Ladies and gentlemen, thank you for standing by, and welcome back. We are now going to begin the virtual Sanofi Capital Markets Day twenty twenty one 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 after this Zoom link for all sessions. I would now like to turn the call over to Eva Schefferjonsen, 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 and 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 Documentorges de Tromont Universal 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 live on our play to win strategy. Olivier Chamet, Head of General Medicines and Julie van Onderwal, Head of Consumer Healthcare will then discuss the new strategic priorities of their respective businesses, followed by a Q and 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 on our Q4 earnings call. I thank every one of you for joining us and staying with us for the twenty twenty one Virtual Capital Markets Day. It's been a little bit over a year since we met at our twenty nineteen Capital Markets Day and 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 and 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. And 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 €3,500,000,000 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. And this is just the beginning for Dupixent's amazing growth trajectory.
Later today, Brian Ford is going to share with you how he and his team are expanding around this mega brand in type two COPD, chronic sinusitis without MP and other diseases. And while we are convinced of its sales potential of being greater than EUR10 billion. Our vaccine franchise has generated EUR6 billion in sales in 2020. Influenza was certainly the strong driver, but also the PPH portfolio grew double digits over EUR2 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're only accelerating demonstrated by 12 projects entering Phase three in 2020 alone. John and his leadership team will share with you the progress on the R and D transformation. So looking at Slide seven, you can see how it demonstrates our ability to execute on capital allocation. Over the last twelve months or so, we engaged in multiple M and 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 Synthorex acquisition, adding THOR-seven zero seven that combines so well with other assets in our oncology pipeline. And for the first time today, we'll speak about THOR-eight zero nine 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. Now in June, before we'd even had a readout in mRNA, we also knew that it was an opportunity for us to simply double down. So we widened that collaboration. We took all of the targets, all the assets, take 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 Chimera and the Orak4, 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 tolobrutinib, the brain balance from PTKI, a potentially truly disease modifying asset that we put into four Phase three trials straight after POD in the middle of a pandemic. We also picked up riluzobrutinib, another exquisitely selective BTKi. You'll hear more about this today. So 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 Euro API 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. The key drivers for this improvement will include this continued strong growth of Dupixent and we announced today that Dupixent is expected to be accretive to BOI margin by the 2022. I suspect that's 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 Health 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. So what do we hope you'll take away from today?
Well, that we set out to do everything we said we would do. Now not everything is perfect. We don't pretend it to be the case and our challenges. But 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.
So 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, '23 onwards, this is about the pipeline. Would like to ask Dietmar to update you on the status of our late stage priority assets. Piedmont, 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 and 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 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 ninety eight percent of patients in our ongoing studies with timelines largely unaffected. So, 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, and Brian Ford will provide more details on our ambitions in new indications later today. We continue to remain excited about our fully owned SERD called mcinestrant, 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 MIRA three trial in second line and third line metastatic breast cancer later this year. We are also looking forward to sharing the compelling combination data from our MIRA one trial, which led us to rapidly initiate our first line pivotal trial in combination with pelvociclib. On fitusiran, we have encouraging news to share. First, fitusiran received Fast Track designation from the FDA in December. And 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 BIIB001, we completed enrollment to meet the end of study criterion in our pivotal trial in December. The study includes a fifty two week follow-up period, and due to the COVID pandemic, we now plan to share top line pivotal results in early twenty twenty two. 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 Parkinson's disease population, biomarker data confirmed the mechanism of action of vantalustat with both meaningful and predictable GL1 reductions in plasma and the cerebrospinal fluid.
More on the progress of vanglustat's development in a moment. And as for nirsevimab and tolubrutinib, 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 through 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 Hemophilia.
And 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 to a lower dose and extend its treatment intervals. In the coming months, we will be engaging with health authorities to discuss the regulatory path forward. So, more to come on submission timelines following our alignment with the regulators. But early feedback from investigators and the hemophilia community has been positive, and the vast majority of patients are continuing the trials at this point. And on slide 14, I want to reemphasize 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 clear proof of concept data in those type three and Fabry diseases, and a potentially transformative effect in the treatment of polycystic kidney disease. And while the recently completed MOVE CD 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 MOOSPD confirm that venglustat exquisitely targets GCS and leads to consistent, predictable GL1 reductions in both plasma and the CSF. And 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, we are now expecting pivotal data in ADPKD in the 2022, which leaves the submission on track for 2022 as previously guided.
And with that, I hand back to Paul.
Well, thank you, Dietmar, that update. And 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, real game changers in our late stage development. So 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 and D, helping us to deliver breakthrough medicines. We will run general medicines even more efficiently being BOI accretive for the group. And on consumer healthcare, we're making good progress to make it stand alone so that 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. Since then, 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, Genmed 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 population, 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 Medicine sales, have the potential to grow mid single digit CAGR over the period of 2020 to 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 Medicine over time. This, however, excludes the sales of Euro 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 attractive 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 impacts from LOE 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 continued to grow with Sanofi as a market leader.
In addition, we expect label expansion for Lovedox 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 incidence of coronary heart disease and ischemic stroke. And 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. Moving to next slide, in our core assets portfolio, we have four patented brands with meaningful differentiation potential. Potential.
As discussed earlier, we intend to focus on selected markets with class expansion opportunity. For example, Praluent is the only PCSK9 associated with a reduction in all cause mortality and offering a once monthly single injection in a prefilled 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 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 Smultak. This is the only antihyretic drug to reduce the risk of severe hospitalization for atrial fibrillation and the only drug currently actively promoted in The U. S. New data was recently published showing the CD 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 one Diabetes and kidney disease. Moving now to Soniqa. 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 OAB segments for patients with A1c levels above nine. Bottom line, we have four differentiated core assets with potential for our key markets. With that, let me now hand over to Alexandre Des Germain, Head of our Global Cardiovascular and Established Product 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 threefour of our General Medicine 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're confident. First, our digital material provides 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 SCP 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 individual customer experience and progress towards a mass based action powered by artificial intelligence. With that, back to you, Olivier.
