Hello everyone. My name is Mitchell Kapoor. I am a Senior Biotech Analyst at H.C. Wainwright. It is my pleasure today to welcome you all to the Fireside Chat with Kyverna. From the company, I have the CEO, Warner Biddle. Thank you for joining us today.
Thank you, Mitchell. It is a pleasure to be here.
Great. I like to start off every Fireside Chat just orienting the room to the company, current developments, and what the near-term focus points should be as we are looking at the Kyverna story.
Sure.
Maybe we could start there.
Sure. Well, at Kyverna, 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, 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 of 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 in autoimmune diseases. This is a really important milestone for us.
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 miv-cel, this transformative therapy, to more patients around the world.
Yeah. It's exciting as the first in the field, right, to potentially become commercial. We will definitely dive into that application and others. I think maybe to start off on something topical, Novartis and Bristol Myers Squibb paused autoimmune CAR T trials two weeks ago. Obviously use different constructs, manufacturing, patient population are relevant to assessing miv-cel, but wanting to think about how many patients miv-cel has been in to date, how safe is miv-cel, and what things can we learn from that? Also, what are the differences that you can draw between miv-cel and Novartis and Bristol Myers Squibb?
Sure. Well, first thing, let's just acknowledge this is really unfortunate to hear these announcements about these patients. It was really difficult to hear that news. I think it does really underscore what we're doing here at Kyverna is different.
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 a CD28 costimulatory 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, miv-cel 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 therapy, 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.
We believe the CAR construct is extremely important, and in the 100+ patients we've now dosed with miv-cel, 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 reporting. This really underscores the importance of the safety of the construct as the first key pillar. But you touched on the 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's extremely important. At Kyverna, 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.
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 miv-cel. Like I said, in over 100+ 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. I think it's important maybe if we can educate the audience about what Stiff Person Syndrome is, how it's an I&I indication, but also kind of like a rare disease, what these patients go through, and 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 are 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 GAD65 and other antibodies, but it is a B-cell mediated antibody disease, which is why miv-cel 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 are 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 will 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 is a huge cost to the system in terms of lost time from work, but also caregiver costs. There are no approved therapies. There are no approved FDA therapies, and the off-label therapies that these patients are taking do not 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 are seeing with miv-cel in our pivotal clinical study are so remarkable.
For the first time ever, with a one-time therapy of miv-cel, we are 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 2/3 of the patients that required a walking device at the beginning of our study, 16 weeks later, no longer needed that walking device.
Patients are literally walking with improved mobility, significantly improved mobility, which is remarkable. It is a one-time therapy, so patients can remove their other chronic therapies that they have been burdened with, and we are doing it 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. As I mentioned earlier, we are on track filing our BLA, and we could be the first approved therapy in this condition. I also think we are setting a bar for how autoimmune diseases could be treated more broadly, and I think we are leading the way here at Kyverna in making that happen.
Excellent. We are approaching the 12-month durability data for the SPS. Obviously, some initial amazing data that can help patients who are in such dire straits. Can you help us understand what we are looking for in terms of the durability metrics for these patients at the follow-up 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 timed 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 that we are able to track. 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 highly clinically meaningful. What we are 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. If you compare that to, again, the natural history for these patients where at best patients remain flat in terms of their disability, but will progressively get worse over time, again, this will help strengthen the overall story of what miv-cel is doing. It will help strengthen our BLA submission, and it will help strengthen our commercialization position once we get approved.
Great. Can you help us understand the advantages of this rolling BLA submission, and what remains to be compiled into that, when you do eventually file that? How does the natural history comparison in SPS help support your regulatory discussions and potential approval of miv-cel and SPS?
Sure. Well, based on the results that we have had in this clinical trial, the KYSA-8 study, we had a positive pre-BLA meeting rather, with the FDA early this year. On the basis of that, they granted us this rolling BLA submission, which we are in the process of doing. In fact, we are 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.
We have now successfully submitted that, which is a positive de-risking event. The only thing left for us is to finish the clinical module. In that clinical module, we want to include this one-year follow-up data from the KYSA-8 study. This will be important for providing additional depth of durability around miv-cel 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 KYSA-8 study and what we are seeing in the study, and how does it compare to the real world. 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.
In that study, we saw on average that patients' mobility got progressively worse over time, that they needed significantly increased use of walking aids.
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 are seeing in the KYSA-8 study, which is completely the opposite on all of those fronts.
We are seeing significant increase in mobility. We are seeing patients reducing their need for walking aids. Patients, by the very nature of the miv-cel therapy, are able to stop their chronic immunosuppressants and actually have a drug-free, disease-free remission. The natural history study is very important because it helps contextualize the fantastic results that we are seeing. The FDA is interested in using this as support for our file.
It sounds like such a wide range between what you are showing and what the natural history progression is for these patients. There is a lot of ways that you are benefiting beyond just slowing down the disease. You are actually helping reverse the disease in a way for these patients.
Definitely. 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 are 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 miv-cel. 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. There is 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 miv-cel to reduce that is not just an improvement in mobility, we are essentially giving them their lives back.
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 the patients that are out there waiting for this therapy, who's diagnosed, since 80% of them will progress to needing a walking aid or a wheelchair. What does that say about the patient's motivation to get on therapy, and what kind of a bolus effect we might see at launch?
