Kyverna Therapeutics, Inc. (KYTX) September 15, 2026 Conference Transcript

Hello, everyone. My name is Mitchell Kapoor. I'm a senior biotech analyst at H.C. Wainwright. It's my pleasure today to welcome you all to the Fireside Chat with Kyberna. From the company, I have the CEO, Warner Biddle. Thank you for joining us today. Thank you, Mitchell. It's a pleasure to be here. Great. So I like to start off every Fireside Chat just orienting the room to the company, current developments, and kind of what the near-term focus points should be as we're looking at the Kyberna story. So maybe we could start there.

Sure. Well, at Caverna, we're leading the world in bringing the transformative power and curative potential of cell therapies to autoimmune diseases. We've got a unique car construct and a well-established manufacturing process. And together, we're accelerating this with a focus on neuroimmunology diseases, starting with stiff person syndrome, which is a rare debilitating disease with no approved therapies and where we've shown transformative results. We are in the process of filing our BLA and on track to complete that BLA filing at Q4 this year, which would mean we would be the first approved therapy in this condition anywhere in the world and also the first company anywhere in the world to have an approved cell therapy and autoimmune diseases. So this is a really important milestone for us. And this becomes just a starting point for the rest of our pipeline and how we're thinking about the neuroimmunology portfolio. We have really promising data in generalized myasthenia gravis, as well as other conditions like progressive MS, and we're continuing to build a long-term future and potential for how we can bring MyvCell, this transformative therapy, to more patients around the world.

Yeah, it's exciting as the first in the field, right, to potentially become commercial. And we will definitely dive into kind of that application and others. But I think maybe to start off on something topical, Novartis and BMS paused autoimmune CAR-T trials two weeks ago, obviously used different constructs, manufacturing, patient population are relevant to assessing MivCell, but wanting to think about how many patients MivCell has been in to date, how safe is MivCell, and what things can we learn from that? But also, you know, what are the differences that you can draw between MipCell and Novartis and BMS?

Well, first thing, let's just say, oh, this is really unfortunate to hear these announcements about these patients. It was really difficult to hear that news. But I think it does really underscore what we're doing here at Kyberna is different. And different in two important ways. And you touched on it briefly. First, we have a very unique construct. We're the only CD19 car therapy in the autoimmune disease space with the CD28 co-stimulatory domain, a fully human design, and other modifications to the car that have been specifically put in place in order to enhance the safety profile of this car. In fact, MivCell was in-licensed from the NIH with the specific intent to actually be used in autoimmune diseases, and it maintained the potency of earlier generations of CAR-T So there's this potential for this potent B-cell depletion and autoimmune reset and long-term efficacy, but at the same time, a tenfold reduction in the potential for cytokine release as well as ICANs and neurological AEs. So we believe the CAR construct is extremely important. And in the 100-plus patients we've now dosed with MivCell, we've seen no high-grade CRS, no high-grade ICANs, no reported cases of the IEC-HS events that some of our peers are are reporting. And this really underscores the importance of the safety of the construct as the first key pillar. But you touched on a second important point, and I think that is the manufacturing, because in the case of CAR-T therapies, the product is the process, and the process is the product. And the manufacturing is extremely important. And at Caverna, we're using well-established, well-validated manufacturing process, the traditional manufacturing process. We're not using rapid manufacturing, and I think this is important, because that can introduce a different set of variabilities into the car itself and could result in a different side effect profile for patients. But because of our well-established manufacturing, as well as our specifically designed car for improved safety, we think this is bearing out in the clinical profile we're now seeing with MIPSEL. And like I said, in over 100 plus patients we've now treated, we have a very well-established safety profile and one that we believe will lend itself well when we scale to commercialization.

Excellent. One thing that I think is important, and a lot of questions we get on the company are now turning to stiff person syndrome and SPS. So I think it's important maybe if we can educate the audience about what stiff person syndrome is, how it's an INI indication, but also kind of like a rare disease, what these patients go through, and kind of what an immune reset could potentially do for an SPS patient.

