights that it had on RSV mRNA with Moderna. There are different areas where it's not a home run. There are things to look at. Again, very promising technology still, and we've seen that with COVID-19, but there are many areas where it might be applicable. There are as many areas where it's not going to be applicable. You all know that polysaccharide vaccines, for example, which is a huge range of the portfolio today, will not be applicable to mRNA technology. Exciting technology, we're looking at it.
We're more than looking at it. We're developing it and we're going full steam, but we'll be able to select the right niches and the right markets to be successful.
I think, look, and we said it in some of the dialogue earlier, in a pandemic, I think we're the first company to accept that we're moving at record speed, mRNA in a pandemic with a single antigen is probably the go-to. No issue there at all. I think we should just be a bit grounded on what the opportunities are. Again, we're fully participating, but we don't expect everything we try and do in mRNA to be a success. I don't think anybody should right across the spectrum, there were some areas where it was unsuccessful on the lead-up, but we're thrilled that it's had some success in COVID-19.
Just to remind you, I'm not the expert that Thomas is, when you get to the multivalent strains in terms of solutions with mRNA, even not all mRNA is so equal in terms of what's your ability to go after multi-strains. We're there. That doesn't scare us, but it's interesting. Okay, good. Next question.
Yes, Paul. I have three questions from Steven Scala from the chat. First one, two actually going to our Gen Med team. What are the patent expirations on MULTAQ? Sanofi previously made the decision to de-emphasize diabetes research. Why aren't Q week basal insulins attractive opportunities? The last one goes to the Consumer Healthcare team. It is clear that Sanofi gains from owning Consumer Healthcare, what does Consumer Healthcare gain by being owned by Sanofi?
Thank you. Thank you, Steve. Provocative. Maybe Olivier talk about MULTAQ LOE.
MULTAQ LOE is 2029 in the U.S.
Maybe we could look at why, Julie, you're interested in being part of Sanofi.
Sure. Today I think it would be a myth not to benefit from the Sanofi. Basically, I want the best of both worlds. I want to be able to create more agility, more speed by becoming standalone. Again, it would be a myth not to benefit from the bigger Sanofi, especially in areas like science and data.
Thank you, Julie. Good to know. Then Olivier, the weekly basal insulin, what have we missed?
General Medicines is of course, key and instrumental to the success of the Play To Win strategy in funding the Sanofi Specialty pipeline. We are at the beginning, mostly in the emerging market, of the story of Toujeo that has not been launched in China, for example. To be more precise, was launched only mid-November. We are also at the beginning of our story with Soliqua. We have really a significant runway. Soliqua has only been launched in a small number of countries in the emerging market. Soliqua will be launched in end of 2022, 2023 in China. We all know, one, that a significant portion of the market in China in insulin remains a Premix market. Still a long runway with assets that have not been fully deployed, especially in emerging market.
We are of course looking to what the competition is also doing.
Thank you.
The next question is from Seamus Fernandez at Guggenheim. Seamus, please go ahead.
Hi, thanks for the question. Just wanted to get a quick update on Obviously, I apologize if I miss questions on venglustat. As it relates to venglustat for ADPKD versus some of the data that is presented in the press release around GBA, just wanted to get a better understanding of directionally the fact that the placebo actually was performing better. If you can provide a little bit more color in that regard. Just again, directionally, just remind us again of the ADPKD opportunity. I believe this is predominantly based on preclinical data that's really driving the assumptions here, but just wanted to get a little bit more color on your conviction in the wake of these data. The second question is actually on interest in gene therapy. How has that changed, Paul, in the context of some of the updates from the agency?
It seems like the path for gene therapy may be growing a little bit more extended and drawn out. Just wanted to get a sense of how Sanofi is thinking along those lines. Thanks so much.
Okay. Thank you, Seamus. Maybe Dietmar, do you want to jump in and then we'll also let John Reed, if you want to add or comment on gene therapy. Dietmar.
Yeah, right. On Venglustat, thank you for the question. Venglustat is really an interesting molecule in considering that it's a pipeline in a pill. Because it inhibits so early in the signaling cascade, we were able to evaluate different hypotheses across different types of diseases. I would think that there are three buckets. One is the lysosomal storage disease bucket, where we have good proof of concept in Gaucher type 3 in Fabry. We're following up on that obviously with studies in those indications. That's simply the deposition basically, and the metabolic pathways that are important there. You've got the ADPKD, and that's a different hypothesis around signaling actually, and secretory information in kidney cells and in the formation of those cysts. That is driven largely by preclinical data, both genetic but then also preclinically in an animal model.
That animal model has been quite predictive actually, which gives us a lot of confidence. It's a different hypothesis, different type of disease. You got the Parkinson's, where it was about deposition of synuclein and can actually the GCS inhibition play a role there. Again, a different hypothesis. The fact that what we've seen in the MOVES-PD study demonstrated no clinical benefit had no impact on those other indications. What the MOVES-PD study also shows is that the GL-1 levels are distinctively reduced. The drug works.
The drug does what it should. It's just that the biology in Parkinson's seems to be different. We remain really confident with regards to the other two buckets of indications. The other information we got from MOVES-PD is that the drug has demonstrated a very encouraging safety profile, so we're even more confident when it comes to that safety profile as well. The ADPKD data, the initial data will be on total kidney volume, and we're looking forward to see those data then in 2022. John?
Yeah, thanks, Paul. Thanks for the question about gene therapy. We remain committed to and interested in gene therapy. We see them as essential to include that modality as one of the ways we tackle problems in the rare disease space or the monogenic disorders where we've had such a trailblazing history at Sanofi Genzyme. Also particularly in the CNS area, we see quite a bit of opportunity there. We did establish an internal capability, we call it Genomic Medicine Unit, recently, and have assembled a team in the Boston area taking advantage of our Genzyme heritage. Genzyme did put a couple AAV-based gene therapies into the clinic back in the day, as well as the gene therapy ecosystem of the Boston area, and are pursuing both viral and non-viral gene therapy solutions for rare diseases in CNS.
We expect to generate two development candidates this year in 2021, and to put those in the clinic in 2022. In terms of the CMC and manufacturing piece of that, we've talked before about how, at least with the viral vectors, there are many similarities to those manufacturing processes and how we have historically made certain vaccines. We're leveraging those manufacturing capabilities and expect to have our first GMP facility come online this year in the Lyon, France area, taking advantage of that. Finally, I would say on the BD front, we're continuing to build up our toolbox of next-generation assets for prosecuting the gene therapy space.
Final thing I would mention, because I think it is a new exciting development for us, is that with the announcement of our intent to acquire Kiadis, a cell-therapeutics company, in their case, exploring the NK natural killer cell platform for oncology, our projects there will involve genome modification of the cells. The first project we've announced is a CD38 knockout NK cell engineered specifically for myeloma, engineered specifically to combine with our anti-CD38 antibody, Sarclisa. That's just the first of what we see as a pipeline of genomically edited, genetically modified NK cell products that we will customize for various types of cancer in the years ahead. We're very actively establishing that capability as well.
