Hello, everyone. My name is Mitchell Kapoor. I'm a senior biotech analyst here at H.C. Wainwright. Thank you for joining us today for our discussion with Kyverna. I have the whole team here, but today I'm gonna have a fireside chat with CEO Warner Biddle. Thank you so much for joining us today.
Thanks, Mitch. Great to be here with you. What a great location.
Yeah.
Nice event so far. Thanks for hosting us.
Thank you so much. Great. Just for those in the room who may not be up to speed with the story, or maybe they've not dove deep into Kyverna at all yet, if you could give a brief introduction to the company, the current pipeline initiatives, and just an overview to set the stage for our more finer questions and discussion.
Sure. Thank you. First of all, we're really excited about the progress we're making here at Kyverna. We've been making tremendous progress over the last few months. We're really leading the way in a few key areas. First, we have a unique construct. miv-cel, our lead construct, is uniquely designed for use in autoimmune diseases. It's been designed for potency as well as significantly improved safety, and we believe that gives us advantages versus other CAR- T therapies and other traditional therapies that are being used across these autoimmune diseases. In addition, we're leading because we are first. We're first to bring these to patients with a focus on our first indication, which is Stiff Person Syndrome. This is a disease with high unmet medical need and with no approved FDA therapy.
For the first time ever, we're demonstrating not just significant clinical responses in patients, but for the first time ever, reversal of disease, which is quite remarkable. We've actually had our pre-BLA meeting with the FDA, we've recently announced that we started our rolling submission. We're on track to finish that submission in Q4 of this year, which puts us on track to be the first autologous CAR- T company to bring these therapies to autoimmune diseases, and certainly the first company to bring a transformative therapy to Stiff Person Syndrome in these patients that desperately need it. Stiff Person Syndrome is just the beginning. As you know, we are building a neuroimmunology franchise here at Kyverna, Stiff Person Syndrome is that first step.
We are looking ahead to myasthenia gravis, where we also have very transformative data in an ongoing phase III study, and other diseases like progressive MS, where we're seeing some remarkable data as well. Overall, really excited about the progress we're making, really excited about leading this space, and really excited about bringing these to patients that desperately need some new therapies.
Excellent. Just jumping into Stiff Person Syndrome, the potential first commercial launch opportunity for Kyverna, would love to understand a little bit more about the highlights of the data we've seen so far, and then, you know, tying that into kind of the investor concern that we hear about the trial design in terms of the FDA, if they would ask for a randomized data set versus kind of what you've shown so far. Maybe you can give us a sense of kinda how transformative these data have been for patients so far, and why that might not be the case.
Can you tell us a little bit about the regulatory discussions you've had on that front as well, including kind of the pre-BLA meeting and minutes that have come out of that, to help us understand, you know, how safe we should feel from a regulatory perspective on the SPS launch.
Sure.
Approval.
There's a few questions in there. I'll start with your first one, though, on the data itself, and you have to put this in perspective with the natural history of Stiff Person Syndrome patients, what we know of these patients, and we've now demonstrated this in a retrospective trial looking at the natural history of Stiff Person Syndrome patients. At best, these patients remain flat over the course of their lives, but inevitably, 80% + of them actually progress into recurring and increasing disability, which includes the use of walkers, wheelchairs, and many of them will actually become bed-bound over time as well. This is a disease with a horrible prognosis, and as I said earlier, there's no approved therapies.
The existing off-label treatments that are used in these patients don't really work. They treat a little bit of the symptoms, have show some minor improvements in some patients, but inevitably, like I said, most of these patients progress. We do know as well that only 19% of patients will still be working four years after their initial diagnosis. This disease has a tremendous impact on patients, then you counter that with what we're actually seeing in KYSA-8, which was our pivotal clinical study, where we're actually showing for the first time ever significant clinical responses across not just the primary endpoint, but all secondary and exploratory endpoints as well, and significant P values across all of those. For the first time ever, a chance to actually reverse the course of this disease and reverse disability.
