Kyverna Therapeutics, Inc. ($KYTX)

Go ahead and get started. Good morning, everyone. Thanks for joining us here at the Leerink Partners Global Healthcare Conference. My name is Tom Smith. I'm one of the senior biotech analysts here at Leerink. It's my pleasure to welcome our next company to the stage, Kyverna Therapeutics, represented by CEO, Warner Be. Warner, thanks for joining us.

Thanks. It's great to be here, Tom. Thank you.

Awesome. And I just want to -- I mean, Kyverna made huge progress in 2025. You reported positive top line results from your pivotal study for your autologous CD19 CAR-T therapy, miv-cel in Stiff-Person syndrome. And we're entering a really exciting period, potentially transformative period in '26. We're expecting BLA submission and potential to address a huge unmet need and a really significant rare disease. So huge '26 coming. Warner, maybe you could just kick us off with some highlights from '25 and then progress in early '26 and what you're looking forward to here over the next 12 months.

Sure. Thank you, Tom. It's really great to be here. As you know, my leadership team and I did a transformative amount of work over the last 18 months to put us in a leadership position, but also differentiate us from the other companies that are operating in this space. And we're doing this in 3 important ways. First starting with our construct. miv-cel is a unique construct. It's been specifically designed as a second-generation CAR-T for potency and efficacy as well as significantly improved safety profile. And we're actually in terms of the second point of differentiation, bringing this transformative therapy to patients first. We're starting with syndrome, as you indicated. This is a rare disease, but one that has high unmet medical needs and is highly debilitating for patients. And what we've seen and read out at the end of last year was simply transformative results in these patients, not only improving the clinical symptoms, but for the first time ever showing that we can reverse the course of this disease. And so we're heads down on track for filing our BLA in the first half of this year, which leads me to the third point of differentiation, which is our pipeline. Stiff Person Syndrome is a valuable commercial opportunity on its own -- but in addition, we're looking forward to actually building a neuroimmunology portfolio and franchise -- moving to myasthenia gravis, where there are significant unmet needs for patients despite available treatments, and we're on track in enrolling our pivotal Phase III trial in that indication. And we're also seeing some really promising early data in other indications like progressive MS, where we're seeing transformative data for the first time with this indication. So we're really excited about the progress we've made, really excited about the pipeline and what we have in front of us, and we're really excited about leading this and bringing this to patients first.

That's awesome. Maybe just start and kind of level set for some of the audience who may be less familiar. Just talk a little bit about the construct. We've dosed now in over 100 patients. Seeing I think, quite remarkable safety profile, right, like low-grade CRS, low-grade ICANS, maybe just talk a little bit more about the differentiating aspects of the construct and the totality of the data that you've generated.

Yes. Well, it is a very unique construct. We in-licensed this construct from the NIH as a next-generation CAR-T. And it was specifically modified in a couple of key ways. First, it's a fully human design as well as some CD8a hinge and transmembrane has been replaced versus some of the older CAR-Ts. And what this means is that it actually is a safer profile. We've actually seen in the head-to-head studies with traditional CAR-Ts a tenfold reduction in terms of ICANS and CRS, which is bearing itself out in the clinic in 10 treated patients as you've indicated, we have no high-grade CRS or ICANS, which is remark and really translates us and puts us in a position when we get to commercial stage that we can use this in an outpatient setting, which I think is going to be really important when we get to treat autoimmune diseases. But in addition to that, one of the other differentiating factors for miv-cel is the fact that we're the only CD19 CAR-T in the autoimmune space that also has a CD28 costimulatory domain. And we believe this is really important because it gives potent B cell depletion and really giving patients a chance of an autoimmune reset, which is why I think we're seeing these transformative long-term durable results from the clinical patients that we've been treating so far.

Yes. That makes sense. Let's talk about Stiff Person Syndrome. And this is -- it's a rare disease. I feel like it's one where we're continuing to educate investors around disease pathogenesis, symptomology, what the unmet need is there. Maybe you could just kind of level set for folks and talk us through what that opportunity looks like for Kyverna.

