This meeting is being recorded. Thank for joining the would like to briefly provide the instructions for our Q and A session, which will follow the presentation. Will have two options to ask a question. Option one, if you would like to ask a question after the presentation has concluded, please click the raise hand icon at the bottom of your screen. During the Q and A session, you will be notified when your line is open to ask your question.
At that time, please make sure you unmute your microphone. Option two, you submit your question by clicking the Q and A icon at the bottom of the screen. During the Q and A session, your question will be read by our panelists. I would now like to turn it over to Felix Loescher from Sanofi Investor Relations.
Thank you, Natalie. Good morning and good afternoon to everyone, and welcome to our R and D webinar. Thank you for joining us on the third of our five part series of interactive webcast events to highlight progress in R and D. Let me remind you Sanofi's virtual R and D event is scheduled for Tuesday, June 23. Now returning to today's event dedicated to Dupixent, our priority asset.
If you are unable to view the presentation during the webinar, you can find the slides to this event on the Investors page of our website, xanofi.com. Moving to the second slide, Slide two, I would like to remind you that information presented during this event contain forward looking statements that involve known and unknown risks, uncertainties and other factors that may cause actual results to differ materially. I refer you to our Form 20 F document on file with the SEC and also our Document d'Investrement Universale for a description of these risk factors. With that, please advance to the third slide, Slide three, and let me introduce our speakers today. With me on this webinar are Brian Ford, Global Head, DUPIXENT Franchise Frank Nestle, Global Head of Research, Immunology and Inflammation Naimish Patel, Global Head, Development, Immunology and Inflammation and John Reed, Global Head of Research and Development.
Joining later for Q and A will be Paul Hudson, our Chief Executive Officer and Jean Baptiste de Chatillon, Chief Financial Officer as well as Bill Seibold, Global Head of Specialty Care. Brian will discuss how we are driving Dupixent's success in atopic dermatitis and asthma, after which Frank will provide a deep dive on Type two inflammation. Naimis will update on our Dupixent line extension plan and John will wrap up with concluding comments. After the presentation, as usual, we will open for the Q and A session. With that, I'd like to turn it over to Brian, please.
Thank you so much, Felix. Good morning, good afternoon to everyone on the call. It's my distinct pleasure to kick off the R and D event on DUPIXENT. You had an opportunity to hear a lot about this really innovative practice changing medicine during our Capital Market Day event. And really more specifically, we spent time on how we believe that by uniquely targeting IL-four and IL-thirteen, we can build a $10,000,000,000 plus mega blockbuster brand across a whole host of type two inflammatory diseases, and you're going to hear more about that today.
Our clinical and our end market experience continues to grow and so does our belief in Dupixent's ability to not only lead but to truly transform the treatment of type two inflammatory diseases. But the reality is we're really at the beginning of this exciting journey. As an example, even just over the past month alone, we achieved several important milestones. We received certainly, first and foremost, an important FDA approval for atopic dermatitis patients between the age of six and 11 years of age, which really speaks to the continued efficacy and safety in this younger patient population. And we also reported impressive preliminary data in eosinophilic esophagitis.
And again, this is another one of those diseases with extremely high unmet medical need with very limited treatment options and is another type of inflammatory disease. But as we also shared at Capital Market Day, the foundation of our success really begins with atopic dermatitis and asthma. So over the next few slides, I'm going to spend more time on those two therapeutic areas. So if you would please advance to the next slide. So the next slide really speaks to DUPIXENT being the first biologic approved in moderate to severe atopic dermatitis patients in The U.
S. Between the ages of six and 11. And really, for us, I think certainly there's the approval, but this really speaks to the hope of these patients. This population has dealt with this chronic condition. It's a high disease burden.
And as you can imagine, with
an age group of six
to 11, that burden also, a lot of that falls upon the parents and the caregivers. And so we're really excited and we're very hopeful that we can help transform the lives, not only of these patients, but also their family members. And with this latest approval, we also extend, if you look at the right hand side of the slide, we also extend the patient population that we'll be targeting to about ninety thousand additional patients in The U. S. And just to put some context around this, this is really represents the most in need patient population.
These patients and I'll describe them a bit more on the next slide, but these patients are have commonly been on oral corticosteroids, injectable steroids or immunosuppressants. And so as you can imagine, the disease is quite significant. But you also see that we're at the very beginning of the journey in the fact that we are about four point four percent penetrated into the biologic eligible population thus far. So we're excited about this new patient population. So as you move to Slide six, what you'll see is this really speaks to the strong efficacy and safety in this 11 year old population.
But I first want to describe the patient population. And just as a reminder, these patients, on average, they're about 8.5 years old, between the age six and 11. These patients, about sixty percent of their body surface was involved with lesions, and they've suffered from the condition for most of their lives, about seven point five years of that eight point five years of their lives on average. They also these patients had a severe itch score upwards of 7.5 to eight on a scale of 10. So as you can imagine, quite a significant condition for these patients who have lived with for most of their lives.
So we were really pleased to see the incredible efficacy that we saw in these patient groups. So what you see is on the left hand side, you look at investigator global assessment of zero or one, we saw that actually we saw a 2x or a 4x greater improvement whenever these patients were on a DUPIXENT plus TCS versus TCS-eleven. As you move to the middle part of your chart, which you'll see is the improvement of a four grade improvement in peak pruritus score, and you saw a 5x greater improvement on the DUPIXENT arms. But then also what you saw, which was quite impressive, is you continue to see a very nice safety profile. In fact, Dupixent arms were associated with numerically lower overall rates of adverse events than those on topical corticosteroids alone.
And now if you will transition to the next slide, that adverse events and the really positive adverse event profile that we have really is contributing to our growing safety robust safety database and in practice experience as well. Today, we have about one hundred and fifty thousand patients treated globally across indications. But also what you see is you see that today, we have no black box warning, no evidence of immunosuppression and no requirement for lab monitoring. So again, as you can imagine, this level of safety profile is very important as we go into this younger patient population. Now on the right hand side of the screen, you see as we intend to go into the younger patient populations, this is also supported by the FDA and our breakthrough designation, as you saw for six to 11 year olds and also the breakthrough designation that we also have for the below the age of six.
So obviously, as we
now continue to advance, this is going to be very important for prescribers as they make their choices for these advanced therapies for these patients and really does support that no matter the age group, really the strong safety profile that DUPIXENT has helps support DUPIXENT selection for these patients moving forward. Now as you'll hear from Frank in a bit, the uniqueness of DUPIXENT really is unlike potential entrants as well and also potential therapies that are on market because it selectively blocks IL-four and IL-thirteen, two key essential drivers of type two inflammation. And we believe this specific MOA contributes to the strong safety profile that we have in proven track record for Dupixent. So now if you advance to Slide eight, Moving to Slide eight, what you see is again further support of this rapid and sustained efficacy in atopic dermatitis patients. And again, this goes back to the adult patient population.
And on the left hand side, what you'll see here is that rapid effect was seen really after the first dose. So these patients would have been a couple of different metrics that were very important, EASI score, NRS score and also quality of life score. And these patients achieved at least one of those after that first dose, and we sustained it over a sixteen week period. And this trial actually goes out to fifty two weeks as well, and we continue to see that sustained effect. Now but if you look at the right hand side, this is some new information as well that we've recently put out, which is it actually shows our continued efficacy over a three year period.
So up to one hundred and forty eight weeks, we see a continued reduction in EASI. But what's also very important is a continued the three year safety profile shows no change from previous studies. And as you can imagine, as we said before, treating these chronic conditions, it's going to be very important for physicians to have not only a rapid and sustained efficacy but also a proven safety profile over a long term treatment horizon. So if you please advance to the next slide. Slide nine provides another very recent piece of information that we just put out.
Was recently published in JAMA, and it speaks to flares. And these are also known as exacerbations for atopic dermatitis patients. And this is normally a sign that the disease long term important treatment goals in atopic dermatitis is to prevent flares, which can potentially result in hospitalizations and associated health care costs. Now what you saw in this trial was actually the patients on TCS alone actually had a 4.5x greater chance of experiencing a flare over the treatment course. And what was also quite impressive
is if you looked at
the patients that had previously had at least one flare, those patients that were treated with Dupixent, about eighty four percent of those patients didn't experience a flare over the remainder of the treatment period, so the remainder of the year. So as we said, long term disease control is one of the most important drivers of therapy selection and will be for physicians moving forward. And therefore, this data will be very important for clinicians and the patients, reinforcing the unique profile of Dupixent. So now if we go back to Slide 10. Slide 10, you see an exciting brand new piece of data as well, and this is also over a three year period, but this makes the transition to asthma.
And so if you look at these Type two asthma patients, they also achieved a rapid and sustained improvement in lung function. And lung function is really important to understand because it is for asthma sufferers, it's commonly associated with feeling better, that immediate feeling of feeling better. And so what you saw here is really after the first dose, saw an improvement in lung function upwards of two twenty ml improvement, And that improvement was sustained over a three year period. As you look at the right hand side of the screen, we're actually showing exacerbations here. And exacerbations are really the things that patients it's a symptom that patients really live in fear most of.
They're worried that these exacerbations will send them into the emergency room. And as you look at the results of the data here, which you see is not only a reduction in exacerbations where they had historical of at least two per year, but a reduction in exacerbation over time. And actually about a little greater than sixty percent of the Type two patients had no exacerbations over a three year period. And what's really interesting is, again, you look at the parallels in these clinical outcomes with Dupixent between two very different Type two inflammatory diseases, both AD and asthma, But the parallels are quite remarkable and really speaks to the potent effective depiction on certain type two inflammatory diseases. And this is important as we move to the final slide.
