Good morning and good afternoon, and welcome to the Novartis Immunology Portfolio Update conference call and live webcast. Please note that during the presentation, all participants will be in a listen-only mode, and the conference is being recorded. After the presentation, there will be an opportunity to ask questions by pressing star one and one at any time during the conference. Please limit yourself to one question and return to the queue for any follow-ups. A recording of the conference call, including the Q&A session, will be available on our website shortly after the call ends. With that, I would like to hand over to Ms. Isabella Zinck, Investor Relations. Please go ahead, Madam.
Thank you very much, Sharon, and hello everyone. Thank you for joining our call, another Novartis call this week. With me in the room are presenters: Shreeram Aradhye, President of Development and Chief Medical Officer, Victor Bultó, President of our U.S. Operations, and Angelika Jahreis, who's the Global Head for the Immunology Development Unit. With that, I'll briefly read the Safe Harbor statement before I hand over to Shreeram. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties, and other factors. These may cause actual results to be materially different from any future results, performance, or achievements expressed or implied by such statements. For a description of some of these factors, please refer to the company's Form 20-F and its most recent quarterly results on Form 6-K that respectively were filed with and furnished to the US Securities and Exchange Commission. Over to you, Shreeram.
Thank you, Isabella. Thank you everyone for joining our immunology-focused call. I'm delighted to be here with Victor and Angelika. Angelika and I have just come back from a very, very interesting and exciting American College of Rheumatology meeting in Chicago. Moving to slide four, immunology has been an area in which Novartis has had a long legacy. If I think of my own journey at Novartis over the last 25 years, it began with getting involved in Simulect and the oral GILENYA, which we actually developed for MS. It's been great to be back for the last 3.5 years as we became a pure-play medicines company and chose to double down on immunology as one of our key therapeutic areas, leveraging then the development of FABHALTA, crossing a number of indications.
In this particular moment in time, I'm super excited about the recent approval of RHAPSIDO, remibrutinib for chronic spontaneous urticaria in the United States, the positive data with ianalumab in Sjögren's disease, as we will discuss, as well as our ongoing efforts with the bold ambition of using our CAR-T therapy, YTB323, for the treatment of multiple autoimmune conditions on the back of positive phase I-II data. Moving to slide five, we have chosen to, of course, remain committed to immunology because immunological conditions present and continue to present a large and growing burden for patients and society. More than 10% of the global population suffers from immune-mediated conditions. These conditions are chronic. They have a progressive nature. They have significant impact on patients and their quality of life with significant physical and psychological burden. Diagnosis is often complicated.
Patients have heterogeneous manifestations, and the patient journey is typically identified as taking a significant number of years before the right diagnoses are made. These diseases represent a significant financial and socioeconomic burden and therefore offer a perfect opportunity for the type of innovation that we are committed to at Novartis. Moving to slide six. We have now chosen as part of our focus to focus on the following core areas. We look at conditions that we consider immunodermatology, like hidradenitis suppurativa, chronic spontaneous urticaria. These are T-cell-driven diseases. We are focused on systemic autoimmunity in diseases like Sjögren's, lupus, lupus nephritis, systemic sclerosis, looking at allergic conditions, as well as the various arthritides.
On the right side, we talk about the multiple platforms that we have expertise in, starting with small molecules, monoclonal antibodies, bispecific agents, as well as the more advanced platforms like CAR-T therapies, with the primary principle being to use the appropriate modality to deliver what we believe is a meaningful difference from standard of care, if some is available, or in order to allow us to treat a disease that has previously been difficult to treat. We aim to break the efficacy ceiling in many of these diseases that we are currently aiming to treat. In our new ways of working, we have complete clarity right from the start as to what is it going to take to have a product that's going to be meaningful for patients such that it can be commercially viable and brings us value both to patients as well as to our shareholders.
Moving to slide seven, we do this both with the significant efforts with internal innovation from our biomedical research teams, but equally by identifying meaningful external opportunities for us to acquire and integrate into our portfolio. A perfect example would be the recent acquisition of the anti-IL-15 antibody from Calypso, which we now aim to advance in multiple T-cell-driven diseases, starting with atopic dermatitis. Again, our key focus over the past years has been on speed, making sure that we're developing the most efficient development programs that are asset-centric and aim to generate the data that is most informative for us for making a decision on whether a product is likely to deliver the value that we expect it to bring to patients.
On the right there, with IFM Due, Monte Rosa, and Kyorin, are good examples of where earlier stage deals are another way for us to complement our own internal efforts, but with agents that we believe have the scientific reason to believe to bring, again, a disruptive difference from the rest of the competition in the space. Moving to slide eight, for quite some time now at Novartis, we've followed this principle of deeply understanding a particular mechanism and its implications in various disorders. Once we've understood that mechanism and have an asset in hand, and the pipeline and the pill, which in this case is, of course, within quotes because the compounds that we're going to talk about today or the programs we talk about today, RHAPSIDO is a pill, but the other two are not. The principle here really is that.
We're now making, as a pure-play company, a considered effort to make sure that we are developing our assets in multiple indications in parallel programs with an attention to being able to maximize the value that we can bring to patients and to the company based on effectively utilizing and delivering on these evaluations. You'll see that play out in the conversations that we're going to have later in the day, I mean, later in this hour. I'm going to take a few minutes to just talk about our efforts in CAR-T with YTB323, which is our next-generation CD19 CAR-T program. If we move to slide nine. Of course, as you all know, the premise here is that in diseases where B cells have an important role to play, effective depletion of the B cell compartment utilizing a CD19 targeting CAR-T therapy has the opportunity to reset autoimmunity.
People have spoken about an immune reset. The premise there, as is depicted in the graphic in the center, is the idea that with the help of a CAR-T therapy, attain deep depletion of B cells with the subsequent reconstitution of the B cell compartment with naïve cells, with the loss of the autoreactive B cells, resulting in a modification of the disease that allows patients to now be managed without ongoing immunosuppression or, if necessary, with the use of drugs with a response that allows them to have a much better quality of life, but with a significantly reduced amount of additional treatment. We began our own efforts building upon our long experience in CAR-T.
