Good afternoon, everyone, and welcome to 2025 Jefferies Healthcare Conference. My name is Nausicaa Zunini. I'm from our Healthcare Investment Banking team, and it's my pleasure to introduce you to Warner Biddle, CEO, and Naji Gehchan, CMO of Kyverna Therapeutics. Just a reminder, this will be a 25-minute presentation.
Thank you. Good morning. Good afternoon, everybody, and thanks for having us here. My name is Warner Biddle. I'm the CEO of Kyverna and really excited to give you an update on the tremendous progress that we're making as we continue to pioneer and lead the way with CAR T therapies in the autoimmune disease space. This is our standard disclaimer for forward-looking statements. At Kyverna, we've got a bold mission. We want to transform the lives of autoimmune patients through the curative power of CAR T therapy. We believe we're uniquely poised in order to make that happen with a number of key attributes that we've been assembling around this organization, starting with our unique CAR T construct, KYV-101, that has been uniquely designed to work in autoimmune diseases, both from an improved safety perspective but retaining a potency and efficacy perspective as well.
We've now treated over 100 patients across a variety of different autoimmune diseases. We see no high-grade CRS or ICANS, and the results that we're seeing in these early patients have really de-risked and really set us up for some positive success in our pivotal clinical studies in stiff person syndrome and myasthenia gravis. In addition, we have a clear pathway in both of these indications with the FDA that will allow us to not only be first to launch a CAR T into stiff person syndrome and myasthenia gravis, but could put us in a position to be the first to launch a CAR T into the autoimmune space, period. In addition, I'm assembling around me, in addition to Naji, others with late-stage development CAR T experience as well as manufacturing experience that will allow us to pull through on these key milestones.
This is a summary of our strategy. We've got a really focused strategy over the next few years, starting with a neuroimmunology benchmark and platform with stiff person syndrome and myasthenia gravis. This will give us a chance at this first mover advantage and establishing Kyverna as a leader into the space. We'll continue to broaden our patient access with our next generation construct, which is KYV-102. This is a whole blood rapid manufacturing construct that will make it easier for patients to get access and reduce our overall cost of goods.
Both of these early strategic components come together as we look further down the line, and some of the early results that we're seeing in larger indications like MS and RA give us a lot of excitement that we can bring these therapies to larger patient pools that have desperate unmet patient needs and that really require new therapies to come to the market. There's a lot of therapies being studied in these spaces, and I think it's really important to really ground ourselves in why KYV-101 and why CAR T therapy could be transformationally different. I think a lot of therapies treat these diseases from different angles. Some of them are B-cell depleting. Some are treating the antibodies or controlling for the antibodies.
What really separates KYV-101 is this ability to treat the diseases at its center, getting this deep B-cell depletion in targeted tissues, giving patients this chance at this long-term durable remission with a drug-free remission, which sets us apart from a really unique perspective from all these other competitors being studied in these diseases. We're starting to see that bear out in the clinical setting. These are the first two patients that have been treated with KYV-101 in stiff person syndrome as well as myasthenia gravis. You can see here in both of these patients, one's approaching two years, one's now past two years with significant clinical reduction in terms of their clinical symptoms.
In conjunction with that, being able to eliminate their background immunosuppressants, the background therapies that they've been burdened with chronically for years, and really set them on a new trajectory and a new perspective in terms of how to manage these conditions. Based on these early results, we've set ourselves up from a strategic perspective with this neuroimmunology focus in both stiff person syndrome and myasthenia gravis. Both of these diseases have compelling initial clinical data, but we're also matching this up with high unmet needs. In stiff person syndrome, there are no approved therapies. With myasthenia gravis, there's still unmet needs even with the therapies that are there.
We believe we have a first mover advantage that we can bring KYV-101 to this marketplace, really setting ourselves up from a commercial and payer perspective, as well as actually using a shared infrastructure and a lot of synergy across these diseases as we continue to advance these products closer to market. In addition, if you take a look at how these patients are being managed in their current condition right now, both from a stiff person syndrome as well as myasthenia gravis, the cost per year to manage these patients is in the hundreds of thousands. Chronic IVIG, FcRn inhibitors, complement inhibitors cost the system, whether you're here in Europe or in North America, hundreds of thousands of dollars from just the drug therapies alone.