So as you look at the final slide here for me on Slide 11, Slide 11 really illustrates that approximately eighty percent to ninety percent of patients who have type two disease also suffer from another type two disease concurrently, highlighting the fact that type two inflammation is systemic in nature and can affect multiple barrier sites in the body, not just the skin or the lungs or the GI tract in isolation. And since DUPIXENT is the only therapy selectively targeting two key and central drivers of type two inflammation, the BIO-four and IL-thirteen, It's no surprise to us that DUPIXENT has been shown in Phase III trials to control type two inflammation systemically across different types of sites such as the skin for atopic dermatitis, the upper and lower airways as in nasal polyps and asthma. And also, we aim to show this in the GI tract for eosinophilic esophagitis. So in closing, as I said before, we're really at the beginning of this journey. We have great expectations for the success of Dupixent driven by our belief in its unique MOA and proven clinical profile in the areas of high unmet medical need.
And I certainly hope that this data, along with the other data that we will be sharing with you, help you also have the same comments that we do in building and the ambition that we have to build this drug to $10,000,000,000 plus in the years to come over a whole host of Type two inflammatory diseases. So with that, it's my pleasure to shift over to Frank, and I'll share with him as he will deal he will dive deeper into Type two inflammation and the deep science behind Dupixent's.
Thank you, Brian. I would like to start by diving deeper into the biology of type two inflammatory diseases and answer the important question why we believe blocking both IL-four and IL-thirteen is important. Remember, our mantra here is that it takes two to tackle type two inflammation, and this dual pharmacology approach is delivered by Dupixent. We believe other mechanisms of action, including mono targeted agents as well as JAK inhibitors, might be either too narrow or too broad. Slide 13 describes what type two inflammation defines.
Type two inflammation is a connected underlying pathology of several chronic systemic diseases that you can see listed here. The historically termed atopic conditions include diseases such as allergic rhinitis, hay fever, asthma, atopic dermatitis, and food allergy. The more contemporary term, type two inflammatory diseases, applies a molecular classification approach focusing on key type two hallmarks and includes not only atopic but also additional type two diseases such as chronic renal sinusitis with nasal polyposis, eosinophilic esophagitis, eosinophilic or type two COPD, and several pruritic dermatologic disorders. Type two immunity evolved as a now largely redundant immune response at body surfaces, primarily to protect us from parasites or toxins. In our modern civilization, the type two immune pathway has been now adapted to react against harmless environmental agents such as plant or animal macromolecules, including potentially your own cat.
When type two inflammation becomes activated, it displays typical molecular hallmarks, including increased type two cytokines and chemokines, inflammatory eosinophils, IgE, and barrier disruption. Slide 14 describes the details of the type of inflammatory cascade we see in type two inflammation. Starting on the left, inflammation begins with an upstream initiation event with allergens penetrating a disrupted barrier and IL-four dependent priming of the helper-two cells. This leads in turn to an amplification of endang tissues with IL-four, driving Th2 and mast cell amplification, IL-thirteen dependent mucous secretion, and the combined effect of IL-four and IL-thirteen resulting in inflammatory chemokine and IgE production, and importantly, neuronal itch sensitization. Finally, on the right side of the slide, the type two inflammatory cascade results in downstream effects with maladaptation across the skin with inflammatory thickening and itch, airways with obstruction and mucus production, and esophagus with narrowing in dysphagia.
Moving to slide 15. This shows the various ways to intervene pharmacologically in the type two inflammatory cascade. There are three potential approaches. You can take an immunosuppressive approach that targets multiple types of inflammation by attempting broad blockade of T cells and cytokines, for example, with cyclosporine or JAK inhibitors. You can block single cytokines in the tissue, which potentially can result in an incomplete pharmacological effect.
Or you can block downstream elements of the type two inflammatory cascade, such as mast cell degranulation with antihistamines, or try to sequester all the IgE with biologics such as umalizumab. What makes Dupixent so unique is that by binding to its target receptors, it is the only agent that neutralizes the activity of not only one, but of two of the key type two inflammatory master regulators, namely IL-four and IL-thirteen. Slide 16 shows how Dupixent selectively inhibits type II effector biology by first preventing upstream initiation and priming of the type II inflammatory response, mediated by IL-four and second, by blocking the amplification effects of IL-four and IL-thirteen in tissues, including T helper-two cell and mast cell amplification, inflammatory cell trafficking, and neuronal itch sensitization. Thus, in aggregate, managing and preventing a whole range of type two inflammation associated signs and symptoms. Dupixent achieves this dual pharmacology by blocking a key receptor subunit shared only by the IL-four and IL-thirteen receptors.
So, the cytokines cannot activate the physiological target receptors. Developing this theme further, now moving to slide 17, please, the type two inflammatory signaling cascade is mediated by two receptor types that present in distinct expression patterns across key immune and non immune cell types. Dupixent binds to the AL4 receptor alpha chain and thus blocks both the type Roman one, IL4 receptor exclusively involved in IL4 signaling and the type Roman two, IL4, and IL13 receptors involved in both IL4 and IL13 signaling. Please don't confuse the type Roman one and two receptor nomenclature with the type one and two inflammation terminology. The right hand chart shows a single cell view of IL-four, IL-thirteen receptor expression in atopic dermatitis samples.
Please note that key effector T cells express predominantly the type one IL-four receptor shown in blue, while non immune cells express both IL-four and IL-thirteen receptors. Dupixent is the only approved medicine that can block both receptor types mediating IL-four and IL-thirteen signaling. So, again, the message here is that it takes two to block type two inflammation. And if you attempt to intervene in this pathway by individually neutralizing cytokines, you might get a less favorable efficacy profile. Slide 18 speaks to the specificity.
Please move to slide 18. It speaks to the specificity of Dupixent compared with other therapeutic approaches. Some of you might remember the slide from Capital Markets Day showing a variety of lymphokine and cytokine receptors that exist in the body. When bound by their respective lymphokines, these receptors signal inside the cell and activate signal transducers such as JAK family kinases. If you want to target B type two inflammatory master regulators ALLO-four and ALLO-thirteen with a JAK kinase inhibitor, you would have to inhibit JAK1, JAK2, and JAK3.
Let me walk you through what might be the unintended consequences of blocking all those JAK kinases. If you block, for example, JAK1, you interfere with IL-two and interference signaling, which you need for T cell activation and proliferation to protect from cancer and viruses. If you block JAK2, you risk interfering with key hematologic growth factors such as G CSF, EPO, and TPO, which you need for the body's production of leukocytes, red cells, and platelets. We note that medicines blocking JAK kinases typically require regular blood monitoring and may contain black box warnings. I would like to remind you in this context what Brian said about the importance of safety in the management of chronic lifelong type two inflammatory conditions we aspire to treat.
On slide 19, I want to introduce powerful additional players in type two inflammation, the epithelial barrier and the butt microbiome. Patients with atopic dermatitis are often prone to bacterial infections, with Staphylococcus aureus leading to abscesses requiring antibiotic treatments, or viral infections with herpes viruses often leading to hospitalizations. This is not only due to an imbalanced immune surveillance with predominant type two inflammation, but also due to an altered skin barrier. Dupixent treatment not only rebalances the immune system, but also helps restore the skin barrier function and a normal microbiome to enable a return to healthy skin. On slide 20, you can see data across atopic dermatitis, asthma, and a specific study on Staphylococcus aureus infection that in aggregate support our belief that Dupixent can reduce infection risk.
On the left, in the last data set of patients with atopic dermatitis, the risk of serious infection was reduced by close to sixty percent. And the risk of ixthema herpeticum, a severe herpes infection often leading to hospitalizations, or herpes zoster, a blistering skin infection often leaving lasting pain, by around seventy percent. In investigational skin microbiome study, the absolute abundance of Staphylococcus aureus in skin lesions was substantially reduced over time. In asthma, overall infections were reduced with roughly fifteen percent to twenty five percent reductions observed in upper and lower respiratory tract infections. This remarkable profile is in marked contrast to other immunosuppressive medications that can often increase the risk of infections.
On slide 21,
turning to
eosinophilic esophagitis, we recently reported positive clinical data, which Namish will detail later. The excellent clinical responses we are seeing in this indication reflect the ability of Dupixent to decrease eosinophils and tissues in addition to acting on multiple other components of type two inflammation. What you can see here is that the impressive changes in gene expression from baseline to treatment with Dupixent at week twelve actually mirror the major improvements in endoscopy findings, histology scores, and moderation of dysphagia. It shows that in addition to atopic dermatitis, also here in eosinophilic esophagitis, we find upregulation of epithelial barrier genes indicating repair of the esophageal barrier. We also find reduction of genes involved in eosinophil trafficking, type two inflammation, and tissue remodeling, indicating a rebalancing and normalization of the esophageal immune system.
On my last slide, 22, I want to reiterate that Dupixent's unique dual pharmacology not only compares high efficacy with specific systemic inhibition of T upstream and tissue master regulators ALLO-four and ALLO-thirteen of the type two pathway, but also accomplishes this with a strong safety profile that is based on rebalancing of the immune system and restoration of normal barrier function. I hope after seeing all these data you will share some of our excitement. I hope you also get a sense that we are just getting started to take advantage of the unique molecular and clinical profile of Dupixent to make major inroads in a whole range of established and emerging type two inflammatory conditions. I would now like to hand over to Danish Patel to update you on where we believe we can build on this science and take Dupixent to the next level in type two inflammation.