Well, Stiff-Person syndrome is an important first indication for us and one that has no FDA-approved therapy and one where there's significant unmet needs. This is a highly debilitating disease that's progressive over time. 80% of patients will progress to needing walking aids or wheelchairs or be bed bound, which is a truly horrible prognosis. And what we've been able to demonstrate with our pivotal data that we read out at the end of last year is not only a significant impact in terms of clinical response across a number of different endpoints, but this ability to actually, for the first time ever, reverse the course of the disease, which I think is something transformative and something that patients desperately want. So this is a very significant patient population, and we're really excited about the fact that we get the chance to be first. We're accelerating, as I said, in terms of filing our BLA and we'll be prepared to launch this construct for these patients at the end of this year. And we could be the first to launch any autologous CAR-T into the autoimmune space for the first time.

Yes. So first CAR-T for autoimmune, potentially first approved therapy for Stiff-Person Syndrome patients. Let's talk about the pivotal KYSA-8 data. And maybe you could start just on the primary endpoint is time 25-foot walk test. Just remind us what you saw there. How important is that for patients? Like how clinically meaningful is that endpoint?

Well, the time 25-foot walk test is a standard validated test that's used across a number of neuroimmunology and neuroinflammation diseases. And what we saw from our pivotal data with miv-cel that read out at the end of last year is not only a clinically significant response, but we saw that as early as 4 weeks and being sustained over time. And by the 16-week primary endpoint, we had a 46% reduction in the time 25-foot walk test. Just to put this into perspective, a clinically meaningful response in these patients is a 20% reduction in the time 25-foot walk. So we're well beyond that. In fact, we're more than doubling that in our clinical trial. And to also put this in perspective with Stiff-Person syndrome, we know the natural history of this disease, at best, these patients will stay flat in terms of their time 25-foot walk and over time, will get progressively worse. So the fact that we're not only seeing a clinically meaningful response, but one that's actually deep and durable and enduring in these patients is actually really remarkable.

You mentioned the natural history. I know you guys have spent a lot of time generating natural history data on your own. I think you've published some of this. Can you just remind us, I guess, sort of the process, kind of comprehensive nature that went into generating the natural history? And then that, I think, kind of dovetails into maybe some discussion around the regulatory pathway and thoughts around getting approval here potentially on the basis of single-arm open-label study.

Well, there's a natural history that's been well documented in retrospective trials right now that, as I mentioned a few minutes ago, the fact that patients at best stay flat despite off-label treatments with a number of other therapies, the disease doesn't get better in these patients. And the natural history is that over time over a 80% of patients will progress to requiring walking aids or worse. What we've seen from retrospective data, this is an analysis coming out of Denmark is that patients over the course of their prognosis with this disease is that they will have a 4x more likelihood of comorbidity. So this is a really impactful disease and it goes beyond just stiffness of the joints. This is highly painful for patients and one that really impacts their lives. So the fact we're bringing something here that can actually reverse the course of this disease is really remarkable.

Got it. And maybe if we could expand on sort of the regulatory angle to this. Obviously, a lot of recent headlines, volatility within the agency, turmoil within the agency. Maybe just talk about your experience with FDA, consistency of the engagement. And then, I guess, specifically, like their feedback with respect to KYSA-8 as it's designed being approvable in this setting.

Well, we've had some really positive interactions with the FDA, they've been continuous, and we're very confident with the pathway that we've established. In fact, as I said, we're on track for filing our BLA in the first half of this year, and we're doing all the necessary work in order to make that happen. We've been actually working with the FDA through the RMAT designation and orphan drug designation. So we're in regular contact with them and seeing the transformative clinical data that we're seeing not only across the primary endpoint, but consistently across all of the secondary endpoints as well gives us confidence that we're doing something here that no other therapy can do and that this is something that patients desperately need.