Thanks, Alex. Now moving to the next slide. You may remember that at the Capital Market Day in 2019, we announced our intention to streamline our sale 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 2020, ahead of target. Clearly, reducing the complexity of our portfolio is a critical level 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 design plants, Reshaping our industrial network to achieve higher utilization rates and greater focus is expected to lead to COGS improvement and contribute to our objective of keeping the Genmab BOI margin ratio stable during the next five years. In summary, on my last slide, I hope we are 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 Medicine 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. This transformation is already underway. And while it should require some time before stabilization of General Medicine 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 CHG 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 CHG 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 broader complex portfolio with over two fifty brands. Our performance has been impacted yearly by product related issues on many of our Kiel 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. And 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 Gen Med, 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 by swiftly divesting our chill brands, concretely reducing the number of brands we operate by roughly 60% in three years from over two fifty 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're well aware, we have two major switches, Cialis and Tamifu, which are expected to be key pillars of our future growth. First, my team and I are getting 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 stand alone THC business is a key enabler to move faster in this journey. Finally, obvious digital, a key driver of this strategy, and 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 the 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 €130,000,000,000 market, which is anticipated to grow 4.5% CAGR over the next five years. And 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 €51,000,000,000 market, overall growing faster than the market, that again is excluding e commerce. To us, they represent today about onethree of our CHG business.
As you can see on Slide 25, indeed, 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 ZYZOL have driven the growth of the business in The U. S, making Sanofi a preferred switch partner in the industry. Rene Crane 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%.
And we have more loved brands such as IcyHot, 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. And as a consequence of the COVID pandemic, it's 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 Unisum, already one of the leaders in OTT sleep and growing faster than the OCC 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 Nova Nights. In December, we launched a new campaign in France with immediate double digit impact on growth, plus 20% growth versus the market at plus 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. And our strategic priorities are all about unleashing the potential of our numerous brands, and as a result, a nothing growth. Now on Slide 27, the creation of our stand alone 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 CHG legal entities by the 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 Allegro and Xyzal. Allegro is the fifth largest RxOCC switch of the last twenty years, and we have a very experienced switch team who, between them, have worked on every US switch over the last ten years.
With a total of €1,000,000,000 in sales potential, not only do we believe that Sanofi's RX OTC switch pipeline is the largest in the industry so far, but more importantly, we intend to provide broad access with this switch 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 US 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 health care systems due to influenza office visits and hospitalizations, particularly in situations like we're currently in today with the COVID nineteen pandemic. Inherent, we've been 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 being 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 US 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. So on Slide 29, just to summarize, we are committed to delivering best in market growth from 2024 with the potential addition of $1,000,000,000 to the top line from the two switches. And 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 key 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. And 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.
Well, thanks to Julie and Olivier and Josephine and Alexander. I hope you get a sense transformation ongoing on those two businesses and how our prioritized portfolio will enable us to continue to drive growth and innovation. Now we also talked to twenty nineteen Capital Markets Day that as part of the play to win, we need to reinvent the way we work. So 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. And I have to say it is uncommon for a Chief People Officer to be invited to take part in a Capital Markets Day, so 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 The UK HR director for AstraZeneca and indeed worked alongside a young poor husband. But I've spent the majority of my career in highly consumer focused businesses like Kingfisher, Sodexo, and Merlin Entertainment, 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 for Sanofi's purpose and in particular to the strategy laid out by Paul. So I spent the last five months listening and learning and thinking about the role that HR needs to play to support the delivery of the phase one strategy over the next five years. And 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. But 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 they're 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.
But, you know, culture can
be a difficult and somewhat vague concept to grasp. So we've identified four play to win behaviors as proxies for the new culture that we need to live and breathe. And 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. And 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 exercise of our new Sanofi people strategy, again, built to underpin the play to win. We wanted the 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 health, Genmed, and neuro API organizations. We will anticipate and acquire future skill needs with a clear focus on digital capability, and 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.
So 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. And 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 place win behaviors that I've just highlighted across the business to ensure that we leave our leave our old ways of working behind us and embrace the new culture we need.
And in 2021 for this year, we will build the play to win behaviors into all of our people journey 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, And 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 and 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.
So 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 priority. We're not starting from scratch at all. We're building on solid foundation, but the trick now is to be highly focused on these deliverables that will tangibly drive our company's performance. And more than anything, this is a super exciting time to be part of the Sanofi story. And with that, back to you, Eva.
Thank you, Natalie. So we're now moving to our Q and A session, And we will now remind you how you can ask a question. Have two questions to participate in the Q and A. Option one, if you would like to ask a question, please click the raise hand icon at the bottom of your screen. Now we will take the first question from Simon Matter at Exane.
Simon, please go ahead.
Good afternoon, everybody, and thank you for taking my questions. And 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 €14,700,000,000 in 2020. If you look
at consensus estimates, they are significantly below this number. And on top of this, consensus expectations for your margin are also significantly below. I'm just wondering if you could help square the circle in terms of what base we should use for 2020. Appreciate you have the value creative API coming up. So that's one aspect, but help there would be very, very welcome.
And then 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 that it should be a standalone by the 2022. I'm just wondering beyond 'twenty two, how we should think about the division and whether or not Sanofi still believes they're the best holders for that asset, especially given the strong growth profile that we'll
be entering in past 2022? Thank you,
Simon. I'll let Olivier comment on the base and the things. But just my own observations coming when you look at our Genmed 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. So plus, I think Sanofi is pretty unique in its ability to work in some of these markets and deliver with this sort of entrepreneurship.
And 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 because 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 a much clearer now route that I see it. Olivier? The general metric base is 14.7%. This includes EUR 500,000,000 of API that will go with the Euro API 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. And it's also about making sure that we stabilize the degrowth of our noncore assets. So it's really growth on the core assets through volume growth and, of course, stabilizing as much as we can the noncore assets.
Yes. And 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 of our Genmed business. You can get a sense of why you shouldn't just make an assumption bucketing such an important piece. So 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 in particular at a time in our evolution after a Baizhou patent expiry where our focus is single mindedly on growth and preparing for switches and we're not thinking about anything else. And we hope to create something incredibly value here inside the organization.
Next question?
The next question is from Luisa Hector at Berenberg. Luisa, please go ahead. Okay. So let me Hi. Can you hear me?
Yes, we can. Thank you. So thanks for taking my questions. On vaccines, you're reiterating 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.
And 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? And is there any color you can provide? You know, presumably, this would have to be single dose to be competitive. And do you think regulators will require head to head studies, and non inferiority or superiority endpoints?
And and maybe if I could just ask a quick one, a second one, on, the relative profitability of general medicines versus specialty today and how you see that in 2025? Thank you.
