Good morning and welcome to the Kyverna Therapeutics investor conference call. At this time, all participants are in listen-only mode. A Q&A session will follow the prepared remarks. Please note that this call is being recorded. I would now like to introduce Jessica Serra, Head of Investor Relations at Kyverna Therapeutics.
Good morning and thank you for joining today's conference call to discuss top-line data from our KYSA-8 registrational trial of mevalcaptagene autolysel, or miv-cel, formerly referred to as KYV-101, in patients with stiff person syndrome, or SPS. Before we begin, I encourage everyone to visit the Investor Relations section of our website, where you can find today's press release and presentation materials. I'd like to remind everyone that we will be making forward-looking statements during today's call. These statements reflect our current expectations and beliefs and are subject to risks and uncertainties that may cause actual results to differ materially. Please review the risk factors discussed in today's press release, our presentation materials, and in our filings with the SEC for additional information. On the call today with prepared remarks are Warner Biddle, our Chief Executive Officer, and Naji Gehchan, our Chief Medical and Development Officer.
For our Q&A session, we will be joined by Marc Grasso, our Chief Financial Officer, Sham Dholakia, our Chief Product Officer, and Dr. Amanda Piquet, Director of Autoimmune Neurology at the University of Colorado Anschutz, as well as the Celine Dion Foundation Endowed Chair. I'll now turn the call over to Warner. Warner?
Thank you, Jessica. Good morning, everyone, and thank you for joining us. We're very excited to share our top-line data from our registrational trial in stiff person syndrome, our lead indication for miv-cel, which is the approved INN name for mevalcaptagene autolysel, previously referred to as KYV-101. For today's agenda, I'll start with some brief remarks on our top-line data and stiff person syndrome before turning the call over to Naji to review the data in greater detail. Then I'll close with some final thoughts on our CAR-T franchise and SPS market opportunity before turning to Q&A. Next slide. Today's landmark results highlight Kyverna's leadership in autoimmune CAR-T and also miv-cel's transformative impact in stiff person syndrome. For those unfamiliar with stiff person syndrome, it is a debilitating and progressive autoimmune disease with no FDA-approved therapies and significant unmet medical needs.
For this reason, we're very proud to share that our trial met the primary and all secondary endpoints with high statistical significance, demonstrating miv-cel's breakthrough in reversing progressive disability while eliminating immunotherapies after a single dose. Today's data supports our BLA submission to the FDA, which is on track for the first half of 2026. Importantly, with KYSA-8 being the first completed registration-enabling autoimmune CAR-T trial, it could pave the way for miv-cel to potentially become the first and only approved therapy in SPS and CAR-T cell therapy for autoimmune diseases. This marks a significant milestone for our company that was achieved through strong execution and a clear strategy. Our path to a valuable commercial opportunity is supported by attractive market dynamics unique to stiff person syndrome and our focused commercialization strategy.
Finally, our first-mover advantage can lay the foundation for Kyverna to expand into broader indications, such as myasthenia gravis, which is a core to our strategic roadmap as the leader in the autoimmune CAR-T field. Now, let's turn to the next slide for our top-line results. Naji will go through the data in more detail, but from a high level, the trial met all endpoints with high statistical significance, a truly remarkable outcome for our patients. From this table, we can clearly see the strength and quality of the data supported by high, significant p-values across the primary endpoint, the Timed 25-Foot Walk test, and secondary endpoints that assess the extent of disability and SPS-specific symptoms, which includes the Modified Rankin Scale, the Distribution- of-s tiffness Index, the Hauser Ambulation Index, and the Heightened Sensitivity Scale.
This level of consistency across data points is a significant achievement and further reinforces the potential of miv-cel in stiff person syndrome. In addition, miv-cel was well tolerated with no high-grade CRS or ICANS. Now, I'd like to show you a video which we believe brings to life the highly debilitating and progressive disease that is stiff person syndrome and the opportunity we have to change the treatment paradigm. This video of a 62-year-old female patient from our trial performing the Timed 25-Foot Walk test prior to receiving miv-cel. Here we see the classic hallmarks of stiff person syndrome: slow, cautious steps, a rigid posture, reduced arm swing, and overall impaired balance. In addition, you see the psychological impact of the disease. She appears anxious and hesitant with each step as she walks unassisted, and here is the video of her walking after miv-cel.