With respect to the BLA filing, any other gating factors we should be aware of? I think obviously, with the cell therapy product, you think manufacturing, maybe you could just give us an update on where you are working through the sort of manufacturing regulatory process, but are there any other gating factors we should be thinking about?

No, we're well on track, and we are where we would expect to be at this stage in the process. And specifically around manufacturing, we've got 2 manufacturing suppliers, Minaris Advanced Therapeutics and ElevateBio. Both of these have been delivering for us within the clinical trial setting at a high degree of manufacturing success rate. In fact, we publicly stated that we have 95% manufacturing success rate in the SPS clinical trial, we actually had 100% manufacturing success rate. So we feel really good about the consistency of manufacturing and working with these suppliers, we are confident that we can scale up for launch as well.

Awesome. Let's talk about the potential opportunity to be the first approved cell therapy in autoimmune disease and how you guys are thinking about pricing, which obviously, like not expecting a pricing decision until approval. But just help us think about are there sort of goalposts on either side? Like just help us think through how you're thinking about what could be a clearly like trailblazing moment for the space.

Yes. Well, we believe the value proposition for miv-cel in Stiff Person Syndrome and in myasthenia gravis is very high. We've got a very, very strong value proposition. So although we're not guiding to specific pricing, if you look at the impact that this disease has on patients, not just in terms of the clinical symptoms, but the chronic use of therapies like IVIg, which cost the system hundreds of thousands of dollars a year. You talk about lost time off work, you talk about impact on families and caregivers. There's a real health economic burden that both of these diseases have on patients and one where we can treat these patients with a onetime therapy like miv-cel and not just have this significant improvement in clinical symptoms, but this chance to actually remove and eliminate all the background therapies that patients are on. So when you factor that into a health economic argument when we go in front of payers, we've got a real justification for charging a premium to current CAR-T pricing, and we're going to continue to work on that. In fact, the feedback from the payers up to this point in our research has been extremely positive about the value proposition that miv-cel is bringing.

That's great. And maybe just continuing down the line of commercial planning, just talk a little bit about potential addressable patient population for SPS, the types of patients that you're targeting and I guess your best kind of like real-world use case in the setting?

Yes. Well, we know from epidemiological studies that are emerging as well as our own ICD-10 claims analysis, the population for Stiff-Person Syndrome in the U.S. is larger than what was initially thought. We know this patient population is roughly about 6,000 patients. And of those, we know there's about 2,000 to 2,500 of these patients that are already refractory to existing off-label treatments. And these are the patients that are in desperate need of a new therapy like miv-cel. And those are the patients that we'll be targeting first these are the patients that are known academic centers and ones that we can actually accelerate and move into a launch phase very quickly. But we do know with any disease where there hasn't been an approved therapy and where the existing treatments are not managing these patients very well, we believe once miv-cel gets on the market and we actually can work with physicians and patients to increase education, we believe that larger patient pool will be addressable over time as well.

You mentioned the highly concentrated nature of the patients in the academic centers. Maybe just expand on that. How many of these centers of excellence are there? How many of the 2,000 to 2,500 of those refractory patients in academic centers? And then just remind us of the KYSA-8 program, like how many centers were involved in that, presumably the leading academic centers?

Yes. Well, we have 3 centers that were involved in the KYSA-8 study, and we were able to enroll that trial in under 7 months. In fact, we were oversubscribing that trial. So there's a huge amount of pent-up demand from patients. And as we look to move to a launch phase, we are targeting at least initially 10 key centers across the U.S. where these patients are highly congregated. In fact, the majority of those 2,500 patients are being either directly managed or being referred into these centers on a regular basis. And we believe this gives us a very focused commercial footprint to start from that we can build on, but one that gives us a chance to get a rapid and early launch takeoff.

Got it. And when we think about sales force infrastructure, like it seems like it should be something quite efficient -- maybe just talk through number of sales reps and I guess the amount of resource that would be required to launch.