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. They're very anxious for us to continue moving our program forward so that we can get this to them as quickly as possible. 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 and being treated in a few academic centers. In fact, we know there's 2,000-2,500 of these patients that are already refractory to existing immunotherapies and rituximab and other off-label therapies that these physicians are using.
These are the readily addressable and immediately addressable patient population that we're going to be focusing on immediately at launch. 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.
These patients are very well aware of their prognosis. They are looking at their friends and their peers that have this disease, and they have told us they do not want to become the person that ends up in a wheelchair. 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 are going to have access to most of those 6,000 patients over the course of the launch cycle. In a sense, we are viewing this as a rare disease launch.
Like typical for rare diseases that never have had an approved therapy before, I think a lot of times it is underappreciated, underdiagnosed, and undertreated.
I think with miv-cel, we are going to change that dynamic, and change it in a big, meaningful way for these guys, for these patients.
Makes a lot of sense to me. Okay. Pricing is obviously a topic that comes about with any upcoming launch. I know you cannot comment formally on pricing, but maybe help us understand how you are thinking about the pricing dynamic for a rare neurologic disease and understanding that miv-cel 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-centric discussion, or is it around the whole future of the therapy and the nature of the franchise?
Yeah. Well, we're looking at it really holistically, 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.
Unfortunately, the cost to 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. 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 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 dysmobility, but a lot of times patients have these freezing attacks, then when they freeze up, they can't control it, and they fall over, so they injure themselves, so they end up in emergency rooms. So there's a lot of additional costs of managing this disease. 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 miv-cel, 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, we're not guiding to a specific price, but what we've been guiding to is a significant premium over current CAR T pricing. 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 miv-cel is bringing, that we'll 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 miv-cel in this indication, as well as what you think phase III needs to show to be competitive?
Well, this is why we're so excited about generalized myasthenia gravis is that the phase II results, which we read out earlier this year, and in the coming couple of weeks here, we'll show an extension of the phase II results, longer-term follow-up. But what we were able to see is, again, a profound clinical impact with miv-cel across a number of different endpoints, including MG-ADL scores. We saw a reduction of 8.5 on MG-ADL, 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 and relief for patients. In addition, we're actually getting more patients to MSE, which is critically important for patients. MSE is Minimal Symptom Expression. This is ultimately what patients want. They want to have a disease-free, drug-free existence, and that's what miv-cel is delivering for them. 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.
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. To your point, this is helping accelerate our phase III clinical development program. So we're well underway with our pivotal phase III study. We started enrolling patients at the end of last year. We're guiding to completion of enrollment of that trial in mid-2027.
That puts us in a leadership position because no other cell therapy company, autologous CAR T therapy company has a pivotal phase III study. We could be first to bring this to patients with generalized myasthenia gravis.
When you think about the ideal patient, or not ideal patient, when you think about a launch profile of miv-cel in MG, maybe extrapolating from the data we have or the data you are hoping to get in phase III, what do you think the patients are that come onto this therapy? Are there multiple buckets? For instance, who would take this before a complement inhibitor, FcRN, or is there another bucket where patients take FcRNs then they are not happy with it, 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 III study the way we have designed it. We are going to take all comers from patients that have been on FcRNs, complements, other more traditional immunosuppressant therapies.
As long as patients have failed one immunosuppressant plus IVIG or PLEX or two immunosuppressants, it does not matter which ones, they will be allowed to come in the trial, assuming that they are above an MG-ADL score of six, so they are moderate to severe patients.
We are going to have a wide variety of patients in the phase III study, which is a similar patient population that we had in the phase II study. This will allow us to open up the aperture and to treat a wide variety of patients. The way we are thinking about here at Kyverna is patients that are, yes, refractory to these existing therapies will be ideal candidates for miv-cel, but we are 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 do not want to be taking chronic therapies anymore.
The problem with FcRNs and complements and all these other treatments is that they are chronic. Patients have to take them, usually in combination with one another. They come with their own side effect profile and treatment burden. A lot of times the symptoms in these patients are waxing and waning as they are trying to just maintain some kind of control around their disease. What patients are realizing is if you can take a one-time therapy, have this profound clinical result that, again, stopping all the things that they are actually taking, this is a real difference. I think we are going to have a variety of different kinds of patients that will ultimately be great miv-cel candidates, including those that have tried other therapies, but those also that just do not want to be burdened with chronic therapy anymore.
Makes a lot of sense. There is a lot of eyes on in vivo CAR T these days, and some players in the field are thinking about their life cycle management strategy of having an in vivo CAR T coming about after their autologous. How do you think about in vivo CAR T versus autologous longer term? Obviously, autologous is here. This is what is real and what we have the most patient data on and the best understanding of. As the field looks towards in vivo CAR T in the future, how do you all consider that and thinking about 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.
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-cel in PMS. And we at Kyverna 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's 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 of manufacturing and cost. 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 Kyverna and, like I said, lead the rest of the world in terms of doing that.
Excellent. The last thing, 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 Kyverna.
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 KYSA-8 study, which is our SPS trial, as well as our long-term follow-up on our MG KYSA-6 phase II study. Those will be coming out in the next few weeks, and like I said, 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 miv-cel, 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. 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 Kyverna team, and thank you to all the audience members who joined for this conversation.
Thanks, Mitch.