Good morning and thank you for joining Kyverna Therapeutics' virtual KOL event. I'm Jessica Serra, Head of Investor Relations, and I'll be your moderator. We have a full agenda today featuring presentations from our management team, as well as key opinion leaders. A Q&A session will be held at the end of the event. You're welcome to submit questions at any time during the webcast using the question submission box. As a reminder, all participants are in listen-only mode. Certain comments made today will include forward-looking statements, which involve risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied. Please read both the disclaimers here, as well as in our publicly filed documents. Now, without further ado, I'll introduce you to Warner Biddle, our Chief Executive Officer. Warner. Thank you, Jessica. Good morning and welcome, everybody, to the Kyverna Investor Relations Key Opinion Leader event. We're really excited that you dialed in. We're going to share with you some tremendous progress that we're making here as a company, as we continue to lead the way and pioneer the way for advancing autoimmune therapies with the CAR-T constructs that we're building here at Kyverna. We're going to cover a lot of ground this morning, but I want to make sure that all of us on the call take away three key points from this event. First of all, that Kyverna is leading. We've got two late-stage pivotal registrational trials in stiff person syndrome and myasthenia gravis that put us in a position to fundamentally change the way these diseases are being treated. KYV-101 is already demonstrating some very, very tremendous early clinical data. In fact, we're going to give you an update on some of the first patients that were treated with KYV-101 in both of these indications. I think you'll find out that these results are turning out to be remarkable for these patients. Secondly, we want to stress that we have a very valuable commercial opportunity here for both stiff person syndrome, which is our initial indication, which has significant unmet needs, and we believe this market is larger than what was initially thought. It also allows us to build a foundation that we can build on in terms of a rapid acceleration into the myasthenia gravis space and a really growing and large market. Third, for the first time, we're really excited to unveil the details of our registrational phase III trial design for KYV-101 in myasthenia gravis. We've aligned with the FDA on this design, and you're going to see that the size of this trial, as well as the design of this trial, really allows us to move and execute on this trial quickly so that we can bring this therapy to the many patients that are waiting for a new advancement in the treatment of myasthenia gravis. This is an overview of today's agenda. We're going to jump in in a few minutes to some background scientific data that's really supporting the rationale of why CAR-T therapies may be uniquely poised to actually address the underlying causes of autoimmune diseases. From there, we're going to move into a deep dive in terms of stiff person syndrome, as well as myasthenia gravis, looking at the unmet patient needs in this space, what the gaps are with current therapies, and how our clinical development program with KYV-101 is set up to address both of these diseases. Towards the end of the presentations, you're going to see we're going to dive deeper into specifics around commercialization, provide a bit more of a commercial framework, and how we intend to bring KYV-101 to the market. Joining me are several members of my Kyverna leadership team, but we're also very, very pleased to have join us this morning three well-known and world experts in the field of CAR-T cell therapy and in the management of autoimmune diseases, and in particular, neuroimmunology diseases. We have Dr. Ricardo Grishaber-Buer from Friedrich-Alexander University in Erlangen, Germany, Dr. Aidan Haghikian, also hailing from Germany from the Hanover Medical School in Hanover, Germany, and someone a little closer to home here on the peninsula, Professor Shirin Mukhedi from Stanford University School of Medicine. I want to thank all three of you for joining us this morning, sharing with us your scientific expertise, and also your clinical insights on how CAR-T cell therapy can help these patients that are waiting. Here at Kyverna, we have a very bold mission. We are not here to make an incremental impact in terms of helping patients. We really want to liberate them from the burden and the chronic burden of autoimmune diseases that they're facing through this curative potential, this really transformative potential that we're seeing with CAR-T cell therapy. We believe that Kyverna is poised to really deliver on this mission because of a number of key factors. First, we have a unique construct. KYV-101 is a CD19-directed CAR-T, but it's the only one being studied in the autoimmune space with a CD28 co-stimulatory domain, as well as a fully human design, which means that it's really built specifically to provide potency and improved efficacy in these patients, as well as an improved safety profile. We're really excited to share that we've now reached a milestone here at Kyverna treating our 100th patient with KYV-101. This is a tremendous accomplishment, and it also provides a lot of confidence for us in terms of not only the efficacy profile and where KYV-101 works, but also in terms of its safety profile across many, many different patient types. In effect, we've de-risked KYV-101, and it allows us to move very, very quickly so that we can address the near-term catalyst that we've put forward in terms of our strategic plan. It also allows us to be potentially first in class in this space to accelerate KYV-101 for stiff person syndrome, as well as myasthenia gravis, with a clear path to BLA in both of these indications. As you can see, we've also been assembling a very experienced leadership team around me in a lot of depth across the organization with late-stage development experience, CAR-T experience in manufacturing and commercialization. We believe, along with a strong cash position, that we're in a position here to deliver on all of these in terms of our strategic plan. A really important point to keep in mind is that although there's a number of new therapies being studied in the autoimmune space, particularly in myasthenia gravis, but across many of these autoimmune diseases, we believe that KYV-101 is doing something uniquely different. This therapy has actually got the on-target specificity, providing deep B-cell depletion in targeted tissues, really setting these patients up for what we're calling an autoimmune reset, which really then sets up the rationale for why we're seeing these long-term, durable, drug-free remissions in patients. We're doing this with a single dose. We're doing this with also eliminating other background therapies that these patients are having to be burdened with throughout the course of their disease. This is something very, very unique that KYV-101 and CAR-T therapies are doing. We think this sets us apart from all the other therapies that are being studied in these spaces currently. We've laid out a strategic plan for Kyverna, and we've really built this around three key strategic blocks. Starting with stiff person syndrome and myasthenia gravis, this allows us to build a first-in-class neuroimmunology franchise and really establish this first mover advantage, which we know is really critically important from a commercialization perspective. This really sets up the groundwork for future indications. We're not going to stop with KYV-101. We've talked a little bit in the past about KYV-102, which is our next-generation construct, and this is really a second pillar of our strategy, where we'll actually make the process for patients' access even simpler by removing the step for apheresis, as well as speeding up manufacturing and lowering the overall cost of goods. Both of these pillars actually lead us to the third strategic block, which is really expanding our reach, where we take KYV-101 and KYV-102 and really look to see how we can treat more patients with autoimmune diseases. We're already generating early and pretty impressive data in multiple sclerosis, as well as RA, and these are pointing us in the direction that we can actually serve larger patient populations with huge unmet needs. Today, our focus is around stiff person syndrome and myasthenia gravis. We believe the strategic rationale of why we've chosen both of these indications is extremely compelling. First of all, we've got really great initial data that we're seeing from our patients. In fact, we're going to share an update on these data later in the presentation. In addition, we know there's high unmet needs with these patients. Stiff person syndrome is a highly debilitating disease. You're going to see that it's very progressive, despite the fact that these patients take symptomatic therapies, their disease just gets progressively worse, and there's no approved FDA therapy. From myasthenia gravis perspective, although there are a number of new therapies being studied and being introduced into this marketplace, we know these are suboptimal. They don't address the underlying causes of the disease. There's a high cost burden to the system, and patients are still strapped with ongoing chronic therapies for life. Overall, we believe stiff person syndrome and myasthenia gravis are fantastic first indications. They give us a first mover advantage. They allow us to move quickly, and we can also build on a shared infrastructure, build with a lot of synergy both from a manufacturing and a commercialization perspective, which creates a lot of efficiencies for a young company like ourselves. Overall, you can see that we've really created tremendous momentum over the past few months. We've got key readouts coming forward in stiff person syndrome, reading out our top-line results in the first half of 2026, as well as targeting our BLA filing for the first half of 2026. With myasthenia gravis, we're going to report out interim phase II results in the fourth quarter of this year. The phase III pivotal registrational trial, which you'll hear more detail about in a few minutes, we're actually starting enrollment with those patients later this year as well. You can also see we have other milestones and other data readouts that really expand and build on the strategy that I spoke about a few minutes ago and how we can take KYV-101 and Kyverna into the broader autoimmune space. Overall, I want to end this section with just focusing on the patients. These are the first two patients that we've treated with KYV-101 in both stiff person syndrome and myasthenia gravis. You can see that in stiff person syndrome, this patient is actually on track or almost approaching the two-year mark. Our first myasthenia gravis patient, Denise, which I've spoken about before, is now past the 24-month mark. Both of these patients have had significant clinical improvement. They're actually free of active disease. They're off background immunosuppressants and other treatments. If you think about it, and we are so close to these data and these patients every day that sometimes we forget the impact that we're having. If you think about the people in this room and the people on this call, and even if you ask the patients themselves, I don't think there's anybody here that would think that these patients could be having this tremendous impact, this transformative impact, as little as two years ago. This is why we're excited here at Kyverna. We're extremely excited about the progress that we're making. We're extremely excited to share with you some of the next steps that we'll be taking as an organization here in the rest of these presentations. With that, I'm going to turn it over to Dr. Ricardo Grishaber-Buer from Friedrich-Alexander University in Erlangen, Germany. He's a clinician, but he's also a scientist that has spent a lot of time looking at the translational medicine effects of CAR-T cell therapy and why he believes that these have a really transformative impact on the underlying course of these diseases and why it may be leading to the fantastic clinical results that we're seeing from these early patients. Ricardo, thanks for joining us. I'll turn it over to you. Okay, Warner, thanks so much for the introduction. I'm happy to be here tonight and to share some of the experiences that we've had with this exciting emerging new therapeutic concept that is deep B-cell depletion for autoimmune disease. I just want to start by highlighting why we are talking about B cells and why they are really the focus right now of autoimmune disease therapy, because there are many treatments around, but actually very few address the underlying immune dysregulation on a mechanistic level. B cells are fundamentally implied across a range of autoimmune diseases. They are not just a source of autoantibodies. This is also important to highlight when we think about disease indications. There's also seronegative diseases in which B cells play a role. They present autoantigens and thereby also directly can lead to T cell activation in an antigen-specific manner, leading also to cytokine production in tissues. We see in many cases a strong collaboration between T cells and B cells in extra follicular tissues, such as the central nervous system driving pathology. This makes B cells really a centerpiece to therapeutically target. There are different targets on the B cell lineage that have different expression profiles. If you look at this graph here, looking at B cell development starting in the bone marrow from the pro-B cell to plasma blasts, which can secrete autoantibodies, you see that the antigen CD19 has very broad coverage across B cell subsets. It's therefore a natural choice to target the B cell lineage in a very broad fashion. This is the theory behind it. Of course, really what launched this field was the incredible proof of concept that was delivered via the first CD19-directed CAR-T cell therapy treated patients across a variety of diseases: acute cutaneous lupus. This was the first woman that was treated, but also myositis and even interstitial lung disease in patients with systemic sclerosis responded. As we, of course, also know, deep B cell depletion has successfully been applied to various other diseases, such as myasthenia gravis, multiple sclerosis, stiff