As you can see, a remarkable transformation. Her time to complete the walk went from 17.3 seconds to 4.5 seconds, a 74% improvement, and comparable to a normal healthy adult. Importantly, she no longer uses her walker. Next slide. As you saw from the video, SPS is a debilitating and progressive autoimmune disease. SPS impacts the GABA signaling pathway that controls the brakes on muscle contractions and helps muscles relax. Most patients with SPS have antibodies to GAD65 or the glycine receptor, which disrupt this braking system, leading to symptoms of severe muscle stiffness and painful spasms due to uncontrolled muscle contractions that impact mobility and gait. Moreover, there's high disease burden given the chronic yet suboptimal unapproved treatment options. SPS has a devastating impact on patients' lives, with the disease often occurring in adults and mostly women during their prime years in life.
Moreover, up to 80% of patients lose mobility over time and require walking aids or wheelchairs. Patients often experience freezing attacks and sudden falls that require emergency care, and most patients experience disease progression, which can lead to the risk of permanent disability and increased mortality. All of these factors underscore the potential for miv-cel to unlock significant therapeutic benefit and quality of life for these patients. Next slide. As there are no approved therapies for SPS, patients often resort to the use of symptomatic therapies, such as multiple daily doses of benzodiazepines, in addition to chronic off-label immunotherapies like IVIG, rituximab, and plasmapheresis. Despite these treatments, most patients have inadequate or no response. Further, immunomodulatory therapies also carry safety risks. Given the debilitating nature of this disease and its psychological impact on patients, many will also need physical and occupational therapy, as well as psychiatric treatment.
With the significant disease burden of SPS, novel therapies are desperately needed to address the root cause of the disease in order to stop or reverse progression. Now, let's turn to slide nine. I'd like to briefly touch on our differentiated CD19 CAR-T construct and why we believe it is optimal CAR-T for treating autoimmune diseases such as stiff person syndrome. KYV-101, or miv-cel, is designed for enhanced potency as the only human CD19-targeted autologous CAR-T with a CD28 co-stimulatory domain that mediates rapid and robust signaling. More than 100 patients have been treated with miv-cel to date across multiple indications through our Kyverna-sponsored clinical trials, IITs, and the compassionate use pathway. Based on the data generated thus far, miv-cel has demonstrated deep and broad B-cell depletion in the periphery and in targeted tissues. As a result, we're able to see profound efficacy in addition to durability.
The first SPS and MG patients treated with a single dose of miv-cel have now achieved durable efficacy beyond 24 months without the need for background therapies. This is truly a remarkable outcome. Finally, miv-cel is also designed for safety with a fully human CAR and other distinct features. Across the patients treated to date, miv-cel has demonstrated a consistent and manageable safety profile with no high-grade CRS or ICANS. Turning to slide 10. Consistent with the outcomes observed in generalized myasthenia gravis, miv-cel also demonstrates the potential to achieve four key therapeutic goals for patients with SPS. First, an ability to improve clinical symptoms and reverse progressive disability. Second, the potential to eliminate chronic immunotherapies. Third, a well-tolerated and manageable safety profile. And finally, fourth, and importantly, durability of treatment effect from a single dose.
Any one of these outcomes alone could represent a significant advancement for these SPS patients. miv-cel's potential to deliver on all four of these therapeutic goals underscores its promise and potential to become the first and only approved therapy for stiff person syndrome. Now, with that, I'll turn the call over to Naji to review our top-line results in greater detail.
Thank you, Warner, and good morning, everyone. I'm excited to be with you all today to detail our registrational data. Let's turn to slide 12. We believe our FDA-aligned registrational trial, along with our RMAT and Orphan Drug Designations for miv-cel and SPS, support a clear and rapid path to BLA. As a reminder, KYSA-8 is a single-arm multicenter open-label registrational phase II trial designed to evaluate the efficacy and safety of miv-cel in patients with stiff person syndrome. 26 patients were dosed to provide a robust assessment of the endpoint at week 16. These patients must have a confirmed diagnosis of SPS and an adequate response to prior immunomodulatory therapy in addition to a stiffness index score of at least two prior to enrollment. Importantly, all patients discontinued immunotherapies prior to a single infusion of miv-cel.