Thank you, Frank, for setting the stage for our line extension strategy. As mentioned, we are just at the beginning of the expansion of Dupixent. We're really excited about where we're going to take it. So let's go to Slide 24. Based on the deep understanding of the biology Frank just explained to you, we recognize the potential for patient benefit in additional Type II mediated inflammatory diseases by applying a molecular classification approach focusing on key Type II hallmarks.
This includes diseases such as EOE or prurigo nodularis, which are overall driven by type two inflammation or other diseases such as COPD where a subset of patients have type two inflammation. Consequently, we've been systematically exploring potential opportunities for DUPIXENT using precision medicine and machine learning, mining public data and leveraging our real world evidence database that which we call Darwin, which gives us access to around four fifty million live medical records. We have prioritized our findings based upon additional key input from external experts and evidence from investigator studies as well. On slide 25, through our prioritization process, we've identified three new dermatology indications, prurigo nodularis, chronic spontaneous urticaria and bullous pemphigoid, where we see strong biologic rationale for testing DUPIXENT. Each is a type two inflammatory skin disorder that severely impacts quality of life for patients and each has reports of striking benefits of DUPIXENT from investigator studies as I'll outline later.
In total, we estimate there are over four hundred thousand patients with these conditions in The U. S. Who would be eligible to receive a biologic with chronic spontaneous urticaria being the most prevalent. Beyond dermatology, we have prioritized eosinophilic esophagitis where we already had strong Phase II data and recently reported compelling results from Part A of the Phase III trial. And of course in respiratory diseases where we have prioritized COPD.
Regarding COPD, given the risks of this indication, we did not include COPD in our DUPIXENT peak sales forecast greater than $10,000,000,000 So it should be a potential upside to our expectations if approved. Moreover, we have reason to be more optimistic on COPD as I will outline later. I will now go into the key line extensions next. Please advance to slide twenty four twenty six, excuse me. With eosinophilic esophagitis, which is a chronic and progressive type two inflammatory disease characterized by typical molecular hallmarks, including upregulation of type two genes, inflammatory eosinophils, high IgE, and
barrier
dysfunction. This disease is triggered by a complex interplay of genetics, food and environmental allergens that damage the esophagus and lead to difficulty swallowing and eating. If untreated, symptoms and inflammation can cause constriction of the esophagus, food impaction leading to medical emergencies and invasive procedures. Importantly, no therapies are approved in The US and surgical dilation is often the only option for these patients. In terms of prevalence, around one hundred and sixty thousand patients in The US are receiving treatment for EOE, of which around fifty thousand have failed multiple treatments and would be eligible for biologic.
On slide 27, we reported positive results last month from Part A portion of the pivotal Phase III trial evaluating DUPIXENT in patients aged 12 years and older with eosinophilic esophagitis. This trial met both co primary endpoints as well as all key secondary endpoints with a high degree of statistical significance. The results are shown here. On the left, the first co primary endpoint, patients reported a sixty nine percent reduction in dysphasia symptoms, and this is by far the most important symptom for patients with this disease. In the middle, on the second co primary endpoint, sixty percent of patients experience a profound reduction in type two inflammation as measured by esophageal eosinophil count compared to five percent for placebo.
Finally on the right, the key secondary endpoint, a thirty nine percent reduction was observed in abnormal endoscopic findings compared to a slight worsening for the placebo arm. This is the first time a biologic has shown clinically meaningful results in this disease as part of a Phase III trial and really suggests that DUPIXENT has the potential to be practice changing for these patients. Advancing to Slide 28 and looking at COPD, we break down the large unmet medical need in this disease and the potential upside to our peak revenue target if we are successful in this indication. Given the heterogeneity of COPD, we are targeting a large potential pool around three hundred thousand eligible COPD patients in The US who have underlying type two pathology and who continue to suffer exacerbations despite available treatment options. These patients have type two gene expression in the epithelium, a high eosinophil level in the blood or sputum, and they appear to be at increased risk for exacerbations and have reduced lung function among other clinical symptoms.
We are testing the hypothesis in a phase three clinical trial that DUPIXENT can improve lung function and exacerbation in patients with COPD who have type two inflammation as identified by a blood eosinophil count of greater than 300. Importantly, we would like to announce today that the interim analysis of this study has passed a prespecified decision criteria, which will result now in the initiation of a second confirmatory study. If successful, we would aim to be making a regulatory submission in the 2024 timeframe. It's very exciting news for us. So on Slide 29, we show some data that we already had on the potential utility of DUPIXENT in COPD.
Here we show data from our pivotal Phase III chronic rhinosinusitis with nasal polyposis or CRS with NP studies on a subset of patients who had smoking history and clinical features of COPD. As you can see from the right hand side chart, patients on placebo experienced a deterioration in lung function as measured at week sixteen and twenty four in the study. However, those on Dupixent were observed to have significant improvements in lung function. Although encouraging, we await the results of our randomized Phase three clinical trials of type two COPD. On Slide 30, I want to move now to prurigo nodularis.
Prurigo nodularis is a skin disease characterized by local type two inflammation and multiple nodules with unremitting itch, which can cause sleep problems and depression. Multiple clinical approaches have been taken with limited success in this disease, including antihistamines, topical and systemic corticosteroids, as well as phototherapy and cryotherapy. No systemic therapies are currently approved for prigon nodularis, which represents a significant unmet medical need with approximately seventy four thousand patients eligible for a biologic in The U. S. And why are we excited about this indication?
We advanced to slide 31 that shows the benefit of DUPIXENT treatment in prurigo modulators from investigator studies, as I referenced earlier, as an input to our line extension strategy. Across six studies shown here, a total of thirty patients had dramatic improvements in itch, resolution of nodules and improved sleep. The level of benefit was broadly comparable across these studies and the treatment was sustained for up to one year in one study. It is particularly important to note that these patients across these studies all had previously failed multiple therapies. Based upon this promising efficacy signal, we are running two one hundred and fifty patient Phase III studies in prurigo nodularis, which we expect will read out in the 2021.
If successful, we would expect to make regulatory filings before the end of next year. Moving to Slide 32, I want to finish my presentation with a large opportunity, chronic spontaneous urticaria or CSU. This condition is characterized by typical Type II hallmarks manifested by swollen skin lesions or hives with extreme itch. It has a potentially severe impact on quality of life and is relatively common affecting one point five million people in The U. S.
Of whom around three hundred and eight thousand would be eligible for biologic treatment. The disease biology of CSU is complex. It involves the release of multiple cytokines as well as histamine and proteases and hyperactive mast cells together with an autoimmune component involving IgE and IgG. At present, patients typically receive antihistamines or the biologic Xolair, a monoclonal antibody against IgE. However, up to half of the patients do not respond well to Xolair.
Against this backdrop, we believe DUPIXENT has the potential to provide patient benefit by reducing mast cell activation in addition to reducing IgE levels. And this takes us back to Frank's mechanism of action slide for DUPIXENT in Type two biology. And on slide 33, my final slide, these are the results of a small case series of six severely affected patients with CSU who had previously failed both antihistamines and Xolair. After three months, each reported dramatic improvements in disease activity scores averaging ninety four percent improvement. In some cases patients reported no urticaria at all following DUPIXENT treatment.
Based on these striking investigator findings and our beliefs in the biologic hypothesis, we have began a roughly two thirty patient registrational study of DUPIXENT in CSU earlier this year, and we expect results in time to file in 2022. And so to conclude my section, we have used a precision medicine approach making use of genomic data, real world evidence, and investigator case studies to explore novel places where type two biology manifests with a goal toward identifying type two inflammatory diseases with high unmet need as potential line extensions for DUPIXENT. Across various line infections I have spoken about today, DUPIXENT may provide a benefit in aggregate for over seven hundred thousand patients in The U. S. And of course, proportionately higher number of patients on a global basis.
So I thank you for your attention, and I would like now to hand it over to John.
Thank you, Naeemesh, Brian Frank, for explaining why all of us are so confident in the potential of Dupixent across a range of Type two inflammatory diseases. I'll now wrap up with some brief concluding thoughts, and let's move to Slide 35. We're really just at the beginning of our journey with Dupixent, as my colleagues have explained, with the potential of this medicine to become the standard of care across multiple diseases where type two inflammation plays an essential role. This slide reiterates the reasons to believe in the line of extensions that we currently have in development. I won't repeat what Naynish said, but we'll simply point out that the supporting evidence base across various indications extremely consistent.
In addition to our approved respiratory and dermatological indications for Dupixent, we're particularly proud of the remarkable recent data in a gastroenterology indication, namely eosinophilic esophagitis. We're excited about the data we've seen to date and what those data possibly mean to tens of thousands of patients whose quality of life is severely impacted by that disease. We're really looking forward to getting our hands on the full data set next year. Let's move to Slide 36. This slide shows what you can expect to hear on our journey with Dupixent's expansion into younger age groups and into new indications in the coming two years.
In the second half of this year, we expect to report the pivotal results of our pediatric asthma study in six to eleven year olds. In addition, we expect to receive the European approval for atopic dermatitis in children six to eleven year old. We're eager later this year to start Part B of our pivotal atopic dermatitis study in still younger children, including infants, which is supported by the increasing body of safety data with Dupixent that you heard about today. Looking to 2021 next year, we will submit an asthma for children ages six to 11 year old, and we will start an asthma study in infants and younger children, again, by the pristine safety profile of Dupixent. We also expect to receive results from our pivotal studies in pyrrigo nodularis and in chronic spontaneous urticaria.