Sure. Well, stiff person syndrome is a rare condition, but an important one. There's 6,000 patients in the U.S. right now that are suffering from this disease, and this is a progressive disease. It is an autoimmune-mediated disease instigated by GAD-65 and other antibodies, but it's a B-cell-mediated antibody disease, which is why MivCell is so uniquely positioned actually to support and help these patients. We do know the natural history of these patients is horrendous. Over the course of their lifetime, and many of these patients were diagnosed in the middle of their lives. So they have a huge amount of their lives ahead of them. But 80% of them will progress to severe disability where they'll need a walker or a wheelchair or even be bed bound. We know that less than 20% of them will be employed in their jobs just four years after the initial diagnosis. So many of them become homebound. There's a huge cost to the system in terms of lost time from work, but also caregiver costs. And there's no approved therapies. There's no approved FDA therapies. And the off-label therapies that these patients are taking don't really work. They help maybe symptomatically for a short period of time. But as I say, most patients progress and become more severely debilitated, which is why the results that we're seeing with MivCell in our pivotal clinical study are so remarkable for the first time ever with a one-time therapy of MivCell. We're able to actually remove all the other chronic therapies that patients are taking and have a significant clinical result, as well as for the first time ever seeing a reversal of disability. So two-thirds of the patients that required a walking device at the beginning of our study 16 weeks later no longer needed that walking device. And patients are literally walking with improved mobility, significantly improved mobility, which is remarkable. And again, it's a one-time therapy, so patients can remove their other chronic therapies that they haven't been burdened with. And we're doing with a well-established safety profile as well. So in a sense, we are really establishing a gold standard for how this disease should be treated. And as I mentioned earlier, we're on track filing our BLA, and we could be the first approved therapy in this condition. But I also think we're setting a bar for how autoimmune disease could be treated more broadly. And I think we're leading the way here at Cavern and making that happen.

So we're approaching the 12-month durability data for SPS. Obviously, some initial amazing data that, you know, can help patients who are in such dire straits. Can you help us understand what are we looking for in terms of the durability metrics for these patients at the fallout period?

Sure. Well, earlier this year, we read out our results from the primary endpoint, the 16-week endpoint, and we saw across the board, primary, secondary, exploratory endpoints, highly statistically significant and clinically meaningful results. The primary endpoint, the time 25-foot walk test, for example, we saw a 46% reduction that was not only seen early in the treatment journey, but sustained out to 16 weeks and beyond for the patients who were able to track. And we saw this again with the other secondary endpoints, which were measuring overall stiffness and mobility of patients, as well as other SPS-specific endpoints. All of these very, very highly, highly clinically meaningful. What we're looking for in the one-year long-term follow-up is a continuation of that. If we can demonstrate that a majority of these patients have this continued response to therapy, this reversal of disability, this ability to throw away their walkers and assisted mobility devices, I think this will be truly transformational for patients. And then if you compare that to, then again, the natural history for these patients where at best patients remain flat in terms of their disc mobility, but will progressively get worse over time. Again, this will help strengthen the overall story of what MivCell is doing. It will help strengthen our BLA submission and it will help strengthen our commercialization position once we get approved.

Great. So can you help us understand the advantages of this rolling BLA submission and what remains to be kind of compiled into that when you do eventually file that? And how does the natural history comparison in SPS help support your regulatory discussions and potential approval of MIPS on SPS? Sure.