Thanks, John. Maybe I'll just add a couple of points. It's been an interesting six, 12 months in the gene therapy landscape and at least in hemophilia. I think John's touched on it, but we're equally important as CMC in manufacturing. I think we all anticipate the future to be where pricing will be pressurized on gene therapy and cost of goods, therefore, needs to be proportionally lower. We're really focused on trying to make, if you like, affordable gene therapies go to market. We'll see how far we get. We do have this extensive history in rare diseases, and I think we're all excited about trying to continue to contribute and stand on that, and open-minded a little bit about the rest. It's not a given the uptake of gene therapies longer term, so we have to work very hard to demonstrate the value.
You see now even when you have breakthrough data, it's not always confirming the opportunity that you have. I think we're approaching it the right way, very sensibly, actually. Okay, do you have time for one more? Okay. Yeah, please.
We take one last question, sorry, from Keyur Parekh at Goldman Sachs. Keyur, please go ahead.
Good afternoon. Thank you, and hope you guys can hear me okay. Two questions, please. The first one for Julie. Julie, you've kind of laid down an exciting plan for changing the growth outlook for the CHC business. I'm wondering if you can talk a bit about your plans from a margin/profitability perspective. Are you seeing this as a need to reinvest in the near term with margins going up post the launch of Cialis, Tamiflu, or do you see enough scope for you to take cost out and reinvest to get that growth? That's question number 1. Question number 2 for Paul and J.B. Paul, we've obviously seen some of your peers do largest acquisition. Just wondering if you can remind us what your priorities are from an M&A perspective. Is it still these Toray, Synthorx-sized acquisitions?
Linked with that for JB, clearly if you look at multiples, you look at your growth outlook, the stock seems incredibly cheap. What's stopping you from being more aggressive on a buyback? You have enough capital, you have enough balance sheet leverage, why not take advantage of the cheap valuation?
Okay, good. Snappy questions there to finish us off, Keyur. Thank you. Very quick comment on CHC margins.
Sure. What I can say is that our operational profitability is expected to remain stable and among the highest in the industry, and divestments will continue in 2021 and 2022. If your question is if we have what we need to unlock the growth that we have planned, the answer is yes.
Okay, thank you. For me, on M&A, I guess, and maybe J.B. will comment. The capital allocation, I suppose they're connected, the questions, really. We want to create value, we want to add to our science, we want to do things. We have said we're more in the bolt-on, sort of tuck-in territory. I think the last four acquisitions over the last year, I think, would support that. We're trying to do things that make sense. We don't think we're a company that needs to do a big piece to consolidate just extra revenue. We think we have efficiencies to gain, opportunities to reinvest, science to accelerate. I think you'd be perhaps disappointed in us even if we did try and do that. We're sticking to the science, and we have enough in hand.
I think you sort of have to understand that having a healthy balance sheet, if you want to describe it like that, is JB's problem. Buybacks were low on our list. Maybe the last thing on our list, because we think we can create more value for shareholders and investors a different way. JB, what's your view?
We are doing a bit of share buyback, as you know, because we can't sell the dilution of any emission we do. We've just done some at the back end of last year or beginning of this year. As Paul said, of course, it ranks quite low in our priority. What we did is, again, increasing for the 25th year our dividend, and I think that's a nice way also to return some of the growth and wealth of the company back to our investors.
Thank you. Thanks, JB. Eva?
Please stay with us. We will now have a five-minute break. We will be back for the second section of our CMD called Emerging Leadership in Immunology. Thank you.
The recording has stopped.
I need to get this off. John, can you hear me?
Only barely.
John, can you hear me?
Now I can hear you, Eva.
Okay. I think we are good to go. I hope your team is set. I will just say a few words, and then I'll hand it straight to you.
Okay.
Natalie, how are we?
Yes, we are.
You tell me when I can go.
You can go, Eva.
Welcome back to the R&D section of Sanofi Virtual Capital Markets Day in 2021. The Sanofi R&D leadership team is excited to spend the next hour with you to share Sanofi's emerging leadership in immunology. John Reed will open the section with some introductory remarks, followed by Brian Foard, Global Franchise Head of DUPIXENT, then Naimish Patel, Global Head of Development I&I, Frank Nestle, Global Head of Research and Chief Scientific Officer, and then John Reed will return to you with concluding remarks, followed by another Q&A session. For those who may have just joined us, I just want to quickly remind you again on the instructions how to ask the question. You have two options. Option one, if you would like to ask a question, please click the raise hand icon at the bottom of your screen.
You will be notified when your line is open to the question. Please remember to unmute yourself. Option 2, you may also submit a question by clicking the Q&A icon at the bottom of the screen, and the question will be read out here. At this point, I would like to hand the call over to John.
Thank you, Eva. Well, now the real fun of this Capital Markets Day begins as we dive into some of the science behind the Sanofi pipeline. Today, we will focus the R&D update on Sanofi's emerging leadership in immunological diseases. Immunology is a very dynamic space for us, and we expect rich news flow throughout the year ahead. Before we dive into our presentation, however, I would like to remind you that since 2018, Sanofi R&D has been undergoing a massive transformation. The first point I would make is that we have completely reshaped the pipeline in the last three years, from heavily primary care oriented to now entirely specialty care. Within specialty care, we have significantly expanded our portfolios in immunology, oncology, and hematology. To quantify this transformation, compared to just three years ago, our immunology portfolio grew from six molecules or products in development to 15.
Compared to just four years ago, our oncology pipeline grew from five molecules or products in active development to also 15, which will grow actually to 18, assuming successful closure of the Kiadis and Kymab acquisitions. Compared to three years ago, our portfolio in non-malignant hematology grew from just one molecule under active development to nine. The second point I would make is that we accomplished this pipeline transformation while maintaining fixed costs essentially flat for the last three years. This required enormous trade-offs. For example, exiting cardiovascular and diabetes, optimizing our sites, and reallocating resources on a large scale. Third, in parallel, we accelerated our R&D transformation through M&A and business development activities, altogether bolting on six companies, providing Sanofi with pipelines, platforms, and talented people, especially top-notch scientists.
The new platforms for accelerating our future drug discovery included the Nanobody platform of Ablynx, acquired in 2018, the synthetic biology platform of Synthorx, acquired in 2020, the tailored covalency platform of Principia, acquired last year. The NK cell therapeutics platform of Kiadis, which we expect to close the first half of this year. You'll see examples later today of how these platforms are empowering our pipeline. Again, big trade-offs were made to absorb the cost of these acquisitions, altogether keeping R&D costs flat between the beginning of 2018 and the end of 2020. On to today's presentation. My colleagues will build on the themes that we introduced at last year's R&D Day investor event.
We will illustrate how our team's leveraging the three Ps of pathways, deep expertise in biological networks, connected disease biology, patients using molecular profiling, digital and data to dissect disease heterogeneity, and move towards precision medicine approaches for solving healthcare problems. Finally, platforms, where today we will focus on differentiated platforms for drug discovery. These three Ps of pathways, patients insights, and platforms are supported by a foundation of improving capabilities that accelerate execution, reduce cycle times, and improve overall R&D productivity. With that brief introduction, I hand over to Brian Foard, Global Head of the DUPIXENT franchise, to share our vision and plans for DUPIXENT, the cornerstone of Sanofi's immunology pipeline. Brian, over to you.