Okay, Louisa. Thank you for those questions. We'll come back, I think, to JB on what we have shared or not shared around relative profitability. And
we'll come
to Tom on the evolution of the business, MRNA. Look, Tom, 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 than our own role in influenza.
Definitely. Thank you, Luisa. So in terms of mRNA description, as mentioned before, definitely we see mRNA as a very interesting technology. That's why we started with the TBIO partnership in 2028, extended it in 2020. And where we see the potential is definitely in getting to new territories, especially in viral diseases.
So we start, as mentioned before, by Phase I in flu. So 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. So
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-nineteen, when we are looking into it, when it's the development of a field where there is already a standard of care for flu, for example. So 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.
So 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 single flu. I remind you that the safety is highly proven and very strong and the same level of efficacy. And I remind you that differentiated two vaccines have seen double digit increased efficacy when compared to standard dose two vaccines. So 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.
So that's going to take a few years. It will ask Phase one, Phase two, Phase three when it comes to seasonal flu. It will ask for comparison, as you mentioned. It will probably require a multiyear check because you want to see not only one year but two years that it's successful. But of course, when you look at the portfolio we have in flu and the partnership we have with mRNA and TBIO, 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. Of course, 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 one trials in the coming years on some viral vaccine target. Now the earlier part of your question was more about the, I would say, target of growth for the vaccine GBU.
I won't say much more specific, 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. And 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 are a multi vaccine company. It's based on two pillars. It's based on pediatric combination pillar. It's based on the coming launch of rslin, narsilumab. So we have a lot of pillars that will shoot that growth.
We take it year by year, but we have this mid- to high single digit ambition for six years and for every year.
Thanks, Thomas. So, Luis, it doesn't change. Our commitment has stated it 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 etcetera. We'll be there and we know how to do it.
So Jean Baptiste, maybe something on relative profitability?
I think you're asking exactly the right question. And 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, and it's a BOI play, and we've seen it today. Not only we want to keep it stable over time in terms of size, but we want also to maintain, and that's what we're looking at, this accretion over time. So what's going to happen relatively to Specialty Care is just that JMA 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. But of course, progressively, it will also happen with other products. Right now, specialty care is where we are investing.
So the R and D effort is increasing on that area. So it will be a slow motion, but it will go in the right direction. Thank you, JP.
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 Peter,
we lost you. We may go to the next question.
Sorry, there you go. I'm here. I think sorry, think you cut me off. I'm sorry. Right, sorry about that.
So let's start again. So question on consumer. So just curious here with regards to the Rx to OTC switches here. Obviously, Thialis is entering use trials sooner than Tamiflu, but Tamiflu potentially launching before that. Is that just related to the complexities, obviously, of the ED market and flu?
Or is it something else we should read into what's required here? And I guess for Paul or maybe also for Julie, just with regards to how important potentially bolt ons are in your consumer strategy. You did mention the potential need to bulk up any of your franchises. And 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? And so just coming back then to JV, just trying to understand, maybe you could give us some clarity, how many years forward should we think about Genmed still being accretive?
Maybe I appreciate you don't want 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. And then just to Thomas, sorry, just back on the mRNA, is there a Phase I immunogenicity or biomarker type read that can give us a quick yesno to if this is good, if you're vaccine, or do
we need multi year studies to know?
Okay, Peter. Well, I'm glad you didn't get cut off. You've got quite a fistful of questions. Sorry. That's all right.
No worries. So Josephine, maybe you just want to share just some flavor around the switch timelines. I mean, I think what we try 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, but we feel confident in and around those guidelines given and we've reached the Cialis was outlined, first patient in actual use study will be this year and nobody's ever even made it that far. So we're doing things that have never been done before, which also increases certainty over time. But Josephine, maybe you want add something.
Thank you, Paul. That's a really great, I guess, answer to the question as well. So like you said, right, we are advancing the programs. We have been able to transform, conduct a number of case studies you know, in 2020 that actually continue to progress us towards the actual use trial for Cialis in 2021, which we're confident that we're gonna be able to meet. And then for TallyFlu, you know, we are going into actual use trial in 2022.
And the only reason we see a difference in both timing is just because of, you know, the timing for when we started both programs and where we are, right, with the pandemic con with the pandemic situation. But, again, like I said, you know, 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 buy things for CHC. I think what we've tried to say is that we think we have enough organically to make the progress and we have the switches. I think what Julie has challenged me is around whether we can add other capabilities in around digital e commerce, 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. And so I think we would look to capabilities and different things. Was there anything you
can No. Again, I 100%, I mean, agree with what you said. That's exactly what we're trying to do. Obviously, we're always looking at ways to grow our business, be it organically and inorganically. And our play to win strategy is not dependent on M and 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 on to our subcategories that we're focusing on and as well, as Paul said, accelerating our digital journey.
Thank you. JB, GMED accretion, what is your outlook?
Well, Peter, it will be very long. This business is incredibly resilient. I love it, by the way. It's so 2025, but after. There's no patent cleaves, there's no there's very little happening there.
But with a very active management, we will keep it accretive for the long time.
Thanks, Shabby. He loves all our businesses equally, just to point that out. Thomas, mRNA Phase one sort of proof of concept, any fast feedback from you?
I'm afraid there's not going to be a Phase one 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 or mRNA will be the same. So 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 can over.
If you have, it doesn't mean it's going to work. You need to check the ability of those to indeed protect. So all three phases will still be required. I don't think it's really changing that part.
Tom, maybe you could just I could ask a supplementary on behalf of Peter, which is where has mRNA not hit a home run-in the development so far?
So there are a few products indeed in the story of mRNA where it's not always been successful. We have 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 in this public information that Merck has given back the rights that it had on RSV mRNA with Moderna. So 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-nineteen. 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. So 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.
Yes. Think we look at 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, but 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 because there were some areas where it was unsuccessful on the lead up, but we're thrilled that it's had some success in COVID-nineteen.
And just to remind you, I'm not the expert that Tom is, but when you get to the multivalent strains in terms of solutions with mRNA, then even not all mRNAs are equal in terms of what's your ability to go after multistrain. There's we're going to be with that. So we're not that doesn't scare us, but
it's
interesting. Okay, good. Next question?
Yes, sorry. So I have three questions from Steven Scala from the chat. First one, two actually going to our Genmed team. What are the patent expirations on Moltek? Sanofi previously made the decision to deemphasize diabetes research, but why aren't Q weak basal insulin attractive opportunity?