The primary endpoint, as mentioned earlier, is the Timed 25-Foot Walk test at 16 weeks. In addition, the therapy's overall safety profile is assessed. Secondary endpoints include the Modified Rankin Scale, or mRS, Distribution- of- stiffness Index, or DSI, Hauser Ambulation Index, or HAI, and Height ened Sensitivity Scale, or HSS. The follow-up period for patients in this trial is one year, and the data I will share today are from our primary analysis, which occurred at week 16. Let's turn to our baseline patient characteristics on slide 13. Overall, the baseline characteristics of our cohort are very much representative of a real-world spectrum of SPS patients. The trial dosed 26 patients with SPS with a median age of 56. The median baseline Timed 25-Foot Walk test was 11.2 seconds, with a range between 7.8 seconds to over a minute.
These times are much higher than the four to five seconds for a healthy adult. The median Distribution of Stiffness Index score was three points, with a range between two to six points, which is the maximum. 88% of patients are GAD65- positive, the most common autoantibody associated with SPS, and 12% of patients are glycine receptor positive, and finally, all patients previously had inadequate response to prior immunomodulatory therapy, which include IVIG, plasmapheresis, or rituximab. Let's turn to slide 14. Before I get into the details of the data, it is important to understand how mobility is assessed for stiff person syndrome. The Timed 25-Foot Walk test is a validated tool to assess walking ability as well as to evaluate stiffness and loss of mobility. For the test, patients perform one Timed 25-Foot Walk, turn around, and do a second Timed 25-Foot Walk.
Then the average time of the two walks is taken. To put things into perspective, the time that it takes a normal healthy individual to walk 25 feet is about four to five seconds. For patients with SPS, that time can be twice as long or even longer, depending on the severity of their disease. For this endpoint, a 20% improvement in the Timed 25-Foot Walk is considered clinically meaningful. Let's go to slide 15. miv-cel delivered robust and sustained improvement in mobility, with a median change from baseline in Timed 25-Foot Walk test of 46% at week 16, which was highly significant, with a p-value of 0.0002. This far exceeded the threshold of 20% improvement that is considered clinically meaningful, which is represented here by the blue line. In addition, it is notable that patients on average saw meaningful clinical results as early as week four.
The null hypothesis represented by the black dotted line at zero indicates that we would expect to see no improvement from baseline in patients on off-label immunomodulatory treatment. Further, 81% of patients exceeded a clinically meaningful 20% improvement in Timed 25-Foot Walk at week 16. This is truly a remarkable response rate, given that all patients had uncontrolled disease despite being on off-label therapies, and of these patients who had reached 24 weeks, all maintained their improved mobility, further demonstrating miv-cel's robust and durable treatment effect. Turning to slide 16. What's also notable is miv-cel's ability to eliminate ambulatory aids for patients. As you can see from this graph, the number of patients requiring walking aids that are the lighter and darker red bars substantially decreased from baseline to week 16, with the majority not needing walking aids after miv-cel treatment.
Notably, of the 12 patients who required a walking assistant device, such as a cane or walker at baseline, 67% no longer needed them at week 16 and through last follow-up. In terms of the impact to help restore quality of life for patients with SPS, reversing progressive disability to this degree is a game changer. Next slide. Now, let's turn to our secondary endpoints, which include the Modified Rankin Scale, or mRS, that measures the degree of disability, the Hauser Ambulation Index, or HAI, which measures the time and degree of assistance to complete the Timed 25-Foot Walk test, the Distribution- of- stiffness Index, or DSI, that measures muscle stiffness in various parts of the body, such as the face, trunk, and legs, and lastly, the Heighte ned Sensitivity Scale, or HSS, that measures the number of triggers of muscle spasms.
These external factors can include noise, light, or spasms can be spontaneous. As you can see, there are many ways to assess disability, and it was important to include all of these measures in our trial to ensure a robust evaluation of miv-cel's efficacy. Turning to slide 18. In summary, miv-cel achieved statistically significant benefit for patients across all endpoints. Patients achieved significant improvement in the Timed 25-Foot Walk test and disability scores by mRS and HAI. In addition, their scores on SPS-specific symptom scales also improved meaningfully. Importantly, these results reinforce the consistency of miv-cel's efficacy across all primary and secondary endpoints. Turning to safety on slide 19. Consistent with the safety profile seen across more than 100 patients treated to date, miv-cel was well tolerated in the study, with no high-grade CRS or ICANS observed. CRS and ICANS events were low-grade, transient, and manageable in all patients.