Great. Thank you so much, John. Again, I really want to thank everybody for joining us for today's event. We are extremely pleased with DUPIXENT's performance in 2020. The brand has performed exceptionally well throughout this pandemic, that really speaks to an amazing team of individuals around the world, but also the strength and the uniqueness of our profile and its acceptance among both physicians and patients around the world. You probably heard a lot about this amazing medicine at our DUPIXENT R&D event this past June, where we expanded on the innovative science behind DUPIXENT. Since then, our confidence has only grown in DUPIXENT's ability to lead the transformation of the treatment of type 2 inflammatory diseases.
Now as you'll look at slide eight, as you can see from the NBRX chart on the right-hand side, when you look at the combined prescriptions of both dermatologists and respiratory specialists, DUPIXENT has emerged as the number one biologic in the U.S., and we enter 2021 in a great position to further accelerate that growth with approximately 230,000 patients on therapy across 47 countries and three foundation indications. This growth is also supported by a best-in-class profile with clinical data out to three years. Let's move on now, and we're going to share with you a bit about how we're building a mega brand with DUPIXENT. This next slide really dimensionalizes the significant growth opportunity in dermatology with a primary focus on atopic dermatitis, DUPIXENT's first indication.
DUPIXENT is indicated as young as six years of age in moderate to severe patients who are not controlled on topical corticosteroids. We are currently evaluating DUPIXENT in patients below the age of six. Today, with an estimated 2.2 million biologic-eligible patients in the U.S. alone and only 5.1% market penetration to date, the growth potential remains significant. As we expand beyond the U.S. to our top eight markets, that eligible patient population more than doubles to 4.9 million, and this includes the opportunity created by our record NRDL approval in China, and that will add approximately 900,000 eligible patients over time. Beyond geographic expansion, I really want to draw your attention to another dimension of growth. We are in the clinic with four adjacent dermatology indications and also AD patients below the age of six.
There is no other advanced therapy pursuing as many dermatologic diseases. This strengthens DUPIXENT's leadership position among dermatologists while also addressing patients suffering from debilitating dermatologic conditions. If these studies are successful, we estimate that we would add approximately 500,000 patients in the U.S. alone who could benefit from DUPIXENT in these adjacent indications and also the age expansion. In summary on this slide, you can see we have an unparalleled opportunity to reach many more patients suffering from dermatologic diseases driven by underlying type 2 inflammation. Now turning to respiratory, we see a very similar opportunity for leadership in asthma and adjacent respiratory indications. Despite a more developed U.S. asthma marketplace, the biologic penetration rate remains extremely low at actually only 17%. Thus, there's ample opportunity to grow via the market but also via market share.
As we exited 2020, our U.S. NBRX share was approximately 25%. There is also significant opportunity to expand outside of the U.S. marketplace, where DUPIXENT is already a leading respiratory biologic in large markets such as Germany and Japan. If you look at our top seven markets alone, we estimate there to be about 1.9 million biologic-eligible patients. Additionally, there remains significant unmet need in moderate to severe asthma patients in China. Consistent with our approach in dermatology, we are also investigating adjacent respiratory indications driven by type 2 inflammation, most notably our type 2 COPD program, a highly underserved patient population where no therapies have been approved for almost a decade.
Beyond our currently approved asthma indication of 12 and above, we expect to add approximately 600,000 patients eligible for DUPIXENT in the U.S. alone through age and indication expansions in respiratory. Again, this uniquely positions DUPIXENT as the leading advanced therapy in specialty respiratory, and certainly supports our leadership ambition in diseases driven by underlying type 2 inflammation. I'm now happy to transfer the call over to Naimish, our head of immunology development, to discuss Sanofi's deepening leadership in type 2 immunologic diseases beyond DUPIXENT. Over to you, Naimish.
Thank you, Brian. At our DUPIXENT R&D event last June, we dove deeply into the biology of type 2 inflammatory diseases and explained why unlocking both IL-4 and IL-13 are critical for DUPIXENT. The mantra was, "It takes two to tackle type 2 inflammation." I'm now thrilled to introduce Sanofi's next wave of molecules for type 2 diseases beyond DUPIXENT. Our approach of developing the next wave of molecule really leverages our deep understanding of the type 2 inflammatory cascade. Here is a very simplified depiction of the process. On the left here, type 2 inflammation starts with allergens or pathogens contacting the epithelial barrier surfaces such as the skin, airways, or GI tract. This leads to alarming events with mediators such as IL-33 or TSLP.
In the next step, OX40/OX40 ligand co-stimulation plays a critical role in immune programming with TH2 cell differentiation, expansion, and memory T cell formation. This is where you can almost say the blueprint is created for chronic inflammation and chronic disease such as atopic dermatitis. These cells produce cytokines such as IL-4, IL-5, IL-13. These cytokines stimulate and prime effector cells like eosinophils and mast cells, they lead to tissue pathology, allergic responses, and symptoms such as skin itching, thickening, and atopic dermatitis. From this, you can easily see how the mechanism of DUPIXENT in blocking IL-4, IL-13 potently inhibits type 2 inflammation in diseases such as atopic dermatitis, type 2 asthma, and CRS with NP. You can also see how rilzabrutinib, a molecule acquired by Sanofi with the Principia acquisition, targets type 2 inflammation.
The BTK enzyme drives allergy by mediating B-cell expansion and production of IgE, and activation of mast cells, eosinophils, and basophils. Rilzabrutinib, a potent and extremely specific BTK inhibitor, we believe has a significant potential to treat type 2 disease. As another example of how Sanofi is really leading with innovation, I will share with you in just a moment three new programs for rilzabrutinib that will start this year. There are more areas to explore. We are also looking upstream in this pathway to develop therapies that afford potential to treat diseases that are not just purely type 2, but also non-type 2 and mixed phenotype. This is where our anti-IL-33 monoclonal antibody itepekimab is being investigated to reach more COPD patients than any other biologic has attempted.
Today, I'm excited to share with you for the very first time the compelling phase II data that led us to launch our phase III trials in COPD. Finally, we believe that OX40 ligand is truly a unique target for type 2 diseases because it represents a critical co-stimulatory step that leads to the programming of immune response for chronic diseases like atopic dermatitis. The Kymab KY1005 monoclonal antibody that Sanofi announced intention to acquire holds promise to reprogram immune response so that durable disease control may be approached across a number of indications. We look forward to discussing more about the promise of anti-OX40 ligand once the acquisition of Kymab is finalized later in the first half of this year. Now we'll dive deeper into these key molecules starting with itepekimab, our anti-IL-33 for COPD.
Itepekimab could be the first molecule to treat most COPD patients. On a personal note, as a pulmonologist who's been practicing for a number of years, it's quite disheartening to think that so few new mechanisms have entered the COPD treatment paradigm over the last 20 years, despite the fact where COPD is a leading cause of mortality worldwide. Today, I'm glad to say we really believe that we think we're about to change this. We took the unique step of studying itepekimab across a spectrum of moderate to severe COPD because of the known effects of IL-33 on both type 2 and non-type 2 inflammation. This is supported by published data shown here on the left in the graph demonstrating that IL-33 levels in advanced COPD patients who are former smokers are elevated compared to healthy controls.