Well, based on the results that we've had in this clinical trial, the KAIS-8 study, we had a positive BLA meeting, pre-BLA meeting rather, with the FDA early this year. And on the basis of that, they granted us this rolling BLA submission, which we're in the process of doing. And in fact, we're well along our way in terms of completing that rolling BLA. In fact, at our Q2 earnings just a few weeks ago, we announced we submitted the CMC module, which, as I think many people in this room are aware, for cell therapy companies, this is a key and crucial module. And we've now successfully submitted that, which is a positive de-risking event. The only thing left for us is to finish the clinical module. And in that clinical module, we want to include this one-year follow-up data from the KAIS-8 study. This will be important for providing additional depth of durability around MIV-CELL and will help strengthen our file, as I said. In addition, we will provide some additional analysis around our natural history study, which will help us contextualize the KAIS-8 study and what we're seeing in the study and how does it compare to the real world. And just to the second part of your question, the natural history study was really remarkable. We were able to follow over 150 stiff-person syndrome patients for up to 10 years. And in that study, we saw on average that patients' mobility got progressively worse over time, that they needed significantly increased use of walking aids, and that they also needed a significant increased use of immunomodulatory therapies and immunosuppressants and other things to try to control their disease. This is a stark opposite to what we're seeing in the Kaiser AIDS study, which is completely the opposite on all of those fronts. We're seeing significant increase in mobility. We're seeing patients reducing their need for walking aids. And patients by the very nature of the MIB cell therapy are able to stop their chronic immunosuppressants and actually have a drug-free disease for your admission. So the natural history study is very, very important because it helps contextualize the fantastic results that we're seeing. And the FDA is interested in using this as a support for our file.

It sounds like such a wide range between what you're showing and what the natural history progression is for these patients. Like there's a lot of, you know, ways that you are benefiting beyond just slowing down the disease. You're actually, you know, helping reverse the disease in a way for these patients.

Definitely. And if you look even further at the data, we have exploratory endpoints that are looking at the quality of life of patients. And this is extremely important. We're seeing both improvements in terms of mobility, in terms of their quality of life, but also in terms of their psychological appreciation for their condition as well, being significantly improved after MivCell. You have to remember that for these patients, this diagnosis really robs them of their ability to move, and many of them makes them homebound. And so there's a psychological component to this. Many of these patients are depressed. They have to stop working. They require around-the-clock care and support. The ability for MivCell to reduce that is not just an improvement of mobility. We're essentially giving them their lives back. And this is borne out in the data, but it also borne out when you speak to patients that have been on this therapy.

Can you give us a little bit of a preview of what we might expect from launch? Obviously, this is a new area, so a lot of wide space for you guys. But help us understand kind of the patients that are out there waiting for this therapy, who's diagnosed. you know, since they're 80% of them are planning to, I mean, 80% of them will progress to needing a walking aid or wheelchair. What does that say about like the patient's motivation to get on therapy and what kind of a bolus effect we might see at launch?

Yeah, well, there's a very high demand for therapy, as you can imagine, with nothing approved and nothing really working for these patients. When we speak to patients and we're very engaged with the patient advocacy group that's supporting these patients, we're hearing directly from them that they're very anxious for us to continue moving our program forward so that we can get this to them as quickly as possible. And you have to think here that there's 6,000 patients in the U.S., which is a significant number of patients, and they're highly concentrated in being treated in a few academic centers. In In fact, we know there's 2,000 to 2,500 of these patients that are already refractory to existing immunotherapies and rituximab and other off-label therapies that these physicians These are the readily addressable and immediately addressable patient population that we're going to be focusing on immediately at launch. And these patients are highly concentrated in a few academic centers. So this is allowing us to build a really capital-efficient, go-to-market commercialization model that will allow us to serve these patients and get off to a strong launch start. But again, we see this as the tip of the iceberg, because as you just pointed out, most of these other patients will also progress over the course of their disease. And these patients are very well aware of their prognosis. They're looking at their friends and their peers that have this disease, and they've told us they don't want to become, you know, the person that ends up in a wheelchair. So we know that as we continue to launch the education around this disease continues to increase and we continue to show long-term durability data we believe we're going to have access to most of those 6 000 patients over the course of the launch cycle so in a sense we're viewing this as a rare disease launch and like typical for rare diseases that never have had an approved therapy before i think a lot of times it's underappreciated under diagnosed and under and under treated i think with miv cell we're going to change that change that dynamic and and change it in a big meaningful way for these guys, for these patients.