Well, with a really focused initial launch center like these 10 centers that I was referring to, we can have a very efficient commercial launch strategy, which is a big reason why we chose Stiff-Person Syndrome, not only are these high unmet needs and allowed us to accelerate our clinical development program in a rapid way, we can go to market in a very efficient way with this initial indication. So we won't need a large commercial team in order to service these 10 initial centers, but they will be important centers that we can go deep in and establish deep relationships and the infrastructure in order to support and manage these patients. And then what's really important with these 10 centers is it allows us to bridge and move on from there because if you think about our next indication is myasthenia gravis. And there's a huge amount of synergy between these academic centers that are treating Stiff-Person Syndrome and myasthenia gravis. We can continue to build on those, adding more centers in preparation for the myasthenia gravis launch. But each new center that we're adding can also treat more Stiff-Person Syndrome patients, too. So there's a huge synergy between these indications that we're going to leverage as we continue to advance the launch program.

That makes sense. Looking ahead to detailed data presentation, like we have viewed AAN. I don't know if you've committed to this or not, but we have viewed AAN as like a logical sort of high-profile medical meeting that would make sense for a detailed data presentation. Any specifics kind of beyond the top line that you would orient us to basically data that we haven't seen that we should be tuned into? I'm thinking PRO metrics or other details that you would focus us on?

Yes. We just put out a press release announcing that our primary readout of the Stiff-Person Syndrome data, the KYSA-8 trial will be at AAN as a late breaker. So we're really pleased to see that come through. And in fact, we'll not only disclose more details about the primary endpoint, this time 25-foot walk. But as you alluded to, we gave high-level overview of the secondary endpoints and how consistently strong and positive those data are. We're going to provide more detail on those during this presentation. In addition, we'll spend more time talking about some of the exploratory endpoints as well. And we'll cover some of the translational data, the pharmacokinetic, pharmacodynamic data that supports the rationale of why we're seeing this really remarkable and transformative impact in these patients in terms of the efficacy.

Great. Let's switch gears myasthenia gravis. And maybe just like take a step back. I envision SPS is a great beachhead indication. You alluded to some of the overlap between the SPS clinicians and myasthenia gravis. But strategically, like where does MG fit into the Kyverna game plan? And then how are you thinking about prosecuting a pivotal MG program?

Yes. Well, myasthenia gravis is a very valuable market opportunity for us and a great second indication because of the synergies that you just indicated. And when you look at the interim Phase II data that we read out at the end of last year, miv-cel doing something completely different from the existing therapies that are in this space. So there are existing treatments. Many of them are treating the symptoms of the disease or trying to manage the antibodies in a partial way. But for the first time ever, we're seeing with miv-cel treated patients, this opportunity to give patients this deep B-cell depletion, this autoimmune reset, if you will, and this chance of this long-term durable remission in patients with one single treatment of miv-cel. In fact, our first patients that have been treated with miv-cel are still doing very, very well, not needing any follow-up therapies or background supportive care. And they've done this with one single treatment in miv-cel and they're now lasting out to 2 years plus. So we know we're doing something remarkably different with these patients, and this is why we're really excited about advancing our pivotal Phase III study, which we're now moving into and actively enrolling.

Your first autoimmune patient, I think, was an MG patient, right? How far has she been followed now?

Denise she's well past 24 months, well past 2 years. And she's a mother of 4. So she's back to living life from a normal perspective and engaging in normal everyday activities and not needing a retreatment and not needing any support of background care as well, which again, I think really reinforces that these therapies like miv-cel doing something transformative different and remarkable and paradigm shifting.

Yes. You started enrolling the Phase III. Maybe just remind us, I guess, differences from the Phase II experience. just high level remind us the Phase II data set. And then, how you're prosecuting the Phase III, the patients that you're targeting. It is randomized study, which is also -- it's a very unique innovative design. Just talk a little bit about the design.