Here on the right, for the first time, we're revealing the results of our phase II study of itepekimab in COPD. In this study of moderate to severe COPD patients, itepekimab reduced COPD exacerbations by approximately 40% in former smokers. Importantly, this effect was similar in type 2 and non-type 2 patients. This effect size is far and above what has been seen by any other biologic in COPD, where many competitor phase III studies have been 20% or less in terms of exacerbation improvement. This is for the sickest patients with COPD. These results have given us confidence to commence the phase III program in a population where no biologics have succeeded. Thus, we have started our pivotal program with itepekimab.
The objective of these studies is to establish that itepekimab can reduce COPD exacerbations and improve lung function in most patients with COPD. This, in combination with the DUPIXENT COPD program, has the potential to address greater than 80% of patients with COPD with frequent exacerbations. Turning now to the rilzabrutinib program. We believe this molecule that came to us with the Principia acquisition has the potential for a pipeline and a product. I'll explain why. I mentioned in the first slide that BTK is a key driver of allergy and activation of type 2 inflammatory cells. It would be logical then that BTK is a potential strategy to treat type 2 disease such as atopic dermatitis, asthma, and urticaria.
The problem has always been that many of the early BTK inhibitors that were first used in oncology indications in the past have tended to have significant side effects, often because of binding and inhibition of other proteins besides BTK. The reason why we're so excited about rilzabrutinib is that it has been designed to try and avoid these issues with Principia's innovative tailored covalency platform. Tailored covalency, what does that mean? That means the drug has two binding sites on the BTK protein, one of which is a reversible covalent bond. These two sites essentially fit like a lock and key, increasing the likelihood that the drug will bind to BTK, but making it less likely that it'll have unintended binding to other enzymes. Thus, tailored covalency has the potential to minimize off-target binding and minimize the risk of side effects, but still maximizing potency.
Safety is a critical issue for type 2 diseases, especially among dermatologists, and we believe that rilza has the potential to deliver it. What is the evidence to support this potential and our commitment to further investigate this product? It is the results of the studies with rilzabrutinib. On this slide, on the left, you see the phase II results in patients with pemphigus vulgaris treated with rilzabrutinib. In this study, 67% of patients treated with rilzabrutinib achieved minimal disease activity by 24 weeks. This shows the very rapid and potent effect that rilzabrutinib has on this disease, where very few patients would have such a response on steroids alone.
On the right here, in the ITP phase II study, you can see that 50% of patients treated with rilzabrutinib for greater than 12 weeks achieved the primary endpoint of two or more consecutive platelet counts greater than 50. This is a significant result when you consider that these patients had failed a median of six other therapies before entering this study. Most importantly, for both of these programs, rilzabrutinib was well-tolerated with no significant safety issues. Now we would like to reveal our plans for the rilzabrutinib program. Our goal is to develop rilzabrutinib as a pipeline in a product with expansion beyond the typical autoantibody diseases into the type 2 space.
We know for type 2 diseases, safety is of major importance to patients and prescribers, and so we believe rilza, via the tailored covalency platform, may be the right molecule to achieve this high bar with oral route of administration and meaningful efficacy. This target profile may be ideal for patients with less severe disease as an option before going to biologics. Thus today, we're announcing our plans to start the phase II studies for rilzabrutinib in atopic dermatitis and asthma and chronic spontaneous urticaria. These diseases represent a total of 3.5 million patients with high unmet need, and each of these indications is expected to enter the clinic in the second half of this year. On my concluding slide here, I want to provide you with an understanding of how we're thinking about these multiple potential first-in-class or best-in-class molecules in the type 2 space.
You saw in Brian's earlier presentation that compared to other disease areas, we are still in the very early days of type 2 disease. It's an exciting time for patients with many potential entries into atopic dermatitis, asthma, and possibly even COPD. Starting with atopic dermatitis on the left, we are building on the foundation of our success with DUPIXENT. This is a very under-penetrated market with heterogeneity in biology and in patient needs. There is space, we think, for multiple molecules that offer choices to patients to tailor to their biology and individual needs. We're excited about promising oral programs with rilzabrutinib and the IRAK4 degrader. We also look forward to exploring the potential of anti-OX40 once the acquisition of Kymab closes.
Moving now to the right, to the respiratory realm, we're pursuing oral and type 2 plus approach in asthma with rilzabrutinib to provide patients with potentially the first oral treatment to enter the asthma space for some time. We also believe that the next wave of transformative molecules in diseases like asthma require a multi-targeting approach to provide step change over current efficacy. We'll get into this in more detail in the next section with the IL-13 TSLP program. Finally, we have the high ambition to transform COPD therapy with itepekimab now in addition to dupilumab to address greater than 80% of patients with COPD, where currently there are no biologic therapies. With this, I hope I've been able to convince you that Sanofi has a lot more coming behind Dupixent with an immunology pipeline rich in potential first-in-class and best-in-class molecules.
For more information now on our next generation of molecules, including nanobody bispecifics program, degrader programs, and really cool science, I will turn over to Frank Nestle, Sanofi's Global Head of Research and Chief Scientific Officer.
Thank you, Naimish. Building on the foundations of our winning strategy in type 2 inflammation, I would now like to discuss with you where we go next in our journey to becoming a global immunology leader, including and beyond type 2 inflammation. I will illustrate this based on multiple emerging immunology assets targeting immune pathways central to tissue inflammation and poised to make inroads in a range of I&I indications. A major challenge in drug discovery, including in immunology and inflammation, has been the relatively low probability of success in early clinical trials, arguably based on a lack of adequate understanding of inflammatory disease mechanisms. To address this, we have built a unique immunology discovery engine providing unprecedented insights into inflammatory and autoimmune disease biology.
Our single-cell immune disease engine combines the analysis of orthogonal data sets, including genetics and single-cell genomics of diseased tissues, for example, blood, skin, joints, kidney, and lung, with proprietary artificial intelligence algorithms. Through this drug discovery engine, we obtain deep insights into underlying disease mechanisms, stratification of molecularly defined patient subsets, reasons for inadequate response to therapy, and opportunities for combination immunotherapy. We unlock the resulting valuable insights into novel patient biology using our advanced technology platforms. Let me give you a few examples. Synthorx redefine tunable cytokine therapy and regulatory T cell expansion for durable disease modification. Multi-specific nanobodies or antibodies allow combination therapy in a single molecule. Reversible covalent small molecule inhibitors allow precise tuning of target pharmacology according to therapeutic needs.
In the following, I would like to give you several examples how unlocking patient biology with our advanced technology platform is turned into reality with concrete assets moving into the clinic in 2021. Several efforts in the biopharmaceutical industry have failed to establish a reliable next generation bispecific biologics platform for immunology and inflammation. With the acquisition of Ablynx, the worldwide leader in Nanobody therapeutics, in 2018, we established a unique position for Sanofi to launch a whole new pipeline of next generation B- and multi-specific biologics with distinct and unique target product profiles. Today, I'm happy to share with you the first example, a multi-specific anti-IL-13/TSLP Nanobody entering phase I in 2021. This asset already benefited from accelerated drug discovery timelines, a general feature of the Nanobody platform.