If we move to slide 10 with our phase I-II study that was conducted by our biomedical research teams in lupus and lupus nephritis, we were pleased to report that in the 21-patient experience, we were able to demonstrate with up to 12 months of follow-up, a meaningful reduction in the SLEDAI score over time. The little residual disease that you see there with the SLEDAI around two is really driven by the fact that any presence of proteinuria from the kidneys results in the score being as such. We need to keep in mind here an important concept that the CAR-T therapy takes care of any disease activity but cannot effectively reverse all damage that has already been accumulated.
If you think about somebody that has renal injury in the context of lupus, while the nephritic component, as we call it, might be taken care of, chronic glomerulosclerosis that has occurred over many years and the proteinuria that comes from it is unlikely to return back to normal. Based on our data and our experience, we made the concerted effort to create a CAR-T program in autoimmunity covering multiple diseases, as you see on the right side, with now a large number of these studies, which are phase II pivotal trials designed in close collaboration with the health authorities, having started now across a number of diseases: lupus, lupus nephritis, systemic sclerosis, inflammatory myositis, ANCA-associated vasculitis, as well as early plans looking at RA and Sjögren's disease. Separately, we are also evaluating our CAR-T programs in neuroscience, in relapsing and progressive MS, as well as in generalized myasthenia gravis.
We’re very excited about the fact that we have more than 50 centers now active, and we are making good progress with moving this forward and will be looking carefully at how we can accelerate our plans for being able to assess benefit risk and then find the appropriate patients that can be treated with this meaningful CAR-T intervention. Moving to slide 11. As I said at the start, we are now super excited about the approval of RHAPSIDO, another example of a pipeline and a pill, remibrutinib, designed and discovered in our biomedical research teams. A BTK inhibitor that is fifth in class, but best in class based on its very precise profile. Super excited that it has now been approved in the U.S. With that, I’ll hand it over to Victor.
Thank you very much, Shreeram. Good afternoon, good morning, everyone. RHAPSIDO was indeed approved by the FDA on September 30th as the only targeted BTK inhibitor for chronic spontaneous urticaria with what we would characterize as a broad and clean label. RHAPSIDO is indicated for the treatment of chronic spontaneous urticaria in adult patients who remain symptomatic despite H1 antihistamine treatment with a clean safety profile, meaning no box warning, no contraindications, and no required routine lab monitoring, and as an oral administration, a 25 mg tablet twice daily with or without food. It's important to note that the initial HCP feedback has been very positive and that we believe that this label fully supports our intended positioning as an immediate treatment post antihistamine failure and before biologic treatment. If we can move to slide 13. I wanted to characterize the size of the market first.
Roughly, the CSU market opportunity is about half the size of the psoriasis moderate to severe market. You can see on the left-hand side chart that if you combine U.S., EU5, China, and Japan prevalence, we are talking about 10 million patients who are actively treated for CSU, and about 50% of them are uncontrolled on antihistamines. Only a small proportion of them are treated with a biologic for a variety of reasons. As you can see, the positioning for RHAPSIDO, based on the label that I just described, is really the next oral option right after that antihistamine failure. I think it's important as well to note that chronic spontaneous urticaria is a highly symptomatic disease. It's a systemic, debilitating, muscle-driven autoimmune disease characterized by red, swollen, and itchy hives.
I cannot emphasize enough the role that each plays in treatment decision and actually the urgency that patients have to seek either a new treatment or treatment for the first time. About 60% of these patients experience mental health disorders, mainly depression and anxiety, with a quality of life impairment comparable to moderate to severe psoriasis and AD, with disrupted sleep being reported as one of the most burdensome impacts and with each another driver of patient dissatisfaction as well. Given this highly symptomatic profile, achieving symptom control as quickly as possible to improve quality of life, we've understood is a key treatment goal for chronic spontaneous urticaria. Now, if we move to slide 14, I want to shift to the clinical profile.
You'll see that RHAPSIDO has demonstrated both long-term safety and efficacy in CSU with a fast onset of action, which, based on what I just described on the prior slide, fits very nicely with what we see as the admin need. You'll see in the REMIX-1 and REMIX-2 trials, we saw meaningful improvement in symptom control across all measures, with results observed as early as week one. In post-op analysis, I'd like to note as well that 50% of the patients achieved well-controlled disease at week 12, and that we saw efficacy regardless of prior biologic exposure, as well as consistent activity across all subtypes of the disease. It's important as well to note that we also saw a favorable safety profile, which included balanced LFTs.
The two quotes that we have on the right here on slide 14 come to broadly represent the HCP sentiment across both dermatology and allergy. You're highlighting both the breadth of the indications, but also the fast onset of action, which really matches what they believe patients are looking for. Now, if we move to slide 15 and hone into this onset of action, to further characterize RHAPSIDO's onset of action and demonstrating our confidence on RHAPSIDO's profile, we started a phase III-B U.S. head-to-head trial versus dupilumab, evaluating the speed of symptom control, which is of critical importance to these patients. This is the RECLAIM study, and the objective is to assess the superiority of RHAPSIDO versus dupilumab in chronic spontaneous urticaria inadequately controlled patients by H1 antihistamines, with a primary endpoint of urticaria assessment score change from baseline at week four.
This is a study that is currently recruiting with an expected readout in 2027. Now, moving on to slide number 16. For the U.S. launch, we do expect an initial uptake mostly from allergists, followed then by dermatologists, both specialties we know really well and where we have been successful launching products in the past. On the left-hand side, you can see the split of target CSU patients by specialty, starting by the fact that 75% of those patients are currently treated by allergists who, on average, have about 60 CSU patients per HCP. You can see it's a highly relevant disease that they treat, and the dermatologists, about five CSU patients by HCP. We believe this split is a reflection of the currently available options. With the launch of RHAPSIDO, we expect this shift to evolve the specialty landscape, bringing more CSU care into dermatology over time.
On the right-hand side, you can see how we are covering the specialty universe with our field force at launch. You'll see there's about 5,000 allergists in the U.S., about 20,000 dermatologists that treat. There's around 415,000 patients who are ready for a change and are not currently controlled with antihistamines. Our current Novartis field force covers about 70% of this HCP universe and about 100% of the high-volume HCPs, which are about 3,500 in allergy and 2,300 in dermatology and cover the majority of these patients. Moving on to slide 17, I wanted to cover the early U.S. launch success factors. The first one is obviously to engage the early prescribers. We are targeting those high-prescribing allergists and dermatologists who treat about 80% of the CSU patients after failure.