person syndrome, and many others. This therapeutic paradigm that has disrupted autoimmune disease treatment has come to stay. I just want to take the time here to focus a little bit on the mechanisms, how this treatment works, and what we've been able to learn so far. Here's a case from Erlangen that I brought: a 20-year-old male with active systemic lupus that had CNS involvement that was severe and progressive, with subtotal paraplegia, and was highly treatment refractory, including to rituximab and cyclophosphamide and plasmapheresis. As you can see at the time in the middle graph, at the time when this patient received CAR-T cell therapy, the patient had B cells in the cerebrospinal fluid. There were B cells left in the cerebrospinal fluid despite previous rituximab therapy, showing that rituximab was not able to completely deplete the target cells. CAR-T cell therapy, despite having no B cells in the peripheral blood, this is seen in the second graph from the left. Despite this, CAR-T cells expanded, showing that they were able to encounter antigens still, and they were able to migrate into the CNS and clear the cerebrospinal fluid B cells, leading to a strong clinical response in this patient. Actually, this ability to cross the blood-brain barrier and to deplete target cells is confirmed also in additional patients. This is work here coming out of Stanford of four patients with progressive MS, where CAR-T cells were measured in the cerebrospinal fluid on day 14. You can see robust CAR-T cell expansion and migration also in the CNS. What this shows essentially is that T cells as effectors are much more potent than antibodies, and they are able, in fact, to cross the blood-brain barrier, leading to target cell depletion also in the CNS. This concept really of a deep B cell depletion is also highlighted here in longitudinal tissue biopsies that we started to really routinely perform in our center to understand if the cells expressing the target antigen are being depleted or not. In this study, by looking at rituximab-treated patients in a longitudinal lymph node biopsy, we can clearly see here after rituximab treatment, there are still B cells expressing CD19 and expressing CD20 in the lymph node. After CAR-T cell therapy, these lymph nodes are cleared of B cells, highlighting the much more efficacious effector mechanism. This is essentially the depth of depletion, but you can go even further, and you can look on the molecular level what such a deep depletion of B cells actually means. This has started to coin the term immune reset. Immune reset is actually still very poorly understood. It's not well defined, but we are starting to see some molecular characteristics that define it and that allow us to track it. I want to share some of those with you in the next coming slides. One of these is on the B cell compartment itself. When we look via single-cell RNA sequencing, we can track the phenotype of each B cell essentially at baseline and after reconstitution. What you can see in the left graph here from pre to post is this expansion of a group of transitional B cells and of immature B cells, showing essentially that you have a new B cell system that is forming. When we look at the repertoire of the B cell, which is something that in the normal system, but also in the disease system, shows class-switched heavy chains, this is seen on the top graph here in these different colors. You see, for instance, the blue is IgG. In this repertoire, you can have disease-causing autoantibodies. When the B cell system is deeply depleted, so deeply, in fact, that it reboots from precursor cells, you see as a result something like in the bottom graph, where you only see this dark blue, which is the heavy chain, the mute chain. This is IgM, and the red is the delta chain, IgD. IgM and IgD both being expressed on naive B cells, showing therefore that you have a very naive B cell repertoire without class switching. This is essentially telling us that the B cells are profoundly different after they have been depleted and after they come back. We thought that perhaps the effect that we were seeing after CAR-T cell therapy was not only related to the B cells itself, because the disease, of course, is not driven also just by B cells. It was a little bit paradox to see these multi-year drug-free remissions without explaining it via other cell types. We performed a very broad and very deep multi-omic immune profiling before and after CAR-T cell therapy, looking at the gene expression profile, but also the surface expression profile and the chromatin accessibility across different cell types, so monocytes, T cells, and K cells, and so on. One result that I want to highlight that came up in this study was actually related to regulatory T cells, which are a very important subset of T cells to keep autoimmunity in check. What we can see here in the heat map on the right-hand side is the expression of several of these proteins that regulatory T cells require to keep essentially the immune system in check. They are expressed at normal quantity in healthy donors, but in patients with autoimmune disease before they received CAR-T cell therapy, in the state of active disease, they had strongly reduced the expression of these inhibitory proteins. Afterwards, in a state of remission, this expression was restored comparable to healthy donors. We're highlighting here on the volcano plot the upregulation of PD-L1 and CTLA-4, which are proteins that the regulatory T cells use to keep the immune system in check. This is something that came out of the analysis of the T cell compartment. We thought maybe we can even more broadly identify changes. We looked at patients that were in remission after conventional therapy versus those that were in remission after CD19-directed CAR-T cell therapy, patients with systemic lupus. As you can see here, there are different molecular signatures of remission depending on how the patient reached the remission. You see, for instance, a decreased score for classical antibody-mediated complement activation, but also a reduced score for type 1 interferon signaling and for innate triggering. This is actually present even in a state of remission, showing that you have different biomarker profiles and very likely a more favorable biomarker profile after a treatment with CD19-directed CAR-T cells. What this leads us to is a more holistic understanding of immune reset. We started this journey by studying and understanding better the B cell, but we now also started to understand the role that an enhanced tolerogenic profile plays, such as regulatory T cells, a disappearance of the type 1 interferon signature across different cell types, and decreased activation of myeloid cells, driving less inflammation. To summarize this, I've shown you today new insights from the translational sciences into how CD19-directed CAR-T cell therapy works for autoimmune disease. I've shown you a broad and deep depletion of pathogenic B cells, both in tissues and in circulation. We've seen in several studies that I highlighted a positive impact on the immune system beyond B cells on a broader set of immune cell types. I've highlighted specifically an impact on regulatory T cells, but also a different molecular remission profile in patients with remission, suggesting that a holistic immune reset is, in fact, possible and that we are starting now also to understand how to measure and to track it. This brings me to the close of my presentation part, and I'm happy to turn it over to Sham Dholakia, the Chief Product Officer, who will talk about establishing a new treatment standard in stiff person syndrome. Thank you very much. Thank you, Ricardo, for that phenomenal talk. It's great to see how we're able to unpack the mechanistic value of how therapies like KYV-101 are really able to provide this long-term durable remission. I'm excited now to switch gears and give us a whistle-stop tour through SPS, stiff person syndrome, and really drill down to how we like to start every single presentation and why we get up and come to work every day, which is the patient. That first patient that Warner shared is now almost two years post-intervention. This is a patient that has had stiff person syndrome for over 10 years. In 2004, at the age of 59, they developed sudden loss of control of their lower limbs. This led to repeated falls, and her disease continued to progress, needing wheelchair support. Despite the plethora of immunotherapies that were given to her, her disease continued to progress, impairing her walking. Before KYV-101, she was on a number of different immunotherapies that had a number of large side effects. It was absolutely phenomenal to see that after a single administration of KYV-101, we were able to see a significant change in this patient, where she's now able to walk with a walker and turn and gain her confidence back, as you can see in this middle panel here. This is obviously where these patients often are having these falls as they're navigating these turns. What is continuing to be amazing in this patient is that there's an innate new phobia that comes as part of the component of this disease. That fear of falling, that awareness of open spaces really limits patients' independence, their ability to move around in their own homes, their ability to go to work, to be an active member of society. In this third panel, what we can see is that this drug-free remission is not only durable and has improved her mobility and stabilized her gait, but it's also now allowed her to walk completely unaided, which is a massive shift into where she started this journey. When we try and unpack stiff person syndrome, this schematic here really gives an overview of what's happening in terms of the mechanism. What we can see here is that the GABA pathway is the braking system of the nerves. What we can see is that antibodies now, namely GAD65, but other antibodies like receptor glycine R and GAD67, can impact this braking system. The way the nerves then interact with the muscles is impaired. This relieves the symptoms and the clinical picture that we're now seeing in our patients, which is this progressive spasm, the idea of painful rigidity, and loss of function. Holistically, this translates into reduced mobility. When we now see these patients, they have this active progressive disease despite the therapy that they're being given. Their walking tends to be impaired. In concert, they're also developing generalized anxiety, new-onset phobias, which you can imagine can be very debilitating for the patient on their own. The way that this diagnosis is now happening and is tested is based on this collection of clinical symptoms in concert with antibody testing. From the time of onset of first symptoms to diagnosis is about six years. This is a long period of time, which we hope is now going to get compressed as awareness of disease has continued to improve. It also means that as you have a long term of disease, there's a risk of permanent disability. As we now look at that progression, the treatment right here is very variable. There are no approved treatments for stiff person syndrome. Patients are often started with muscle relaxants and painkillers to try and support the symptoms as they've continued to flare with disease. As they now move to immunotherapy, a lot of these therapies are all used off-label: IV rituximab, IVIG, azathioprine, cyclophosphamide, many of these given in combination, anything to slow the progression of the disease. I think that is the mainstay of the current therapy now. It's to slow the progression, knowing that these patients will continue to progress despite these medicines. There's a lot of heavy lifting to support these patients in terms of occupational therapy, physical therapy, as well as psychiatric support and mental health support as they manage all aspects of this disease. Why is walking so important? Obviously, it's a big part of ambulation. There's a big lift on the types of immunotherapy that we're giving to try and keep these patients independent as possible. IVIG is often used in this disease, but it's shown to give only modest improvements that last several months. Despite that temporary benefit, it wanes over a period of time. The ongoing burdens to these patients are significant, where they have to make sure that they're well enough to go for their infusion, scheduling it around their life, have to take a day off work. If they get sick, they'll have to move their infusion date. Many of these patients get side effects from having the infusion and often feel ill several days after having that. IV rituximab is just the same in terms of targeting anti-CD20, which Ricardo showed lacks the ability to penetrate those deep tissue compartments compared to therapies like KYV-101. It has very moderate benefits, which can take potential months to see any type of effect, but still doesn't stop the disease from progressing. We're excited to set a potential new future of care when we now look at the standard of way SPS is being managed. By delivering the first FDA-approved treatment, we think we can really move the needle for this particular disease. We're going to take a deeper dive now into the mobility, as we talked about why we're using this endpoint and that first patient that we talked about. The timed 25-foot walk test is an approved, validated endpoint that has been used in other neurological diseases, such as MS. The clinically significant change in this is a 20% change. Our clinical trial, KYSA-8, is powered at a 25% change. What does this mean? It means that a normal patient with stiff person syndrome is walking 25 ft, which is 5.5 meters, in about double digits, 15 seconds, 16 seconds, 20 seconds, whereas you and I would be walking that same distance in four to six seconds. There's a large delta between normal and abnormal in the starting point. This is really important now when you look at the first two patients in this series, where you see the average baseline is 17.7 seconds. After a single dose of KYV-101, we're able to create a significant shift in the ability for them to ambulate, with improvements going down to eight to nine seconds. Over the course of the disease, you can see now the patient who's now approaching 23 months has reduced now to 6.3 seconds. Continued to improve over that long period of time. The other patient now who is eight months post-therapy has also continued to improve. We're