The nanobody demonstrates superior efficacy compared to single agent anti-IL-13 or anti-TSLP monoclonal antibodies in a translationally relevant allergen-driven human tissue mimic assay shown on the right side of the slide. The target selection rationale is straightforward. Blocking IL-13 has the potential to enhance the more modest impact of anti-TSLP blockade on lung function, while anti-TSLP targeting provides the opportunity to treat a range of asthma subtypes. Taken together, the combination of targeting IL-13 and TSLP in one molecule promises the potential of enhanced efficacy in a broad range of asthma. Further distinguishing attributes of this multi-specific nanobody include a straightforward regulatory and development path, tunable half-life and resulting extended dosing schedule, and finally, convenient patient administration via an autoinjector. Let's move now to protein degraders as next generation products in inflammatory disease.
We have partnered with Kymera Therapeutics, a world leader in protein degradation, to develop the very first oral protein degrader in immunology and inflammation, targeting atopic dermatitis and hyperimmunoglobulin E syndrome, planned to enter phase I clinical studies in 2021. IRAK-4 is a master regulator of TLR and IL-1 family-dependent inflammation, controlling the production of key pro-inflammatory cytokines such as type I interferons, IL-6, and TNF alpha. IRAK-4 does this via two critical biological functions, a kinase function and a scaffold function. First generation attempts of targeting IRAK-4 kinase function using ATP competitive kinase inhibitors validated IRAK-4 as a target in indications such as rheumatoid arthritis, but did not reach the level of efficacy required to be competitive as monotherapy in the fast-moving oral immunology field. Sanofi and Kymera's next generation IRAK-4 protein degrader, SAR444656, allows blockade of both the scaffold function of IRAK-4 in addition to the kinase function.
Preclinical experiments shown on the right demonstrate the superior inhibition of phospho NF-κB and the superior inhibition of combined stimulation of PBMCs with TLR in IL-1 stimuli. It also demonstrates the very potent degradation of IRAK-4 protein in critical target organs such as the skin. These data provide a convincing framework for advancing our first-in-class I&I focused IRAK-4 oral protein degrader into the clinic. We have spoken a lot about THOR-707, our non-alpha IL-2 for immune oncology. Today, I would like to introduce you to THOR-809, our non-beta IL-2, entering the clinic this year with potential in a broad range of autoimmune diseases. THOR-809 takes advantage of the same unique synthetic biology platform for precise attachment of polyethylene glycol to IL-2, enabling selective targeting of the IL-2 receptor alpha chain.
The key goal for THOR-809 is durable disease modification and rebalancing of the immune system through the expansion of regulatory T cells. On the right side of the slide, you can see pre-clinical experiments demonstrating up to 46-fold expansion of regulatory T cells by THOR-809. This translates into superior dose-dependent inhibition and control of skin inflammation compared to cyclosporine A. Today, I hope I was able to convey my excitement with you that we're just getting started in immunology, with multiple emerging immunology assets moving into the clinic this year and the creation of a sustainable I&I discovery pipeline. I'm now handing back to John for concluding remarks.
Thanks, Frank. I will now briefly summarize the pillars of the Sanofi strategy for leading in immunology, and then will provide a more comprehensive overview of our emerging pipeline in immunology medicines. As we outlined here today, Dupixent is the foundation. We will maximize the potential of this remarkable medicine, which has already created medical history as the world's first biologic to be approved for atopic dermatitis, the world's first biologic to be approved for chronic rhinosinusitis with nasal polyps, and which has the potential to be the first biologic approved for COPD. Dupixent is the cornerstone of Sanofi's emerging leadership in dermatology and also in respiratory. Building on the success of Dupixent, we have a strong pipeline that continues to focus on the type 2 inflammatory pathway while also crossing over into other immunological pathways to tackle diseases that have a more mixed picture.
The molecules referenced here today include itepekimab, the anti-IL-33 monoclonal antibody from the Regeneron alliance, now in phase III for COPD. itepekimab operates at a very upstream step in the type 2 inflammatory pathway. rilzabrutinib, the oral reversible covalent BTK inhibitor from the Principia acquisition, now in phase III for a dermatological indication, a molecule that we plan to explore in eight different indications by the end of this year. rilzabrutinib operates at a very distal step in the type 2 inflammatory pathway. Finally, KY1005, the anti-OX40 ligand monoclonal antibody from the Kymab acquisition, of course, pending regulatory approval, which operates at a nodal point involving TH2 cells and regulatory T cells with promising data generated so far in atopic dermatitis.
The third pillar in our strategy is to expand beyond the type 2 and adjacent immunoinflammatory pathways with innovative medicines that leverage several of the powerful platforms to which Sanofi has recently gained access. Examples of potentially transformational molecules in this category include our oral small molecule IRAK-4 degrader that you heard about, which is incidentally the world's first degrader molecule that will enter the clinic for a non-oncology indication, access via the partnership with the biotech company Kymera. The IRAK-4 degrader has the potential to play across multiple immunoinflammatory conditions where IL-1 and IL-33 are culprits, but offering an oral medicine option. Also of note is our non-beta interleukin-2 molecule, THOR-809, which is produced using the synthetic biology platform coming from this acquisition of Synthorx. THOR-809 has the potential to become a best-in-class expander of regulatory T cells for restoring immune homeostasis across multiple indications.
The multispecific Nanobody should be mentioned here, coming from the Ablynx acquisition following our acquisition of that company in 2018. We expect to put multiple Nanobody drug candidates into the clinic this year, each of which neutralizes not one but two lymphokines or cytokines that have been clinically validated as relevant disease targets. These Nanobodies will push beyond the limits of monospecific agents, helping to break the efficacy ceiling observed currently for most biological treatments. Here in our last slide, I illustrate the breadth and depth of the emerging Sanofi pipeline in immunology products and product candidates. The molecules are organized according to the specialty care area where they're most likely to play, but I should note that many, if not most of our molecules have the potential to be effective across several areas of medicine.
You'll note that Sanofi is building a particularly broad portfolio of product candidates in the dermatology and respiratory spaces where we aim to lead the industry. We are laying the seeds for meaningful participation in GI and rheumatology in the future. Altogether, Sanofi has today 15 molecules in development for immunology and inflammation indications. Furthermore, the same immuno-science that's the foundation of our dermatology, respiratory, and emerging GI and rheumatology portfolios. Also spreads into our hematology, neurology, and immuno-oncology therapeutics areas, with examples found in the BTK inhibitors rilzabrutinib and tolebrutinib, as well as our anti-CD40 ligand antibody and our emerging portfolio of complement-inhibiting antibodies.
As we pointed out in our R&D investor event last year, expertise in immuno science is a core competency at Sanofi, and we leverage this science across the company's entire R&D portfolio because it touches on almost every therapeutic area in pharma and, of course, also in Vaccines. I'll close there and open for Q&A, for which I'll serve as the moderator.
Thank you, John. Yes, we are moving now into our last Q&A session for today with an emphasis on R&D, since we are now joined by our presenters as well as Dietmar, our Chief Medical Officer, and I also have Paul and John Martuccio still with me in the room. Natalie, can we start with the first question, please?