And then finally, in 2021, we expect the Part B data from our Phase III in eosinophilic esophagitis to readout. And then looking to 2022 for our pivotal trial readouts should be occurring then, we expect to submit in the new indications of chronic urticaria and paragranodularis. Let's move to Slide 37. Our ambition with Dupixent is to maximize patient benefits across a spectrum of Type two diseases. As a reminder of the key take home points today, Type two inflammation is a maladaptive immune response that leads to systemic barrier dysfunction and drive several chronic often co occurring diseases.
IL-four and IL-thirteen are two key components of the Type two cascade and Dupixent is the only medicine that was designed to specifically block both of these cytokines by receptor blockade. This unique profile leads to a best in class efficacy and safety profile. The evidence base continues to build in favor of Dupixent with our first pediatric approval, namely for atopic dermatitis, the long term extension results in adults with AD and most recently, the compelling Phase III results in eosinophilic esophagitis, we are seeing a clinical profile that is consistent across diverse disease states, making the benefit of Dupixent difficult to match by other mechanisms of action or other drugs in development. While we're making great progress, we still have a way to go to address all the potential unmet need that patients have across the Type two spectrum. The clinical data and real world evidence give us great confidence in our line extensions with still much, much more to come.
On Slide 38, my final slide emphasizes that when it comes to Type two chronic inflammatory diseases, Dupixent is the only medicine that checks all the boxes. Dupixent's best in disease efficacy has been demonstrated in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps and now an ESM phyllic esophagitis. No other therapeutic has such broad efficacy against the landscape of Type two inflammatory diseases. This goes back to what I said at the Capital Markets Day in December. It takes two, as we point out today, it takes the right two to address Type two inflammatory diseases.
Dupixent's unique dual mechanism of action, blocking not one, but two lymphokines, IL-four and IL-thirteen, makes it stand out among the other treatment options. Furthermore, the safety profile of Dupixent is remarkable. Dupixent doesn't interfere with immune defense against cancer or pathogens unlike some types of medicines in this space. And our long term safety data and the emerging profile emerging approvals for treatment of children speak volumes to the safety profile of Dupixent, making it the medicine of choice. With that, I hand over to Felix to start the Q and A.
Thank you. Thank you, John and the other speakers. We will now open the event to your questions. We have already a number of questions in the line. Natalie, would you kindly remind everyone and the participants of the options of how to ask questions?
Thank you, Felix. You have two options 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. You will be notified when your line is open to ask your question. At that time, please make sure you unmute your microphone.
And now we will take the first question from Peter Verdult at Citi. Please go ahead, Peter.
Thank you, Natalie. Can you hear me?
Yes. We can.
Thank you. Thank you. Thanks for
the call. Pete Verdult from Citi. Two questions, please. A development one for Namish and a commercial one for for Brian or Bill. Namish, when you look at some of the academic literature out there, it suggests up to forty percent of COPD patients display type two inflammation.
It looks from the slide decks you provided that you're assuming maybe less than twenty percent. Is that conservatism on the part of Sanofi? Or am I missing a step in how you arrive at the addressable, U. S. Patient population?
And if I could squeeze one, a Part B into that question. Are you able to share anything about the data that you saw at the interim analysis, be it lung function or exacerbation data, that gives you this increased confidence in utility and COPD? And then one, I'm sure you're expecting Brian or Bill, anything you're willing to say about recent trends you're seeing for Dupixent in The U. S. As it relates to new starts, continuation of therapy and latest thoughts on how you're sizing up the opportunity in China?
Thank you.
Namish, you want to take the first question there? Namish is trained as a pulmonologist, so I think it's a perfect question for Naymus.
Thank you for the question, Peter. It is a great question. I think there's a bit of a difficulty in how we define the Type two population. There's patients who because we're using a blood test, the blood eosinophil count. And, a certain segment of patients have, high eosinophils all the time, and a certain segment of patients have somewhat fluctuating eosinophil count.
And depending on the patient population you study, you can get slightly different numbers. We we are being a little conservative and and with the twenty percent figure because we know those are the the patients that are reliably type two, and those are the patients we're focusing on in terms of the studies we're carrying out. With respect to your question on the interim analysis, I would the interim analysis was a part of a very strict prespecified criteria around efficacy, involving both efficacy and lung function, and was the analysis involved in an external DMC that reviewed the data. We're unable to say much more around the specifics of it, but we know that we're quite excited by the decision criteria and moving forward with the second study.
Thanks, Amish. And Brian, do you want to take the question on the commercial question?
Yes. Thanks, Pete. Yes, we fully expected some questions in reference to performance and certainly on China as well. So really despite COVID, we've seen really nice resiliency in The U. S.
As it relates to Dupixent and treatment of the patients there. As we shared in the past, obviously, our TRx is holding up very robustly. And a lot of that really contributes to the uniqueness of our molecule, really, the fact that it's not immunosuppressant, the fact that it doesn't require monitoring. It really allows for physicians to feel comfortable both initiating as well as maintaining patients on therapy. Now as it goes to the initiation part, obviously, we've shared with you in the past that certainly practices, in many cases, we saw decreased patient volume of upwards of sixty percent.
So naturally, as you can imagine, that's hard to make it up for completely with telemedicine. Although they've done a very nice job, so many have come on and really started using telemedicine. We have seen them initiating patients there. But we have seen our NRx decline a bit, up to about thirty five percent. But we do see that rebounding as the year goes on.
We're already starting to see practices opening back up now and having more access to patients. So we're bullish on the fact that, that will recover shortly and we'll continue to maintain patients from a TRx standpoint. We're quite excited about China. Obviously, we fully expect later this year, second half of this year to be launching in China. They're an important part of our growth trajectory.
We actually are seeing somewhere in the range of over the next five years, somewhere in the range of seven new indications potentially in China as well for Dupixent. So we're excited about the opportunity there. The patient population represents about 900,000. We calculated that approximately of those patients that would qualify for biologics. And the team is doing really an exceptional job there getting ready for launch.
Thank you.
The next question comes from Wimal Kapadia at Bernstein. Wimal, please go ahead.
Wimal Kapadia from Bernstein. So firstly, on CSU. I'm aware that you're testing DUPI post Zolev. Could DUPI compete with Zolev for the antihistamine refractory patients due to the superior safety profile? Just trying to get a sense of opportunity earlier in the paradigm.
My second question is just on the strategy in place to extend the patent life beyond the end of the decade. Do people clearly be quite significant patent expiry? I want say, appreciate it. So some time away, what lifecycle management plans do you have? And then if I can just get a third one, across CSU, PN and BP, what is the overlap to atopic dermatitis and asthma for each?
I appreciate you've given the patient numbers, but I'm trying to get a true sense of incremental population without double counting. Thank you.
All right. Thanks for your question. I'm going to ask Frank, who is trained as a dermatologist, to take your questions because they mostly concerned derm indications. So Frank, can you lead us off with this?
Yeah, absolutely, John. I mean, terms of chronic spontaneous urticaria, I think it's a huge opportunity out there. I think the indication has just been discovered and the unmet need now established. And I think what really what it does need is a differentiated approach, which is number one safe. And I think we really convinced you hopefully about the safety aspect of Dupixent.
But also, in terms of its mechanism, I think the role of IL-four and IL-thirteen, especially in the mast cell pathology, is just beginning to be established. I refer you to a really nice preclinical paper on, for example, asthma in this case, but it shows the role of mast cells in regards to IL-four and IL-thirteen. There are really interesting case reports emerging. So, really, I think CSU is a fantastic opportunity for a safe drug you can essentially apply to long term management. This is exactly what patients with chronic spontaneous urticaria need.
And Dupixent is a perfect example where we add an additional mechanistic approach to urticaria.
Good. And then on the patent extension, don't know that we'll be able to share much with you here today. But of course, it's on our radar, let's say. So that's about all I can share today probably. Good.
Should we next question. Did we get did we cover everything you wanted to?
Actually, just on the overlapping population for CSU PM and BP with respect to atopic dermatitis and asthma.
Frank, can you speak to that?
Yeah. I mean, is some overlap, I would say, between prurigo nodularis and atopy in general. I wouldn't call it always atopic dermatitis. A lot of patients with prurigo nodularis have some degree of atrophy, I would say about fifty percent. But then if you look at CSU and at BP, they're really quite distinct diseases.
I think it's really not like you're treating atopic dermatitis, you're capturing that automatically. These are really distinct populations where not necessarily you see a lot of overlap, clearly not between atopic dermatitis and Willis Bentonville. Also, not a lot of overlap between CSU and atopic dermatitis.
Great. Thank you
very much. Maybe I can just add to that, Frank. Mean, keep in mind that so we're labeled for severe moderate to severe asthma, moderate to severe AD, and although there's overlap, there's rarely overlap on the severity. So are also a few patients that have moderate to severe asthma and moderate to severe CSU. So it's not necessarily the same label.
Yeah. Could define those. Thanks.
Great. Thank you very much.
Next question.
The next question is from Graham Perry from Bank of America Merrill Lynch. Graham, please go ahead.
Great. Thanks for taking my questions. So the first one is on the COPD second trial. So you can just help us understand exactly what the specific recruitment criteria are for patients. So are you just using eosinophil higher?