excited about this value shift that we're able to do. Why this is so differentiating is that the background immunosuppression is stopped at the point of infusion, and in both cases, has not needed to be restarted. This is now mirrored through the change in antibody titer, where the absolute numbers are not important, but the trends are. You can see in the right panel of the screen here how we're able to create this downward shift in antibody titer, which goes in concert with the clinical improvement of both of these patients. This dramatic change in treatment effect, where we're now seeing over a 60% change, is then allowing us to create a very highly powered study, where 25 patients in a single arm powered for a 25% change would allow a positive endpoint of that primary endpoint. In addition to this primary endpoint, we're also now looking at a number of validated measures for this disease that are described in the literature. The modified ranking scale, which is originally developed for stroke, is another measure of disease in terms of how much you're able to ambulate and loss of function. That's also being used as a key secondary endpoint, as well as the measurement of the stiffness index. All of these patients have received a flat dose of KYV-101 at 100 million cells with the standard Ziflu regimen. We're excited to say that all of these patients have been fully dosed and now are waiting for the top-line results to be reading out. We're excited by this and absolutely believe that SPS on its own is an indication that can stand up to create significant value because we were fully able to recruit this trial from only three centers. We were oversubscribed. We ended up having to send patients away, and we're able to execute full enrollment in seven months. This has now given us real confidence into the clinical unmet need of these patients, but also the number of patients that are out there that are really asking for something better while they continue to have these immunosuppressants that are really not getting to the root cause of the disease here. In terms of timing, we're anticipating to be able to file the BLA in 2026, and we're excited to share the top-line results as they come out. As we think about the value creation here, we know that stiff person is progressive. We know that it's debilitating, and we know that there are no FDA-approved therapies. This is because the disease is complicated and unpacked, but we're all excited to be the first ones to potentially bring and unlock the promise of CAR-T to deliver that first FDA-approved therapy in the future. The long-term data, we are super excited that this ability to create a durable response is something that we're excited about and really creating a disruption in the way that chronic infusions are delivered and how patients see treatments in the future. We're aligned with the FDA in terms of the tracking of what we're doing this year, and we've had continued strong engagement from all aspects of the SPS community. Excited to share more as we unpack this. With this, I'm going to hand over to my friend and colleague, our Chief Medical Officer, Dr. Naji Gehchan, who's going to introduce the next section. Thank you, Sham. I'm excited to be here today sharing about how we will be reshaping the treatment paradigm in MG. I'm really pleased to be joined by two leading experts in neurology. Professor Aidan Haghikian, who is the Chair of Neurology at Hanover Medical School, his work focuses on neuroimmunological and neurodegenerative diseases. He's passionate about both innovation and patient care. Aidan has treated the first myasthenia gravis patient worldwide with CAR-T and specifically KYV-101. I'm also delighted to welcome Professor Shirin Mukhedi from Stanford University, a leading expert in neuromuscular and autonomic disorders. His research has advanced outcomes measures like MG-ADL, and he has been deeply involved in clinical trials for myasthenia gravis and other neuromuscular diseases. Before we dive in, we'd like to share with you a video of Denise, the first MG patient who was treated with KYV-101 through the compassionate pathway. Warner introduced Denise earlier in the presentation. Here is her journey. [Foreign language]. [Foreign language]. In Germany, we have a law, the so-called individuelle Heilversuche. This allows the physician to apply therapeutic approaches that are not approved in those patients where the regular and approved drugs have been exhausted or there is nothing available. I was intrigued by the option to apply CAR-T cell therapy. Denise is one of these cases. We have been trying to stabilize her disease for the past three years. She needed ICU care several times with ventilation and intubation despite an efficient immune therapy. [Foreign language]. After having seen the patient clip, which showed the patient journey from her own perspective, I'm going to give an overview of the patient journey from the neurologist-clinician point of view and how we came about to introduce CAR-T cell therapy in this case and why I think this may, in fact, transform the field of neuroimmunology beyond MG and SPS, as we just heard earlier. This is Denise's disease course. She was admitted to us late 2021 after about 10 years after she received her diagnosis of MG. In that time, she was fairly stable. She had a couple of myasthenic crises and had needed also ICU treatment. Her disease really flared up around this time. She was transferred to us from a peripheral hospital in an intubated state where she required ventilation. They had already infused two doses of rituximab, high-dose rituximab, and were not able to wean her off. When we received her at our ICU, we were quite desperate also. That's why we moved on to a treatment option, which we had established a couple of years back in Bochum with Botulinum MIP, which presumably depletes the plasma cells. The hypothesis was that we cannot get rid of the antibodies. Maybe if we deplete the plasma cells, we'll be able to stabilize her disease, which also worked, but not in a very efficient and also sustainable way, as you see. This is the follow-up two years after that. She required Botulinum MIP a couple of times. We added MMF to target also the mycophenolate to target also the T-cell arm. She required oral prednisolone throughout the next two years. This is a kind of a patient that gives you really sleepless nights as a clinician. Despite trying everything we had at the time, we're not really able to stabilize this young woman. She required several times of ICU treatment with ventilation and intubation, as we heard earlier on. This was around the time when I read about the work of Georg Schett and his team in Erlangen, where they applied CD19 CAR-T cells for the first time in an autoimmune disease, which is not a neurological disease, systemic lupus erythematosus, but which shares several pathomechanistic features with MG and other neurological diseases. We teamed up with our hematologist at the time, Dimitros Muyakakos, who was part of the team back then in Erlangen, had some experience as a hematologist. We asked Kyverna Therapeutics, which was quite a young startup at the time, if they could provide us the cells to apply it in this, as we call it in Germany, the individualized healing attempt or compassionate use for this case, which was treatment refractory, obviously, as you could just see. This is the patient just before and right after CAR-T cell therapy, Denise, just after lymphodepletion on the right-hand side, on the left-hand side, where she could, in a presumably stable condition, just remember, she had a triple therapy by the time. She could lift her arms for about 20 seconds and was not able to walk even by a walker. She needed a wheelchair. Six days after, in just roughly a week, she was able to walk with a walking aid. Two weeks after that, on the right-hand side, for the first time after two years, she was actually able to walk freely. She was weak on her legs, obviously. Today, more than two years after the infusion, she's able to walk an unlimited distance and doesn't have any symptoms without any further therapy. We had obviously some expectations when we decided to move on and to apply KYV-101 for Denise. This clearly exceeded our expectation by the time. I think it was life-changing for her and eye-opening for us. This is the antibody levels of Denise. On the left-hand side, you see the titers of the antibody directed against the acetylcholine receptor, which dropped markedly, never vanished, but dropped. At the same time, on the right-hand side, you may appreciate that her protective antibodies, so these are the vaccination antibodies, clearly plasma cell-driven, remain almost unchanged. We're quite confident that this is also the reason why she didn't have any increased frequency of infections, what we usually see under immune therapy, especially under combined multiple immune therapy. For the next slides, I would like to digress and take an excursion, a brief excursion to the pathomechanisms of MG. We have known the antibody for roughly 50 years now. I've known that the antibody blocks the receptor, which is the receptor which receives the signal from the nerve and transports it into the muscle cells, which lead to depolarization and to muscle contraction at the end. The blocking aspect of the antibody has been known for quite some time. We have since then learned also that the secondary complement deposition leads to a destruction of the neuromuscular junction. That's why we see also a progressive nature of the disease. It's not if you remove the antibody that the disease is gone. We see a progression. We see a muscle weakness and atrophy after several months and years if they're untreated. That's the basis for that. Since then, we have learned, obviously, some more about the immune pathomechanisms. This slide is quite busy, but depicts quite well the different scenarios of immune reactions that are involved in this autoimmune antibody-mediated neuromuscular disease with some specific targets, which we can, as you can see here in the red boxes, target more or less specifically. We will hear about that more by Professor Mukhedi later on. I'm not going to go too deep into that. We have learned that the B cells play a central role in this disease, as in many other neuroimmunological diseases. We heard multiple sclerosis, SPS, encephalitis, other neuroimmunological, severe immunological diseases. When you hear or read that MG is a B cell disease, this is not accurate. It reflects quite well the central role that the B cells play in this disease, not only as antibody-producing cells, as we heard earlier on, but by various mechanisms that the B cells are involved in as activators of T cells, of cells of the innate and the adaptive immune system, but also as, in certain scenarios, as producers of pro-inflammatory cytokines and, in some cases, even as tissue resident memory cells when they tend to form the so-called tertiary lymphoid structures. We heard multiple sclerosis where the TLS are discussed as the main drivers of disease progression. That's where we don't get with the depleting antibody, as we heard also earlier on in the talk. Since Denise's case and the experience we had, we moved on and treated several more cases of MG. The second one was an elderly man who had quite a short disease duration of only one year. Usually, in the elderly MG, we don't see such a high disease activity. Once in a while, we also see that in that age range. What all these patients have in common is that they had multiple pretreatments, including CD20 depleting antibodies, namely rituximab. What I'm asked frequently is why don't you, if it's so effective as you have shown now, why don't you move in much earlier with the CAR-T cells? If you ask me, I mean, we are not there yet. I'm quite convinced if this all holds true also in the next phase clinical trials, at some point we will get there, as it is often the case with new approaches, just a matter of time. As already mentioned, the first patient is Denise, who has now more than two years of freedom of disease, of freedom of symptoms, if you like. These are the clinical scores, the MG-ADL, which is the more we will hear about that also later on in the talk of Professor Mukhedi. This is the more subjective score of deficits, neurological deficits of the patient, and the QMG, which is the score that we investigate as neurologists. As you can appreciate here, both scores dropped markedly and remained low or absent for, in the case of Denise, even more than two years. This is quite remarkable, an effect that we haven't seen and hadn't expected in the field of neurology so far. When it comes to safety, this was obviously crucial to move on and to include other patients and also the clinical trial. We can sum up that the treatment is quite safe. The often the side effects that we fear, the CRS or the inflammatory syndrome or the ICANS, the neurotoxicity syndrome, which is seen frequently in hematological oncological diseases, were absent in our cases, almost completely absent. We saw a mild moderate CRS in the elderly patient, which was resolved quite swiftly and with standard measures. We haven't seen any ICANS so far in any of these patients. We did see some prolonged anemia and lymphopenia, which are described in the publications, but which were able to stabilize and to reverse in all of the patients. We haven't seen so far for more than two years in the very first cases any unexpected severe adverse events, which is, I think, the basis to move on and to apply this approach in clinical trials as it is ongoing right now. I'm coming to the end with this slide depicting Denise, who appears, and this is something that we don't appreciate enough and also not in our clinical scores, the socioeconomic aspect of the disease. Denise had a disability pension, so she could have moved on and lived off that for the rest of her life. Since one year, one year ago, she realized that she's strong enough and healthy enough to support her family and has started working part-time despite having access to the disability pension. This supports her and I think gives her also self-esteem and has some positive secondary effect on her life and the disease that she has. With that, I'm coming to an end and hand over to Professor Shirin Mukhedi. Thank you so much, Dr. Haghikian. I think we all aspire to provide the kind of care that you were able to provide to Denise. I think