Yes, sure. Thanks, Eva. The first question is from Thibault Boutherin at Morgan Stanley. Thibault?
Hello. Hi, can you hear me?
Yes, we can. Thanks.
Okay, thank you very much for taking my question. I just wanted to come back on your development strategy for your new immunology assets, in particular, in terms of sequencing and combining these assets. Would you consider using a GP as a backbone on which to potentially add new treatments? Is your approach more to use your new immunology project as alternative to Dupixent and a way of ring-fencing your leadership in type 2 inflammations? If you could share your view on how to determine which patients would benefit from which pathway and how to sequence or potentially combine these assets. Thank you very much.
Thanks for your questions. I'm going to call on some of my colleagues to help, but I'll start off by just saying, of course, we're early in the exploration in the clinic of many of these molecules, and so really fleshing out their fits in the landscape of various immunological diseases is something that we'll be doing in the months and couple of years ahead. We do recognize that many immunological diseases are complex and heterogeneous, and that's why we emphasize our efforts in the precision medicine work that Frank outlined in really beginning to better dissect the disease biology and match the right medicine to the right patient.
We think this portfolio will enable a number of different strategic approaches as the data emerge and we have better insights into really how best to position the molecules, whether they're combined with Dupixent or used for patients that don't respond as well to Dupixent or tackling with those that have maybe a more mixed picture, for example, that Naimish outlined. Patients that are simply their disease evolves over time and they switch to different therapies over time. Dupixent clearly is a great foundation, and it's arguably a best-in-disease solution today, but we know that there'll be opportunities to build on top and around that. Maybe I'd hand over to perhaps Frank first. Maybe you could embellish on that a bit and then Naimish.
Yeah, happy to, John. I just would like to say from a very personal opinion, I think we've built one of the most exciting emerging immunology portfolios in the industry, and all of our decisions are science and data led. This is what we have been doing over the last four or five years. I just would like to remind you, there's still a huge unmet need out there in immunology and inflammation, and this is really driven by efficacy ceilings. If you're looking across rheumatology and dermatology and respiratory, there are massive efficacy ceilings where patients do not get the drugs they deserve. Durable responses are really just on the horizon, but not really implemented yet. As John was pointing out, there are really different patient populations defined by their molecular mechanism. Also in terms of market penetration, these markets grow.
Physicians are experienced now with biologics, and you can see that if the right medicine comes along, which is really transformative, patients will come, and physicians will prescribe. What you really need is a portfolio which is waterproof in the short term, medium term, and long term. I think in the short term, we have first choice Dupixent. No question about it. It's a stunning biologic. With these 15 biologics and orals we're having now in our pipeline, we have also the medium and long-term strategy to really create a sustainable portfolio. If you think about itepekimab potentially open up the COPD space, if you think about BTKI as really an oral immunology leader, very safe, but going into multiple different immuno mechanisms, for example, autoantibody-mediated disease or in the type 2 space.
Finally then our long-term strategy with an oral protein degrader, first time ever that a pharmaceutical company is bringing an oral protein degrader targeting IRAK4 into chronic autoimmunity or our bispecifics platform using Nanobody, where we can actually mix and match and dial in the appropriate features for a winning TPP, including the schedule of dosing, breaking efficacy ceilings, and actually having, hopefully, a good cost of goods and good economics with great patient convenience. It's a portfolio. It's like a winning portfolio strategy.
Naimish, anything to add before we move on?
Thanks, Frank. You both covered it completely. I think as mentioned, atopic dermatitis is a great example, 5% penetration, 95% of patients eligible still haven't taken any. There's things to consider like differing biology across that segment, different individual patient needs. There's plenty of room for a number of different mechanisms to fit patient needs.
No, absolutely. I think one thing is that the heterogeneity of patients also plays out in racial differences. For example, atopic dermatitis in Asian patients compared to Caucasian patients, for example, tends to have different biology. Same for Black patients. There really is a need for different mechanisms for different patient populations.
If I could just follow up on another question. I was just wondering, obviously there are a lot of bispecifics in development. If you could just maybe give us a bit more color on the points of differentiation of your bispecific with the Ablynx platform compared to what your competitors are doing.
Sure. Frank, do you want to take that?
Yeah. Number one, obviously the bispecifics have been a success in immuno-oncology. Bispecific engagers, T-cell engagers are really going from success to success. However, in the I&I space, if we look at what has really happening is that a lot of bispecific approaches in I&I have failed, either because targets were not properly engaged or ADAs problems were arising. What we actually have built over the last year since our acquisition of Ablynx, we've built probably what is the most advanced, what I call Biologics 2.0 technology using nanobodies. Nanobodies are very interesting because you can actually combine them like pearls on a string to make multi-specifics. For example, we can dial in half-lives by binding to albumin. We can dial in multiple targets, because we can sort of combine these nanobodies in one molecule.
Actually, the clue is not only in the platform which is differentiated, and we have now phase II data demonstrating that the Nanobody platform is really very effective in the clinic in chronic inflammation. It's also the target selection, and this is where the precision immunology element comes in. We, for example, the targets we are convinced about today, and for example, the reason why we are also interested in OX40 ligand as a target is that already in 2016, 2017, we mined data sets, and they told us what are the winning targets are going to be. Already we're seeing with the targets now in phase II trials being winners, that we actually make the right pick. There's more to come. This is just, we've titled the session emerging, so there will be much more coming, but we're very confident about our technology platform.
It's very differentiated, number one, with Nanobodies, and second, the choice of the targets.
Good. Eva, next question.
Yeah. The next question is from Tim Anderson at Wolfe Research. Tim?
Hi. Can you hear me okay?
Yes.
Yes.
Okay. I wanted to ask about two of your higher priority assets, oral SERD and oral BTK. Just a high-level question. It kind of seems like everyone is claiming to be best in class, and not everyone can be best in class. In the oral SERD space, you and Roche and Astra all claim it. In the oral BTK space, you and Roche claim it. Can you just update us on why you think your molecules are best in class? It seems like some of the data sets with some of the compounds are just too early to make comparative claims. Second question on DUPIXENT. In asthma in China, if I understood it right, those trials are still ongoing. What would be the timing of getting approval in China and potential an NRDL?
Okay, good. Several questions there. Why don't we do the BTK first, because that flows right from the presentation that Naimish gave. Naimish, can I ask you to take that then and explain the differences in the various BTKs and why we believe that the Principia molecule that we have, rilzabrutinib, has the potential to be the best-in-class choice?
Sure. As I got into a little bit in the discussion, we had just the tailored covalency part of it. The issue has been with a lot of BTKs that they've either had off-target side effects such as liver function abnormalities, platelet dysfunction, atrial fibrillation, that had limited their scope in terms of the indication space. rilzabrutinib has been designed specifically with this platform to be very specific to the BTK enzyme and limit the off-target sort of binding to other proteins that many of these side effects often come from. We think it's ideal in that way for the type 2 space.
You can see some of the other BTK enzymes or BTK inhibitors have tried in CSU, for example, but even though the efficacy is there, the safety hasn't quite what is needed in that space to really be a drug that prescribers and patients feel safe taking. I think that is the crux of the matter. Our phase II data thus far hasn't shown any similar side effects profile, so that's why we're very confident that we can enter the space with the compound we have.