And the last one goes to the Consumer Health team. It is clear that Sanofi gains from owning Consumer, but what does Consumer gain by being gained by Sanofi?
Thank Thank you, Steve, from Octavez. Maybe Olivier, talk about Milltec LOE.
Milltec LOE, 2.29 in The U. S.
Then maybe we could look at why, Julie, you're interested in being on Senator. Sure.
I think I think today, think it would be a myth not to benefit from the social Sanofi. Basically, I want the best of both worlds. I I wanna be able to to and not I mean, create more agility, more speed by by becoming stand alone. But 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. And then Olivier, the weekly basal insulin, what have we missed?
So general medicine 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 OctuGeo that has not been launched in China, for example, or to be more precise, was launched only mid November. We are also at the beginning of our story with Soliqua. So we have really a significant runway. Soliqua has only been launched in a small number of countries in the emerging markets.
Soliqua will be launched in 2022, 2023 in China. And we all know that a significant portion of the market in China in insulin remains a credit market. So still a long runway with assets that have not been fully deployed, especially in emerging markets. 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. So just wanted to get a quick update on obviously, I apologize if I missed questions on venglustat. But 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.
And then just, you know, 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, you know, 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. So just wanted to get a sense of how Sanofi is thinking along those lines. Thanks so much.
Okay. Thank you, Seamus. Maybe, Dimar, do you want to jump in, and then we'll also let Sean Reed if he wants to add or comment on gene therapy. Dimar?
Yeah, right. On vanglustat, thank you for the question. Venglustat is really an interesting molecule considering that it's a pipeline in a pill. And because it inhibits so early in the signaling cascade, we were able to evaluate different hypotheses across different types of diseases. And 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 III, in Fabry, And we're following up on that, obviously, with studies in those indications. And that's simply the deposition, basically, and the metabolic pathways that are important there. Then 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 preclinical in an animal model. That animal model has been quite predictive, actually, which gives us a lot of confidence.
But it's a different hypothesis, different type of disease. And then you've the Parkinson's, where it was about deposition of synuclein, and can actually the GCS inhibition play a role there? And again, a different hypothesis. So, 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 MOVED PD study also shows is that the GL1 levels are distinctively reduced.
So, the drug works. The drug does what it should. It's just that the biology in Parkinson's seems to be different. So we remain really confident with regards to the other two buckets of indications. And the other information we got from MOOSE PD is that the drug has demonstrated a very encouraging safety profile.
We're So 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? Yes. Thanks, Paul, and 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 and the monogenic disorders where we've had such a trailblazing history at Sanofi Genzyme.
And then also particularly in the CNS area, we see quite a bit of opportunity there. We did establish an internal capability we call the Genomic Medicines Unit recently and are 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 nonviral 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.
And so 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. And then 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 Keyatus, a cell based a cell therapeutics company, in their case, exploiting the NK natural killer cell platform for oncology. Our projects there will involve genome modification of cells. The first project we've announced is a CD38 knockout NK cell engineered specifically for myeloma and engineered specifically to combine with our anti CD38 antibody Sarclisa.
And 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. So we're very actively establishing that capability as well.
Thanks, John. Maybe I'll just add a couple of points. I mean, it's been an interesting sort of six, twelve months in the gene therapy landscape and at least in hemophilia. I think John's touched on it, but equally important is CMC and manufacturing. I think we all anticipate the future to be where pricing will be pressurized in gene therapy and cost of goods therefore need 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. But 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 in the outbreak data, it's not always confirming the opportunity that you have.
I think we're approaching it the right way, very sensibly, actually. So do you have time for one more? Yes, please.
We take one last question from Keiyo Parekh at Goldman Keayu, please go ahead.
Thank you and hope
you can you guys can hear me okay. Two questions, please. The first one for Julie. Julie, you kind of laid down an exciting plan for kind of changing the growth outlook for the CEH business. But I'm wondering if you can talk a bit about kind of your plans from a marginprofitability perspective.
Are you seeing this kind of as a need to reinvest in the near term with margins going up kind of post the launch of Cialis panic flu? Or do you see enough scope for you to kind of take cost out and reinvest to kind of get that growth? That's kind of question number one. And then question number two, kind of for Paul and JB. Paul, we've obviously seen kind of some of your peers kind of do largest acquisition.
So just wondering if you can remind us kind of what your priorities are kind of from an M and A perspective? Is it still increased in Tori's kind of Cynthia signed acquisitions? And then linked with that for JP, clearly, of 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. So why not take advantage of the cheap valuation?
Okay, good. So snappy questions there to finish us off here. Thank you. So very quick comment on THC 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. And 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 and A, guess, and maybe JB will comment. The capital allocation, I suppose, that 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. 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. So I think you'd be perhaps disappointed in us even if we did try and do that. So we're sticking to the science and we have enough in hand. And I think you have to you sort of have to understand that.
Having a healthy balance sheet, if you want to describe it like that, is JB's problem. But 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. But JB, what's your view?
We are doing a bit of share buyback, as you know, because we cancel the dilution of any emission we do. So we've just done some at the back end of last year or beginning of this year. But as Paul said, of course, Itrong is quite low in our priority. But what we did is, again, increasing for the twenty fifth 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, and we will be back for the second section of our CMD called Emerging Leadership in Immunology. Thank you. The recording has stopped. This meeting is being recorded.
Hello? I need to get this off. How Only
barely.
Ron, 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 just two words, and then I hand it straight to you. Okay.
Natalie, how are we? Yes. We are. You tell me when I can
go? You
can go, Igor. Welcome back to the R and D section of Sanofi's Special Capital Markets Day in 2021. The Sanofi R and 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 Ford, Global Franchise Head of Dupixent then Namish Patel, Global Head of Development, I and 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 and A session. So for those who may have just joined us, I just want to quickly remind you again on the instruction 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 two, you may also submit a question by clicking the Q and A icon at the bottom of the screen and the question will be read out here.
And 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 and 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 and 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 KIATIS and TIMEV acquisitions. And 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 and D transformation through M and 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 Synthorix acquired in 2020, the tailored covalency platform of Principia acquired last year and the NK cell therapeutics platform of Keyatus, 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.
And again, big trade offs were made to absorb these costs the cost of these acquisitions, altogether keeping R and D costs flat between the 2018 and the 2020. Okay. So on to today's presentation. My colleagues will build on the themes that we introduced at last year's R and D Day investor event. We will illustrate how our teams 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 health care problems and 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 and D productivity. So with that brief introduction, I hand over to Brian Ford, 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. And 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, and 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.