Sure. Well, just starting with the Phase II, which we read out an interim analysis on that at the end of last year, and we'll have a full analysis actually coming at AAN as well. So that will be an additional presentation for us. But what we saw in that interim readout is remarkable. We saw MG-ADL score reduction of 8, QMG reductions of 7.7. No therapy in the treatment of MG has shown this dramatic impact in terms of these key clinical endpoints. But in addition, we were actually able to see more patients actually reach MSE, which is minimal symptom expression. This is ultimately what patients want. They want to live without the burden of their disease and they want an MGA score of 0 or 1, which is MSE. And we're seeing more of our patients actually reach that level. And again, doing so with a onetime treatment that allows you to actually remove the background therapies that patients are chronically on. You look at FcRn trials or complement trials or any of these other trials in MG, these are all additive. These therapies are being added on to a backbone of immunosuppressants hydrosteroids, which we don't have once they enter our trial with miv-cel, which again, tells you the paradigm shifting work that we're doing here in terms of not just the clinical impact, but also reducing the overall burden of care. Based on those results, we actually got the nod from the FDA to truncate that Phase II trial early. So we actually now are moving into the Phase III portion of the trial. We're actively enrolling those patients. And if you look at the outcome and the efficacy impact that we were having in the Phase II, we're in a sense derisking the Phase III because we know that the clinical results and how we powered that study will allow us to show a really transform result for these patients as well.

And this is a randomized study versus -- just remind us, I guess, how you landed on what goes into standard of care, I guess, like what you're actually going up against here in the Phase III?

Well, you're right. It is a randomized trial with 60 patients randomized to standard of care or miv-cel. We're including a variety of patients with backgrounds. Patients can be on FcRns or complement inhibitors or other more traditional therapies. They come into the trial, they're apheresis and we manufacture their cells and then they're randomized to either standard of care or miv-cel. And we're going to be tracking the primary endpoints, MG-ADL score reduction and QMG reduction as of week 24, and we're aiming for superiority. So this is a very unique design. It's one that we're a very bold design, one that we're very confident given the results that as I said we saw in the Phase II study, we believe that we can beat and exceed.

Excellent. Maybe just talk about commercially where you see a product like miv-cel fitting into MG. I think investors broadly view this as a rather competitive space, a number of approved biologic options, a lot of things in development, but nothing that we've seen that has the sort of transformative effect that you've seen with miv-cel in your Phase II. So how do you think about like what are the ideal MG patients that you're going to end up targeting commercially?

Well, first of all, the MG market is a significantly larger market than SPS. So there's a huge market opportunity more broadly. And if you take a look and you subseg that market a little bit further out of the 80,000 patients that are there, 40,000 of them are readily addressable that we believe could be CAR-T illegible patients. And of those, we know there's about 12,000 to 13,000 patients that are already refractory to existing therapies. We think this is an initial starting point for miv-cel in that there's -- if you look at FcRns alone, 1/3 of patients are not doing well and have high MG-ADL scores of 6 or greater. This will be a readily addressable patient population for us coming right out of the gate. But again, with increased education, with increased durability of effect, and we've seen more patients like Denise get out to the 2 years and beyond, we believe this will be more applicable to a broader patient population.

Interesting. And I guess coming back to manufacturing and scale of, like how should we think about the capacity when we start talking about thousands of patients with myasthenia gravis that could be addressable? Do we think we have sufficient capacity with our 2 suppliers today? Are we looking to add additional supply? Like just help us think through that.

Yes. We're very confident with the manufacturing supply we have to not only support this SPS launch and the ongoing clinical program we have, but also to support the initial launch -- initial launch stage of myasthenia gravis as well. And we're going to continue to evaluate this over time, and we'll continue to assess the need for adding additional manufacturing support as we continue to advance through different stages of launches.

Now you have significant experience coming from KYSA-8 -- basically the build-out of CAR-T in oncology and the scaling up of that. Maybe could you just sort of compare and contrast for us how are you seeing on the autoimmune side. And I guess there's competition for space and capacity overall. So how do you see, I guess, scaling over the course of 2 to 3 months to really, I guess, scalable process?