In the first weeks of launch, we are actually seeing 80% of the prescriptions coming as predicted from prior biologic users in CSU and about 75% of those prescriptions coming from allergists. We are also prioritizing what we call RHAPSIDO-ready patients. We're, of course, focusing on those 400,000 CSU patients who are uncontrolled on antihistamines to drive early positive experiences. As I mentioned before, two key determinants of readiness for these patients are intensity of itch, but also sleep disturbances. It is important to note that pre-launch, as part of our pre-launch efforts, we identified about 20,000 patients who were hand raisers and are now being activated and are mainly the focus of initial patient activation activities. Lastly, an important point is that particularly in this disease, with a high degree of symptomatology and the urgency to treat, we see support of patient access as a critical success factor.
Therefore, we are providing a simplified experience with a robust bridge program or the free drug program with sampling as well. We aim for rapid coverage expansion with payers. For the initial months, while we secure our intended broad access, most of the utilization will be through either bridge or sampling. As access unfolds in the first half of 2026, we will focus on converting these patients into paid fills, and you will start seeing then the net sales uptake. All in all, we expect a fast uptake once access is established, positioning RHAPSIDO as the first-line treatment option of choice after antihistamine failure. Now, moving on to slide 18. For this new launch, we're again leveraging the commercial capabilities that we have honed over the last three years with a U.S. commercial organization that has been successfully launching between three to five new drugs or indications per year.
On the customer engagement side, we're very proud of a field team that has been increasing its effectiveness year after year, with customer-facing teams both in dermatology and allergy that have strong knowledge and expertise across these areas. From a patient support standpoint, we have developed industry-leading bridge support to accelerate onboarding with a fully owned end-to-end patient support program that usually results in three to five days to dispense on average once a physician has written either a script or service request form. Finally, from a market access perspective, we have secured about 70% access to label within six months for recent launches. Once we have secured that access, we have about 30 days average conversion from free to paid drug.
These are some of the compounding capabilities that we've developed through the multiple launches across key therapeutic areas over the last years that we are now bringing in full force for this launch. Now, moving on to slide 19, we wanted to make an important point. It is that CSU for us represents the first of many potential futures for RHAPSIDO. This launch provides what we see as the foundation for future indication expansion and a path to multi-billion dollar potential across all indications. If I move to the left-hand chart, you'll see that in CIndU, we are currently in phase III with a readout expected for 2026. It's important to note that there's about 400,000 patients in the U.S. alone that could benefit from this treatment and that currently there's no biologic approved.
HS is a market that we know well, and based on the phase II data that we already saw with HS, we see potential for biologic-like efficacy with a rapid onset of action. This phase III has an expected readout in 2028. Now, lastly, in immunology, food allergy that, as we know, affects 3.4 million patients in G6 countries, and where we are seeing early strong XOLAIR uptake, which we see speaking to the high unmet needs for patients who today, besides XOLAIR, only have food avoidance as a baseline treatment. Now, as a reminder, we're also developing remibrutinib in both multiple sclerosis and myasthenia gravis with readouts expected in 2026 and 2028, respectively.
Important to note, if I move to the right-hand side, that these future potential launches will fully leverage both the existing infrastructure capabilities and knowledge that we already have in-house, with CIndU having a complete overlap with the CSU footprint, HS having a complete overlap with our current COSENTYX HS footprint as well, food allergy building on the CSU allergy footprint, and finally, with multiple sclerosis and myasthenia gravis, could build on our neuroscience footprint. You can expect not only compounding capabilities and infrastructure, but of course, important investment synergies as well. Now, moving on to slide 20. Now we're going to move from RHAPSIDO, a pipeline in appeal, to another asset with multi-billion dollar potential across several indications, ianalumab. For that, I will now hand it over to Angelika.
Thank you, Victor. On slide 21. We depict Sjögren's, which is a severe systemic and heterogeneous prototypical B-cell-mediated autoimmune disease.
Sjögren's is also called the chameleon of rheumatic diseases because it can manifest with so many different organ manifestations, as depicted on the right-hand side. Most of the patients have debilitating eye and mouth dryness. Just to highlight a little bit what that means for patients, it is as if you have sand in your eyes. I think everyone has experienced that, how this impacts our quality of life. These patients do have that every day of their life. They also experience that. My apologies. They have debilitating dryness of their eyes and their mouth. With respect to mouth dryness, it is as if their tongue is stuck to their palate. They have difficulty swallowing, difficulties speaking. Often, these patients then, in addition, due to the lack of saliva, have dental caries, candidiasis, periodontal disease, and loss of teeth.
The more severe patients suffer as well from potentially irreversible organ and system damage, as you can see on the right-hand side. In particular. I want to share one example of a patient that had pulmonary involvement. That patient was a young woman in her 30s who was very athletic, energetic, a physician, and was in the middle of her life. After the birth of her son, she had a flare. With that, she developed constitutional symptoms, fever, about 30 lbs weight loss, night sweats, and debilitating fatigue, as well as interstitial pneumonitis, which meant she could hardly walk up a flight of stairs. It was a life-impacting set of symptoms for a patient that developed Sjögren's disease. I really want you to keep that in mind.
As a physician, I am most worried about these systemic organ manifestations and the increased mortality risk that is associated with patients that have systemic manifestations of Sjögren's disease, including the 20 - 40 times lifetime risk of lymphoma. That means up to one in every 10 patients with Sjögren's disease will eventually develop lymphoma. With that, I wanted to also talk a little bit on slide 22 about the pathway to getting diagnosed. Patients, as I have said before, often have oral symptoms, and they go to the dentist for that, but they do not share their additional symptoms with the dentist. They go to the ophthalmologist for their sore ophthalmia and do not share additional symptoms, to the neurologist for the polyneuropathy, or to their pulmonologist to share their shortness of breath.