When you add on top of that the additional cost for care, the psychological treatment that many of these patients are under, the lost time for work, the health economic benefits of CAR T therapy, and specifically KYV-101 are tremendous in terms of what we could do here in transforming these diseases. This really sets us up for the near-term catalyst that we're focusing on as an organization. For stiff person syndrome, this is our first indication, which we have moved up our top line guidance to read out in the early part of 2026 with our pivotal clinical study and our BLA filing in the first half of 2026 as well. With myasthenia gravis, we've now demonstrated and shown our interim phase two results, and that's allowing us to pivot to a registrational phase three design, which we have FDA alignment on.
We have started enrollment, or we are indicating we will start enrollment by the end of this year in terms of that pivotal study. In addition, we continue to track the tremendous results we are seeing early on in MS as well as rheumatoid arthritis as well as lupus. These provide a gateway and an aperture, if you will, to additional indications that are larger and where the value of KYV-101 could have a bigger impact on a larger group of patients. As I indicated earlier, we are on track to file our IND for KYV-102, which is our next generation construct before the end of this year. Diving in a little deeper on stiff person syndrome, because for a number of us who may be unfamiliar with this disease, I think it is really important to note this is an autoimmune B-cell mediated disease that really has tremendous potential.
There are no approved therapies, as I mentioned earlier, in this disease. What patients suffer chronically over time is a progressively worsening of their disease, starting initially with just spasms and maybe facial tics and lower limb spasms that progressively get worse over time. The natural course and history of this disease is that patients will eventually have difficulty walking, will require walkers or wheelchairs, and many of them, over 80%, will become bedbound. The patients' progressiveness and worsening of their disease is horrific in and of its own. These patients also endure a number of psychological components of their disease because of their fear of falling. They end up not leaving the house. They end up reducing their social networks and really have restricted lives.
There is a really tremendous potential here for a new therapy that will treat the underlying course of this disease and really open up the lives for these patients. Unfortunately, what patients are being exposed to now in terms of treatments are just unsatisfactory. Pain medications, antispasmodics, IVIG are chronically used in different combinations with these patients, sometimes immunosuppressants as well. The natural course and history for these patients just gets progressively worse over time. This is why the results that we have seen with our first two patients with KYV-101 are so remarkable. This shows you a graph of the first two patients that were dosed with KYV-101.
You can see their initial scores in terms of their time 25-foot walk, which is the amount of time it takes a patient to walk 25 feet, which is a validated clinical endpoint in a number of neuromuscular conditions like MS. You can see in these patients, they were in the high teens to low 20s. After a single dose of KYV-101, after a number of weeks, you can see these patients' time 25-foot walk test significantly reduced by over 50%-60%, down into sort of the 7-8 second range. Just to put this in perspective, a normal person like you or I could walk the time 25-foot walk in about 5 seconds.
Although these patients are not quite at the normal range yet, you can see a significant reduction in terms of their time 25-foot walk and actually puts them in the perspective of getting back to close to a normal life. If you couple that with what is on the right-hand side of this graph, I think this is what is truly remarkable, is these patients have been on a number of background immunosuppressants and background therapies, and in both of these patients, we are able to eliminate those. Eliminate coming off their background therapies and actually have this transformative clinical impact, which again, I think really separates what KYV-101 can do from a clinical perspective and really differentiates this from other therapies in this market and space. This is a summary of the pivotal clinical study that we have ongoing now.
It is fully recruited and dosed, so we're just preparing to read out this data, as I signaled earlier in the first part of 2026. We're on track to file the BLA in the first half of 2026 as well. The primary endpoint here being the time 25-foot walk test, which you saw on the previous chart where we have this significant impact on patients. We're also measuring key secondary endpoints as well, like the MRS scale, which is again a standard ranking scale, as well as stiffness indexes as well in these patients. The totality of these primary and secondary endpoints, I think, are going to tell a really compelling story about what we're doing with these patients.