In fact, two-thirds of patients that needed walking aids while coming into the study were able to remove those walking aids after just 16 weeks. We're really seeing not a marginal improvement in Stiff Person Syndrome in these patients, but actually a remarkable improvement from a clinical perspective. When you think about that and putting that into perspective with your second part of the question, which is really around the dialogue we've been having with the FDA, the FDA's been actually really supportive of us and really supportive of our work in this indication. They also understand that there's no approved therapies and that this is a horrible prognosis for these patients. The dialogue has been extremely constructive.
In fact, through our pre-BLA meeting, we have alignment on the core components of our file, including the question you asked about the single arm study. Yes, they are supportive of the single arm study, the primary endpoint, the timed 25-foot walk, 16-week endpoint, the CMC package, the safety package, the preclinical package. All of these things have come together really, really nicely. We have that full alignment with the FDA on the core components, and then we're continuing to work on providing them with some additional analyses of this natural history data that will support and contextualize the KYSA-8 study, and we're well on track for making that happen and ensuring our filing goes in Q4 of this year.
Excellent. That natural history ask that the FDA had for you all seems like a rational thing for a disease that's, you know, there's no precedent for how this can be treated. Can you discuss like how you furnish the FDA with a study like that without making the filing depend on some kind of formal analysis of, versus the external control? You know, just talk about how patients don't spontaneously improve.
They don't spontaneously improve. That's what the headline from the study shows. We presented this at AAN just a few weeks ago. Over the course of 10 years, we know that patients at best may have some marginal improvements at certain points of their disease. Inevitably, they just worsen over time, which again puts it into context with what we're seeing with KYSA-8. In fact, within the natural history data itself, we know that patients increased their use of mobility devices like canes and walkers. They also had to increase their use of immunosuppressants as well, and treatments during the course of their disease. You juxtapose this with what we're seeing in KYSA-8, where we saw just the complete opposite.
We're seeing a significant reduction in walking aids. We're seeing a significant reduction in immunosuppressants and background therapies. In fact, all patients by design of using miv-cel remove their background therapies when they go on miv-cel and stay off these background therapies. This is a remarkable difference versus what patients are traditionally exposed to over the course of their disease.
Great. Okay. When we think about the value from a patient-physician perspective, assuming that they're aligned on the patient's goals, can you help us rank what, you know, you think physicians value most and kind of explain why? Is it something, you know, Give a list of things, and then you can expand or whatnot. Timed 25-foot walk improvement, reduced walking aid use, the reversal of disability or the freedom from, you know, background therapies and immunosuppressants.
Yeah. I honestly think that you it's the entire package. You ask physicians and patients what makes miv-cel so distinct and what makes this so remarkable is this ability to have, you know, not just a marginal impact on these clinical symptoms, but a highly significant and clinically meaningful impact across all of them, while at the same time doing so with a one-time therapy that allows you to remove the other background therapies that patients have been chronically burdened with for years. I think ultimately patients wanna feel like they're free of their disease and wanna go on as much as possible with what they would consider a normal life.
For the first time ever, we're hearing stories from physicians and patients that this is actually happening, and we're doing it with miv-cel, and we're doing it in this clinical trial. This is why we're so excited about getting it to patients as quickly as possible.
Excellent. The second half of the year, we'll have the one-year SPS follow-up data, which I assume will be a big catalyst and focus for investors. What durability threshold would let you call this a sustained drug-free functional recovery versus just seeing a temporary effect on patients and their impact?
What's really remarkable is we are seeing some of these durable effects with patients already. All of our patients reached the 16-week primary endpoint as a part of the clinical study, and this, again, is off background immunosuppressants and other therapies that they've been exposed to. We had 16 of the patients actually re-reach the 24-week milestone. We're gonna be continuing to track those patients and providing, as you noted, out to one year. In addition, we know from the first patients that we dosed through our compassionate use programs, we now have our first patients out to two years and beyond. Again, off background immunosuppressants, off background chronic IVIG that they've been burdened with and living free of their disease.