that that's what our patients want, and that's what we would like to offer. If we have the same degree of improvement in everybody that I see, then you don't need clinical trials. You can treat a few patients, and you'll get a drug approved. In practice, we look for more data consistent across the breadth of spectrum of patients. As new therapies come into picture, it's always good to go back and look at where the current MG treatment landscape is because there's been an incredible development in MG therapy days and where newer therapies such as CAR-T might fit into the picture. These are some of my disclosures. I will definitely talk about therapies such as CAR-T that are not currently FDA approved. One of the things to think about when you start learning about myasthenia gravis as a disease, we have already heard about it being an autoimmune disease, an antibody-mediated disease. Not all patients behave the same. We are looking at large cohort studies, for example, trying to understand how patients behave and what are the type of patients who might benefit from newer therapies. This is a study from Europe, which looked at a cohort of almost 200 patients over a period of time. Like most things in life, green is great, red is not good. If you look at the top part of the graph, these are patients followed from onset of the symptoms longitudinally for 10 years. A significant portion of the patients do become green over a period of time. There are a small proportion of patients, about 30% of the patients, who turn green within year two, as in they have very good control and they remain fairly well. There's a small proportion, which is the top, so the bottom right part of the graph that you will see, the treatment-resistant part. These are patients that continue to have symptoms even after one or two years of treatment, continue to fluctuate between mild symptoms to severe symptoms. These are the cohort of patients we call it remain treatment-resistant, difficult to sort of control completely. One of the challenges is that we don't know a priori who these patients are. If I go into clinic tomorrow and see four myasthenic patients who were recently diagnosed, I couldn't tell you who they are. That remains one of the challenges of the field. One of the ways we try to capture how patients are doing is by using different outcome measures that are MG relevant. These are relevant because these are outcome measures we use in clinical practice to capture disease burden. We use these so that we can get some of the newer therapies approved for our patients. Fortunately, these are the same outcome measures that are used in clinical trials, including the most commonly used one, which is MG-ADL. This is a fairly simple patient-reported outcome measure. A physician can guide patients regarding the relevancy of the symptoms as it relates to myasthenia. As you will see, there are eight questions. These are the common areas that myasthenia frequently affects. If you go to the right, sort of severely affected versus zero normal function. It is fairly simple to use, range from 0 - 24. At least a two-point improvement is considered meaningful. The advantage of this is that since it's a primary outcome measure in many of the clinical trials and it's easy to use in clinical practice, we're able to actually capture patient improvement both in clinical practice and try to simulate what we see in clinical trials. Another important outcome measure that's relevant and sometimes used in clinical trials, including the phase III clinical trial for Kyverna Therapeutics, is the QMG scale. QMG is different from MG-ADL. QMG is physician-derived. It's a little bit more extensive. As you can see, it has 13 items. Each one, again, goes from 0 to 3. However, these are all items that are performed by a physician and assessing strength, assessing fatigue ability, muscles getting weaker. We don't usually use this in clinical practice except for rare situations, but we use it in clinical trials. It's a very well-done, valid, and reliable outcome measure and captures sort of a different spectrum of disease burden and then captures subtle changes that MG-ADL might not be able to capture. Another important one that you will see as you look into data for myasthenic clinical trials is this combined measure called MG composite. This one is a mixed measure. If you read through the questions, you will see some questions are very similar to MG-ADL. It has some patient-reported metrics as well as some physician-derived metrics by examination of strength. This is a very well-developed measure that's valuable and works really well both in clinical trials, but easily can be done in clinical practice. You might be thinking about different therapies that have been approved over the last few years. There have been a whole group of therapies in two buckets, complement inhibitors and then FcRn antagonists. There have been three complement inhibitors that have been approved in the last six to seven years. The first one is eculizumab, which is a C5 binding monoclonal antibody. This is given every two weeks intravenously. In In the clinical trial, as you will see, the blue line is the drug and the red line is the placebo, the top left side. You will see the patients clearly improve pretty quickly within a couple of weeks. In the clinical trial, it had a refractory MG population. The second drug that was approved is ravulizumab. Again, a monoclonal antibody binds to C5, but this has a much longer half-life, given every eight weeks. The third drug is zilucoplan, which is a peptide given subcutaneously, but daily. All of these complement inhibitors are only FDA-approved in ACHR-positive MG patients. These are patients who have active disease burden. The second group of drugs that have been approved are the FcRn inhibitors. This is a novel mechanism. Prior to myasthenia, these drugs were not FDA-approved. Myasthenia remains one of the only sort of one disease. There is one other disease since then that these drugs have been approved for. There are three drugs that have been approved in the last four years, five years. Efgartigimod, which is given, initially was approved for IV, given as cycles of four weekly for four weeks. Since then, there is a subcutaneous option and a subcutaneous self-administration option. If you concentrate on the graph on the top left, you will see the blue is efgartigimod, red is placebo. The impressive thing about these drugs is that after starting the treatments, patients clearly improve. What you're able to see once the four weeks of treatment is done, there is a return of symptom burden. The similar thing pans out with rozanolixizumab. It's given weekly for six weeks, clear improvement in symptoms, but some return. More recently, the last drug that has been approved in the line of these therapies is called nipocalimab. This one is not given in cycles. It's given every two weeks intravenously. The complement therapies and the FcRn therapies have had a remarkable effect in patients. We use these drugs in our clinical practice. They are currently predominantly FDA-approved for ACHR-positive myasthenia patients. These drugs suddenly increase the ability to achieve a minimal symptom state. They reduce the symptom burden. Because they work relatively quickly, we were able to reduce the prednisone dose in these patients, prevent chronic prednisone side effects. In spite of the dramatic effect that they have had in patients with myasthenia, one of the challenges we currently face is that these are expensive therapies. It takes sometimes a bit of a challenge to get these approved for a particular patient. The second one, and this is the more important one, is that they require continuous treatment. To date, there is no data that if you try these drugs and then you stop the drug, you have persistent benefit after you stop the drug. That has not been proven. In most of the patients, they also require their background oral immunosuppressive agents. You might be able to reduce the prednisone dose a little bit, but you still require additional background immunosuppressive therapy. There is one other mechanistic we have briefly touched upon earlier, is the CD19 monoclonal antibody. There is one drug called inebilizumab. Data was recently published in the New England Journal of Medicine. This is not FDA-approved currently. In this study, patients were given inebilizumab versus placebo. The infusions were given every six months. There was a predetermined way of reducing the prednisone dose in both groups. As you can see, there's a clear improvement in MG-ADL reduction, and all patients in both groups were able to reduce the prednisone. However, this has not resulted in a dramatic improvement to a state where patients were symptom-free or disease-free. This goes back to some of the earlier talks by Dr. Ricardo Grishaber-Buer and Professor Aidan Haghikian about the fact that we might need far superior B cell suppression than some of these monoclonal antibodies are able to provide currently. This is where CAR-T cell therapy really is able to offer some. Deep B-cell depletion that these patients require for persistent symptom control. There are other CAR-T therapies being studied, including mRNA CAR-T therapy. This is publicly available data targeting a BCMA CAR. In the mRNA CAR-T therapy, these patients were given weekly infusions for six weeks. It did result in some improvement in symptom burden, but again, there's sort of a return of symptoms by year one or so. This is unique in terms of this particular drug being studied in myasthenia along with multiple other CAR-T therapies. One of the questions that patients ask me and my own trainees ask me and colleagues ask me is, where do you put the CAR-T therapy? Let's just say these are approved and where do you put them in the treatment paradigm? This is my current approach. We try to individualize everything to a single patient that I see. If you think of generalized myasthenia gravis, there are two subsets. There's ACHR positive MG and then there's MuSK-MG. MuSK-MG is a very small subset with a different mechanism of action. For the ACHR positive MG, I generally talk to my patients regarding therapeutic options based on how bad their disease is. If they have mild symptoms, moderate symptoms, or severe symptoms. If they have mild symptoms, we generally start with pyridostigmine, which is a symptomatic drug, oral prednisone, and immunosuppressive agents. If they're not improving, they are not able to tolerate the medications, we do use FcRn therapies because they're rapidly acting. Whereas if it's moderate and severe symptoms, I'm more likely to use FcRn therapies early because they have a quick onset of action and then switch to an oral immunosuppressive agent or add an oral immunosuppressive agent. We use complement therapies further down the line. It goes without saying, and I emphasized this earlier again, that the problem with FcRn complement therapy is that you have to be on them. The current therapies do not provide you that kind of control where you try them for three months or six months and then you have a prolonged period of symptom control. This is where, since the B-cell therapies have not lived up to the expectations, CAR-T really comes into picture. As you will see on the right side, where I feel like the CAR-T might come into picture in terms of taking away the second line of therapies, offer patients much more persistent control of symptoms. Like many things in clinical practice, once a therapy is available and if it's safe and effective, we will certainly try to use it in all the patients that it could benefit from in spite of the first and second line therapies. I personally think CAR-T therapy can potentially be a paradigm shift in how we approach MG care. As I emphasized earlier, there are many therapies available in MG, including novel therapies that have been developed in the last few years, but they require ongoing continued treatment. We aim to get to a very low MG-ADL or minimal symptom expression state with these therapies. However, those two, low MG-ADL, minimal symptom expression state doesn't capture the treatment burden that patients experience, also doesn't capture any disease fluctuations that patients experience. Patients are ready for a situation where they can get a one-time treatment and then move away from any disease burden as well as treatment burden and live as disease-free as Denise that you saw a video is planning to live and currently living. That's what we aim to aspire. One of the challenges is that this is still early in the development. We would like CAR-T therapies to be safe. We would like them to have a prolonged period, at least one year, of symptom control. We certainly need both short-term and long-term safety data as we move into CAR-T therapies for myasthenia. With that, I will stop and then I will take it away, Naji. Thank you. Thank you so much, Professor Mukhedi, and thank you, Professor Haghikian, for giving us an overview on myasthenia gravis and the current treatment options for patients. As I said before, I'm Naji Gehchan. I'm the Chief Medical Officer here at Kyverna Therapeutics. Patients living with myasthenia gravis do deserve better, as we just heard. They are currently living with an unmet medical need, suboptimal results with costly chronic therapies that are persistently taken, and a continued reliance on background therapies. With KYV-101, we have here a shot to free them from the burden of their disease. KYV-101 can provide the promise of a drug-free, disease-free remission that is durable with a single dose, eliminating the background therapies and dramatically improving their quality of life, as we just saw. When you look at the current treatment options, there are several treatment options available. The majority of them is targeting the downstream of the disease. Whether it is acetylcholinesterase inhibitors, where it increases acetylcholine in the neuromuscular juncture, or the more recent biologics like complement inhibitors tackling the complement activation pathway or FcRn inhibitors decreasing the autoantibodies in the system, all of those are really tackling the downstream of the disease. KYV-101, with its broad and deep depletion of B cells, has an opportunity to act on the source of the disease. As we also just heard from Dr. Ricardo Grishaber-Buer, it does impact the B cell depletion, but also Treg, cytokines, interferon, providing