It makes a lot of sense to me. Okay. And pricing is obviously a topic that comes about with any upcoming launch. No, you can't comment formally on pricing, but maybe help us understand how you're thinking about the pricing dynamic for a rare neurologic disease and understanding that MIV cell is potentially going to be indicated for multiple different diseases. How do you think about this setting the precedent for moving into potentially mg do you think about pricing as just an sps uh centric discussion or is it around the whole future of the therapy and the the nature of the franchise you know well we're looking at it really holistically but but starting with stiff person syndrome we have to sort of look under the hood and see what is the cost of actually managing these patients and unfortunately the cost of the system is extremely high.

Most of these patients, like I said, are on chronic immunosuppressants. A lot of them are on chronic IVIG, either monthly or many of them are biweekly IVIG, which costs hundreds of thousands of dollars a year and doesn't really work. I mean, they might provide some symptomatic relief for patients temporarily, but most of these patients will, again, as I said earlier, progress over time. You layer on top of that lost time from work because many of these these patients can't work anymore. There's a high degree of caregiver costs. There's psychological costs. I didn't mention this earlier, but part of the condition is not only this increasing dismobility, but a lot of times patients have these freezing attacks. And then when they freeze up, they can't control it and they fall over. And so they injure themselves. So they end up in emergency room. So there's a lot of additional costs of managing this disease. And when you add it all up, costs hundreds of thousands of dollars a year and patients aren't getting better. They're just getting worse. So if you put that into contrast with MivCell, where, again, we can deliver a one-time therapy, and for a majority of our patients have this transformative clinical effect, while also removing all the other background therapies that patients are taking, this is a high-value proposition for payers. So what we've been guiding, not guiding to a specific price, but what we've been guiding to is a significant premium over current CAR-T pricing. And when you look at current CAR-Ts, they are priced between $500,000 to $600,000 for a treatment. We believe the cost benefit and the value proposition that MipCell is bringing will be able to have a significant premium to that when we come to the market.

Excellent. Great.

Moving to GMG, can you help us understand what the data we've seen so far tell us in terms of the confidence of MipCell in this indication, as well as what you think Phase 3 needs to show to be competitive? well this is why we're so excited about generalized myasthenia gravis is that the phase two results which we read out earlier this year and in the coming couple weeks here will show an extension of the phase two results longer term follow-up but what we were able to see is again a profound clinical impact with miv cell across a number of different endpoints including MGADL scores. We saw a reduction of 8.5 on MGADL, a reduction of 11.3 on QMG. These are results you just don't see from any other existing therapy or approved therapy or therapies that are being studied right now. This is really a transformational step change in terms of what we're delivering in terms of symptom relief for patients. But in addition, we're actually getting more patients to MSC, which is critically important for patients. MSC is minimal symptom expression. This is ultimately what patients want. They want to have a disease-free, drug-free existence, and that's what NubCell is delivering for them. And again, it's a one-time therapy, so patients can come off their background immunosuppressants, high-dose steroids. A lot of times, this is layered on top of FCRNs and complement inhibitors that these patients are taking and have been largely ineffective in treating these patients. And again, we can come in and have them stop doing that while still having this profound clinical result. So we're really excited by these initial data. And to your point, this is helping accelerate our phase three clinical development program. So we're well underway with our pivotal phase three study. We started enrolling patients at the end of last year. We're guiding to completion of enrollment of that trial in mid-2027. And again, that puts us in a leadership position because no other cell therapy company's got a pivotal or autologous CAR-T therapy company has a pivotal phase three study. And we could be first to bring this to patients, generalized myasthenia gravis.

And when you think about the ideal patient, or not ideal, when you think about a launch profile of MIV cell in MG and maybe extrapolating from the data we have or the data you're hoping to get in phase three, what do you think the patients are that come onto this therapy? Are there multiple buckets, like for instance, who would take this before a complement inhibitor, FCRN, or would it be, is there another bucket where patients take FCRNs and then they're not happy with it and then they come onto therapy? How do you see this type of a cell therapy working in MG?