The potential here is not just for a short-term clinical benefit, but one that can be endured over time that will completely change these patients' lives.
Okay. On the payer front, when they think about the durability that we may see in the second half, how does that You know, from your perspective, your discussions with the payers, how are they thinking about the impact of durability on pricing and kind of coverage and formulary? Are payers kind of engaged now in discussions, or are they waiting for that more fulsome durability to have discussions with you on the launch?
Well, we've been actively engaging with payers now and conducting payer research in advance of our launch. They've actually seen now when we've shared the pivotal data that we shared at AAN, and the feedback's been remarkably positive. Again, we're talking about a disease with no approved therapies, and the existing therapies for patients not only have a very marginal, if any, impact on the patients' lives, they cost the system considerable amount of money. IVIG alone, and many of these patients are on monthly or biweekly IVIG, costs the system hundreds of thousands of dollars a year, it doesn't work. It doesn't address the underlying cause of the disease, patients inevitably get progressively worse over time. We're bringing something to the market that's, again, a one-time therapy that has a significant clinical impact.
In patients, we're starting to see a durable impact to your other point, but you're doing it with a one-time therapy. You're actually able to save the system money while actually offering patients ultimately what they want, which is freedom of the burden of their disease.
Got it. Coming up on the launch, you know, you'll have 10 key academic centers that cover roughly half of the immediately addressable refractory SPS population. Between now and then, what still needs to happen before launch to make sure that you're ready to go?
Well, we're targeting 10 centers to start. We may adjust that number slightly as we get closer. We're targeting 10 centers because we know these patients are highly concentrated in a few academic centers and being treated by a few physicians, and that allows us to move forward with a very efficient commercial infrastructure to get us into a launch position. We are working in advance of the BLA filing, et cetera, and everything. We're continuing to work in the background on site onboarding with these centers. We're also working on building the systems and infrastructure that we need in order to support the patient journey, so things like the cell orchestration model and the patient support systems that need to be in place. We wanna develop that in advance of the launch.
In addition, we are working with payers, as you indicated earlier, to start to get our dockets and our rationale for supporting the pricing and market access for miv-cel. We are also, of course, working with our manufacturers because we're working with them on the forecast and how we're projecting this launch to go so they can be ready and scale up, so we can address the patient populations that we're looking to address here coming into the launch phase.
Great. You know, on an initial launch, sometimes you have a bolus of patients, especially in a disease where there have been no real options. I'm wondering You know, what are your thoughts on there being a potential bolus at launch? Are there wait lists that, you know, physicians have their patients on? Can you help us quantify any type of bolus effect that you might see of pent-up demand?
Yeah. I think you're touching on a really important point. You know, these patients are desperately waiting for something, and we know even within the Stiff Person Syndrome diagnosed patient population, there's a subset of patients between 2,000- 2,500 that we've talked about before that are already refractory to IVIG, already refractory to existing therapies. These are patients that are frankly calling physicians. They're calling us. They're highly active and engaged through the patient advocacy networks, and they're anxiously waiting for a new therapy like miv-cel to reach the market.
We're not guiding to a specific bolus, but we know there's a pent-up demand, which is why all the work we're doing in advance to make sure that our centers are ready for miv-cel at the time of launch, makes us ready to serve these patients right out of the gate.
Excellent. Okay. Can you give a sense of, you know, these patients, I guess the target launch patients, the patients who are refractory. You know, how often do they see their physician, and how does that determine how quick the launch is? For example, does a patient see their doctor typically every quarter, every half year, every year? I guess, like, if they saw their doctor once a year, you would expect more of a measured launch uptake whenever they go for their routine visit. Help us understand kind of like, you know, how in touch with the physicians these patients currently are.