Just to add a little more on that, I'm very familiar with both molecules. The Roche molecule is a fully reversible molecule. The downside with that is getting enough target exposure. What we've learned about BTK is to get the efficacy, you have to hit the target hard, and you have to keep it hit hard, which is where the covalent piece of rilzabrutinib comes in, because that then completely inactivates the target and keeps the exposure longer. At the same time, that tapered aspect of it prevents you from interacting with and staying on other targets. We think it really threads the needle well in terms of both getting the target exposure you need, which has to be like 95% all the time in order to have the efficacy, but at the same time avoiding the off target.
For that reason, we think it will outperform a fully reversible molecule, which is going to be hard to keep that target really engaged all the time. On the SERD, I'm going to ask Dietmar to help me with that one and why we think amcenestrant has potential to be the best-in-class solution of an oral SERD for women with hormone receptor-positive breast cancer. Dietmar.
Happy to. Thank you, John. Before I go to the SERD, let me just talk about the other BTK, which is tolebrutinib. Again, the question about best-in-class comes up there, and there it is really the brain penetrance. Besides the BTK inhibition and really the impact on innate and adaptive immunity and the impact on peripheral and central, we really think that we have best-in-class potential as well. For all of these molecules, I am switching to amcenestrant here, eventually it is going to be about benefit-risk and about application to the specific patient population. You may note in hormone receptor-positive breast cancer, really that question of benefit-risk becomes quite important. We are looking forward to present more data at a conference towards the middle of the year.
Really the data from the phase I-B study around the combination with palbociclib, that data that gave us confidence to kick off a study in first-line metastatic breast cancer, exactly that combination, a pivotal phase III trial. When we look at the data that we've presented so far, I find efficacy, and you look at the data at ASCO last year, I find the efficacy data very encouraging. You do see the right clinical benefit rate. You do see the right degradation of the estrogen receptor. You do see activity in the estrogen receptor mutants, in the ESR mutants. We do see a really encouraging safety profile, which will be important as we develop this molecule across the different lines of therapy. The big prize is obviously usage in the adjuvant setting, and there the risk profile becomes even more important.
As we see the data emerge, I remain very confident and, let's say, even more bullish around the molecule that this really has best-in-class potential. You're going to have to see this then eventually as you see the data emerging over the year from a benefit risk perspective.
Yeah. Thanks, Dietmar. I think that safety difference is most clearly seen in the lack of any cardiac signal that we have with amcenestrant compared to other molecules. It's those effects on cardiac ion conducting channels of the competitor molecules that have resulted in the need to reduce the dose, and that then also then jeopardizes the ability to cover the target and get the efficacy you need. Threading the needle on the molecules that have those cardiac toxicity issues is less than ideal, let's say. That's not a problem with amcenestrant, and it's why we think particularly moving into the places like the adjuvant space where safety matters so much, that we'll have the best-in-class profile. The final question was about DUPIXENT in China. Brian, maybe we can get you into the mix here and let you handle that.
Of course, maybe for Dietmar, could chime in if you need any help. Brian?
Yeah, absolutely. Thanks so much, John. Obviously, we've got the ongoing program with nirsevimab in late 2022, early 2023. We're looking at potential approval into 2023, early 2024. Typically, we assume an NRDL approval about a year later. Now, as witnessed by our record time for DUPIXENT and really the local recognition of innovation, I think, by the China authorities, getting record time for atopic dermatitis in adults of five months, it could potentially be shorter than that. We would be optimistic, but that's the current timeframe we have for China.
Thank you. All right. Thank you. Good. On to the next question, Eva.
The next question is from Emmanuel Papadakis at Deutsche Bank. Emmanuel?
Thank you for taking the question. Can I just take a couple of follow-ups on DUPIXENT? The first one, maybe existing utilization in asthma. If you have it, could you give us a little bit of color on how use is skewed in the patient population? I'm thinking in terms of eosinophilic markers in particular, and perhaps your perspectives in the light of that on the potential implications, if any, of the recent tezepelumab data, particularly in the eosinophilic low subgroup of patients. The second one on DUPIXENT, just the regional expansion opportunity. You mentioned it earlier, it still remains extraordinarily dependent on the U.S. How soon, for example, is the European opportunity like to mirror what we've seen in the U.S.? Is there an inflection point coming on the back of reimbursement access opening up, or is that going to be a slower build?
Maybe Brian, you could give us a bit more color on the NRDL listing in China and AD. What kind of price cut did you have to take? When will the volume s tart to kick in now. Thank you.
All right, Emmanuel. Thank you for your questions. I'm going to have Brian tackle those, and if there any elements around the eosinophilic phenotype that we don't cover there, maybe Naimish will help him out. Brian, over to you.
Yeah, for sure. Thank you, Emmanuel, for your questions. Really good ones. I think if you think about the asthma space, in that moderate to severe uncontrolled asthma space, it's really the way we look at it is that it's the type 2 patient population. It's really not just identified by eosinophils. Obviously, you think about FeNO, of course, IgE levels. We actually designate about 80% of that population is really type 2. We really don't, again, align ourselves with just the FeNO, or excuse me, the EOS levels from that standpoint. Now that being said, we have access to all those patients. Actually, we have basically above 150, as we've shared with you guys before. Especially in the U.S., we have fantastic coverage. We have the access of those full type 2 patient population above 150 EOS levels.
Now, that said, you asked to compare this a little bit to what we've seen with the recent TSLP data. I think the recent TSLP data, again, really highlights a lot of what the organizations, both Amgen and AstraZeneca articulated, that it really largely seems to be sitting in that much smaller patient population below the 150 EOS levels, which as we articulated, that is again about 20% of the patient population alone. If you look a bit further, as we've seen in the recent failure with OCS-dependent patients, that actually further narrows that population because DUPIXENT, as you know, without an eosinophilic biomarker, actually we are approved for OCS patients as well, again, regardless of eosinophilic phenotype.
We really feel strongly that our platform, if you will, for Dupixent, this type 2 platform, and our profile remains the strongest profile in asthma of all the current agents and the agents to come. A little bit about China. Obviously within NRDL, that was really exciting news. Obviously record time, as we just mentioned, five months, and that is a really great signal that China is continuing to recognize the innovation of these medicines. From a price standpoint, the price will be out and be public in the March timeframe. Again, all we can really share right now is that we're extremely positive about their recognition of the value of Dupixent in China.
Okay.
Brian. Sorry, if I could just add a little bit color on the TSLP point. Going back to the slide I presented on the type 2 inflammatory cascade. You could see how DUPIXENT is well lined in that sort of decision point in the cascade, inhibiting IL-4 and 13 to inhibit really type 2 inflammation. For asthma, what that really means is airways inflammation. We know that FeNO is a great marker of airways inflammation, and DUPIXENT has a much stronger effect on FeNO and also a much stronger effect on lung function improvement in the type 2 space compared to TSLP. The OCS population is another example of really a type 2 population. The biomarkers aren't so reliable for OCS, but we've seen in our studies if you withdraw the OCS, their eosinophil counts go up, and they're really just type 2 patients.