16 patients had grade 3 or 4 neutropenia, which is a known adverse event associated with CAR-T treatments. All neutropenia events were manageable, and the majority of the cases were resolved within less than 28 days of infusion. Moving to slide 20. To further illustrate the potentially transformative nature of miv-cel, I'd like to share a patient case from our KYSA-8 trial. This was a 52-year-old male patient who had been diagnosed with SPS for about 8 and a half years, but had been experiencing symptoms of disease for about 20 years. When he was first assessed, he clearly had diminishing benefits of IVIG and was demonstrating clear disease progression. He was also on Valium three times a day to control spasms, was struggling to walk with a walker, and was no longer able to work.
Following infusion, a rapid response to miv-cel was observed, and by week 16, he showed remarkable improvement. His baseline 25-foot walk time improved from 18 seconds to five seconds, which is the normal walking speed of a healthy adult. In addition, he demonstrated improvements in other functional and SPS efficacy measures assessed in the study. Further, miv-cel was well tolerated. I can describe it further, but it would be easier for me to show you this video that demonstrates his remarkable progress. In this video at screening, you can see that this patient is holding his body in this uncomfortable-looking position. This is due to hyperlordosis, a common symptom in advanced SPS patients caused by stiffness in the trunk, resulting in a permanently arched back. He is walking sideways for better stability and due to extreme fear of falling. Here he is, week 16, after miv-cel.
This video tells the story all by itself. miv-cel not only improved this patient's ability to walk, but restored much more than can be measured by endpoints on the study. After treatment, this patient is starting to do things he has not been able to do in a long time, which includes working again on some projects. Since he lives in a city, he now is able to do everyday activities that people like you and I might take for granted, like crossing city streets by himself again. Turning to slide 22. In summary, these are extremely exciting results that represent a significant breakthrough in SPS and autoimmune CAR-T. First and foremost, KYSA-8 is the first and only registration-enabling trial of CAR-T in autoimmune disease to support a BLA filing. We observed highly statistically significant benefits on primary and all secondary efficacy endpoints.
miv-cel delivered durable clinical improvement while reversing disability scores. Importantly, all patients were able to eliminate the use of ineffective off-label immunotherapies after just a single dose. The therapy also has a well-tolerated and manageable safety profile, and finally, today's data support our BLA submission, which is targeted for the first half of 2026, and with that, I'll turn the call over to Warner. Warner?
Thank you, Naji. Moving to slide 24. With Naji's summary of our data, today marks a pivotal milestone in solidifying Kyverna's leadership in the autoimmune CAR-T market. For patients with SPS, we're paving the way for miv-cel to potentially become the first FDA-approved therapy in stiff person syndrome, helping patients reverse their disease.
For the emerging autoimmune CAR-T field, miv-cel is poised to potentially become the first CAR-T cell therapy ever approved in autoimmune diseases, where we believe there's tremendous opportunity for miv-cel to shift the treatment paradigm away from chronic disease management and towards long-term remissions and potential cures. SPS is only the beginning. For Kyverna, if approved, we will have a first-mover advantage with miv-cel, bringing us closer to delivering patient impact at a commercial scale and affirming our pioneering role in this space. In addition, this advantage provides a springboard to launch into broader indications, including myasthenia gravis. Turning to slide 25. I'd like to briefly touch on our compelling commercial opportunity in SPS for miv-cel. As we've previously mentioned, there are approximately 6,000 diagnosed patients in the U.S., which is a larger than previously reported prevalence, and this number is supported by both epidemiology and claims data.
Further, there continues to be ongoing work in SPS diagnostic and treatment guidelines, which we believe will increase awareness of this disease and improve diagnostic rates and access to treatment. Our initial priority will focus on patients with the highest unmet need, who are ready for better treatment options. This accounts for 2,000 to 2,500 patients, or roughly 30%-40% of the diagnosed patients who have inadequate response to off-label immunotherapies. In this patient population, we believe miv-cel has the potential to be quickly established as the first and only FDA-approved therapy to deliver an effective and safe treatment alternative. In addition, given the inadequate responses associated with symptomatic treatments, which are used by approximately 90% of diagnosed patients, we believe we can also effectively target these patients over time, based on the real-world clinical evidence, the longer-term follow-up data from our KYSA-8 trial, and with increased education.