Yeah. We're not really looking at it exactly the same way. In fact, we're thinking about it in a different manner. First of all, these patients are known to these physicians and are seeing them on a regular basis. In addition, because we're talking about these patients that are refractory to therapy, they are already getting treatment, regular treatment, either biweekly or monthly. They are in constant contact with the healthcare system, and we are, you know, very aware that at launch, we're gonna be able to communicate through the patient advocacy groups and through the physicians that miv-cel is now available. We believe that these patients that have the highest unmet need will seek treatment relatively early.
They're not gonna wait for their next appointment to come up in order to ask for this therapy, given how new it is, how transformative it is, and how much interest we're seeing from the patient community already.
Gotcha. It sounds like there's a good tie-in with the doctor and the patient that they're in constant communication about this, and they're ready to come onto therapy if it becomes available.
Yeah. The SPS patients are well-known. All these treaters have databases of the patients that they're treating, either actively or the ones that have been referred to them before. We know through our conversations as well as with others, that they're anxiously waiting for something to be approved that can actually work for them.
Great. Okay. What do you see as the biggest hurdle for uptake? Is it the lymphodepletion, hospitalization, payer access, durability, uncertainty? Is there anything that you're thinking, you know, between now and launch that you need to iron out and work on that could lower the hurdle for launch?
Well, again, there's nothing approved for these patients. There's already a high unmet need built into this system, and we've done some physician research, and based on the profile that we presented at AAN, we know that 90% of the physicians, SPS treaters find this profile highly compelling. 85% of them said they would use them in their moderate to severe SPS patients at the time of launch. We know there's not only a high unmet need, but physicians are already thinking about the patients that they'd be using this therapy in. You know, when you think about things like lymphodepletion, we've had no issues with regards to recruiting patients into our trial with our low-dose lymphodepleting regimen.
That said, we are looking at alternative lymphodepleting regimens as well, including bendamustine and no lymphodepletion, so more on that data as they continue to mature. Overall, we know that this is a therapy that works very, very well, and is now, as the evolution of CAR- T therapies has been coming to the market, is becoming easier and easier to administer. For us, it's more about execution and some of the things we spoke about earlier with site onboarding that we need to get in place so that we can be ready for the patients once this is approved.
What are the key differences from an oncology CAR- T launch to the SPS CAR- T launch that you're looking to, you know, have a successful outcome for? Can you kind of draw the key differences for investors?
I think this is, again, really, really important. Yes, it's a CAR- T launch, but we're actually looking at it through the lens of more of a rare disease launch. I think there's some really important differences that I think should be taken into consideration here. First of all, pricing. We see miv-cel and the value that we're bringing to the system, particularly with the chronic burden of treatment and these high-priced therapies that cost the system hundreds of thousands of dollars a year, not just in Stiff Person Syndrome, but frankly, in myasthenia gravis and other indications that we're looking at. We see miv-cel coming to the market at a premium to current CAR-T pricing. I think that's really important. Second, what makes this launch different is the high concentration of patients.
We talked about the 2,000-2,500 patients that are well-known and documented to physicians in the academic centers. Again, we can move forward with a very efficient commercialization structure in order to address those patients by going to the 10 academic centers and expanding from there and seeing a very successful launch with that. In addition, from a manufacturing perspective, what we've been benefiting from is the ability to use CDMOs that have already established, you know, high rates of success, and we can leverage the capacity to meet the demand rather than pay for, you know, a fixed, you know, manufacturing infrastructure that we may not be fully utilizing at the launch phase.
This is providing a lot of flexibility, as well as utilizing a lot less capital in order to get us into a launch position and puts us into a really, really strong position of success. If you add all those things up and you think about the model that we're going to the market, I think it's very different than maybe what CAR-T companies had to do in the past when these things and options weren't available. That puts us in a position to have biologics-like margins to start and allows us to expand on that to the additional indications that we wanna grow into as a company.
Excellent. On that manufacturing point, you know, it's critical to be able to scale as you move into different indications. I know this initial launch is a little bit more concentrated. Can you tell us about your initial ability to meet demand with your current ability to scale for SPS and then how that might evolve, as you're moving into MG, et cetera?