Well, this is why we designed the phase three study the way we've designed it. We're going to take all comers from patients that have been on FCRNs, complements, other more traditional immunosuppressant therapies. And as long as patients have failed one immunosuppressant plus IVIG or Plex or two immunosuppressants, and it doesn't matter which ones, they'll be allowed to come in the trial, assuming that they're above an MGVL score of six, so they're moderate to severe patients. So we're going to have a wide variety of patients in the phase three study, which is a similar patient population that we had in the phase two study. And this will allow us to open up the aperture to treat a wide variety of patients. And the way we're thinking about here at Caverna is patients that are, yes, refractory to these existing therapies will be ideal candidates for MivCell, but we're also getting a number of patients that are inquiring about the trial and wanting to be in the trial that are earlier on in their disease journey simply because they don't want to be taking chronic therapies anymore. The problem with FCRNs and complements and all these other treatments is that they're chronic. Patients have to take them usually in combination with one another. They come with their own side effect profile and treatment burden. And a lot of times the symptoms in these patients are waxing and waning as they're trying to just maintain some kind of control around their disease. So what patients are realizing is if you can take a one-time therapy, have this profound clinical result, that again, stopping all this other things that they're actually taking, this is a real difference.

So I think we're going to have a variety of different kinds of patients that'll ultimately be great MIV cell candidates, including those that have tried other therapies, but those also that just don't want to be burdened with chronic therapy anymore makes a lot of sense okay uh there's a lot of you know um eyes on in vivo car t these days and uh some some players in the field are thinking about their life cycle management strategy of having an in vivo car t you know coming about after their autologous um how do you think about in vivo car t versus autologous longer term obviously autologous is here this is what's real and what we have, like, you know, the most patient data on and the best understanding of. But as the field looks towards N vivo CAR T in the future, how do you all consider that and thinking about, you know, bringing on something of your own for that?

Yeah, I think what you said, though, is extremely important is patients are waiting for therapy. And we've got something that we know is de-risked and that is highly effective and is highly safe in these patients. And we have an opportunity to bring it to them first. So we've got stiff person syndrome patients that are waiting. We've got generalized myasthenia gravis patients that are waiting. We've got some very interesting data in progressive MS as well that could show the transformational impact of MIV cell in PMS. And we at Caverna are really focused in on the here and now and bringing this to patients because we know we can do it. And we're actually leading the entire world in terms of making that happen. That said, we're also thinking to the future. We're looking at advances in our manufacturing platform, advances in automation, things like whole blood, other things that will make this easier for patients to take CAR-T therapy and bring the therapy closer to where patients are living and working. And we are also looking at additional platforms and other advances in the future, potentially in vivo as well. But in vivo is a long way out. There's a lot of questions that still remain to be answered, questions around durability, questions around safety, questions around scalability and manufacturing and cost. So there's a lot of things that still need to be worked out. What we do know now is we've got a very effective therapy that we can bring cost effectively to the market and start to build this neuroimmunology portfolio here at Caverna and, like I said, lead the rest of the world in terms of doing that.

Excellent. So the last thing, we just want to wrap up with a preview of the next 12 months. We talked about a lot, so maybe give us a highlight of the milestones ahead, what we can expect for the value inflection points for Kyberna.

Sure. Well, coming up in the next couple of weeks, we've got some extended long-term data, the one-year follow-up on the Kaiser 8 study, which is our SPS trial, as well as our long-term follow-up on our MG Kaiser VI Phase II study. Those will be coming out in the next few weeks, and like I said, I'm hoping to show this longer-term durability effect. In addition, we're going to be showing additional follow-up data on our MS patients, our progressive MS patients with MivCell, and that will be coming in Q4. We did talk about the completion of the filing of the BLA in Q4, and once we've done that, plus the acceptance of the file, we'll announce that. And then, of course, we'll be ready to be launch ready in 2027, because, again, we'll hopefully be leading the world here in terms of bringing these transformative therapies to patients. Excellent.

Thank you, Warner. Really appreciate it. Thank you to the Caverna team, and thank you to all the audience members who joined for this conversation.

Thanks, Mitch.