Turning to slide 26. We have a strong conviction in our ability to deliver on this valuable commercial opportunity in SPS and beyond. First, the market dynamics of SPS are attractive given the high unmet need and no approved therapies. There is a meaningful prevalence of approximately 6,000 diagnosed patients. In addition, disease awareness and the adoption of standard diagnostic testing continues to grow, further reinforcing that SPS is an important and defined market. Against these attractive market dynamics, we have a differentiated commercial strategy that will enable us to unlock miv-cel's potential in stiff person syndrome. If approved, we'll be first to market and have the opportunity to establish a price with payers and become entrenched with key centers and physicians. Importantly, we'll be able to do this in a focused way. Patients are concentrated at academic centers, and we know where they are.
And we'll be able to leverage our focused commercial organization and scalable CDMO model, in addition to the existing CAR-T ecosystem, to effectively reach our initial addressable market. Finally, we have a proven leadership team that has significant experience in establishing and growing the CAR-T market. The commercial foundation is just laying the groundwork for SPS and will be critical for supporting our fast-follower strategy for myasthenia gravis, where we have significant franchise synergies and will help us enable a successful and scalable launch into this larger indication. Moving to slide 27. With today's positive results, along with the many other clinical and regulatory milestones we've achieved across our pipeline, we believe we have a promising path forward for our neuroimmunology CAR-T franchise and beyond. We've had a tremendous year of execution in 2025.
We've delivered landmark registrational data in SPS, supported by a valuable commercial opportunity and a clear path forward, and we're preparing for a BLA submission expected in the first half of 2026. In myasthenia gravis, we've seen unprecedented interim phase II results, and we're now on track to enroll the first patients in our registrational phase III study. Beyond neuroimmunology, we are strategically pursuing a broader pipeline in autoimmune diseases. Recently, we shared early IIT data in multiple sclerosis and rheumatoid arthritis, highlighting miv-cel's potential across multiple indications. In addition, for KYV-102, our next-generation CAR-T construct featuring a rapid whole blood manufacturing process, we've delivered on our goal to file an IND by the end of 2025. Importantly, our current financial position supports our BLA filing in SPS and our phase III MG trial while we accelerate our pre-launch activities.
We're excited to head into the new year with tremendous momentum across our programs and look forward to updating you on our progress. Before we turn to Q&A, I'd like to close with the video of the patient we introduced at the beginning of this call. Let's see their transformative outcomes once again. And with that, I'll turn the call over to our operator for the Q&A.
Thank you. I'll now open up the call to a question-and-answer session. If you'd like to ask a question, please press star one one . If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. Our first question comes from Brian Cheng with JP Morgan. Your line is open.
Hi, Warner. Hi, guys. Thanks for taking our question this morning, and really congrats on the data.
As we think through the phenotype of SPS, there's always these painful spasms that are clearly a notable characteristic of the disease. Can you speak to the level of improvement, either in the frequency or the severity of the spasms and possible contraction in the patients? Can you talk about the influence that miv-cel has in those patients? And then we'll have a quick follow-up. Thank you.
Thanks, Brian. Maybe I'll turn that over to Naji just to comment a little bit on that, but I'd also like Dr. Amanda Piquet, who we have on the line, to also comment from her clinical perspective. Naji?
Yes, thanks for the question, Brian. So as you've seen, it's really remarkable results we're seeing here with impact on all our primary and secondary endpoints, which is a consistent result across those endpoints and is very powerful.
So in those scores, we have, as we've shared, ambulation scores and also disease-specific scores that capture those spasms and how the sensitivity of those to happen and also the stiffness index on all the different muscles. And we have seen consistent, highly statistical results on all of them. So additional detail, obviously, we'll be following with more efficacy data in a future conference. But I'd love for Dr. Amanda Piquet, who is with us, if she wants to give a little bit more color on the efficacy from a patient's lens too. Amanda?
Yes, so thank you. I just want to reemphasize that, you know, in my expert opinion, the results of this trial are just truly remarkable, and when you look at the stiffness index and the height and sensitivity scale, those account for those painful muscle spasms that we see in the patient.
Obviously, with the data presented, we saw a significant reduction there.
Great. And then just, you know, back to your first filing in the first half next year, what are some remaining factors before the filing? What is left to do now that you have your pivotal results in hand?