Yeah. We're really confident with our manufacturing and our CMC overall. We're working with two manufacturing suppliers right now, ElevateBio out of Boston and Minaris Advanced Therapies out of Philadelphia. We've been manufacturing, we publicly stated, at 98% manufacturing success rate. In fact, during our SPS trial, we had a 100% manufacturing success rate. We're continuing to improve on that as things evolve. We've been sharing with these companies, obviously, our short-term and longer-term forecasts, and we're very confident that we can scale, not just for the commercial launch, but continue to fuel the ongoing clinical work that we're doing in the other indications like myasthenia gravis.
On the MG front, just touching on it briefly, KYSA-6 showed deep responses in a small cohort. Could you walk us through your phase III planning, the design, the optimal patient population you're looking to treat with miv-cel in that population?
Sure. I'll just briefly touch on the MG results from our KYSA-6 phase II, which are remarkable. Frankly, no one has demonstrated the results that we've seen in our KYSA-6 phase II in any other clinical trial setting. We're seeing reductions in MG-ADL scores of 8.5, QMG 11.3. This is, you know, at least double what you're seeing from any other therapy that's being studied in this space. Then you add onto that the fact that you're doing it again with a one-time therapy that allows you to remove the other background immunosuppressants and treatments that these patients have been burdened with. No other therapy's doing that. On the basis of that, we've pivoted very quickly into our phase III.
We started enrolling our phase III at the end of last year, this is a comparative head-to-head study of miv-cel versus standard of care. We're looking to show a superiority of miv-cel versus standard of care across those two key primary endpoints, MG-ADL and QMG. Recruitment is going well for the trial. We're now in 15 centers in the U.S., 15 centers globally, including the U.S. and other sites globally. We're really excited by the reception we're hearing from physicians based on this clinical response that we're seeing from the phase II study.
Excellent. Lastly, wanna touch on MS. Can you just walk through your data to date, and what additional data or anything else contextually would help you justify moving MS into a priority indication behind both SPS and MG?
Yeah. The results that we're seeing from miv-cel in progressive MS have been truly remarkable. In fact, Jeffrey Dunn from Stanford University, who's doing some of our early IIT work, has publicly stated in many forums he's never seen, you know, a treatment have this kind of an impact on patients. What we're seeing with a single dose of miv-cel is an ability not just to stabilize EDSS, but in a majority of patients, actually improve EDSS and improve fatigue scores.
We actually know based on the mechanism of action that we talked briefly about at the beginning of this fireside chat, we know that miv-cel's doing something transformationally different with this ability to penetrate the blood-brain barrier, get across the CNS, have a deep B-cell depletion in these targeted tissues, and give this autoimmune reset. It seems to be playing out in these early clinical results that we're seeing in progressive MS. We're watching, we're seeing the data evolve. As you said, this will be informing our next stages of how we think about progressive MS as a potential next indication for us.
Wonderful. Last, if you will, just give us a view into Kyverna in 2026 and 2027, the look ahead, and just set the stage for investors as we move along with the catalyst windows.
Sure. We're just really excited about the progress. We're very excited about the opportunity to continue to lead with the chance to continue and finish the filing of our BLA in Stiff Person Syndrome and be the first to launch an autologous CAR-T therapy into autoimmune diseases. We're quickly following that up with myasthenia gravis. We'll have an update on the progress of our enrollment of our phase III study, as well as the maturing data in myasthenia gravis as well in the second half of this year. We'll have an additional update on the progressive MS data, as you indicated, as well as a phase II study in rheumatoid arthritis, which will be shown in the second half of this year as well.
All of this coming together really well, that creates a lot of positive momentum about what we're doing, how we're leading, and certainly galvanizes our company to continue to do all this for the patients and physicians that are waiting.
Excellent. Thank you so much, Warner. Really appreciate your time, and thank you to all the investors in the room who came to join this fireside chat.
Thanks, Mitch.