this holistic immune reset that is possible with KYV-101 to give this promise of a durable, drug-free, disease-free remission. Professor Mukhedi went through the current treatment landscape and the different drugs that are available today. Several immunosuppressive with steroids or steroid-sparing drugs, but also the more recent drugs like FcRn inhibitors, complement inhibitors, all of those require constant, chronic, persistent treatment and still the reliance on the background therapies that patients are taking. Those drugs really impact the living of patients. They do come with a significant burden on patients' lives. Let's take a moment to look at what this looks from a patient perspective. All those drugs approved in investigational therapies in MG, they come with this high administration burden. They require frequent dosing. They require consistent and persistent dosing and a reliance on background therapies. If you look at it from a patient lens, patients plan their lives around those dosing. They plan their lives around those treatments, but also they are planning their lives based on the fluctuation of the symptom relief they are having within those therapies. When we look from an efficacy standpoint, and Professor Mukhedi shared with you the different scales that we use in this disease, we can see here those treatment options are improving MG-ADL by three to four points, QMG by four to six points, but none of those drugs is providing enough for patients from a symptom relief. We only see 33% - 40% of patients achieving a minimum symptom expression. The majority of patients are still living with their disease. Beyond the burden of taking the treatment, they are living with the disease symptoms across during their life. When we think about what Professor Mukhedi just shared about MG-ADL, if those patients are still living with three to four points of MG-ADL, depending if it's breathing, swallowing, walking, those have a significant impact on their daily life. Thus, a significant portion of those MG patients still have a high unmet need and they lack a durable, drug-free, disease-free response. Let's look at KYV-101 in myasthenia gravis patients. This is an update on our compassionate use pathway, and Professor Haghikian has just shared about those patients. Denise, we just shared her video. Professor Haghikian's first patient treated with CAR-T is now drug-free, disease-free for 24+ months. Also, look at this graph and those numbers. All three patients have dropped to an MG-ADL of zero after a couple of months, and they are still at a disease-free state with 15+ months and 24+ months for Denise. When you also look at the QMG component of the disease, which is, as Professor Mukhedi shared, a more objective measurement done by physicians, all patients have dropped from a double digit to zero or two, and it's maintained up to 15 and more months now. Also, a key component of what KYV-101 is doing that no other drug is doing is the drug-free remission. The three patients here are all off myasthenia gravis background therapies, and that's a really important piece in how we're thinking about the potential of KYV-101 and what it can bring to patients living with this disease. Our goal with our phase II data is to demonstrate those positive trends towards drug-free, disease-free remission with our drug. Four trends we're aiming to see with longer-term follow-up. The first one is a meaningful reduction in MG-ADL and QMG. The second is setting a new standard for this minimum symptom expression. We've seen improvement with 30%, 40% of patients reaching it. We're really looking at a dramatically better answer with KYV-101. The third one is elimination of background therapies, and then a manageable and predictable safety profile, as we've seen so far with our asset. We're well executing on this trial and hope to have a readout. Looking forward to our readout in Q4 2025, where we will be sharing top-line efficacy and safety data for six patients with up to nine months of follow-up. We won't stop here. This is why we're excited also to be here today and share with you a little bit more about our plans with myasthenia gravis. When we see this impact on patients and patients' lives from a compassionate use standpoint, at Kyverna, we really wanted to make sure that this drug and this fascinating science gets to patients fast. We're excited to be sharing today our phase III registrational trial, KYSA-6, for myasthenia gravis. As we think about it, I want to focus on three important points with our design. This is an innovative FDA-aligned trial. We amended our KYSA-6 phase II trial into a phase III registrational trial, which will allow us a clear and a rapid path to BLA. With this, the sites that we have currently on our phase II trial will be able to start quickly our phase III trial and start our enrollment before end of this year. Second point, it's an efficient and robust design. With the effect size that we've seen with KYV-101, we are now randomizing the patients for a superiority trial with a control arm of standard of care that will be able to demonstrate the meaningful effect size clinically for KYV-101 versus standard of care. The third important point is a differentiated to show durability. We intentionally designed a trial that is unique and different, where we're looking at an endpoint of 24 weeks measurement and a follow-up up to 18 months to demonstrate this durable, drug-free, disease-free potential that KYV-101 is promising. Let's look now at our design. As we can see here, we will be screening, washing out, and freezing approximately 60 patients. Those patients are on current standard of care. They can have also FcRn inhibitors prior to being included in the trial. Patients are washed out, they freeze, and we are randomizing them one-to-one between KYV-101 or standard of care. The standard of care arm has traditional agents and complement inhibitor pathways. In the standard of care arm, patients will not be allowed to have FcRn, and this is because of the cyclical dosing, the variable cyclical dosing of those agents, as we just heard from Professor Mukhedi, and also the fluctuation in the efficacy during this dosing period. Our co-primary endpoint is MG-ADL and QMG at 24 weeks. Having patients at the center of our thinking, we wanted to make sure that all patients, approximately 30 in the standard of care arm, have the opportunity to cross over to KYV-101 after 24 weeks. All patients will be followed up to 18 months from randomization. Let's now look at our key inclusion criteria. Those are MGFA 2 to 4, so mild to severe patients with positive ACHR or MUSK, and patients who have failed one immunosuppressive therapy and required chronic plasmapheresis or chronic use of IVIG, or those who have failed two immunosuppressive therapies. Immunosuppressive therapies can be any prednisone, like any steroid or steroid-sparing or biologic, but it's not required to be on biologic before. Our co-primary endpoints, as just shared, is a change from baseline in MG-ADL and QMG score at 24 weeks compared to standard of care. Secondary endpoints are MGC, the MG composite that Professor Mukhedi just shared, at 24 weeks compared to standard of care. We will also be looking certainly on the proportion of patients reaching MSE, which is a minimum symptom expression, at 24 weeks compared to standard of care. Some of the exploratory endpoints are looking into evaluating the durability of efficacy and our safety for up to 18 months, at one year and a year and a half, and certainly looking at this important component and one of the differentiators and innovations with KYV-101, which is the use of immunosuppressant therapies over time. What this trial is set to demonstrate will radically change the treatment paradigm for patients with MG and for those who are living with the burden of the disease today. From suboptimal treatments with costly, chronic, persistent treatment options, always relying on the background therapy, here with KYV-101, we have this opportunity to provide patients a durable, drug-free, disease-free remission with one dose. We're well on track to be executing and delivering the phase II data with the hope to see and reinforce the positive trends in efficacy and safety that we've seen in the compassionate use patients. We're really committed here at Kyverna Therapeutics to bring this fascinating science that we have to patients fast. This is exactly what this MG phase III trial allows us to do. It's an FDA-aligned registrational trial, beginning enrollment by end of this year, and it will support us to have a clear and rapid path to BLA. As a physician, and as we've heard from the physicians with us today, the hope to provide patients a drug-free, disease-free remission that is durable was practically inimaginable a couple of years ago. Really today, with KYV-101, this future is foreseeable. This is why I wake up every morning. This is why I come and with my teams. This is why the team wake up every morning here at Kyverna Therapeutics. We really are committed to make this a reality for people living with neuroimmunological diseases. With this, I'll hand it over to Dan Maziasz, our Chief Business Officer, who will take us through how we are doing this and the path to commercializing our neuroimmunology franchise. Thanks, Naji. Appreciate it. I'm Dan Maziasz, Kyverna's Chief Business Officer, and look forward to walking through the market opportunity as well as a framework for our commercial strategy for KYV-101. Everyone at Kyverna is excited, like we've talked about today, to have the opportunity to launch the first CAR-T therapy in autoimmune. In addition to being first, we can go fast. As we've talked about, there's patients waiting in SPS given high unmet need and no approved therapies. We can leverage our progress in SPS to get a first mover advantage and hit the ground running in MG. We can also do this in an efficient way through giving the synergies across both SPS and MG. Starting with SPS, which is a rare neurological condition, there's approximately 6,000 patients in the U.S. and no approved therapies. This estimate is based on a recent epidemiology study from the University of Colorado, as well as an internal claims analysis that we conducted at Kyverna. Both of these estimates are higher than previously reported figures in terms of the SPS market. This historical analysis was done in 2018 and we believe is outdated and does not reflect current trends in the field. Historically, patients were underdiagnosed, misdiagnosed, and more recently, there's increasing awareness and use of standard diagnostic tools. This phenomenon is similar to other rare disease markets where the understanding of the market size has evolved over time. A relevant example is Reata, which had also a neurological product where the understanding of the market evolved as the product moved through clinical development and commercialization. There's now reports of increased usage and diagnosis within that disease. Given the size of the SPS market and also the high unmet need and no approved therapies, we think this is a valuable commercial opportunity. Our initial focus will be on the patients with the highest unmet need, including those that are treated with off-label immunotherapy. We estimate that to be about 1,000 - 2,500 patients in the U.S. Over time, with increased experience with KYV-101, as well as more education, we believe the total addressable market for KYV-101 and SPS is approximately 5,500 patients. Today, those patients are treated with symptomatic therapies and, as we've talked about today, often have poor results in progressive disease. We've made significant progress in collaboration with the SPS Foundation in terms of education and awareness, and we look forward to continuing that work. We will also support, where we can, rapid and efficient diagnosis of disease. We're also excited about KYV-101 in MG. This is a large growing market. We estimate approximately 100,000 patients in the U.S. Of those 100,000, 80% or 80,000 are diagnosed with seropositive generalized MG. Of that 80,000, roughly half are treated with immunosuppressants and have an inadequate response. Today, those patients are considered for a biologic. Importantly, in this market, physicians and patients have shown that they will quickly adopt new therapies. This is evidenced by the growth in FcRn inhibitors and complement inhibitors over the last several years. We believe this is a promising sign for KYV-101 and the uptake that we can potentially see in the future. Within MG, our strategy approach will initially focus on the highest unmet need patients. Those are today treated with a biologic, and we will focus on those that are treated and have an inadequate response to a biologic. We estimate that to be about 12,000 patients in the U.S. However, over time, the total addressable market for KYV-101 in MG is 40,000 patients, including those that are treated and have an inadequate response to immunosuppressants. As Naji and others have talked about today, given the differentiated profile that we're seeing in the initial patients, we believe we can compete directly with biologics, given that we have the potential for a durable, drug-free, disease-free remission with a single dose. We also have a compelling opportunity in terms of value relative to current treatments. Those treatments today have a high cost burden and suboptimal outcomes. As shown on the left, we estimate the three-year cost of care for an SPS patient to be approximately $700,000 - $1.5 million. This range is reflected based on severity of disease, as well as different treatment options. This includes both drug and non-drug costs for SPS patients. On the right side in MG, drug costs are substantially higher, driven by complement inhibitors and FcRn inhibitors. We estimate the three-year total cost of care for an MG patient to be approximately $2 million. The chronic nature of both of these diseases, if we modeled these costs over a longer period of time, the numbers would be even higher. We really believe at Kyverna that this is underappreciated in the market in terms of not just the patient burden, but also the cost burden to the system. Even with this really high cost burden, there's suboptimal outcome for patients. As we've talked about, there's impact on quality of life for many of these patients. There's a subset of patients that are not able to work or to drive, a portion