Are you screening for or at the very least randomizing by the other markers of Type two inflammation that you highlighted on Slide 28 that might allow you to better identify the more niche target patient population on the back of the results from that trial? Secondly, on CSU, obviously, Xolair, as you highlight, is well penetrated into that market. We hear from physicians that they have to give Xolair to patients who are already on Dupixent for asthma, for example, for their CSU, which indicates that there could be perhaps discrete subpopulations that just respond differently to the two different drugs. How much credence would you give to that view? And what biomarkers are you using in your studies to try and identify those patients commercially?
Or are you just going go for Xolair failures? And then the last question I'll ask on behalf of everyone who emailed us after the last call. As we've got Paul on the line, just the a quick question on thoughts on how to build in M and A. You got $11,000,000,000 extra in your pocket now. Has that changed your thinking on M and A?
Are you still looking at early stage augmenting of the pipeline? Or any change in thought process on what you might need in commercial spaces and or gene therapy? Thank you.
Well, thanks for all those questions, Graham. So I guess some very good ones. So let's let Namish handle the COPD question first about the eligibility criteria for the patients in the studies. EOs greater than or equal to 300 is the main eligibility. But anything else to add on that, Namish?
Yeah. The studies are replicative studies, so very identical in terms of the inclusion criteria. Of course, we are doing a thorough biomarker profile and looking at other Type II biomarkers as exploratory examinations during the study. But overall, the enrollment criteria are similar really replicated, I should say.
Good. And then on the CSU, Frank, don't you take that one? I know one of the questions was whether we're going to focus on the Xolair failures. And the answer to that is no, we're going to go about for patients who are naive to a biologic as well as other failures. So we do have a broader ambition.
But I think there were some questions more around the overlap. I guess, whether they're heterogeneous populations of patients that might respond to one, not the other is what I gathered. Frank, can you take that?
I think you're still on mute, Frank.
You're on mute, Frank.
Okay. This is typically what we are seeing when we're bringing these targeted therapies to patients that we are exploring really new biology. I think the proof will be in the pudding when we bring in Dupixent to chronic spontaneous urticaria. I think we clearly have seen with Dupixent decreased levels of IgE, so clearly an impact on that. And then also the role of IL-four in activating mast cells is very differentiated from, for example, what omalizumab is doing.
You know, I think we have to do the clinical experiment and then build it on there. We clearly have a variety of biomarkers in our trials which are related to IgE and also the alpha alpha alpha gene pathway we know very well, for example, TALK. So we will be able to really disentangle them, you know, superior responder population. A good question. We're very keen on that precision medicine type of approach where we go into patient subsets, but that's something which the clinical experiment and the clinical trials need to establish.
Thanks, Frank. And Paul, do you want to explain what Sanofi is going to do with the $11,000,000,000 of we acquired through the Regeneron stock sale?
Paul, I think you were on mute. I may have to unmute.
Paul may be saying about as much as he can. It's just probably not very much, but
Maybe we will come back to this question in the meantime.
Yes, we can. The meantime, you would understand there's not a lot we can say. I think we've talked about that we are open to exploring ways to supplement the pipeline, and we've shown some evidence of that earlier this year with the acquisition of Synthorix and excited about that Synthetic biology platform and the pipeline that it brings on engineered lymphokines, actually one of which is going into this space here with an engineered version of IL-two that increases regulatory T cells. And so Frank and Amish are going to have fun with that molecule. We'll more to come.
Yes. Maybe we take a question here in the Q and A chain, which was sent to us by Marc Purcell from Morgan Stanley. And maybe that's a question in the same context. How does Sanofi seek to build a portfolio of medicines around Dupixent, whether it is complementary mechanisms or mechanisms to help Dupixent refractory patients in atopic dermatitis, complementary mechanisms in asthma and other Type II indications. Are there assets in the Eplins pipeline which could build on Dupixent?
Or indeed, are there any potential Dupixent two point zeros? John?
Felix, can you hear me? It's Paul.
Yeah. Now we can hear you.
Alright. Sorry about that. I was giving you a beautifully put together answer that you couldn't hear, and so more training required for me on the audio visual. I think John was spot on as always. I think it's worth saying a couple of quick things.
We did the sale because it was right for both companies right at that moment. And it was perhaps a perfect moment to do it. Both the companies aligned. And so now we go into our planned approach, what to do with the proceeds. So news to follow.
I think what we should add, because I think it's quite important. I don't think it's a surprise, but where we have world class development, drug development expertise and commercial expertise in areas that we already participate in, it would make sense to add assets because they become accretive faster and because we think we can get to unmet need faster. So you should look towards trying to add to areas we are first and then beyond that only if we think it makes sense and news to follow. Sorry about that Felix.
No worries.
Yes. And then maybe from the Q and A chain, let's I think that's an important question about where do we go from here. And I'll provide kind of an outline, but then I would encourage Frank and Amy to jump So there are several dimensions to it. One is in terms of understanding how patients respond to Dupixent. Frank has established a precision immunology capability with single cell RNA sequencing and other advanced technologies using machine learning and AI to really try to understand when you have an occasional patient who doesn't respond to Dupixent, what might be going on, what might be alternative targets that we could go for.
And so that has helped to inform our thinking around some next generation therapeutics. And Frank has been using the Abilenex platform and the ability to produce multi specific biologics to tackle that and has put three molecules this year into our development Our development, we're finishing the IND enabling studies and hope to bring those in the clinic probably early next year given the delays from COVID. And then the pipeline does now have some assets with that are in the clinic early in their journeys, CD40 ligand antibody that interrupts TB collaboration in a number of which we think is important in a number of indications, a small molecule oral RIP kinase inhibitor. RIP kinase, to remind you, works downstream of TNF receptors. So an opportunity to intervene in some of the same pathways as TNF, but with an oral.
And then I mentioned very briefly a minute ago, the Synthorix acquisition has given us access to a molecule THOR-eight zero nine that is an engineered version of IL-two that preferentially stimulates the proliferation of regulatory T cells to try to dial up one of Mother Nature's ways of putting the brakes on the immune system. So, are some of the pillars of our effort. But, anything you'd like
to Yeah. Thank you very much. I have to say, the reason why I joined Sanofi as head of immunology research was to kind of open a textbook chapter of type two information and be a category leader in the type two space, definitely. And I'm happy to report that after three years, we assembled a team with incredible talent. We have a type two information cluster led by Paul Bryce, a professor we hired from Northwestern in Chicago.
And we built sort of the tools to really understand, number one, patient biology much better in terms of potential response, what it takes for long term responses to really go at the single cell level. As John said, we put just some data in there as a little teaser where we can now actually go at a single cell level, remember five to 10 micron per cell, and get 2,000 genes per cell. This gives us a whole new way to understand best in class approaches, first in class approaches in terms of target biology and understanding patient journeys. And I think the other really key element is combining real world elements with genomic algorithm based AI approaches where we can really leverage genetic and genomic data. All this comes together to kind of get a completely new understanding, not only on type two inflammation, but it is as a biology.
It gives us new targets. And then, really, the two to tango is the modality. And I think bringing in AppLINX gave us this multimodal biologic toolkit where we can take these single chain, essentially, nanobodies and put them on a string of beads and we can dial in, for example, tissue targeting, conditional activation. We can modulate half lives, coming back to some of your questions. So, this is really like this biologic two point zero toolkit, which we match with our sort of target IBS efforts and understanding patient biology better.
And we're already in record time bringing molecules into the clinic, and this is for another R and D day when John feels it's the right time.
Good. We should probably move on. We could spend quite a bit of time on that topic.
Absolutely. Natalie, we will go back to
the audio questions and but we will take care of all the other questions in the Q and A chat room. So we'll try to handle them all. Thank you, Please go ahead.
Yes. We will now take a question from Jo Walton at Credit Suisse. Jo, please go ahead. Jo, please make sure that you unmute your mic.
If she is not around, then we go to the next question. I think it was Peter, Yes.
So we can now take the question from Peter Welford at Jefferies. Please?
Hi, hopefully you can hear me. I've got three very, very brief questions, please. Firstly, I wonder if you could just talk about atopic dermatitis specifically, what the potential advantages could be of blocking IL-four and IL-thirteen versus IL-thirteen alone, focusing particularly on the efficacy angle, if you could?
And secondly, I wonder if you
could talk a little bit about the nonproportional patients you think who are on more frequent doses of Dupixent. We've heard numbers as
high as a fifth or a quarter
of patients require more frequent than biweekly dosing. I wonder if you could comment on that. And then finally, wonder if you've done any work on the cases of facial rashes and conjunctivitis, which seem to be the most troubling for that physician conversations. Is for a small minority of patients into what could be causing that, whether there's potential, I guess, mechanistic real ground and how that could potentially be improved upon? Thank you.
Well, thank you for your question, Peter. Frank, why don't you take the first one about atopic dermatitis, IL-thirteen monotherapy versus IL-four. I think you tried to cover that in your slides around the basic biology and talking about IL-four playing a role both upstream and downstream, IL-thirteen being more of a more in the middle of the slides, more downstream. But let's touch on that. And then I'd like Manish to pick up the issue around the schedule, how frequently you make some dose dosed as well as the topic of the conjunctivitis, which is seen in some patients with AD.
Thanks,
John. Exactly as you said, mean, takes two, we believe it takes a right to in type two inflammation. Maybe a lot has been said and is presented on IL-thirteen. Maybe let's start with IL-four. IL-four is such an important molecule.