Now you've probably heard a lot about this amazing medicine at our DUPIXENT R and D event this past June, where we expanded on the innovative science behind DUPIXENT. And since then, our confidence has only grown in DUPIXENT's ability to lead the transformation of the treatment of type two inflammatory diseases. So now as you 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.
Now this growth is also supported by a best in class profile with clinical data out to three years. So let's move on now, and we're going share with you a bit about how we're building a mega brand with DUPIXENT. So this next slide really dimensionalizes the significant growth opportunity in dermatology with a primary focus on atopic dermatitis, DUPIXENT's first indication. Now DUPIXENT is indicated as young as six years of age in moderate to severe patients who are not controlled on topical corticosteroids. And we are currently evaluating Dupixent in patients below the age of six.
Now today, with an estimated two point two million biologic eligible patients in The U. S. Alone and only 5.1% market penetration to date, the growth potential remains significant. And as we expand beyond The U. S.
To our top eight markets, that eligible patient population more than doubles to 4,900,000. And this includes the opportunity created by our record NRDL approval in China. And that will add approximately 900,000 eligible patients over time.
Now 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. Now this strengthens Dupixent's leadership position among dermatologists while also addressing patients suffering from debilitating dermatologic conditions. Now if these studies are successful, we estimate that we would add approximately five hundred thousand patients in The U.
S. Alone who could benefit from DUPIXENT in these adjacent indications and also the age expansion. So 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 II inflammation. So 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 seventeen percent. 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's also significant opportunity to expand outside of
The U. S. Market 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 one point nine million biologic eligible patients. And additionally, there remains significant unmet need in moderate to severe asthma patients in China.
So consistent with our approach in dermatology, we're also investigating adjacent respiratory indications driven by Type II inflammation, most notably our Type two COPD program, a highly underserved patient population where no therapies have been approved for almost a decade. Now beyond our currently approved asthma indication of 12 and above, we expect to add approximately six hundred thousand 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 two inflammation.
So I'm now happy to transfer the call over to Naymesh, our Head of Immunology Development, to discuss Sanofi's deepening leadership in Type two immunologic diseases beyond DUPIXENT. Over to you, Namish.
Thank you, Brian. So at our DUPIXENT R and D event last June, we dove deeply into the biology of type two inflammatory diseases and explained why unlocking both IL-four and 13 are critical for DUPIXENT. The mantra was it takes two to tackle type two inflammation. And I'm now thrilled to introduce Sanofi's next wave of molecules for type two diseases beyond DUPIXENT. So our approach in developing the next wave of molecule really leverages our deep understanding of the type two inflammatory cascade.
Here is a very simplified depiction of the process. On the left here, type two 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-thirty three or TSLP. And 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 then produce cytokines such as IL-four, IL-five, IL-thirteen. These cytokines stimulate and prime effector cells like eosinophils and mast cells and they lead to tissue pathology, allergic responses and symptoms such as skin itching, thickening and atopic dermatitis. So from this, you can easily see how the mechanism of Dupixent in blocking IL-four, IL-thirteen potently inhibits type two inflammation in diseases such as atopic dermatitis, type two asthma, and CRS with NT. You can also see how riluzibrutinib, a molecule acquired by Sanofi with the Principia acquisition targets type two inflammation. The BTK enzyme drives allergy by mediating B cell expansion and production of IgE and activation of mast cells, eosinophils and basal cells.
Thus, riluzibrutinib, a potent and extremely specific BTK inhibitor, we believe has a significant potential to treat type two disease. And 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. But 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 two, but also non type two, a mixed phenotype. This is where our anti IL-thirty three monoclonal antibody, ipapekumab, is being investigated to reach more COPD patients than any other biologic has attempted.
And 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. And finally, we believe that OX40 Ligand is truly a unique target for Type II diseases because it represents a critical co stimulatory step that leads to the programming of immune response for chronic diseases like atopic dermatitis. The KY1005 monoclonal antibody that Sanofi announced intention to acquire holds promise to reprogram immune response so that durable disease control may be approached for across approached across a number of indications. And 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. So now we'll dive deeper into these key molecules starting with itapikumab or anti IL-thirty three for COPD.
So itapicimab could be the first molecule to treat most COPD patients. And on a personal note, as a pulmonologist who's been practicing for a number of years, it's it's it's quite disheartening to think that so few new mechanisms have entered the COPD treatment paradigm over the last twenty years despite the fact where COPD is a leading cause of mortality worldwide. But today, I'm glad to say we really believe that we think we're about to change this. We think we took the unique step of studying itapekumab across a spectrum of moderate to severe COPD because of the known effects of IL-thirty three on both type two and non type two inflammation. This is supported by published data shown here on the left in the graph demonstrating that IL33 levels in advanced COPD patients who are former smokers are elevated compared to healthy controls.
And here on the right, for the first time we're revealing the results of our phase two study of itapekumab and COPD. In this study of moderate to severe COPD patients, itapekumab reduced COPD exacerbations by approximately forty percent, four zero, forty percent in former smokers. And importantly, this effect was similar in type two and non type two patients. This effect size is far, far and above what has been seen by any other biologic and c COPD where many competitor phase three studies have been twenty percent or less in terms of exacerbation improvement. And this is for the sickest patients with COPD.
And these results have given us confidence to commence the phase three program in a population where no biologics have succeeded. Thus, we have started our pivotal program with ipilpecumab. The objective of these studies is to establish that ipilpecumab can reduce COPD exacerbations and improve lung function in most patients with COPD. This in combination with the Dupixent COPD program has a potential to address greater than eighty percent 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, and I'll explain why. So I mentioned in the first slide that BTK is a key driver of allergy and activation of type two inflammatory cells. And it would be logical then that BTK is a potential strategy to treat type two 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. And the reason why we're so excited about riluzibrutinib is that has been designed to try and avoid these issues as Percipio's innovative tailored covalency platform.
So 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. And thus tailored covalency has the potential to minimize off target binding and minimize the risk of side effects by still, but still maximizing potency. And safety is a critical issue for type two diseases, especially among dermatologists.