that have crisis events requiring hospitalization or ICU visits. Shifting gears a bit to our commercial model, our strategy is to build a neuroimmunology franchise and grow into MG. SPS will allow us to start and develop a first mover advantage. We will build strong relationships at the sites. We will be able to activate those sites in a commercial setting. We will establish commercial contracts. Importantly, we will also be potentially the first company to set price in the market. Given the synergies across both SPS and MG, we believe we can do this with a lean team, a focused lean team. Another reason we believe that we can have a lean model is both SPS and MG patients are concentrated at academic centers. They're often treated by neurologists, as we've talked about, and also the same care teams at these centers. We will launch with approximately 10 centers in the U.S., and our strategy is to grow to approximately 50 - 75 centers in total across both SPS and MG. We will focus on sites that have high volume within their center, but also can act as referral hubs for other sites. All of these sites will have CAR-T experience and most likely accreditation as well. In addition to all the progress we've made internally, the macro environment around us for CAR-T continues to evolve. CAR-T over the past decade is now an established modality, and we believe a lot of the progress will translate to autoimmune. There has been increased capacity at treatment centers. Access has improved through outpatient treatment. The FDA has updated their REMS guidance in terms of monitoring. Importantly, there has also been quite a bit of commercial experience in the field and also reimbursement work that's been done for CAR-T. All of that will give us tailwinds in terms of KYV-101, which also fits perfectly with the attributes of our product. We can leverage the capacity at the sites. Our autologous model with a single dose fits in the familiar existing processes that exist. Importantly, also our product profile with no high-grade CRS or ICANS across 100 patients allows us and is conducive to outpatient treatment. On top of that, we continue to dose patients in clinical trials, which will build enthusiasm for the product. In summary, we have an attractive opportunity in front of us. We think there's a large addressable market in both diseases. We can set a new treatment standard in SPS, drive a new treatment paradigm in MG, and we have a really compelling opportunity in terms of the value story that we can build here. We can do this in an efficient, scalable way. The first mover advantage in SPS will allow us to hit the ground running in MG. Finally, the ecosystem has evolved in CAR-T, which we believe sets us up for a successful environment. In summary, we're uniquely positioned at Kyverna Therapeutics to be the first company to launch a CAR-T in autoimmune. We look forward to sharing more progress. With that, Warner, I'll turn over to you to wrap up today's presentation. Thanks, Dan. Thanks to all the presenters for an excellent overview of the scientific background here that we're building with KYV-101, the important unmet needs for patients, and also what we're doing here at Kyverna in order to continue to advance our programs to meet the needs of these patients. I hope everyone walks away from the three key takeaways that we talked about at the beginning of the presentation. First of all, and most importantly, we believe Kyverna is positioned to really take advantage of these opportunities. We're doing something fundamentally different here for both myasthenia gravis patients as well as stiff person syndrome patients. KYV-101 is starting to show, as the data matures, this really strong, durable, drug-free, disease-free remission in patients that patients clearly need an option for. As Dan started to outline, we started to put together the initial framework for our commercialization strategy. More importantly, there's a valuable commercial opportunity here in stiff person syndrome to start that really creates an opportunity for us to create some synergies in the neuroimmunology space so that we can continue to propel to our second follow-on indication with myasthenia gravis. Finally, I think it's really exciting that we unveiled this innovative registrational phase III trial. This is the first trial with under 100 patients using less than 100 patients in the myasthenia gravis space. The design of this trial is really innovative in that it allows for a prospective control despite the fact that it's difficult to do a placebo-controlled trial with CAR-T. We think this unique design is going to be very attractive to patients, and the size of the trial is going to allow us to execute this trial very, very quickly and enroll this quickly and rapidly as we move forward to a pathway to an eventual BLA. Overall, I'm really, really excited on behalf of the entire team here at Kyverna with the progress that we're making. There's clearly unmet needs here that Kyverna has an opportunity to be first and fast in terms of delivering. We're really excited about the progress we're making and more importantly about where we're going as a company. With that, we're going to take a little bit of a break, and we're going to actually open it up to some questions that are coming through on the question line. Thank you, Warner. At this time, we'd like to open the floor up for questions. As a reminder, you can submit your questions to the question submission box. There are a lot of questions that we have so far, so we'll do our best to address as many of them as time allows. Please give us a brief moment to gather the questions. Thanks, Jessica. While she's doing that, I'll also introduce, in addition to the team, Kyverna team that you heard presenting a few minutes ago, we also have Marc Grasso on the line, our Chief Financial Officer. He'll be joining us on the call as well. Welcome, Marc. All right. Our first question is from Tom Smith at Lyrinc. There's a couple of questions here, but we'll take them one at a time. For the Kyverna team, can you elaborate on the powering assumptions for the pivotal MG study and what you have assumed for treatment and standard of care effect on MG-ADL and QMG at week 24? Yeah, thanks, Tom. I think it's really critically important that we were able to take advantage of the unique aspect of KYV-101's significant clinical impact on patients and the huge effect size that we have. I think this is allowing us to power the study in a very effective way. I'll turn it over to Naji, who touched on some of these details in his presentation. Naji, maybe you could elaborate a little bit more on how we've incorporated that into this design. Sure. The study is well-powered to show it's well-powered over 90% to be able to show a co-primary endpoint positive that will allow for BLA. The important piece also in MG-ADL, as we know, an improvement of two points, as Professor Mukhedi shared, is clinically meaningful. QMG is an improvement of three points. We're well-powered to be able to show beyond that. On the question about the standard of care arm, those patients are on standard of care and are coming in the trial afterwards, remaining on the standard of care. We're aiming to show a superiority between KYV-101 versus the standard of care arm based on the powering that I just shared. OK. The next question is for Professor Shirin Mukhedi and Professor Aidan Haghikian. Can you describe the MG patients you think would be ideal candidates for KYV-101? Where will this live in the treatment paradigm? Reserve for truly refractory patients who have failed all other available therapies, or do you expect to use more broadly in less severe patients? Finally, what proportion of your MG patients would be ideal candidates? Shirin, maybe you want to start with that. Aidan, you can jump in after. Are one of you guys on mute? Thank you. The key question is that, you know, we will probably look for patients who are symptomatic. That's the first criteria. Patients have to have continued symptoms. If you're asymptomatic, this would not be really an option for you. Earlier clinical trials, as I showed in the complement therapy pipeline, the first drug was for refractory patients, and the second drug and third drug were not for refractory patients. Even though in this clinical trial, patients have to have failed at least one drug and remain symptomatic, in the future, I'm not sure whether we will always need refractoriness to be a candidate for these therapies. I think it's much more relevant regarding the degree of symptom burden and how disabled they are with the ongoing therapies and what a CAR-T cell therapy might be able to provide in addition, and above and beyond what we are currently able to do with biological therapies. Thank you, Shirin. As you already said, and also during our presentations, you usually start out with new approaches and are more careful and would like to have data and long-term data before we apply these approaches more broadly. As things are moving so swiftly ahead, I'm quite optimistic that at some point in the near future, this can be applied to a more broad range of patients when it comes to disease activity. For the time being, obviously, as outlined also in the trial, this is the patient cohort that we're looking at. I think what was interesting from my perspective, having worked in the heme CAR-T space in the past, is just this phenomenon of going to earlier lines of therapy and seeing improved clinical impact on patients and even more robust safety profiles as well. I'm wondering if you physicians could maybe comment as well as do you see that possibility happening here in the autoimmune space as well? At least in the U.S., I can speak to it. You know, when FcRn inhibitors were approved, they weren't necessarily used right off the bat as an early therapeutic option. Because they provide rapid improvement in symptom control, now we certainly use them very early, sometimes use it as a bridge to rapidly reduce the symptom burden. I think when you have a new therapy that comes across, becomes available, if it's safe and effective, and it has the kind of benefit that CAR-T promises, I really expect it to be used earlier and earlier. Totally agree. Yeah. Thank you. OK, we'll take the next question. This is from Derek Archulaf from Wells Fargo. Can you discuss how you think the control arm should perform in the pivotal MG trial? How have you powered the trial, and must all the patients in the KYV-101 arm need to come off other therapies to be viewed as successful? OK. That sounds like it's building on the previous question. I think the options in the control arm and how this reflects real world, I think, was some really careful thought that was put into this design. Again, Naji, maybe you want to provide a little bit more color specifically on the control arm and how it relates to the powering of the study. Sure. Yeah, I answered part of it. It's really the innovation, and this design comes in the second part of the question too. Patients will be off immunosuppressant and background therapy in the KYV-101 arm. This is really one of the big promises of our CAR-T, this ability to have a durable, drug-free, disease-free remission. Patients in this arm will be off immunosuppressants and background therapies. The powering versus standard of care is, again, it's well-powered, and it's based on the clinical effect size. If you go back and look at our compassionate use patients, like we've seen those patients moving, and Professor Shirin Mukhedi can comment on this, they dropped from seven points to zero. There's a significant drop in MG-ADL. Similarly, in QMG, we've seen them drop from 15 to 2 and even to 0 for 1. This clinical effect size made us comfortable and confident that we can build a trial while discussing with the agency to be able to show this benefit and the clinical effect size compared to standard of care, regardless of which standard of care patients are on, whether it's complement inhibitors or more traditional agents. Yeah, if I may ask, I completely agree, Naji. What, as I said, really surprised us was not only the depth of the efficacy, but also the swiftness. Usually, when you think of depleting B cells, you imagine that there is a lag until all the products of the B cells drop. What we usually see was rituximab and other B cell depleting therapies. This was quite striking, how fast we saw the translation into the clinical efficacy. This entails all the mechanisms that we heard about, which are B cell related. That's probably the reason. Great. Our next question from Derek is, would you expect all the MG patients in the trial to have stepped through FcRn and complement inhibitors? If not, what percent are you trying to enroll with these background therapies? Yeah, maybe Naji, you can comment on this. I know that part of the design is that we're allowing patients with different background treatment rates and different background treatments and immunosuppressants into this trial, including FcRn. That's not a limitation into this trial. Maybe you want to elaborate a little bit more on that, Naji. Yeah, correct. As you just said, Warner, FcRn patients can be included after a washout period, and then they need to transition to the standard of care that we're allowing in the trial. The main point is we're not looking at a population who have had FcRn inhibitors or complement inhibitors. There are patients who might have had the other standard therapies. An important piece is we're stratifying for biologics, biologic naïve or non-biologic naïve. We're not now sharing or looking at specific percentages, numbers in those, but the trial is allowing biologic naïve too. I think maybe just one point to add there is this, as Professor Shirin Mukhedi shared, that there is a lot of variation in clinical practice of how the cyclonic therapies are used. To Naji's point, we're welcoming all comers of all these types of therapies that are all being used for this disease. Certainly, there's no segmentation or cap for specific agents, but really a real holistic measure of how these drugs are being used in clinical practice. Thanks, Sham. OK, we'll take our next question from Sammy Corin from Lillian Blair. This question is for Ricardo. Could markers of holistic immune reset be used as early predictors of clinical response? Thank you for this question. It's something that we also are very enthusiastic about. I think we need better