Number one, it's like it primes the immune system, the type two immune system. If you think about type two immunity going wrong, it's like an orchestra going rogue. And AL4 is really the director, which sets essentially a tone for that kind
of type
two orchestra. And if you block that, you can actually go to the very causal origins of what type two inflammation is all about. So IL-four is really key. But it also plays an important role, like John said, in the tissues. It amplifies not only Th2 effector cells.
And I hope you remember the single cell data from atopic dermatitis where you saw that all the blue was on the T cells. So, those T cells in there we know on a single cell level they respond to IL-four. So, you have to block it. And then there's another player we didn't even talk about. It's the mast cell.
Mast cells explicitly express this what we call type Roman one IL-four receptor. So you're actually getting into the mast cell biology. We had a lot of interest about CSU. That actually contributes to our confidence that Dupixent is a great player in there. IL-thirteen especially can work in combination with IL-four, everything from class switching, IgE production to really mucus production in the asthmatic lung and has a lot of also synergies with ALLO-four.
I think there's an ALLO-four specific component we're specifically leveraging. That's why potentially some of those single cytokine approaches are what we feel incomplete. If you look at our clinical footprint now across four type two inflammatory diseases, a lot of the other ones are just in an individual indication. For example, only in AD, but not in us now, for example, you know, only in certain indications. There's this kind of notion that if you're blocking one, it might be an incomplete kind of approach to type two information.
Yes. It could be very important for that restoration of barrier function, too, which is really what begins to create the opportunity for more long term disease modification. Let's ask, Namish, can you tackle the issue of the Dupixent schedule and the conjunctivitis that's seen in some patients with AD, but interestingly, not in typically in patients with asthma or ischemic esophagitis, some of the other indications. So, Namish, over to you.
Sure. John, that's exactly right. Maybe I might pass over to Brian after I'm done just because the question is also about real world use. But in terms of the dosing schedule, in our Phase III program, we did extensively compare the efficacy of QW and Q2W dosing of DUPIXENT. And over a broad population, there wasn't really much difference in efficacy.
Whether there are subpopulations within the AD sphere that might benefit more from QW dosing is, I would say, an unanswered question, unproven question, but at this point, we haven't been able to rule it out either. And and and just about, the conjunctivitis piece, exactly right. Relatively uncommon in atopic dermatitis and actually not seen at all in, for example, asthma or EOE. What we do understand about conjunctivitis is, as I mentioned, relatively uncommon, but it actually frequently occurs in AD patients who are not treated with DUPIXENT, so something about atopic dermatitis specifically with conjunctivitis. We also know that in general, the reactions with conjunctivitis are relatively mild.
They can be treated conservatively with eye drops, and very rarely does it ever lead to the requirement to stop dosing DUPIXENT. So it usually gets better over time with continued DUPIXENT therapy. And maybe I can hand it over to Brian to address the other question.
Yes. Brian, anything to add?
Yes, absolutely. I think that in reference to the question about the dosing, right, two week, maybe two week, what we tend to see is we don't have a quantification of how what is the percentage of that. But what we tend to see is we or we tend to hear is we hear that very infrequently. And when we do hear it, it's normally from the KOLs, those individuals that have maybe been involved in the previous trials, and they're trying, in some cases, the higher dose of going with a more frequent dose. But it's a very low percentage.
Most of what we see is within the label, which is every two weeks.
And I guess no matter what the frequency is, we're working on an auto injector, which we hope to be able to provide soon to make the experience of taking your DUPIXENT even more convenient for the patients going forward.
Should we go to
the next question?
Yes. The next question is from Geoff Porges at Leerink. Geoff, please go ahead.
Thank you very much for taking the questions. First, perhaps I'll ask one to Bill Sybalt, who's been very serious in front of his beautiful painting. First, could you, Bill, comment on what effect do you think payer mix is going to have on your revenue trajectory for Dupixent in the second half of the year? Obviously, we've had a huge surge in unemployment, and presumably, patients might transition over to Medicaid. So can you just give us a sense of what sort of headwind that might be?
And then secondly, could you talk a little bit about perhaps, Brian, about JAK inhibitor competition? Like it or not, JAK inhibitors seem destined for approval in atopic dermatitis. So we'd love to hear what your market research is telling you about how JAK inhibitors might slot in to the landscape that you're competing in? And then lastly, perhaps Namish could talk a little bit about bullous tempagore, if you didn't give us any information there about the relative size, timing and indeed the current clinical evidence for efficacy in that indication. Thanks.
Okay. Several good questions. So Bill, you want to kick us off?
Okay, Jeff. Thanks for the questions. I'll look a little bit less serious. Look, thanks for the question. It's a little premature to know what, if any, impact there's going to be as we look to the second half of the year.
The way we approach this is we've made sure that we have the appropriate patient assistance programs in place to help patients, first of all, go in uninterrupted if they have any kind of change in status. So that's where we've been focusing. I think overall, the message that I would give is that we're starting to see more practices that are opening. So more patients are going to get to practices to be prescribed. And we see the growth growing through any of these changes that may or may not happen from a payer shift perspective.
But until we know what that ultimately looks like, goal number one, make sure that we've got the programs in place, patients stay on therapy, uninterrupted access, then we've got at least three or four good programs in place. So I think we'll be in a better position to report out on that. As we get to the Q2 call, we'll have our first sign and then certainly after that, as we get more back to fully open practices to give you an update on it. But it's certainly on our mind. We're monitoring.
And I'll turn it over to Brian.
Yes. Brian, you want to tackle the class of medicines with the black box warnings, maybe say a few words about them?
Yeah, absolutely. I think that, obviously, it's a really interesting time for the development of these agents. And as we've expressed in the past, I think, in Capital Market Day, the JAK class, what we're seeing is pretty consistent with what we've seen with previous JAK therapies, Really, the broad immunosuppressive type approach is creating a profile that you see that you're going have to go up in strength to get the efficacy required in this particular patient population. And with that comes some side effects. And I think that Capital Market Day has clearly laid this out that in this particular community, in the dermatology community, when you have that type of profile, our research is really suggesting that this is going be a second line therapy.
They'll be really reserved for patients that have potentially no other options at that particular point, but after they would have considered DUPIXENT. So we'll see how it continues to develop. I think we have to see the remaining data for each of them and see what the labels are that they actually get. But for the time being, obviously, we feel incredibly bullish about our profile remaining the best in class profile for the foreseeable future.
All
right. And there was a question about bullous pemphigoid, which I think, Ninglish, can you tackle that?
Sure. So mean, this this gets back a little bit to our our our theme about Dupixent where I think we're just scratching the surface. We're we're just beginning the journey in in all the indications where Dupixent can be, and we prioritize a few of the larger ones for discussion today. Both pemphigoid is one of those very important indications that we are advancing Dupixent on. The phase three program has already commenced.
And it is an important disease. It's a relatively smaller indication than the others, about twenty seven thousand patients biologics eligible eligible in The US. And it's a very type two disease similar to the others one we we've discussed with the with the same hallmarks characterized by eosinophilia, high IgE levels, and autoreactive IgE to skin causing blistering. And it's really a a quite severe disease with a high mortality for these patients, and we we believe that DUPIXENT can really make a difference for these patients. It's a a disease primarily of the elbow, and we're very interested in advancing the study in this area.
We just haven't discussed it extensively in this presentation.
So just to chime in from a dermatology perspective, I think it's really a paradigmatic example how we are now establishing type two inflammation as a connected pathology with these type two hallmarks and actually bringing diseases in, which in the textbooks I was reading, didn't feature under type two inflammation, but clearly with high IgE eosinophils, the IgE probably even involved in the blister formation, a very interesting indication. We have now case reports lined up to basically support the mechanistic hypothesis. But also think about the patient population. It's typically elderly patients. They need chronic treatment.
They can be on steroids, which is the only other all steroids, the only other really therapy you often have for these patients. If you have a safe drug which is on mechanism and can be given in a chronic treatment paradigm, I think Dupixent is right up for the game as a potential breakthrough therapy.
Okay. Thank you. So let's move on to the next question.
Yes. We may go back
to the Q and A line. It's getting increasingly difficult to find and to make sure that we address every question which has not been addressed before. There's a question from Richard which is in line with what we heard before, but there was one additional element, Richard Wasser from JPMorgan. In terms of your €10,000,000,000 peak sales ambition, how much of a contribution are you factoring in for AD and asthma? I think the other question was already addressed.
All right. Brian, do you want to take that? I don't know how much of the detail you've been revealing on the mix of indications contributing to that $10,000,000,000 aspiration, but over to you.
Yes, absolutely. I think we as we said in Capital Market Day as well, there's multiple ways to get to the $10,000,000,000 and beyond, quite frankly. We the foundation of that, however, atopic dermatitis and asthma are two really foundational indications. So we don't really kind of share what the split or we think the split will be. All we really share is that we think that, first, think atopic dermatitis.
That's the best way to think about it. First, think about atopic dermatitis. Big population, high unmet medical need, very low penetration rate today. And then think asthma as well, obviously, big population, still pretty low penetration rate and again in spite of having five competitors now in the marketplace. So those are really our two foundational indications.
I think the other way
you should think about it and
this is why it's multiple ways to get there. As you see the indications that are now coming, these are adjacent indications and further strengthen our dermatology and respiratory plays. So they're as Namish laid out, oligos pemphigoid and pragunoduliris and others, they share some characteristics which further strengthen your AD profile and further strengthen your asthma profile respiratory side. So that will help, I think, in further defending ourselves in both the AD and the asthma space as well. But multiple ways to get there.