And we believe that RILSA has the potential to deliver it. Now what is the evidence to support this potential and our commitment to further investigate this product? It is the results of the studies of with rilzabrutinib. And this slide on the left, you see the Phase II results in patients with pemphigus vulgaris treated with riluzibrutinib. In this study, sixty seven percent of patients treated with riluzibrutinib achieved minimal disease activity by twenty four weeks.
This shows the very rapid and potent effect that rilsabrutinib has on this disease where very few patients would have such a response on steroids alone. On the right here in the ITP phase two study, you can see that fifty percent of patients treated with riluzobrutinib for greater than twelve 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 the study. And most importantly for both of these programs, rilzabrutinib was well tolerated with no significant safety issues. So 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 two space. We know for Type two diseases safety is of major importance to patients and prescribers And so we believe Rilsa, 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. Just today we're announcing our plans to start the phase two studies for riluzobrutinib in atopic dermatitis and asthma and chronic spontaneous urticaria. These diseases represent a total of three point five million patients with high unmet need.
And each of these indications is expected to enter the clinic in the second half of this year. So 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 two space. You saw in Brian's earlier presentation that compared to other disease areas, we're still in the very early days of type two disease. Indeed, 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 successes with DUPIXENT.
This is a very underpenetrated market with heterogeneity in biology and in patient needs. There is space we think from multiple molecules that offer choices to patients to tailor to their biology and individual needs. We're excited about promising oral programs of rilzabrutinib and the IRAK4 degrader. We also look forward to exploring the potential of Antiox40 once the acquisition of Kymab closes. Moving now to the right, to the respiratory realm, we're pursuing oral and type two plus approach in asthma with riluzobrutinib 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. And we'll get into this in more detail in the next section with the IL-thirteen TSLP program. And finally, we have the high ambition to transform COPD therapy with isopecumab now in addition to dupilumab to address greater than eighty percent of patients with COPD where currently there are no biologic therapies. And 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 Nesli, Sanofi's Global Head of Research and Chief Scientific Officer.
Thank you, Nenish. Building on the foundations of our winning strategy in type two 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 two 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 INI 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 off the gonadal data sets, including genetics and single cell genomics of disease 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 drawable insights into novel patient biology using our advanced technology platforms. Let me give you a few examples. Synthorins redefined tunable cytokine therapy and regulatory T cell expansion for durable disease modification.
Multispecific 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 M multispecific biologics with distinct and unique target product profiles.
Today, I'm happy to share with you the first example, a multispecific anti IL-thirteen TSLB 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-thirteen 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-thirteen 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-thirteen 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, patient administration via an auto injector. Let's move now to protease integrators as next generation products in inflammatory disease. We have partnered with Chimera Therapeutics, a world leader in protein degradation, to develop the very first oral protein integrator in immunology and inflammation, targeting atopic dermatitis and hidradenitis suppurativa planned to enter Phase I clinical studies in 2021. IREC4 is a master regulator of TLR and R1 family dependent inflammation, controlling the production of key pro inflammatory cytokines such as type one interferons, IL-six, and TNF alpha.
IRAK4 does this via two critical biological functions, a kinase function and a scaffold function. First generation attempts of targeting IREC4 kinase function using ATP competitive kinase inhibitors validated IREC4 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 Chimera's next generation ARIC-four protein integrator, SAR444656, allows blockade of both the scaffold function of REX4 in addition to the kinase function. Preclinical experiments shown on the right demonstrate the superior inhibition of phospho NF kB and the superior inhibition of combined stimulation of pABMCs with TLR and R1 stimuli. It also demonstrates the very potent degradation of Rh4 protein in critical target organs, such as the skin.
These data provide a convincing framework for advancing our first in class, IonI focused, iron fork oral protein integrator into the clinic. We have spoken a lot about THOR-seven zero seven, our non alpha IL-two for immuno oncology. Today, I would like to introduce you to THOR-eight zero nine, our non beta IL-two, entering the clinic this year with potential in a broad range of autoimmune diseases. THOR-eight zero nine takes advantage of the same unique synthetic biology platform for precise attachment of polyethylene glycol to IL-two, enabling selective targeting of the IL-two receptor alpha chain. The key goal for THOR-eight zero nine 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 preclinical experiments demonstrating up to 46 fold expansion of regulatory T cells by THOR-eight zero nine. 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 and 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 we'll 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 potential to be the first biologic approved for COPD. DUPIXENT is the cornerstone of Sanofi's emerging leadership in dermatology and also in respiratory.
Next, building
on the
success of Dupixent, we have a strong pipeline that continues to focus on the Type two 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 etepecumab, the anti IL-thirty three monoclonal antibody from the Regeneron alliance, now in Phase III for COPD. Itapekumab operates at a very upstream step in the Type II inflammatory pathway. Riluzabrutinib, 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. Riluzibrutinib operates at a very distal step in the Type II inflammatory pathway.
And finally, KY1005, the anti OX40 ligand monoclonal antibody from the KymaVam 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 two and adjacent immuno inflammatory 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 IRAK4 degrader that you heard about, which is incidentally the world's first degrader molecule that will enter the clinic for a nononcology indication accessed via the partnership with the biotech company Chimera. The IRAK4 degrader has the potential to play across multiple immuno inflammatory conditions where IL-one and IL-thirty three are culprits, but offering an oral medicine option. Also of note is our non beta interleukin-two molecule, THOR-eight zero nine, which is produced using the synthetic biology platform coming from the acquisition of Synthorix.
THOR-eight zero nine has the potential to become a best in class expander of regulatory T cells for restoring immunohomeostasis across multiple indications. And the multi specific nanobody should be mentioned here, coming from the Abilinx 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 antibodies 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. And 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 tolobrutinib as well as our anti CD40 ligand antibody and our emerging portfolio of complement inhibiting antibodies.
As we pointed out in our R and D investor event last year, expertise in immunoscience is a core competency at Sanofi, and we leverage this science across the company's entire R and 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 and A, for which I'll serve as the moderator.
Thank you, John. Yes. So we are moving now into our last Q and A session for today with an emphasis on R and D since we are now joined by our presenters as well as Stiebner, our Chief Medical Officer. And I also have Paul and Jean Baptiste here still with me in the room. So Natalie, can we start with the first question, please?
Yes, sure. Thanks, Eva. So the first question is from Thibault Boutin at Morgan Stanley. Thibault?
Hello, hi. Can you hear me?
Yes. We can. Thanks.
Okay. Thank you very much for taking my question. So 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 GP as a backbone on which potentially add new treatments?