In terms of the size of the market and the market opportunity for stiff person syndrome, I think we've learned a lot over the last couple of years with regards to the epidemiology of this disease. It was once thought to be quite rare, but probably less rare than what was initially indicated. We believe there's now 6,000 patients that have got a confirmed diagnosis in the U.S. We've looked at this both from an ICD-10 code perspective as well as independent epidemiological studies through the University of Colorado and others are being published that show the natural history of this disease as well as confirming the size of this patient population. We believe this is a significant opportunity, particularly for a young company like ourselves where there's no approved therapies.
If we can actually come to market and address a significant proportion of these patients, it really sets us up for building a foundation to a larger set of indications like myasthenia gravis and others further down the line. This is how we break down those 6,000 patients. We know that between 2,000-2,500 patients are severely refractory to existing medications. We believe those are the low-hanging fruit, if you will, when we come to market, at least initially. We know that the remaining number of these patients are progressing over time. With improved education, improved access to CAR T therapies, we believe these patients will be addressable as well.
Taking a couple of minutes and diving into our second indication with myasthenia gravis, we believe this is another important disease that, despite existing therapies that are in the marketplace right now, we know that patients have inadequate symptom control in between 30%-50% of the patients that are being treated right now. Few of these patients actually meet or reach minimal symptom expression or MSE, which is the ultimate goal in treating these patients. They want to move on with their lives and not be burdened by this condition. The ultimate goal is to get them to MSE. Few patients actually reach that point at this point. All of them require chronic therapy. They require chronic ongoing immunosuppressants and background steroids, even as they layer on top the newer therapies like the FcRn and complement inhibitors.
All of these therapies, obviously, not only from a treatment burden perspective, are costly to the system, which really sets up a real, I think, unique and unmet need here that KYV-101 can address. This is our value proposition, and this is why we're really, really excited about the clinical progress we've been making thus far and why we're really excited about how we're advancing this in the clinic. We believe that KYV-101 can do something very, very unique here, not only reducing and improving the symptom control and doing it safely in patients, but getting more of these patients to MSE, giving them an opportunity to remove their background therapies and doing this with a one-time therapy where they can also reduce all these other chronic therapies.
This is a very unique value proposition that I think changes the paradigm in terms of how MG patients are being treated right now. Again, we're seeing these really transformative results coming through on our early clinical results. This is an update on our interim phase two results that we presented a couple of weeks ago at AANEM. You can see here not just significant clinical reductions in MG ADL scores and QMG scores, but seeing the significant reduction as early as two weeks in being sustained over the 24-week period and even beyond. These are interim results, so not all patients have reached the 24-week period. We will read out the entirety of this data set in 2026 as these data continue to mature.
In addition, what's really remarkable is that we've seen all patients respond at this point, 100% of patients responding, seeing clinically and statistically meaningful reductions in their MG ADL scores and their QMG scores. We're getting more patients to MG or getting more patients, rather, to MSE, which is this ultimate goal that patients want to achieve. At this point, even at this interim result, we're seeing 67% of patients getting to that point, which is really remarkable. We're also reducing their treatment burden, 100% of patients getting off of background immunosuppressants, reducing their steroids to below physiological levels, which is actually critically important for them from a treatment burden perspective. Again, doing this with a really manageable and consistent safety profile that we've seen in the other 100+ patients dosed up to this point.
This gives you some perspective, and this is not a head-to-head study, of course, but looking at what other available therapies are doing in this marketplace, you can see a significant reduction in terms of the depth of response, both in terms of the MG ADL and QMG score reductions. Reductions of 8 and 7.7 at 24 weeks are truly unprecedented in this space. It gives you an idea of the effect size that we're seeing in this patient population and how we're thinking about the design of our clinical study. In addition, 100% of patients are responding, as I said, and we're getting a significantly greater number of patients to MSE, even in this immature data set, which is really, really exciting for us.