All right. Thank you, Brian. Next question.
The next question is from Luisa Hector at Berenberg. Luisa, please go ahead. Hi, thank you for taking my questions. So the two questions really linking to atopic dermatitis. The first question is on the patients who do respond really well to the drug.
I wanted to check that you feel comfortable that you're well positioned for long term persistency of therapy. I'm wondering whether there might be a temptation over time to dose taper. And then secondly, it's kind of the flip side to that. The patients who are not super responders, maybe they don't respond so well or not at all. The question there is really why don't they respond so well?
Do you think there is a mixture of misdiagnosis? They were never truly AD to start with or a mixture of diseases or perhaps an under dosing if they are, let's say, heavier patients, some kind of weight element or any other reasons? Thank you.
Thanks for the questions, Luisa. Nimish, why don't you start with the dose the long term dosing, whether patients will be tempted to taper dosing, etcetera. Brian, you may also have some insights into that from your work in the field. So let me ask Amish to start and then Brian to follow. And then Frank, I'll have you take the nonresponder question because that's an area of science I know you're very passionate about.
So Amish?
Sure. So I could start with Lucia, thanks for the question. I can start with the data we've accrued. So the SOLO CONTINUE study in AD, which has been published, is a study in which we took patients who responded really well to dupilumab IGA-one and tapered their doses to a q four regimen, q eight regimen. And what we did did know from that study is there's definite loss of efficacy if if you go to a less frequent dosing regimen.
So and I think the strongest sort of incentive for patients to stay on q dosing is the the the superior efficacy of of Dupixent. But q two dosing, as we've seen with the long term extension trials, is very effective for years on and then with even increasing or continued dosing with even increasing efficacy over the long term. So that's one of the really strong sort of incentives of staying on Q2 dosing. And Brian, I don't know if you have anything to add to that.
Yes. We've seen very strong persistency rates. I think we've shared in the past upwards of seventy percent, seventy five percent at a year. And again, this really speaks to I think it's really important to understand the disease states. These patients didn't have a lot of therapies beforehand.
Obviously, as they came on to therapy and they saw, in many cases, obviously, most cases, very positive results from DUPIXENT. So, patients are really quite persistent with their treatment. So, we have no reason to believe that that will change over time, and we're quite confident in that.
All right. Thanks, Brian. Amy, Frank, on the non responders, you shared
your First, when I came, I said, Where are the non responders? And there weren't actually many because it's really interesting how basically every patient responds to Dupixent with some degree of response, which is often satisfactory. But then, if you're on a chronic disease journey over twenty or thirty years, there might be patients who are coming off Dupixent and that might be for a variety of reasons, you know, maybe not injecting regularly anymore, taking a drug holiday, or any other possibilities out there. We're studying these patients very, very intimately, I would say. We're understanding what molecular sort of underpinnings are and we're using that to kind of design our next generation therapeutics, which is not the topic of today's discussion.
But obviously, as John was alluding to, we are very passionate about establishing a whole portfolio of medicines around Dupixent to establish that Type II leadership and that's probably for now.
Good. Okay. Thanks, Luisa.
Thank you. We want to go back to the Q and A room. There's a long list of questions from Joe Walton at Credit Suisse. Maybe some of those questions have already been addressed. I will read them all of them.
What do you expect to see from triloquinimod this weekend and AAD and later perhaps on lebrikizumab? Given they are only going after AD and are with derm focused companies, do you feel them coming in with limited indication but much cheaper? In particular, how important is speed of onset in treating itch? How do you expect to see pricing in Europe as you keep adding indications in this is this an issue? You have presumably less flexibility on pricing in any one indication given the breadth of your sales.
Can you help us on the most recent patient split in scripts so we can assess the level of penetration today in AD and asthma? Potentially, some of the questions have been addressed before, but John, you may want to
Yes. No, there's some new ones here. So on the competitor molecule coming up at the dermatology meeting, Frank, are you familiar with that molecule? Do you want to make any comments about that?
Yes. Actually, probably I mean, number one, it's always to predict anything, especially if it's the future. But, you know, and we don't have any particular insights into those datasets. But maybe, I mean, I talked a little bit about the kind of incomplete elements based on the science. I already alluded to that.
Maybe Brian wants to kind of take this and talk about the positioning where he sees Dupixent versus the IL-thirteen class on a commercial success if that's okay, John? Yes.
Yes. Very good. Yes, absolutely. There was a lot of questions in the gist, so I'll try and keep them apart.
Actually, you have the floor, you can maybe take the issue about the pricing for different indications in Europe or what that means as well as the there's a question around the relative proportion of prescriptions being ascribed to different indications and sort of a follow on, I guess, to what you said previously. So maybe you can take all of those. Well, and then the other question was about speed of onset, which I know is a topic that's near and dear to your heart, Brian. So I think you can take all of these.
Yes. Yes, I'll try to remember all of these. But yes, speed is absolutely very important. I think as you saw in the presentation, we really we've been very pleased. And I think the and we hear in the real world as well, the physician audience is very pleased as well as are the patients with the onset of action really after the first dose.
We see this across atopic dermatitis and we see it as well in asthma. Very impressive results. Really after that very first dose, patients start to feel the effect immediately or see the effect in some cases like in dermatology. But as you look at the
and I think, Frank,
you started it off. As you look at the new products, the new potential entrants, IL-13s, I the think word incomplete is something that comes to mind that we actually we've shared with you today really the importance of the role of IL-four and IL-thirteen. And we're seeing this really in the data. Now while we haven't seen the Phase III data yet for Trelo or for lebri, either one of those, What we have seen is obviously we've seen their Phase II data. And while there are some interesting results in there, one of the things that we do see is that in both cases, we haven't seen them work across Type II diseases.
So in both cases, we've seen or excuse me, lebrikizumab not tried that there, at least to our knowledge, but trilaciclib obviously did not work in asthma previously. So again, getting back to the importance in type two inflammatory diseases of both four and 13. So I expect I'm interested to see the results this weekend, but our market research really suggests as well, much like the JAKs, that these will be reserved for second line therapy behind Dupixent. Now as you think about the future the additional questions, obviously, dermatitis, we've said, is a big part of our success. We've actually said as well that the penetration rate, however, and I think this is one of the questions about the splits, penetration rate is still extremely low.
So we're in about if you look at The U. S. Alone, about 4.4% penetrated. We see this marketplace growing like what we saw in the psoriasis marketplace. So we still have enormous growth potential ahead of us, and we're really excited about that.
Asthma has just recently launched, of course. I mean, we're still relatively recent, and still there's a lot of markets still to launch. So we should see asthma continue to come on and contributing a higher portion of the growth in the future. Now last one in reference to price. Price is very important, it really begins with payers ex U.
S. Especially, really helping them understand the burden of these diseases. And I think the teams have done really an exceptional job of sharing the information about the burden of these diseases, the cost to the systems and really making sure that we establish our product as an effective and safe therapy that provides value to their patients. And we've seen that. We've secured nice positions, nice pricing ex U.
S, really very strongly competitive versus what we've seen actually across psoriasis marketplace and certainly in other markets. And we believe we can sustain that over time because we thought about the other indications as we went in to speak with the payers. And that was an important part of our ex U. S. Pricing strategy.
But a lot more work to come. First and foremost, it begins with innovative treatment for patients of high unmet medical need.
Thank you, Brian. Peter,
Yes. Can take the
We have only a very few minutes left, but still a long list of people who want to ask questions. So we go back to audio and please try to reduce your questions to only one in order to allow for another two or three questions. Thank you. Natalie, please go ahead.
The next question is from Tim Anderson at Wolfe Research. Tim, please go ahead.
I look at how the psoriasis market evolved over the course of a decade, initial biologic agents like the TNFs were clearly much better than standard of care at the time, but their absolute levels of efficacy on things like PASI90 weren't that high. And sure enough, over time, you had other classes like IL-17s and IL-23s that came in that really went into a step change. So when I look at atopic derm, it makes me wonder if the same might occur because if I look at EASI 90 scores with DUPI, the absolute levels really aren't that high. It's 25% to 30% or so, which is certainly better than what's been out there. But I tally up all the companies and different mechanisms going after atopic derm, and it's a really long list.
I know we don't have Phase III on a lot of these, but we're really in them. A lot of cases, we're to have Phase II, but could that psoriasis precedent be worrisome?
Yeah. Thanks for your question, Tim. I think that's a great one. I'm gonna ask Frank, as our dermatology expert to start off, and then we can, maybe ask. Yeah.
Happy to
help you. And maybe even our CEO, Paul, has something to say about that because I think he knows a little bit about the psoriasis space.
Should that kick off? Yeah. Go ahead. So I think it's a great analogy. And I started off my career the academic clinical side, we first started to use biologics.
And, actually, my first first patient was a was a patient on infliximab, and I still remember a psoriasis patient who came home and next next visit was with a lot of shopping bags. For the first time, she could wear clothes she never dreamt about wearing. I have to say when you come into the type two space and you try to kind of put this into perspective versus the type one, I think number one, the type two space seems to be much more interesting into many, many diseases where we're moving in and the connected pathology is like much wider in terms of where the pathological net captures patients and establishes disease pathologies. Also, many different organ systems can be involved. And in terms of therapeutic success, I have to say, I was there in Enbrel, the early anti CNFs were there, and you're right.