Or is your approach more to use your new immunology project as alternative to Dupixent and a way of ring fencing your leadership in type two information? If you could share your view on how to determine which patients will benefit from which pathway and how to sequence or potentially combine these assets? Thank you very much.
Well, 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 and 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 David outlined or 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. So maybe I'd hand over to perhaps Frank first. Maybe you could embellish on that a bit. Then Naymish?
Yes. Happy to, John. And 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. All of our decisions are science and data led. This is what we have been doing over the last four or five years.
But I think I just would like to remind you there's still a huge unmet need out there in immunology and inflammation. 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. And as John was pointing out, there are really different patient populations defined by their molecular mechanism.
But then also in terms of market penetration, these markets grow. Physicians are experienced now with biologics you can see that if the right medicine comes along, which is really transformative, patients will come and physicians will prescribe. So what you really need is a portfolio which is waterproof in the short term, medium term and long term. And I think in the short term, we have first choice Dupixent. No question about it.
It's a stunning biologic. But with these 15 biologics and orals we're having now in our pipeline, we have also the medium- long term strategy to really create a sustainable portfolio. If you think about itipekumab potentially open up the COPD space. If you think about BTKi as really an oral immunology leader, very safe but going into multiple different immunomechanisms, for example, autoantibody mediated disease or in the type two space. And finally then, our long term strategy with an oral protein integrator, first the first time ever that a pharmaceutical company is bringing an oral protein integrator targeting REG-four into chronic autoimmunity or our bispecifics platform using nanobody where we can actually mix and match and dial in the appropriate features for 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.
So it's a portfolio. It's like a winning portfolio strategy.
Maybe is there anything to add before we move on?
Thanks, Naj. Frank, and you both covered it completely. I think, as mentioned, atopic dermatitis is a great example. Five percent penetration, ninety five percent patients eligible still haven't taken any, and there's things to consider like differing biology across that segment, different individual patient needs. So there's plenty of room for a number of different mechanisms to fit patient needs.
No, absolutely. I think one thing that's 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. So there really is a need for different mechanisms for different patient populations.
Let's see. If I could just follow-up on another question. I was just wondering, I mean, there are a lot of bispecifics in development. So if you could just maybe give us a bit more color on the points of differentiation of your bispecifics with Abil's platform compared to what your competitors are doing?
Sure. Frank, do want to take that?
Yes. I mean, number one, obviously, bispecifics have been a success in immuno oncology. Bi specific engagers, T cell engagers are really going from success to success. However, in the INI space, if we look at what is really happening is that a lot of bispecific approaches in INI have failed, either because targets were not properly engaged or, you know, ADA's problems were arising. So, what we actually have built over the last year since our acquisition of Outlinks, we've built probably what is the most advanced, what I call, biologics two point zero technology using nanobodies.
And nanobodies are very interesting because you can actually combine them like pearls on a string to make multi specifics. So, 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. And actually, 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, but it's also the target selection. 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 oxford veligatinib as a target is that already in 2016, 'seventeen, we mined data sets and they told us what are the winning targets are going to be. And already we're seeing with the targets now in Phase II trials being winners that we actually make the right pick. So, 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?
Yes. The next question is from Tim Henderson at Wolfe Research. Tim?
Hi. Can you hear me okay? Yes. Okay.
I wanted to ask about two of your higher priority assets, oral SERD and oral BTK, just a high level question. So it kind of seems like everyone is claiming to be best in class and not everyone can be best in class. So 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. And then 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 NRDL?
Okay. Good. So several questions there. Why don't we do BTK first because that flows right from the presentation that Namik gave? Namik, can I ask you to take that then and explain the differences in the various BTK's and why we believe that the Principia molecule that we have, riluzobrutinib, 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. Riluzobrutinib has been designed specifically with this platform to be very specific to the BTK enzyme and limit the off target binding to other proteins that many of these side effects often come from. So we think it's ideal in that way for the type two 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. So I think that is the crux of the matter. Our Phase II data thus far hasn't shown any similar side effects profile, that's why we're very confident that we can enter this space with the compound we have.
Yes. And 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 hard target hard and you have to keep it hit hard, which is where the covalent piece, riluzolevitin comes in because that then completely inactivates the target and keeps the exposure longer.
And at the same time, the tapered aspect of it prevents you from interacting with and staying on other targets. So 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. And 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 Deepmar to help me with that one and why we think this molecule has potential to be why ensignestrant has potential to be our best in class solution of an oral SERD for women with hormone receptor positive breast cancer DMARC.
Yeah, happy to. Thank you, John. And before I go to the SERD, let me just talk about the other BTK, which is tolobrutinib. Again, the question about best in class comes up there, and there's really the brain penetrance. But besides the BTK inhibition and really the impact on innate and adaptive immunity and the impact on non peripheral and central, we really think that we have best in class potential as well.
For all of these molecules and I'm switching to emcinestrant here eventually, it's going to be about benefit risk and about application to the specific patient population. And you may note, even 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 around from the Phase Ib study around the combination with parvo ciclib. 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. But when we look at the data that we 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. And we do see a really encouraging safety profile, which will be important as we develop this molecule across the different lines of therapy. And the big prize is obviously usage in the adjuvant setting, and there the risk profile becomes even more important.
And 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.
Yes. Thanks, Nibar. I think that safety difference is most clearly seen in the lack of any cardiac signal that we have with ensignity compared to other molecules. And 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 antinephrine and it's why we think particularly moving into the places like the admin space where safety matters so much that we'll have the best in class profile. Then the final question was about Dupixent in China. Maybe Brian, maybe we can get you into the mix there and let you handle that. And of course, maybe if you need more, you could chime in if you need any help.
Brian?
Yes, absolutely. Thanks so much, John. And obviously, we've got the ongoing program with ReOptin late twenty twenty two, early twenty twenty three. So we're looking at potential approval into 2023, early twenty twenty four. And 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. So we would be optimistic, but that's the current time frame we have for China.
Thank you. All right. Thank you. Good. On to the next question, Eva.
So the next question is from Emmanuel Papadakis at Deutsche Bank. Emmanuel?
Thank you for taking the question. And I
guess like a couple of follow ups on Dupixent. So 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 light of that on the potential implications, if any, of the recent tezepelumab data, particularly in the eosinophilic low subgroup of patients? And then the second one on Dupixent, just the regional expansion opportunity.