Yes. Well, I think there's going to be 3 components to scaling up and being ready for launch. We talked about the first one we're manufacturing and then again we're confident we can scale up with this initial launch with Stiff-Person Syndrome and beyond with the manufacturing suppliers we have. The second component is the cell orchestration and the delivery of the cells to the patients. We've obviously put in place to service our clinical trials, and we're busy modifying that including adding additional patient support services, reimbursement support, travel and lodging, things that are going to be critically important for supporting patients from a commercial perspective. And then the third key element that we're working on and putting in place, of course, is the reimbursement strategy. So we're engaging with payers now. We're doing research. We're developing the value proposition for miv-cel for this initial indication, and things are progressing along very, very well on that front. In terms of capacity, we know all these academic centers are starting to shift and they're building up their capacity. They're moving from just being a pure CAR-T-focused academic centers for oncology only, and they see the scientific and academic desire of doing this, but also from a patient treatment perspective moving into autoimmune diseases. And this is a real advantage for us at Kyverna being the first mover here and being first to the market. This not only allows us to set the price and set the reimbursement guidelines, but allows us to establish those relationships in these key centers, which is what we're doing now in order to prepare and then we can expand on in terms of future launches. So all of that is going very well. The other point I would add is that because of our safety profile and the fact that we have what we believe is an outpatient administered drug, we believe that the ability to optimize the existing capacity that's in these centers will be a huge advantage for us because we can have a less burden of a footprint on every treated patients that we administer miv-cel.

Yes. That makes sense. We're also expecting data across a number of other indications, data updates, Phase I data from LN. We also have investigator-initiated studies looking at RA, MS -- like how should we think about the cadence of these readouts and the substance of those readouts?

Yes. Well, I think as I said at the beginning, one of the key differentiators for Kyverna at this stage is our pipeline. And we're looking beyond Stiff Person Syndrome and myasthenia gravis to building longer term a neuroimmunology franchise. And when you start looking at some of the early data coming in progressive MS, for example, we've got centers in Stanford and UCSF that have been treating patients. And if you ask the experts of these institutions what they're seeing with miv-cel. They will comment, but they haven't seen anything like this in 30 years that they've been treating and managing these progressive MS patients. As you know, there's a few treatment options for these patients. And once they start failing, the patients just do progressively worse in terms of their overall prognosis. And for the first time ever, we're not only seeing stabilization of EDSS in PMS, for example, we're actually seeing significant improvements in these patients as well as improvements in disability and fatigue score. So really remarkable early data. We're really excited about that, and this gives us an opportunity to open up the aperture, if you will, to treat even larger patient populations and bring something transformative like miv-cel to even more patients.

That's great. Just in the last 30 or so seconds that we have, you do have an IND submission for KYV-102, which is your kind of next-gen manufacturing process, leverages whole blood manufacturing. Maybe just give us like a quick soundbite update on KYV-102 and what this could mean for Kyverna, economic scalability longer term?

Yes, exactly. We filed our IND for KYV-102 at the end of last year. And this is building off the backbone of KYV-101 or m-cell. So it's got the same CAR construct, but it's on a different manufacturing platform that allows a couple of things. First of all, we can start with whole blood rather than patients, which is a real important advance for improving patient access and will allow us to start the CAR-T journey for patients even closer to their homes, which we believe will improve access for patients over time. In addition, because it's a rapid manufacturing process, we're speeding up the turnaround time, obviously. But more importantly, we're actually significantly reducing cost of goods for patients, which, again, as we start thinking about larger indications and how we expand the portfolio over time, this is going to provide a lot more opportunities and flexibility for how we commercialize this and bring this to more patients.

That's great. And what's last question, sort of the next update on the KYV-102 front? Like is it -- do we need a bridging study? Like what is needed, I guess, to implement this into clinical practice?

We're working on that right now. We'll provide more updates on the specifics of that development program in due course.

Cool. All right. Well, unfortunately, we're up against time. Thank you, Warner and Kyverna for joining us. Thank you, Warner.

A pleasure.

An exciting 2026.