This really de-risks and I think really gives us a lot of confidence that we've powered our phase three study and our pivotal study in a really meaningful way. This greater-than-expected magnitude of effect, as well as this ability to have this deep and sustained effect with patients over time, gives us confidence that our interim phase two results will translate into a strong pivotal phase three result as well. This is the design of our phase three trial design. We released this a few weeks ago, but we believe this is a really unique and bold design that allows us to compare KYV-101 versus standard of care. Patients will be washed out at the time of screening and assessed and randomized. They will then go back on standard of care or KYV-101 and the primary endpoints at 24 weeks.
We will be measuring both MG ADL score reductions as well as QMG reductions, which is the data that you saw earlier. The standard of care patients will actually have the opportunity to cross over at 24 weeks and come back on KYV-101, which we think will give us additional data and insights into these patients. I think it has been actually a big part of the ability to recruit and attract patients into the study, given the unique design here that we have been putting forward. In terms of market opportunity, the myasthenia gravis market is significantly larger than the SPS market. Even with the additional therapies that are in this market and space right now, we know that up to 50% of the MG-treated patients, or about 40,000 patients, have these significant unmet needs and are refractory or inadequately responding to current standards of care.
We're targeting patients in our clinical study that have failed an immunosuppressant and failed IVIG or plasmapheresis or failed two immunosuppressants. Patients that have failed FcRn inhibitors and complement inhibitors will also be included in this study. We'll have a wide range of patients in the real-world setting that we'll be able to see the true impact and effect size of what KYV-101 can do. This will allow us, I think, access into a large proportion of these patients as we continue to move towards commercialization. In addition, and I don't have time to go into details here, we're really excited by some of the initial data that we're seeing in the MS patients that we've treated. We've now treated 11 patients through our IIT program and compassionate use program.
At this point, seeing all patients respond and having a stable or improved EDSS score, which in primary progressive MS, I think, has been unheard of up to this point. Some really transformative results that we're seeing in these MS patients, as well as reinforcement that our safety profile in this neurological condition can carry forward as well. In addition, we've also read out part one of a phase I study in rheumatoid arthritis and seeing significant clinical responses in patients with refractory RA that have been treated on multiple treatments chronically for a number of years.
In the initial follow-up that's going between 28 days here to 175 days, we're seeing four of the six patients actually reach the ACR 20 response, and two of these patients actually achieving an ACR response of 50 as well, which, again, for a relatively immature data set and in a chronically treated refractory patient population that we're addressing here, some fairly remarkable results that continue to keep us excited about this larger indication as well. This gives you a summary of our priorities as a company. We are focused on stiff person syndrome and myasthenia gravis in this interim period, as well as the filing of our IND for KYV-102. These become the key priorities for us in 2025. You can see that we continue to execute on these priorities and keep this as an initial focus.
These additional opportunities, we're continuing to keep an eye on as well. As the data continues to mature, we're continuing to assess how do we want to move into that third and fourth indication as a company and really take a look at what the opportunities are for us as we continue to evolve. In summary, we are really proud of what we're doing as a young organization. I think we are doing something here remarkable, bringing these therapies quickly and with this first-mover advantage with KYV101, have this opportunity to deliver this really durable, drug-free, disease-free remission in patients and doing it with a one-time therapy. We believe this is really transformative.
We have an opportunity here to be first in class, not just with stiff person syndrome and myasthenia gravis, but be the first CAR T company to bring these to the autoimmune space in general, which is a really, really important milestone for us. In addition, it really creates an opportunity for us to set the bar commercially from a pricing and market access perspective, as well as the relationships that we're going to continue to create in these key academic centers with these really attractive market opportunities, particularly if we can be first to market in these prevalent patient pools. We're in a very, very strong financial position. We have a cash runway that takes us into 2027. It's been reinforced by some recent debt financing that we announced a couple of weeks ago.
We continue to advance our future pipeline opportunities because we know that the power of CAR T therapies to go beyond these initial neuromuscular conditions is huge. The potential for us to be first and continue to pioneer that continues to make us excited and gives us confidence that we can continue to have an impact more broadly in this disease space and more broadly across this industry. With that, I will end the presentation. Thank you very much.