It is difficult for these specialty physicians to then understand that this is truly a chronic, systemic autoimmune disease. As such, the referral pathway is very long to the rheumatologist. We know from the latest data from the Sjögren's Foundation that it's typically four years before a patient gets diagnosed from the onset of symptoms. Now, the diagnosis is not difficult. We can do serologic testing. We can do labial biopsies. With that and the clinical symptoms, we can arrive at a diagnosis of Sjögren's disease, but it requires the expertise of the rheumatologist often to come to that diagnosis. I believe that also physicians do not always refer because currently there is such a lack of treatment options. On slide 23, we see that Sjögren's actually is a really prevalent disease. It's the second largest disease that rheumatologists treat after rheumatoid arthritis.
It represents truly a significant unmet need because to date, there are no approved treatment options. Estimates the prevalence at 4 million people, but it is not very clear if there are not far more patients out there because of the lack of diagnosis and the slow, long time to diagnosis. About 2 million patients are diagnosed with Sjögren's disease. These are the typical patients that I described, female between 30 and 50 years of age at the prime of their years. I want to talk a little bit of current treatment options because as a physician for 20 years, we have seen trial after trial in Sjögren's disease, and none of them met the primary endpoints in later stage trials. Currently, we rely on off-label therapies, and many of these off-label therapies are then associated with side effects.
It is now an evidence-based field, not an evidence-based treatment, and that is certainly something that leaves physicians with a lot of uncertainty about how to treat patients with Sjögren's disease. I want to share on slide 24 our gold standard to assess clinical disease activity in Sjögren's trials, which is the ESSDAI score. It measures disease activity, and on the right-hand side, you see the score. It has been developed by experts, and it measures all of these heterogeneous clinical and laboratory domains to come up to that overall score. While the score goes up to 123 points, patients typically, even if they have severe disease, have two to three organ involvements, and it is typically a flaring disease.
I would like to point out that based on the scoring system that has been established and has been validated, patients with less than 5 points have low disease activity, 5 - 13 moderate, and greater than 14 high. There have been some attempts to assess the minimal clinically important difference. It is important, as was noted during the ACR presentation, that the minimum clinically important difference that has been defined by the EULAR Sjögren's Path course and published in 2016 refers to the difference in patient difference from baseline to end of treatment. It does not describe a difference between treatment arms. With that, there are other endpoints as well in clinical trials. Patient-reported outcomes, importantly for patients who have systemic manifestations, global assessments by the patient and physician will capture the patient burden in a much broader way.
A patient with interstitial lung disease and the shortness of breath will be assessed by these global assessments, but not by specific PROs that c apture fatigue, dryness, or pain. Lastly, clinical tests, just like glandular function assessment through stimulated salivary flow, can objectivize some of these endpoints. Now, let's go to slide 25 because this is a critically important slide. This is depicting why ESSDAI and disease activity is such an important outcome. We know, based on literature and multiple studies, that higher ESSDAI scores are associated with a higher risk of adverse outcome, damage accrual, a higher risk of developing lymphomas, interstitial lung disease, cardiovascular events leading to higher mortality in patients.
Achieving lower ESSDAI scores is critically important for patients with Sjögren's disease because they are linked to better quality of life, increased work productivity, as well as improved long-term outcomes, including mortality. It is critically important that we reduce the disease activity as measured by ESSDAI. With that, I'll share with you the very exciting data. That's really the data that were the buzz of the ACR that Shreeram and I just attended. It is the data of ianalumab in Sjögren's disease. ianalumab, on slide 26, is our afucosylated fully human monoclonal antibody targeting the BAFF receptor through a novel dual mechanism of action. Importantly, we have NK-mediated antibody-dependent cytotoxicity and killing of B cells. I'll show you some data that includes killing of B cells in the tissue, not only peripherally.
Once there is a depletion of B cells, and that has been shown in Sjögren's as well as in lupus, they increase BAFF levels, which is the B cell activation and survival factor. That binding of BAFF to its BAFF receptor, that pathway of B cell activation and survival, is also blocked with ianalumab. We are targeting both B cell depletion in the tissue as well as survival of the remaining B cells. Here I can show you a slide from a mechanistic study that was also presented at the ACR just this week in Chicago. It depicts, on the left-hand side, the salivary glandular tissue from a patient with Sjögren's. What I want to highlight is that this is not normal. You see these ectopic lymphoid tissues that are a hallmark of the disease that are not seen in healthy tissue.
They are stained in purple and in brown by purple CD20s B cells and CD3s T cells. You see how much infiltration you have and how much destruction of glandular tissue you have in Sjögren's disease. On the right-hand side, after 25 weeks of treatment with ianalumab, you can see that we have an 84% reduction in salivary gland B cell density. It's a clear sign that we deplete the tissues in the target, the B cells in the target tissue. A clear difference to prior B cell depleters. With that, on slide 28, I want to share with you the two studies that we conducted. These are two adequate and well-controlled phase III studies, NEPTUNUS-1 and 2. These are global studies conducted on the background of standard of care for these patients, and both of them are 52 weeks in duration.
We compared ianalumab 300 mg monthly subcutaneous dosing versus placebo. In NEPTUNUS-2, we also included a ianalumab quarterly dosing arm. The primary endpoint was the ESSDAI change from baseline. We also looked at ESSDAI responders, so the proportion of patients with a greater than five-point reduction, and those with low systemic disease activity, and then patient and physician global outcome measures, as well as, importantly, safety and tolerability. We predefined a pooled analysis, and a lot of the data I will share with you today are from this pooled analysis. Now let's go to slide 29, where I can share with you the primary endpoint data of both of these studies. You see two almost parallel graphs here on NEPTUNUS-1 and NEPTUNUS-2. Importantly, we have an early separation of both graphs. In gray, you see placebo. In blue, ianalumab.
Both studies met their primary endpoint, changed from baseline in ESSDAI as the disease activity measure at week 48. If you go to slide 30, you then see the quarterly dosing in yellow, and you see that there was a nice dose response between quarterly and monthly dosing, and that only the monthly dosing, which was the dose that achieved full BAFF receptor blockade at trough levels, truly led to a statistically significant outcome at week 48. With that, I will also share with you then as a next slide, slide 31, the pooled data with a rapid and sustained reduction in disease activity compared to placebo. On slide 32, from the pooled analysis, you see now the continuous secondary endpoint. I hope that you also see and agree with me that if you look at this slide, all of the endpoints clearly favor ianalumab. That is an important outcome.