You can see that TSLP wasn't successful in that population where Dupixent has been hugely successful in that population. That type 2 space, the type 2 asthma space, we think Dupixent is really the winning molecule there.
Good. Next question, Eva.
We have time for one last question from Graham Parry at Bank of America Merrill Lynch. Graham?
Great. Thanks for taking my question. Just earlier when you were talking through the amcenestrant data points, you didn't highlight the proof of concept study in early breast cancer, but you have expressed optimism around that. Is that data still coming, the window of opportunity study in early breast cancer proof of concept, is that still coming this year? Has that been delayed? On the IL-33, were there any other biomarkers other than former smokers in the phase II that drove the exacerbation reduction? Are you stratifying for any of those biomarkers in phase III? Any potential to sort of target particular subpopulations, even if the overall data set is less successful, given that this has been a very difficult indication to get meaningful data in?
Finally on DUPIXENT in chronic spontaneous urticaria, that could be one of your biggest phase III readouts this year. Physicians using this off-label report mixed results, suggesting quite a heterogeneous patient population. Is the trial set to detect that, again, use of biomarkers or anything else? Thank you.
Thanks for your question, Graham. I'm glad we were able to get to you. Maybe I'll take the questions in reverse order. You mentioned the DUPIXENT and CSU. The trial is ongoing. We won't comment on what investigators may be saying. I would only say that as we move into diseases adjacent to our core areas like atopic dermatitis, we're going out into areas that sometimes may have a more mixed picture. I think we have to be prepared that DUPIXENT may not benefit every patient, and that's why we do have these other molecules coming. If you think about, for example, rilzabrutinib is a really good solution potentially for CSU if DUPIXENT doesn't resolve their issues. I don't know if Naimish has anything else to add on that while we're on DUPIXENT.
Sure. Yeah. There are these subpopulations in CSU with autoantibodies to the Fc epsilon receptor and also autoantibodies to thyroid proteins that might have a differential response to Xolair. The beauty of Dupixent is that the IL-4 receptor on mast cells is an important activating factor for mast cells, so it's a different pathway from what Xolair and mepolizumab are targeting. We're definitely looking at these biomarkers, and we'll see how the outcomes come, but we think there's actually a potential that we could really have a differentiated population that responds to Dupixent versus what Xolair does in this space.
While you have the floor, Naimish, would you comment on biomarkers in infliximab applications of COPD? Any further insight you want to offer there?
Sure. To take a step back about these results for IL-33. COPD in adults is extremely common. 6% of the U.S. population has COPD. However, we're zeroing in on a very specific segment of COPD, the patients who are extremely having frequent exacerbations and lots of symptoms, so it's a small segment. Within this segment, you have patients who are still actively smoking, about 30%, and 70% who are not actively smoking. Within this, the 30% who are actively smoking, they're having significant symptoms, significant exacerbations, and they're smoking, which is essentially tobacco smoke contributing to inhaled particles, toxins, other things into the lungs as a constant exposure. There's lots of biology to back this up. The biology in those patients is probably fundamentally different than the other segment of patients who's no longer smoking, yet they're still having exacerbations, frequent symptoms, and the like.
Smoking, of course, causes a very diffuse sort of immune activation, so it might be a hard thing for a single agent like IL-33 to provide efficacy. In the non-smokers, there's pretty good preclinical evidence that the patients who are not smoking but are extremely symptomatic, as I presented, have high levels of IL-33 in their lungs, and IL-33 is a specific contributor to both exacerbations and frequent symptoms. We don't necessarily yet have good biomarkers for IL-33 or the like. They're certainly in development. We think this paradigm of smoking and ex-smoking also contributed by our own internal data showing that IL-33 levels tend to be elevated in former smokers versus current smokers who are very confident that we have this population and the clinical data of 40% reduction in exacerbation just really suggests that we've targeted the right population.
Further biomarker development, of course, is in the works and we're going to have more sort of mechanistic studies to better understand how IL-33 is specifically working in these patients. We feel like we really have targeted the correct population.
Yeah. Thank you, Naimish. We're really looking forward to getting these data published and presented at meetings where we can get into more of the details. As you pointed out, a 40% reduction in exacerbations. When do you see that in COPD? It's really quite profound. We're optimistic about our phase III program, and I think we've really come on with some interesting biology here and an interesting difference between some of these subsets of patients. The final question on amcenestrant and the window study, this is in the neoadjuvant that has been delayed because of COVID. There were fewer women going in for those procedures, but we are re-engaging with that, and irrespective, we're pushing forward with our plans to move amcenestrant into the adjuvant space. Dietmar, could you provide Graham with an update on that?
It's exactly as you said, John. It's a tragedy. We do see a delay of procedures in oncology patients during COVID. Having said that, we do see solid recruitment into the study. Yes, it's delayed. We do have solid recruitment. We will be able to utilize study outcomes this year for our internal decision-making, for sure. We have not taken a final decision at what point then to present the full study data externally. Yes, we will have data this year.
Good. Well, thank you, Graham. Eva, is that all the questions-
I would like-
For now?
Yes.
Would you like-
Yes. Thank you. I'm going to hand it now back to Paul for some concluding remarks.
Okay.
Well, thank you. Thanks, Eva. I don't know if you can see me. Hopefully, at least you can hear me. I just want to thank the team for the work today and indeed for the sessions this afternoon. I think for all those that are following the company closely, you knew that it was going to be a transformation story for us. I personally believe we're ahead of schedule. I think our financials are strong. We checked on them earlier. Our confidence going forward is strong. Our belief in DUPIXENT being the winner is strong. When you see the quality of the science and the thinking, particularly in immunology, and it applies across our teams, but you wouldn't have heard this afternoon, I think you start to see the joined-up connected thinking.
All of our wisdom, all of the experience of this team putting together something quite incredible, recognizing subpopulations, recognizing heterogeneity where it is, understanding the value of rilzabrutinib, which I think is not well appreciated. Everybody got excited about tolebrutinib, too. Rilza just keeps getting better and better the more we understand it. Confidence on a third for sure, but it's staying in immunology. The IL-13 TSLP nanobody. I inherited the Ablynx deal, I get to see the benefits of it. I'm really looking forward to it doing some extraordinary stuff. As the team pointed out, the risks, the probability of success is so much higher in our nanobody platform, and we understand enough about these platforms where TSLPs will disappoint, where 13s on their own will disappoint. You bring them together exquisitely, which is a word I'm learning more about at Sanofi.
You really get to understand some of the magic that's going on. It's infliximab, which was just mentioned. Perhaps because of our checkered past the enthusiasm comes late to some of our assets, you choose to watch from the sidelines a bit longer. 40% reduction in exacerbations in COPD is completely game-changing. Yes, we have to get there. Nobody's ahead of us on this. We're blazing a trail. I'm proud of the team, what we're putting together, you cannot miss the fact that the prioritization in Gen Med, in Consumer, and the desire to free up resources, continue to grow, but be as strategic to reinvest in these assets, to double down and go to Play To Win is what we're about.
As an executive committee, this is our job, is to lead the team, to make the choices, to deliver on the science and deliver the financials. I know for many of you who want to see that unfold, it's okay. We are ahead of where I expected and very proud of the work that's going on. Thank you to everybody for joining.