I mean, they obviously were eclipsed now by the IL-23s the entire IL-17s. But I would say we're much closer to the pathology, to the real master regulators, IL-four, IL-thirteen. I haven't seen as a scientist and as a clinician scientist not a better master regulator. I was involved in discovering IL-twenty three and and knew immediately that's the master regulator in psoriasis with IL-seventeen as downstream, and TNF is all over the place. So so clearly, Dupixent is not this all over the place anti inflammatory.
It it had it really acts at these master regulators of of IL-four and IL-thirteen. So we'll we'll wait and see. I mean, there might be always something coming, and we certainly work on some next generation drugs. But we're pretty close to the causal mechanisms of that type two inflammatory disease with two master regulators combined. It's a pretty good start.
Paul, do you want to contribute anything given your history?
Hi, John. Can you hear me okay? Yes.
Yes. Okay.
Great. So the beginning part of the question was a little faint. But so if you wanna repeat it for me, it'd be great. Otherwise,
and I
think Frank just said it, I mean, we're probably right at the limit of efficacy and tolerability in a single medicine we're ever going to see in these disease areas. I think we have set an efficacy and safety bar that is going to be almost impossible for many of the entrants to reach in almost all of the indications. They'll play around the edges. They'll try and carve out a position, am sure. But fundamentally, derms, palms, everybody that's using the medicines knows We have set such a high bar.
It's very difficult because of the reasons Frank and the team have outlined to imagine, anybody considering something else. Think while while we're on, I just wanna say thanks to the team because, I think as we start to broaden the impact of this medicine and really start to get under you, I I hear the enthusiasm. I see it every day, but I think thank you to them for how they've shared it. We are really, you know, and I think, Brian said it, like four percent penetrated of patients that could benefit from a medicine that is probably gonna be the standard of care, for a decade plus. Think we just have to recognize where we're at and say we haven't even started yet.
And that's incredible for patients and indeed to create value for the company and those that invest in us.
All right. Thank you, Paul. Brian, did you have anything you wanted to add? I saw you trying Yes.
Of course, obviously,
I've been in this space for a long time in dermatology. So we're and the truth is we're really going to benefit, and I think that's the way to look at this, right? We're going to benefit in atopic dermatitis from the way in which the psoriasis market develops. So if you think about it, the psoriasis, a lot of the physicians, as Frank indicated, the same type of thing. They didn't have these advanced therapies at the beginning more than fifteen years ago.
And the first the number of them, one of the big issues was safety. There were some struggles with safety. And this particular community, think as Paul very nicely laid it out, safety is of utmost importance. So I think as you think about how the profiles changed over time, it wasn't just on efficacy. The profiles changed over time in psoriasis on their balance of efficacy and safety.
And that was a big transition point, I think, for the psoriasis space as it grew. And I think what you see for us is just as Paul is laying out, we really have a nice balance of both efficacy. We don't give up anything on the efficacy side. But certainly, that safety profile is going be incredibly important for the physicians, certainly in an atopic dermatitis space. But we will benefit from the lessons learned in psoriasis for sure.
All right. Great question, Tim. Felix, do we have time for another one or two?
Yes. I think we take two more questions. So please, one question each. We have many more, but we will handle it. And after the call, Natalie, please go ahead with the two last So
the next question is from Seamus Fernandez at Guggenheim. Seamus, the floor is yours.
Okay. I managed to mute from multiple different screens. So thanks for taking the question. Just a quick one. Really wanted to understand a little bit better the dynamics of eosinophil counts, the interaction from that perspective in COPD, in particular.
I think you've emphasized the importance of eosinophils there. Can you just help us understand what was the choice to advance that program today? I think the announcement was just made with regard to advancing into a broader COPD program. And is it related to sort of the pneumonia and bronch itis dynamics around ICS? Is that an opportunity to see a real meaningful improvement in the treatment of COPD?
Or is it simply just eosinophil counts? Because when we look at some of the other programs, in particular, the benralizumab program, which actually knocks down eosinophils very quickly and very effectively, we didn't see that big of an effect. So this feels a little bit like a trial design benefit more so than a molecule, but please just correct me if I'm wrong. Wrong.
Seamus. Thanks for your question. I'm going to ask Namish to kick us off in terms of trying to answer that. I would clarify though that the second study is essentially the same as the first. We're not broadening a low eosinophil population or something.
It's really for purposes of having two studies, one of which will be confirmatory for purposes of registration. But Neamus, can you handle the detail there again?
Sure. Seamus, thanks for the question. I guess one way to say it is sort of eosinophils are important, but eosinophils are team players. The team they play on is actually type two inflammation, and they're just a marker for type two inflammation. We are identifying a subset of patients with COPD who have active type two inflammation.
We're using the eosinophil count as sort of a biomarker to identify that, but it's much more than just eosinophils is what's going on. As Frank alluded to extensively in his presentation, IL four thirteen have effects on airway, mucus production, airway hyperplasia. All these things are very important aspects of what we think is the pathogenesis of COPD. And that's why we think Dupixent has a real chance to be different than what we've seen with Ben or Mepalizumab, excuse me, in terms of efficacy and COPD. And the data we had from CRSNP study, excuse me, really outlines patients who had COPD in that study had a lung function benefit from Dupixent, and that hasn't been seen previously with any biologics of in COPD, that's what gives confidence.
In terms of the other big confidence driver is the interim analysis that we had, that was, as I mentioned, had a strict gono go night criteria based on efficacy conducted by an independent DMC, and that figured prominently into the decision criteria of launching the second study. I hope that answers the question.
Yes. Great, Nimish. Thank you for the question, Seamus.
All right. Natalie, last one from the line.
Yes. So the last question is from Jean Jacques Leffier at Bryan Garnier. Jean Jacques?
Thank you for taking my question. A question regarding a commercial question regarding market share in atopic dermatitis. When you will reach the €10,000,000,000 mark in sales also, what could be or what do you expect as a market share level you will reach at the same time? I know you will not give me a precise figure, but could it be in the low double digit level range, 20%, much more than 20%? So just to understand where you will be in market share for AD since you have a quite very strong dynamic right now?
Thank you.
Ryan, do you want to take that? And then Bill can supplement if he cares too.
I think Jean Jacques is right. It's really hard to share a number there because as we said, there's multiple ways to get there. So it's we don't have a formula, like I said, that says, okay, at that particular point, we'll be at AD this much and asthma this much and some of the others. But I think the best way to think about it is that you should think about that market the dynamic of the penetration rate into the atopic dermatitis, so if you think about the big contributors to the ability to reach $10,000,000,000 as we mentioned and to exceed it, quite frankly, it's first start to atopic dermatitis and really the growth of the marketplace. So as we said earlier, we're only about 4.4% penetrated into that patient population as we speak today.
And so that will certainly be in the double digits for sure as far as penetration rate goes. Now our share of that obviously will be determined based upon obviously the competitors and how we continue to maintain our leadership position. But I would say I'd sum it up by saying, it will be based on the market growth there without a specific number. We will still be the leaders in market share significantly within what's in that particular marketplace. And there will be other contributors like asthma and other indications by that particular point.
Maybe John? Bill, yes, Please
force that a little bit. As you think about AD and you think about what's the biopenetration look like and you've seen where psoriasis is that we talked about earlier in the call, being in that over twenty percent range finally after a lot of years, you know, we see that Dupixent and AD or pardon me, that biologics and AD get, you know, over that twenty percent, twenty to twenty five percent. Question is what's going to be the time? Not sure of what the timing looks like because, you know, the specialty is getting used to still treating atopic dermatitis. But what I will tell you and what I believe very strongly is that we will be the leading player in the space.
Brian mentioned it, but we don't see anything that displaces Dupixent. We've said from the start, we're just getting started. There's still this enormous breadth potential based on the mechanism of action. We're going to go to other places where the Type two inflammation takes us. The enormous depth, we're just getting started with all the penetration rates that Brian referred to when we talked to about the during the call.
And there's just not any other profile out there that we think displaces it. So I mean, we are still remain bullish on this and believe in the potential of this product. It is a once in a career product, and we're excited.
Thanks, Bill. Good. All right. Thanks for the question, Seamus. What next, Felix?
One more maybe?
I think we have come to the point that we are already fifteen minutes over time. If you want to maybe take a couple of minutes to conclude and then we let people call us again, we tried our best to address as many questions that we have in line as possible, both on the phone as well as in the Q and A room. So please forgive us. We will do this separately and individually.
Good. Well, let me start by thanking all who joined us today to get an update on Dupixent. Dupixent really is a flagship product of the Sanofi portfolio. I think my colleagues hopefully did an outstanding job of really explaining the fundamental biology behind Type II inflammatory diseases, the diversity of those diseases in terms of how they manifest. It's fundamentally a systemic problem with how the immune system is regulated but manifests in different organs.
And you've seen already with approvals in four indications and hopefully soon another with moving into the eosinophilic esophagitis, which takes us then in from respiratory and dermatology into even gastroenterology. You've seen how the manifestations of these type of diseases in different organ systems can be very effectively and safely addressed by Dupixent. It is really a remarkable, very special medicine that is beginning to address enormous unmet patient need. The stories of these patients who've suffered all their lives with these conditions are heart wrenching. And so to be in a position to address those needs is about as good as it gets for physician scientists like me and my colleagues.
So I thank you for your attention. We'll look forward to further updates. A lot of news flow obviously ahead of us with the broad program that investing in for DUPIXENT and trying to make the most of this medicine because there are so many patients that are really urgently need Dupixent. So thank you again, and we'll look forward to further updates.
Thank you. Thank you. Thanks.