Two of them have nominal statistical significance. These are patient global assessments, which assess how a patient feels on a global scale. That is truly important for those patients who have such heterogeneous disease manifestations that we have included in the NEPTUNUS study. Physician global assessment scores concur with what we have seen for patient global assessments. On the next slide, you see the binary outcomes from the pooled data. Again, consistently, you see that all the outcome measures favor ianalumab over placebo. Importantly, as I talked about the intrapatient change from baseline to week 48, you see that more patients achieve a five-point reduction in ESSDAI, in disease activity. I've highlighted to you how important it is to reduce disease activity over time.
We have nominal significance with respect to a higher proportion of patients on ianalumab achieving low ESSDAI activity, low disease activity associated with better outcomes, better mortality outcomes, better morbidity outcomes, as well as reduction of long-term damage over time. Now, let me dive a little bit deeper into the patient global assessment. This assessment, as you can see here, very similar to ESSDAI, achieved a fast and sustained symptom relief as early as week 8 and up to week 52. Consistent with these data, we have seen nominal significant difference also in the physician's assessment of disease burden, and there is a separation between the placebo and the ianalumab curves along the way. Now, let me go to slide 37 because that is a very intriguing finding from this study.
In those patients who still have maintained glandular functions with a stimulated salivary flow of greater than 0.4 mL per minute at baseline, those patients, we were actually able to increase the stimulated salivary flow. This is quite remarkable, and it goes along with improvements in oral dryness in these patients. Our hypothesis is that those patients who have a stimulated salivary flow of less than 0.4 mL per minute likely already have damage in their gland and destructive glands and not salvageable glandular tissue. This is incredibly exciting because it suggests that there is some disease modification. Next, I want to go over the safety slides with you here. Ianalumab showed a favorable safety profile. It was comparable to placebo.
We have the data here side by side, and as you can see, ianalumab across the endpoints did not lead to an increase in adverse events and serious adverse events. For B-cell depleters, typically, we first look at infections, serious infections, and opportunistic infections. As you can see on this slide, they were all well-balanced. There was no suggestion of any safety finding. The only B-cell malignancy that we observed in this trial was in the placebo arm with the Waldenström macroglobulinemia. With that, let me briefly summarize the results. These results were really seen with lots of excitement in all the many discussions I had at ACR with the rheumatologists because these are, in my view, really watershed data because they are the first-ever successful global phase III studies in Sjögren's disease, a disease that we have tried to find a new treatment for now for decades.
They showed a statistically significant ESSDAI improvement consistently across both NEPTUNUS trials. Rapid and sustained reduction of disease activity. We have consistent improvement across secondary endpoints. In particular, we achieved low ESSDAI disease activity, which is such an important outcome measure. We improved and reduced the overall patient global assessment of disease activity, so patients also felt that the treatment really improved their quality of life. Physicians concurred with that, and we have numerical improvements in other patient-reported outcomes. I do think the data on the salivary function and oral dryness are very encouraging. They are making us think about next studies to profile that more. Importantly, we have seen with respect to phase safety that the adverse event profile was comparable in general to placebo. Now, with these very exciting data on slide 40, you see our plans.
We already have FDA fast-track designation since 2016, and now we are going to submit across all regions. We will be building on the NEPTUNUS studies. We have already extended our extension studies to now follow these patients for six years with respect to efficacy and safety. We are exploring for future studies, as I have indicated, in different and diverse Sjögren's populations. We’ve already had a lot of excitement with the physician community who also wants to conduct studies with us. We will share the data more broadly in publications that are planned to start. Now, with that, I hand it back to you, Victor.
Thank you very much, Angelika. Now, I'll dive into the U.S. market preparation perspective.
The first thing we're doing is launching a disease state education campaign to increase recognition of Sjögren's disease as a serious, systemic, and autoimmune disease that goes well beyond the apparent symptoms of mouth and eye dryness. The context that I think is important for us to note is that, as Angelika noted, there's a lack of approved therapies and there's low familiarity with clinical endpoints. We do see an opportunity to expand the understanding of the systemic nature and the burden of Sjögren's disease to provide a framework for physicians to identify moderate to severe patients and, of course, engage and empower Sjögren's disease patients. Now, if we move to slide number 43, I also wanted to provide some color on the expected initial adoption from rheumatologists.
Currently, we have segmented rheumatologists, which, by the way, we know really well through our work with COSENTYX and ILARIS, between early adopters and late adopters. You will see that we do expect that the early biologic users, those who are proactive today, the use of label biologics early to prevent disease progression, will be among the first adopters where we are concentrating some of the initial efforts. We will be concentrating some of the initial efforts at launch. They represent about 15% of the HCPs, and they treat about a third of Sjögren's patients. We have the later biologic users who are a little bit more reactive. They do rely on frameworks to identify what they call biologic-ready patients. That's another 20% of the HCPs and about another third of the Sjögren's disease patients.
I think it's important to note that about 70% of the patients then are treated by rheumatologists who have a clear understanding of the need to treat these patients with advanced therapies. About 65% of the HCPs will be characterized as more symptom-focused HCPs. They focus more on the symptom relief and typically, as of today and up until now, have not used label biologics. Most of our disease state education, patient activation, and ianalumab approval is expected to shift more of those symptom-focused HCPs into biologic users over time. I think it's important to note from a launch perspective that more than 90% of overlap exists between these physicians and the COSENTYX and ILARIS field force and these rheumatologists treating Sjögren's disease with 100% coverage of the early adopters by our current teams.
Now, moving to slide 44, I also wanted to note from a patient segmentation perspective that we are looking at the overall landscape. Sjögren's has an overall prevalence of about 660,000 patients in the U.S. About half of them are diagnosed today, and about 175,000 are under active rheumatologist care. About 100,000 of those patients have current organ system involvement, as described by Angelika, which are the patients that we believe will be initially most likely to receive this treatment. At launch, we will be combining the targeting from an HCP perspective on those who have already been treating patients with biologics and targeting this 30% or 40% pool of diagnosed Sjögren's patients who have organ and system involvement because we see higher urgency to treat those.