I mean, mentioned it earlier, it still remains extraordinarily dependent on The U. S. How soon, for example, the European opportunity like to narrow 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? And maybe, Brian, you could give us a bit more color on the NLDL listing in China and AD. What kind of price cut did you have to take? When will the volume start to kick in there? Thank you.
All right, Manuel. Thank you for your questions. I'm going have Brian tackle those and if there are any elements around the eosinophilic phenotype that we don't cover there, maybe maybe she'll help him out. But Brian, over to you.
Yes, for sure. Thank you, Emmanuel, for your questions. Really good ones. I think from a 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 the Type II patient population. And it's really not just identified by eosinophils. Eosinophils. Obviously, you think about FeNO, of course, IgE levels. And we actually designate about eighty percent of that population is really type two.
So we really don't, again, align ourselves with just the FeNO from or excuse me, the EOS level 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.
So we have the access of those full type two 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. And 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. But then 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. So we really feel strongly that our platform, if you will, for DUPIXENT is type two platform, and our profile remains the strongest profile in asthma of all the current agents and the agents to come.
Now a little bit about China. Obviously, with 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. Now from a
price standpoint, the price will be out and
be public in the March timeframe. And again, all we can really share right now is that we're extremely positive about their recognition of the value of DUPIXENT in China.
Brian,
sorry, if I could just add a little bit color on the TSLP point. I mean, going back to the slide I presented on the type two inflammatory cascade, you could see how DUPIXENT is well aligned in that sort of decision point in the cascade inhibiting IL four and thirteen to inhibit really type two inflammation. And that and and 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 pheno and also a much stronger effect on lung function improvement in the type two space compared to TSLP. And the OCS population is another example of really a really a type two 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 two patients. And you can see that TSLP wasn't successful in that population where Dupixent has been hugely successful in that population. So that Type II space, the Type II asthma space, we think Dupixent is really the winning molecule there.
Good. Next question, Eva.
We have time for one last question from Graham Perry at Bank of America Merrill Lynch. Graham?
Great. Thanks for taking my questions. So just earlier when you were talking through the Amnacestrant data points, you didn't highlight the proof of concept study in early breast cancer, but you have expressed optimism around that. So is that data still coming, the window of opportunity study in early breast cancer proof of concept? Is that still coming this year?
Or is that being delayed? Secondly, on the IL-thirty three, were there any other biomarkers other than former smokers in the Phase two that drove exacerbation reduction? Any stratifying for any of these biomarkers in Phase three? Is there 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? And 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. So is the trial set to detect that, again, use of biomarkers or anything else?
Thanks for your questions, Graham. I'm glad we were able to get to you. Maybe I'll take the questions in reverse order. You mentioned Dupixent and CSU, you know, the trial is ongoing, so it's 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.
And so 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, riluzabrutinib is a really good solution potentially for CSU if Dupixent doesn't resolve their issues. I don't know if Naynish has anything else to add on that while we're on Dupixent.
Sure, yeah. I mean, there are decent populations 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-four receptor on mast cells is an important activating factor for mast cells. So it's a different pathway from what Xolair and legolizumab are targeting. We're So definitely looking at these biomarkers, and we'll see how the outcomes come.
But we think there's actually a potential that we could have really have a differentiated population that responds to Dupixent versus what Xolair does in this space.
Then while you have the floor, Naveesh, would you comment on biomarkers in atopecumab, applications of COPD? Any further insights you want to offer there?
Sure. So to take a step back about these results for IL-thirty three, COPD in adults is extremely common. Six percent of The U. S. Population has COPD.
However, we're zeroing in on a very specific segment of of COPD, the patients who are extremely, having frequent exacerbations and lots of symptoms. So it's a small segment. And within this segment, you have patients who are still actively smoking, about thirty percent, and seventy percent who are not actively smoking. And within this, the thirty percent 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. Probably, and 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.
And and and smoking, of course, causes a very diffuse sort of immune activation, so it might be a hard thing for a single agent like IL thirty two to provide efficacy. Whereas in the in the nonsmokers, 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-thirty three is a specific contributor to both exacerbations and frequent symptoms. We don't necessarily yet have good biomarkers for IL-thirty three or the like. They're certainly in development, but we think this paradigm of smoking and ex smoking also contributed by our own internal data showing that IL-thirty levels tend to be elevated in former smokers versus current smokers. We're very confident that we have this population.
The clinical data of forty percent reduction exacerbations really suggest that we've targeted the right population. Further biomarker development, of course, is in the works, we're going to have more sort of mechanistic studies to better understand how IL-thirty two is specifically working in these patients, we feel like we really have targeted the correct population.
Yes. Thank you, David. I mean, we're really looking forward to getting these data published and presented at meetings where we can get into more of the details. But as you pointed out, I mean, a forty percent reduction exacerbations, I mean, when you see that in COPD, it's really, really quite profound. So we're optimistic about our Phase III program, and I think we've really come on to some interesting biology here and interesting difference between some of these subsets of patients.
The final question on amsonextrin 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 reengaging with that. And irrespective, we are pushing forward with our plans to move amisenetra 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, but 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, but 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. But yes, we will have data this year.
Good. Well, thank you, Graham. Eva, is that
all the questions I can take for
now? Thank
you. So, I'm going to hand it now back to Paul for some concluding remarks.
Okay.
Thanks, Alberto. Don't know 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 session this afternoon. I think for 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 touched 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 teeth, but you wouldn't have heard this afternoon, I think you start to see the joint of 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 riluzabutinib, which I think is not well appreciated. Everybody got excited about tolobutinib us, too. Riluzabutinib just keeps getting better and better the more we understand it. Confidence on a certain for sure, but staying in immunology, IL-thirteen TSLP nanobody, I inherited the Ablynx deal, and I get to see the benefits of it.
I'm really looking forward to doing some extraordinary stuff. As the team pointed out, the risks, the probability of success is so much higher in our antibody platform. We understand enough about these platforms where TFOPs 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. And then it's a pecanal, 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. Forty percent reduction in exacerbations in COPD is completely game changing. Yes, we have to get there. Yes, we have to get there.
Nobody's ahead of us on this. So we're blazing a trail. I'm a fan of the team that we're putting together. And you cannot miss the fact that the prioritization in Gen Med and 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 is what we're about. As an executive committee, 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, you'll want to see that unfold. It's okay. But we are ahead of where I expected. I'm very
proud of the work that's going on.
Thank you to everybody for joining.