molecular biomarkers in translational trials and early development trials in autoimmune disease. This is commonplace in hematology-oncology, and it has lagged behind, unfortunately, in the INI space. I do think in the current scenario, it's not so likely to get established in the near future. I think as the landscape also at the agency changes again, then we might see this. I do see them as promising and potentially predictive. It's just about what the regulators also make of them. Great, thank you. Next question from Sammy is, the MG-ADL score of the patients at baseline is lower than in trials of Vyvgart and mRNA CAR-T cell therapies. Do you think the patients treated with KYV-101 were less sick, or is MG-ADL not always representative of the disease severity? I think the. Is that? Sorry, go ahead. I was going to just say that we're really targeting the moderate and severe patients in the clinical trials. We're also targeting that in these initial patients that we saw in the compassionate use program that you guys clearly outlined early in the trial. Maybe you want to comment specifically, Aidan, because you were helping us on designing the clinical study and ensuring we had a broad group of patients that could benefit from this therapy. Yeah, thank you. If this is based on our cohort, the compassionate use cohort, let's call them, as already mentioned by Dr. Mukhedi, the MG-ADL, as any clinical score, we don't have any perfect scores. It has some weaknesses. Besides being a quite subjective score, it doesn't distinguish between the severeness of the different deficits. You can have the same score whether you are just about to be ventilated as having ocular symptoms. It doesn't really do a, how do you say, grading of whether or not it's vital the deficit that you have or not. It has some deficits there, but also it doesn't show the dynamics of the disease. How fast, with the complement inhibitors and the FcRn inhibitors and three, you can add something to that. You see swift changes which go back again, and then you would need a median to really get the differing for that. That's one part of it. As you said, Warner, with this, we wanted to have with this score that is included in the inclusion criteria, we wanted to get some broad range of patients who have been treatment refractory independent of the symptoms they have reported. In that sense, the QMG is more objective, is more reliable. Also, the QMG has some weaknesses, obviously. Yeah. What I would add, thank you so much, Aidan. What I would add to that, in our phase III trial, as you've seen, the MG-ADL has to be 6 or more, and the QMG has to be 11 or more as an inclusion criteria to capture those patients. I think the question relates to exactly what you explained, Aidan, on one of the patients in compassionate use. Sri, you also talked about this. Depending on S3 that is impacting breathing, it's very different than three in the ocular. This is probably in the compassionate use, Aidan, as you just shared, why this patient was treated. Can I just add one thing? Of course. If somebody asks an outcome measure, I can't not stop talking about it. One of the challenges that we have is that in clinical trials, there is a subgroup of patients with the higher levels of score. Let's say you are ventilated. You cannot actually participate in a clinical trial because you are thought to be too unstable to be enrolled into a formal clinical trial. I think there is value in how we characterize patients, especially in compassionate use situations where you're able to capture disease burden that's specific for the patient. In clinical trials, it's a slightly different dynamic. Wonderful. We'll take the next question from Brian Chang at JPMorgan. This question is on SPS. A few questions here. First, how does the baseline of the KYSA-6 patients compare to the two patients that you have shown earlier? Were you in preparation for commercial launch in SPS? Can you remind us patients are currently diagnosed and identified in your market research? Thanks, Brian. I think we'll take that in two parts. Just getting to the clinical profile of the patients, I know that we are targeting patients that are similar to what we saw in the initial compassionate use program. Sham, maybe you want to provide a little bit of color on that. I'll turn it over to you, Dan, and you can provide a little bit more context around the numbers you showed around the size of the SPS patient population that we're targeting at launch. We know there's 6,000 diagnosed patients out there now, but we're targeting an initial group that are in highest need as a starting point and then use that as a bridge in terms of the rest of our launch plans. Sham, maybe you want to start with the patient profile and what we're looking at in KYSA-8. Thank you. What we can see in KYSA-8 is the patients have had to have failed at least one type of immunotherapy. Most commonly, this is IVIG. These patients are aimed refractory because they've got active disease while on immunotherapy. Their baseline walking time is in the high double digits. What's really important here is each patient in the trial is their own control. There were three time points before any intervention to really confirm that baseline change. This is now in comparison to a healthy person that is walking four to six seconds. In that instance, it's very comparable in terms of the magnitude of change that you've seen in the IH patients. Dan, do you want to take the commercial? Yeah, I mean. Yeah, Dan, go ahead. Sorry, Warner. In terms of the addressable market, as I mentioned in the presentation, we estimate there's approximately 6,000 patients in the U.S. Our initial focus will be on the highest unmet need patients that are treated today with immunotherapies. We believe we can have a high and rapid penetration rate in that segment of patients. Over time, as there's more experience with the product, we believe we can address virtually that whole 6,000 patient population. Great, thank you. Next question is regarding pricing from Brian. How should we think about pricing for KYV-101 given SPS is the first indication followed by MG? Yeah, thanks, Brian. As you know, we're not disclosing specifics around the pricing for KYV-101 at this point. It's too early to do that. I think we wanted to put up the patient impact and the total cost of care impact analysis that we started to pull together for both SPS and MG to really demonstrate that there's a huge cost burden on the patients. There's a huge clinical impact on these patients having to take all these therapies and still not resolve the course of their disease. There's a huge cost to the system as well. Just in drug costs alone, IVIG can cost hundreds of thousands of dollars a year. We know that the FcRn inhibitors and complement inhibitors that are now being used more routinely in myasthenia gravis can cost patients and cost the system hundreds of thousands of dollars a year. Overall, we believe there's a really strong value proposition here for a one-time, potentially curative therapy that not only is able to remove these background therapies to patients, but more importantly, actually get them to a disease-free state so they can actually improve their quality of life and begin to contribute back more to society on a more constructive level. Dan, I don't know if you want to add anything further to that, but I know that we're going to continue to evolve our pricing research. Obviously, looking at the final clinical data that we have in the clinical trials will help us finalize that as we get closer to launch. Yeah, exactly. I think you've covered it, Warner. Great. Thank you. Our next question is from Michael from Morgan Stanley. In terms of durability, you have patients responding for more than two years so far. What do you think the ultimate durability could be, and could it be different from different diseases? That's a great question. I think we're all very excited to see some of these initial patients now reach this two-year mark or coming past the two-year mark in both of these key indications. If we can relate this to other diseases where CAR-T cell therapy has been used on the hematological side, we know there's a tipping point once patients get to this two to three-year mark where these Kaplan-Meier curves tend to flatten out over time and truly is indicative of a long-term potential of a cure, which I think is ultimately exciting, really exciting for all of us. Maybe I'd let the physicians comment a little bit on this from their perspective because they're seeing these patients. They're seeing this in relation to other therapies that they've used in the past. Obviously, we're getting to something here really transformative as the data continues to mature. Maybe I'll start with you, Shirin, and your perspectives on what the long-term potential for durability could be for these patients. It's a great question. The field hasn't had an opportunity to decide on what is considered optimal just because we haven't had therapies that could offer the potential that CAR-T does to date. I think the reality is that we're hoping for at least a one-year relatively symptom-free and therapy-free state. I think that would be a great achievement by itself. It's entirely possible post one-year or longer period if you achieve both of those disease-free and symptom-free states. I think that's amazing. It's also possible that there might be some return of symptoms, but these patients who are on multiple therapies have a much more simplified and easy-to-navigate therapy post one year or longer. That is also a plus because these are patients who are on multiple therapies with complicated dynamics of scheduling things. If you sort of take that patient and then provide them symptom-free state for a period of time and then get to a much more simplified, easily manageable therapy, I think both of those or a combination of them. I think most patients would want that. I think most physicians would look at that as a major win. Thank you, Shirin. Aidan, I don't know if you want to comment at all from your perspective and how you're seeing this. Yeah, I mean, we are learning as we are observing these first patients, obviously. We have still a lot to learn. Looking at the first patients that were treated by Dirk Schetz, who have now exceeded three, four years with SLE, these are obviously not new immunological diseases but share some similarities. We can be optimistic that we may see even more than two or three years. I agree that at some point, we will have to start stratifying those patients and maybe find markers who are long-term and longer-term responders and those who may need also a second infusion at some point, which is still a significant improvement to what we have now. Thank you. Thank you, Aidan. Ricardo, I don't want to leave you out here. I know you've also had some thoughts on the underlying impact that CAR-T is having on the course of the disease. Maybe that's why we're seeing these clinical results that we're starting to see in the clinic. Yeah, that's true. I mean, if I reflect on our cohort here in Erlangen, which comprises more than 50 patients across different autoimmune diseases, the vast majority of them is in a drug-free remission state. Even though the longest follow-up now is not quite five years yet, and certainly the median follow-up is well below that, I think we're starting to see a clear picture that the response rate and the durability of drug-free state is much higher than what we're able to achieve with conventional therapies. It's much more consistent across patients. There is always this one patient that responds very well to a standard therapy and stays in remission for a longer time. We've never seen this really so broadly across the bank in so many patients. I think that this is something that's unique to the therapeutic approach and not to the specific patient population, which shows also that it can very likely be more generalized to a broader patient population. I think, I mean, as a community, we don't want to set the bar too high. I think, you know, it doesn't matter in the end if it ends up being 80%, 85%, 90%, 95% after five years or so. It's just a transformative outcome that's moving the field forward and helping many patients and achieving a result that they previously were not able to achieve with other therapies. Well said. Great, thank you. We'll take the next question. This one's from Mitch Kapoor from HC Wainwright. This is on the phase III study for MG. You've selected MG-ADL and QMG at 24 weeks as co-primary endpoints. Why 24 weeks? Is that enough time to show durability for a one-and-done therapy? Do you expect regulators to want longer follow-up for that approval? Yeah, I mean, we've actually been in constant contact and regular contact with the FDA through the RMAT designation, which has allowed us to finalize this design. We have high confidence that this is going to be acceptable as a primary endpoint by the FDA. 24 weeks is actually a fairly standard endpoint in measuring the effect of treatments in the MG space. We feel very confident this is going to provide a consistent benchmark that we can have some relatability across different therapies as we sort of get to the end of the clinical trial. The other comment I will add as well is that we're going to continue to follow these patients, as Naji indicated, officially out to 18 months. We're also going to be tracking these patients over the long term to see the impact of this long-term durable effect that we just talked about in the previous question and how long this can translate into this cohort of patients over time. Naji, maybe you want to add a little bit more color to this as well because I know this is something we've been thinking about as we continue to advance the trial and look at the long-term impact that KYV-101 is having. Yeah, I think you covered that, like it's a used 24 weeks, something that is used. It's also differentiated for us because we are looking versus standard of care arm, which is an important milestone to read out the primary endpoint. It's FDA. We discussed with the FDA, so it's also aligned with FDA expectations. We will follow up to longer term. Another important piece is also we wanted to give the opportunity for patients on standard of care to move and cross over to KYV-101. We also followed up to 18 months. We wanted to make sure that this 24 weeks is long enough to show the durability, but