Over time, we will work to continue to expand both the active treatment and also the diagnosis rate as part of our responsibility in this space. Now, moving on to slide 45, I wanted to follow a little bit of the same exercise I followed with RHAPSIDO, showing that these positive phase III studies in Sjögren's, which is a highly heterogeneous disease, actually do increase our confidence in other B-cell-driven diseases. In the same way that with CSU, we saw it as the foundational indication for RHAPSIDO, we see Sjögren's as the first foundational indication for ianalumab with a number of potential indications following. You'll see that for SLE and lupus nephritis that affect about half a million patients in the G7 countries, we expect readouts around 2027, same for systemic sclerosis.
On the hematology side, where we also have significant expertise and presence, as you all know, we had positive readout in the phase III and second-line ITP, and we do expect readouts in 2026 as well for first-line ITP and second-line wAIHA. I want to highlight as well that these future potential launches will also leverage existing infrastructure, capabilities, and expertise. The SLE launch will build on COSENTYX rheumatology experience. Lupus nephritis will build on both our rheumatology and our established nephrology expertise. Systemic sclerosis will have high overlap with rheumatology, and ITP and wAIHA builds on our provocative hematology footprint as well. In closing and moving to slide number 46, I would like to highlight that we have a broad and deep immunology pipeline with multiple late-stage assets targeting areas of high unmet need.
We're very excited about RHAPSIDO being poised for a strong CSU launch as the first oral option post-antihistamine failure and before biologic, with multiple LCM readouts starting next year. I also wanted to highlight that ianalumab has demonstrated a meaningful clinical benefit in Sjögren's disease, which was consistent across studies over time and across patient and physician-reported outcomes. That positive Sjögren's data de-risks in our mind ianalumab's lifecycle management across a number of B cell diseases, supporting the multi-blockbuster potential we see for this asset, and that we have, over time, compounded commercial capabilities that will drive launch excellence and maximize pipeline value across our portfolio. With that, I would like to open it up for questions.
Thank you. To ask a question, you will need to press star one and one on your telephone and wait for your name to be announced.
Please limit yourself to one question and return to the queue for any follow-ups. To withdraw your question, please press star one and one again. We will now go to your first question. Your first question today comes from the line of Simon Baker, Rothschild & Co Redburn. Please go ahead.
Thank you very much for taking my question. On the ianalumab, typically in Sjögren's studies, you see a plateauing of the placebo response at 48 weeks, whereas you saw a reduction in the placebo response at 48 weeks. I just wondered if you could give us any thoughts on that, particularly in NEPTUNUS-1, but also, and forgive me if this is a naïve question, we see this very strong placebo response across all Sjögren's studies, and the level of response you saw was not wildly different from that which we've seen elsewhere.
I wonder if you could just give us some thoughts on why the placebo response is so high in these studies. Thanks so much.
Thanks, Simon. I'll take a start and then hand it over to Angelika. I think when it comes to placebo and supplements, one thing to keep in mind is that our trials were designed to allow patients not randomized to ianalumab to continue getting treatments that they were otherwise on. There was a different proportion of patients that were on other therapies that they were being given by their physicians. I think that typically the placebo response in terms of being part of a trial and then being managed in a manner that actually, in some sense, alters the patient's perception of their symptoms and how they feel is one contributor.
These are large studies in a heterogeneous disease run across multiple centers across many countries, and therefore, the observation of how that response evolves over time and the change towards the end that others have called out as well is simply, in my mind, a reflection of the conduct of two large trials across multiple geographies in what is a difficult heterogeneous disease. Angelika, do you want to add?
Yes, sure. I fully concur. I wanted to call out that I think it's quite stable on NEPTUNUS-2, the placebo arm. On NEPTUNUS-1, we see a slight increase in placebo, but I would not make too much out of this. This is probably variability in the trial or maybe the realization from patients or from physicians that the placebo does not work that well.
I do think as we have longer-term studies ongoing, we will see how patients fare once we switch them over.
Yeah. I think, Simon, I also want to add, and when we've spoken previously, we've discussed the fact that the team actually did a lot of work over the years in the conduct of the trial to actually assure the quality of trial conduct. I recall telling all of you that I was super proud of the team as having made all the efforts we could to ensure that in this complex, difficult disease with multiple outcomes being assessed, we paid attention to the quality of the data being collected, how investigators were being trained.
I do believe that that's actually at the heart, in addition to the tremendous, we were able to actually discern, if you will, the benefits of the dual mechanism of action of ianalumab as a result of a well-conducted trial resulting in this unprecedented two replicate positive phase III studies in Sjögren's disease. Next question.
Thank you. Your next question comes from the line of Thibault Boutherin from Morgan Stanley. Please go ahead.
Yes, thank you. My question is actually on the RHAPSIDO and food allergy. Just if you could help us understand testing reimbursement in that market and how to think about it. I mean, as you mentioned, we saw a very strong uptake from XOLAIR in the U.S. 85,000 patients treated. The theoretical number of patients is very large, but presumably we need to break down in terms of population of patients, in terms of disease severity.
How to think about how to break down the population, who can have access to treatment and reimbursement, to basically be able to save the opportunity. Thank you.
Thank you, Thibault. I'll give this to Victor.
Thank you very much, Thibault, for the question. I think it's important to note, as you say, that on food allergy, we see both a very substantial unmet need in terms of size, particularly in the U.S. market. Thank you for noting a very strong uptake on the XOLAIR side. I think it's early days to discuss about access projections, particularly when we are this many years out. Right now, what we are seeing on the XOLAIR front is that when patients are in need and are prescribed by the allergist, they tend to get their medicine.
I think that's a strong indicator that we can start thinking about how to further shape this development program. We are starting to think about how a launch could look like. All in all, as you point out, very exciting opportunity potentially for this asset as well in food allergy.
Next question.
Thank you. Your next question comes from the line of Richard Vosser from JP Morgan. Please go ahead.
Hi, thanks for taking my question. I was just wondering whether you measured clinical ESSDAI at all in the study. Some other trials are measuring that, and I wondered if the data was stronger on clinical ESSDAI. I also wanted to ask on the ESPRI benefit that was a trend but not statistically significant. My understanding, which could be wrong, is that that's more of an endpoint for a European approval.
I'm just wondering how the data looks from that point of view, given that endpoint wasn't statistically significant, how the Europeans will look at that. Thanks very much.
Let me give that to Angelika. Angelika?
Yes, we are looking at the data to also assess the clin ESSDAI. We certainly have an impact on the biologic domain, but we also have seen when we look at our domains that we have improvement across most domains, biologic or clinical. When it comes to the ESPRI, the ESPRI is measuring dryness, fatigue, and pain. Yes, it is. Let me say the primary endpoint for the European submission is the mean change in ESSDAI, which we have met across both clinical trials. We are very confident also when we submit our data to the European health authorities. This endpoint was discussed with both FDA as well as the European health authorities.
ESPRI is a patient-reported outcome that is focused more on glandular disease, whereas we will be focusing the significant data with respect to the patient global assessment because we believe this describes more the patient symptoms that occur in those patients with systemic manifestations in this very heterogeneous disease.
That's super helpful. Thank you very much.
Thank you, Angelika. Next question.
Thank you. Your next question comes from the line of Benjamin Jackson from Jefferies. Please go ahead.
Brilliant. Thank you for the question. Look, one for Shreeram, if I may. On YTB323 at the start of the presentation, you described the MS cohorts as relapsing and progressive for those early trials, whereas for RHAPSIDO, it seems to follow more of the traditional MS wording that we've been using for some time.
Is this perhaps a shift in the way that patients are being either defined or recruited for the earlier trials that are now coming through, perhaps more reflecting a peer approach to that? Is this Novartis-driven or regulator-driven? As a result, what does this mean for remibrutinib and remodel when we get that readout next year? Could this ultimately be a label definition which is independent of relapse activity? Any color or thoughts around that definitional recruitment would be great. Thank you.
Yeah. I think, Benjamin, I won't read too much into the implications of how I described to you the CAR-T programs for how the remibrutinib programs have been designed. Those have been designed for a while, and they reflect the relapsing MS population that we have enrolled.
The thinking behind the exploration of CAR-T in MS was around the principle that eventually we expect CAR-T to be evaluated for patients who are considered refractory in some sense, given the burden of the treatment, its nature. To that end, picking people with relapsing MS who have had severe activity and continued persistent inflammation despite the use of multiple agents. When it came to progressive MS, again, a bold exploration of whether a CAR-T offers the opportunity to impact what we now call progression, be it secondary or primary, but thinking of more a combined term, for the lack of a better word, that aims to address progression independent of inflammatory activity is the thinking. Early days, again, those are trials where the initial sentinel patients are now being done. There is a lot of interest. We'll keep you posted on how things evolve.
Great. Thank you. It's useful.
Next question.
Thank you. Your next question comes from the line of Sachin Jain from Bank of America. Please go ahead.
Hi, there. Thanks for my questions. Just briefly. First, on the ILARIS data, I wanted you to talk to those responses you've seen and whether you've considered investigating even more frequent dosing or higher doses and whether the PK/PD that you saw in phase II was actually replicated in phase III. As we think about the midterm opportunity in Sjögren's, can you just provide your perspectives on the FcRn potential competition? Thank you.
Angelika, do you want to talk about those responses?
Yes. I think we are looking at our PK/PD. As we speak, we've just received these data and presented them now at ACR. As I've alluded to during the presentation, we know that the three-monthly dosing is a trough, not inhibiting BAFF receptor signaling.
We see a clear dose response, and we think the monthly dosing is the appropriate dose to carry forward to the health authorities.
Your commentary on the potential competition from FcRn?
We have seen phase II data from FcRn, and we are waiting for their phase III data. I think it will be important to see not only efficacy but also the safety, as these molecules deplete immunoglobulins, and we need to see that these patients do have an adequate response versus an adequate vaccination response maintained. I think the data will show. We are now very excited about having the first pivotal global phase III studies in our hands that have read out positive and are really focused on bringing this to patients, ianalumab, to patients as quickly as possible so that they can benefit from ianalumab.
I mean, I think, Sachin, Angelika and I both just spent time in Chicago, and I must have met, I don't know, 20, 25 at least, different rheumatologists as well as representatives from the patient community. What was interesting to see and quite exciting was that, one, the fact that nothing's been available and approved, as well as the nature of the disease itself, has sort of created this deep pent-up, unmet need demand where people have suffered with what they think is being treated with eye drops and maybe drinking a little bit of water and not quite having the right answers for what patients were suffering with. I met a community rheumatologist with a large practice as well as specialized centers.
It was reassuring to see that having delivered two positive trials that essentially demonstrate control of disease activity, and it's the disease activity that is at the heart of what patients feel, what they do over time results in additional complications, as Angelika pointed out. I almost got the feeling that once we make this treatment available, pending regulatory approvals and discussions, the interest in people wanting to try this treatment, for the lack of a better word, seemed pretty high. Next question.
Thank you. Your next question comes from the line of Peter Verdult from BNP Paribas. Please go ahead.
Yeah, thanks, Peter Verdult here, BNP Paribas. If you forgive me, maybe one commercial and one clinical. Shreeram, you said you spoke to 25 docs, but we spoke to three overnight who have been at ACR. The message was pretty uniform. They're going to put 50% of their patients on ianalumab, assuming approval and access is not an issue. It's a question that I know you're not going to answer, but I've got to ask it, which is because I think the willingness to use is clearly there. How should we think about pricing? This is a classic immunology drug, or we know that there's nothing out there. This will be the first systemic therapy approved. FcRns that are being developed, their price point is $200,000 net.
I know you're not going to give me an answer, but just qualitatively, should we be thinking about this as a standard immunology priced asset? If I may, on the clinical side, Angelika or Shreeram as well. You talked about following the NEPTUNUS patients up to six years. When you think about other plans, and I know it's only 24 hours since you've presented, but you have had the data in-house for a bit longer, should we anticipate that you'll be doing trials where you will be enrolling patients with that baseline salivary function above 0.4 to see how that goes? Thank you.
I'll take the second part of your question first, Peter. Our standard practice now, of course, is having completed the phase III studies. There's already been a lot of conversations going on about what is the additional evidence that's going to contribute to accelerated adoption into clinical practice for the appropriate patients. Our process of what we call integrated evidence planning to provide additional data has been going on for some time. Angelika, I don't know if you want to add any specifics around it, but there will certainly be additional plans for additional data generation. She doesn't have much to add. I think, and on this meeting, since I also have Victor here, Victor, let me give it to you to discuss whether it's too early to talk about price.