also that patients can cross over and have the opportunity to have KYV-101 after. Thank you. Our next question is from Noah Eisenberg of UBS. This one's on phase III trial for MG. You mentioned that the phase III trial was well-powered. Just to clarify, is this trial powered to show superiority over standard of care or just non-inferiority? It's powered to show superiority. As Naji indicated earlier, we've got a 90%+ power on both of the co-primary endpoints that were outlined. OK, great. Another one from Noah. Can you speak to patients with MG or SPS willingness to go through reconditioning? Yeah, I'll let maybe Naji start and Sham start as well because he was close to this on the SPS side. We could also get the physicians' perspectives on this. Naji, maybe you could start. Yeah, and we're seeing it through our trial enrollment, right, where we have SPS has been enrolled. Patients without any other FDA-approved therapy, obviously, are eager to have an opportunity for a drug-free, disease-free remission. It's the same across either KYSA-6 or also the compassionate use patients. I'll hand it over. I'm sure Aidan, you have a perspective also on this. And Ricardo, Shirin. Aidan, I'll hand it over to you first since you treated the knees and others. Yeah, I mean, from previous experience with this severe and later on also with the study cohort, the patients have been surprisingly compliant. Keep in mind, these are patients who have undergone multiple different immunotherapies in the past, and they're used to having also cytotoxic treatments. Also, keep in mind that in neurology, those dosages that we're using for the lymphodepletion are quite low still. I mean, we're talking about cyclophosphamide, which is a fraction of what we use, for example, for vasculitis and other autoimmune diseases. So far, this hasn't been any concern or any limiting factor from the clinical practice. Thanks, Aidan. Shirin, anything to add? You know. I think there is a lot of interest in patients from the published data. I think patients tolerate these reconditioning fairly well, so much so that there are conversations among CAR-T programs about whether some of these treatments can be given as an outpatient. I don't see that as the main limiting factor in adopting these therapies in the future. Sham, I know you were looking at this from the SPS enrollment perspective. We enrolled that trial very quickly. I don't think that was a hurdle at all for these patients coming into the trial. Absolutely. I mean, we were oversubscribed. We were turning patients away. We were able to over-enroll that trial, finishing in seven months. Certainly, just three doses of KYV-101 is not perceived as a barrier at all for patients that are used to having chronic treatment. Effusions, you know, bi-weekly for the lifetime of their disease. We see this as a very trivial step, and as Shirin is saying, there's a big push now for many centers to now deliver this as an outpatient. Yeah, I think that's a really important concept, that the patients here that we are addressing have got a huge burden with the existing disease and all the chronic therapies that they're having to endure, versus this one-time, low dose of lymphodepletion. The other point that didn't come up here in this dialogue is that we're also exploring alternative lymphodepletion regimens, including the use of bendamustine and others. I know this is something that we're going to continue to generate data on that will help us explore other options for patients as they go through this step. Hey, great. We have a couple of questions from investors, so we'll do those first, and then we'll turn it back over to a few more analyst questions that have come back to the queue with additional questions, and we'll take those as time allows. First question from investors. This one is for the KOLs here. How does incidence of CRS and ICANS compare in oncology versus neuro autoimmune disease? Sure. Aidan, do you want to start with that? Shri, maybe you could follow up with that? Yeah, so far it's much, much lower because, I mean, we as neurologists are involved also in the hematology-oncology cases. I mean, in Germany at least, I don't know how it is in the U.S. Each patient that is infused with CAR-T cells for any oncology indication is observed by us, and it's no comparison so far. Obviously, we don't have the numbers yet. We have to wait and collect and observe and be vigilant. Also, looking at other autoimmune diseases, as in rheumatology, in SLE, and myositis, it seems to be a different game, which is probably, we don't know yet for sure, probably due to the much lower cell burden that is depleted and less cell debris and cell compartment that is released. Yeah, but so far it's not comparable. It's much, much lower. Yeah. I agree at our center too for the ICANS part of the sort of the potential short-term complications. The neurology team is routinely involved, and from our experience, it's really very, very minimal in terms of these kinds of complications in patients with autoimmune diseases. Thank you, Shri. I think it's important to note that the selection of KYV-101 as a construct and why we were excited here at Kyverna to leverage this and license it in from the NIH is because of the specific work that was being done to design a potent CD19 CAR-T cell therapy, but one that was also designed for improved safety. I know, Ricardo, you were commenting on this a little bit in some of the preparations for this meeting, just the fully human design and how that could actually help, in addition to the diseases that we're studying, but the actual construct we have here in terms of the overall safety. I don't know if you want to add any color to that as well, Ricardo. Yeah, sure. What I can add is I think, in our experience, we have seen immunogenicity of mouse-derived, so essentially humanized, CD19 binders. If you have a fully human construct, then naturally the immunogenicity of such a construct is lower. That's of course important for patients with autoimmune disease that are prone to mount also an autoreactivity, and can mount an immune response against the CAR, which could lead to treatment failure, similar to in our patient that we had to retreat. I think this is definitely an advantage. With regards to the co-stimulatory domain, the data from oncology is very compelling on CD28 for autoimmune. It's therefore differentiated and more data will then show this in the clinical trials. Great, thank you. The next question is, looks like it's for Professor Shirin Mukhedi. Can you speak to the CAR-T infrastructure at Stanford? Do you feel academic centers like Stanford can manage both autoimmune and oncology CAR-T patients, i.e., capacity, staffing? Short answer is yes. At Stanford, we have a model where we have a CAR-T specialist and a disease specialist. For example, myself, my senior specialist, or MS specialist, and then there is a CAR-T specialist. We work as a dyad model for any of these studies, and we expect to do the same going forward. There is not only a bandwidth, but it's actually an interest in expanding the CAR-T program to include autoimmune diseases going forward. We are participating in many of the trials, and we hope to have these available for our patients and expand that program. I suspect many of the large academic centers have a similar model or plan to have a similar model to accommodate the rapid developments in the field. I think it's something that is so novel and so new, and most centers are trying to figure it out. Most large academic centers, I'm confident, will have a program that can meet the demand and the need of these patients. Thank you, Shirin. Dan, I know we've been doing some research here looking at the expansion of CAR-T centers beyond Stanford across the U.S. I think that's an important thing, that it's not just in Stanford alone, but other centers are also gearing up their capacity and their systems. I don't know if you want to elaborate a little further on that. Yeah, no, I think, Warner, it's consistent with what was just said in terms of the early market research we've done, as well as the data that's out there through other sources. We see the capacity growing and also have received a lot of feedback that centers are building additional capacity in anticipation of autoimmune CAR-T. Agreed. I think the other thing to keep in mind too is we advanced KYV-101 and we know the safety profile is predictable and well managed in the majority of patients. This really lends itself well to an outpatient setting, which is something we're going to continue to look at as we advance our development program. This is important because it also allows us to use the existing capacity and expanded capacity in an even more efficient way. If those patients don't require as big of a burden on the hospital system while they're going through therapy, that means the hospitals and these academic centers can treat more patients. I think both those things working together is going to expand capacity over time for patients. I'm seeing some of those trends now, and it's going to help us when we're getting in a position to launch. Thanks, Warner. I think we have time for probably one or two more questions. Next question, I think the next question on SPS. This is from Derek Archilla, Wells Fargo. For the Kyverna team, with respect to the SPS compassionate use data, it appears you have autoantibody levels for patient number two out to 16 months, but mobility follow-up to nine months. Is there any update you can provide on the mobility for this patient beyond the nine-month time point, even if qualitative? Yeah, Sham, maybe you want to take that. I think the question's kind of highlighting some of the limitations around the IH program, but please jump in here. Yeah, so the patient is doing well. I think to Warner's point that this was a compassionate use patient, so we don't dictate the timings of investigations and what investigations are done at each time point. At that 16-week time point, there was no walking speed measured, but the antibody titer was taken. Overall, the macro view is that patient has continued to improve. Yeah, I would add they are still off immunosuppressants too. In the next question, given it takes years to diagnose SPS patients, does Dr. Dholakia believe an approved treatment will help that time shorten? What are the challenges in diagnosing these patients? Is it a misdiagnosis or lack of awareness? Sham, maybe you want to pick up on that one. Go ahead, Sham. Certainly, the historical nature of SPS, it wasn't something that was taught at medical school or if you'd even just done generalized neurology, and you would have had to have done an autoimmune neurology fellowship to understand what that disease was. That is a changing paradigm where we now have patient advocacy from the SPS Research Foundation. We have increased awareness across the world in terms of more data and emerging papers coming out from key centers. Also, now, obviously, a spotlight on the disease with a celebrity now coming out about a disease to really allow this patient advocacy and empowerment. In concert, what's also really important here is that access to testing has changed considerably over the last several years, where this antibody was measured originally at the Mayo Clinic, but now you have large stream labs such as Labcorp, ARUP that are also able to carry the test. Access to testing to allow patients to get their GAD antibodies tested is much more standardized and accessible. This is now proved with an overall improvement in education for the clinician as well as patients to allow patients that may have been mislabeled with historic neuropathies, anxiety, or another neurological disease to be correctly managed as a stiff patient first. Great, thanks, Sham. We will now be concluding our Q&A session. I'll turn the call back over to Warner for closing remarks. Warner? Thanks, Jessica. I want to thank everybody for staying on and for such a robust set of questions. There's obviously huge interest in what we're doing here at Kyverna Therapeutics. I also want to thank all of our speakers, Ricardo, Aidan, and Shri. Your expertise, both from a scientific perspective and your clinical perspectives, were really, really valuable here, not just in terms of the presentations, but I think adding additional color around the questions we were getting from the investors and analysts. I do want to thank my team, all the speakers here, Sham, Naji, and Dan, and Marc for coming on for Q&A, as well as the entire team that's helped us prepare for today. We are obviously very, very excited about what we're doing here at Kyverna Therapeutics. We really believe we've got a potential here to deliver something unique for patients that desperately need new therapies, both from a stiff person syndrome disease state as well as from the myasthenia gravis side. We really believe we've got an opportunity here to be first in class and best in class with this neuroimmunology focus that we have that's allowing us to use our resources in a very efficient way to come to market and address the needs for these patients. As we talked about as well, there are really attractive commercial opportunities here for these initial indications. Us being first, I think, allows us to tackle these prevalent pool of patients that are waiting in a very cost-effective and also adding a huge value to the system from a health economic perspective. We're really, really excited about the advances we've been making so far. Also excited about, as I alluded to earlier in my presentation, this being the first building block that allows us to build on for future advances in our pipeline, both in terms of the next generation construct KYV-102, as well as advancing into other diseases and indications where CAR-T cell therapy could have huge benefits for patients. Thanks again, everybody, for joining us. I'm very, very excited to have you all here and for the tremendous interaction here over the last couple of hours. We look forward to updating you further on our progress as we continue to advance our clinical development programs. Thank you. Thank you, Warner, and thank you all for joining us today. You can find a replay of today's webcast, as well as accompanying slides, on our IR website. We look forward to seeing you at the Morgan Stanley, Wells Fargo, and HC Wainwright conferences coming up in a few weeks. Have a wonderful day and a holiday weekend. Thank you.