It is certainly too early to talk about pricing. What I wanted to reinforce is what Shreeram and Angelika have brought up. In our discussions with rheumatologists, as I mentioned, we know really well through our work on COSENTYX and ILARIS, we do see that very consistent value perception on both the unmet need, but also on the potential tool that they can gain with ianalumab. We will certainly bring that up to payers as we discuss. As you know, one of the main drivers of adoption and then access will be actually that precise experience that physicians and patients gain as they utilize the drug, right? That's exactly what we expect. Of course, that will be our job at launch, to foster that utilization. The patients I described and the physicians that I described will be a priority.
Based on first, the safety profile, but also the overall efficacy profile, we do expect that to happen and to happen fast at launch. I want to stop just for a second on the safety profile because I think it's of extreme importance here. On that trial, right? Physicians, the initial reports were very reassured, as Angelika mentioned, by that safety. We believe that's a prerequisite for trial, particularly in a disease that does not have anything else approved. I'm very excited to get to work and continue to prepare the market and this potential launch as well once approved.
Thank you. Your next question comes from the line of Graham Parry from Citi. Please go ahead.
Great. Thanks for taking my question. I think a skeptic in the market would say that the biologic therapies that are used out there are effective, but they just didn't have decent trials run for them, and that ianalumab is only as effective but ran a better study. Of course, you haven't been able to compare versus biologic therapy because they're not approved, so you've got a placebo-controlled study. How would you plan to sort of get around that perception if it crops up in your marketing? Thank you.
Hey, Graham. I think that just running a better study seems like a relatively odd way to represent. Two pivotal phase III studies designed carefully, run across the world, and delivering two positive results that actually allow for a drug to be taken to the regulators and potentially get it approved with a label. I think to the skeptics, I say that, I'm just going to say that we have studied the drug in a meaningful way. The consistency across two trials, as you said, the overall data sets, especially the way patients assess, feel their disease, and the physicians see it. I see that as a really, really strong position to be in. I'm going to hand it to Angelika because having been the one that actually led the units that run the two trials, Angelika, how would you answer the skeptics?
Yeah, I would also add that some of these trials, I think, were run quite well as well and did just not show any evidence of effectiveness. I would not just negate it. I know, I think right now, physicians are using some of the therapies like hydroxychloroquine or rituximab, but I do think it is out of despair that they don't have other treatment options. We do know that rituximab does not affect B cells in the tissue, which is where the insult happens to the tissue. I would not concur with that. Secondly, if you look at our studies and our trial size, these are not hugely overpowered studies, but these are reasonably sized studies that have shown a very good effect size and consistent across endpoints, across all patient and physician-reported endpoints, as well as over time, fast onset of action.
If you look at the lines, they are really beautiful. I would respectfully disagree with you, Graham.
With the skeptics. Thanks, Graham. Next question.
Super. Thanks.
Thank you. As a reminder, if you would like to ask a question, please press star one and one on your telephone and wait for your name to be announced. Please limit yourself to one question and return to the queue for any follow-ups. We'll now go to the next question. Your next question comes from the line of James Quigley from Goldman Sachs. Please go ahead.
Great. Thank you for taking my question. How are you thinking about sort of the label? What are you going to look for in terms of the label indication? Is there a trend in any of the domains that could lead to leaning more towards one domain or the others or sort of narrow the label from a domain perspective? How confident are you that this salivary flow or fatigue data can get on the label, given the lack of statistical significance there? Are those benefits covered in the physician's global assessment? Also, a very quick sort of second one. Was there any reduction in steroid use or DMARD use in the trial that you noted with ianalumab? Thank you.
James, I'll give the steroid question to Angelika in a second. I think on the label, I'm just going to say that, look, it's a little bit too early to start commenting on the label. We now have the data. Our core incoming position is that we have a rich data set. In two well-done trials with consistent effects across multiple endpoints, we believe that we want to make this drug available to all the patients that can benefit from it. To that end, we'll be making the case for a label that allows us to accomplish that. It would be too early to start commenting on precise elements of the label. Angelika, on the steroid use?
Yes, we are looking at the steroid use as we speak. I, unfortunately, can't answer that question yet. Thank you.
Okay.
Thanks, Angelika. All right. Next question.
Thank you. We will now take our final question for today. Your final question is a follow-up from Thibault Boutherin from Morgan Stanley. Please go ahead.
Yeah, thank you. Just a couple of follow-up on RHAPSIDO pipelines. Next year, the CIndU trial, a phase III trial, has different primary endpoints by type of induced urticaria. If the trial doesn't hit primary for all the subtypes, but only some of them, can you still get approval by subtype? Or do you need to hit everything to get CIndU indication? You previously had interesting phase II data for RHAPSIDO on Sjögren's. Decided not to move in phase III. Now that you have all the data and more experience from a clinical perspective, could you reconsider running a phase III for remibrutinib and Sjögren's? Thank you.
Angelika?
Yes. Maybe I can talk about CSU and pediatric development. We have an adolescent study ongoing, and we are certainly looking to also go into pediatric patients, but we will do that a little bit sequentially. We have an adolescent study that is enrolling very well. Now, with respect to CIndU, we are studying the CIndU, obviously, across three different manifestations of inducible urticaria forms. I think it is too early to speculate. We are positive that the three forms will read out positive. If not, we will have the adequate discussions with the health authorities to define what is the path forward. As we know to date, there are no treatments approved for CIndU. XOLAIR is not approved for CIndU, and no other treatment. There is a real big need for those patients with inducible urticarias to have a first targeted therapy.
That's a lot. I think that was the last question. Thank you, everyone, for joining us. We, again, let me reiterate, are super excited about the recent data from our immunology portfolio. We look forward to additional data from ianalumab on the ongoing indications in the 2027 timeframe. Remibrutinib, having been approved in the U.S. as RHAPSIDO for CSU, is also on track with all the other evaluations that we are doing. We look forward to your continued interest. Thank you for joining us. Bye-bye.
Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.