Thanks, Brian. As you can imagine, we're really excited by these data. So we're pivoting right now to completing all the necessary steps for a pre-BLA meeting and conversation with the FDA. But we're excited, and as we've been saying, we're on track to file that BLA in the first half of 2026.
Great. Well, thanks again, and congrats.
Thanks, Brian.
Thank you. Our next question comes from Thomas Smith with Leerink Partners. Your line is open.
Hey, guys. Good morning. Congrats on the really stellar data here, and thanks for taking our questions.
Maybe I could just start with maybe two for Dr. Piquet. Could I just ask you to elaborate on how you're thinking about the profile here and the balance between efficacy and safety with miv-cel? And just help us understand within your center, you know, how many patients do you think are candidates for miv-cel, and how are you thinking about positioning miv-cel relative to other off-label treatment options? An d then I have a follow-up.
Sure. Amanda, do you want to take that? There's a question about the balance of efficacy and safety and then the profile of patients that we're looking at.
Sure. I'll start with the efficacy and safety question. So with the clinical trials you saw from the data, you know, there was nothing that was unanticipated or unexpected in terms of the safety profile. So I felt very comfortable with that.
And as you can see through those videos and meeting every primary and secondary endpoint, the efficacy is amazing. So looking at that risk-benefit, truly, you know, favorable there. And again, I just want to say very unprecedented results here for that favorable benefit and risk profile compared to, especially when you look at the off-label therapies that we generally use in SPS, we don't see that kind of clinical response. And then, Warner, let me know which follow-up question. There were multi-level questions in there.
You just want to repeat the second part of your question there? I think you said you had a follow-up.
Sure. Yeah. No, I was just hoping you could comment on sort of within your center, Dr. Piquet, how many patients do you think are candidates for miv-cel, and how are you thinking about the positioning relative to off-label treatment options?
I gotcha.
You know, this therapy, I think, is going to be very beneficial for patients, even beyond the eligibility criteria that we saw in the clinical trial. We know this disease to be progressive. Even patients that are stable right now in our clinical practice, you know, likely won't be in the future. Given the fact that I said these off-label treatments are often inadequate or the durability of response is not sustained for our current off-label therapies, these patients may be candidates for miv-cel in the future.
Got it. That's super helpful. Yeah, I appreciate the insights. Then maybe one for the company.
Just from a regulatory perspective, based on the transformative efficacy and the huge unmet need in this population, could you comment on, I guess, your level of engagement with FDA and whether you plan to pursue one of the Commissioner N ational Priority Vouchers? Thanks so much.
Yeah, thanks, Tom. Yeah, as we've spoken about before through the RMAT Designation, Orphan Drug Designation, we have a really strong and consistent dialogue with the FDA. And given the conversations that we had with the FDA prior to setting up this trial and in partnership with setting up this trial, we believe now that we're seeing this data that we've not only met, but highly exceeded the expectations in terms of what would be needed in order to grant an approval in this indication. The CMPV voucher is also very interesting. We continue to assess that.
We obviously feel really strongly about the transformative nature of what miv-cel is bringing for patients. So we're continuing to assess the opportunity to accelerate the development and the filing and BLA filing for miv-cel moving forward. But we believe we've got a really strong position here with the RMAT and Orphan Drug Designation in order to capitalize on this.
Makes sense. Thanks so much, guys. Congrats again on the data.
Thank you.
Thank you. Our next question comes from Mike Ulz with Morgan Stanley. Your line is open.
Good morning. Thanks for taking the question, and congratulations on the data as well. Maybe just one on the Timed 25-Foot Walk. There were a couple of patients that didn't meet that 20% threshold. Just curious if those patients also had a benefit and if there was anything unique, maybe in the baseline characteristics for that group of patients. Thanks.
Yeah.
Thanks, Tom. I think this is a really remarkable result, seeing over 81% of the patients achieving a really statistically and clinically meaningful result beyond expectations here, which is truly remarkable given the fact that all current treatments, unapproved therapies, are suboptimal and don't lead to any clinical improvement. But Naji, maybe you want to comment a little bit more on that from a clinician's perspective and maybe put that in perspective.
Sure. So what you see here, Mike, is really never seen with any other therapy so far. We're seeing improvement in 81% of patients beyond what is clinically meaningful.
Then you're seeing this response not only on the Timed 25-Foot Walk, but also across all the secondary endpoints, whether it's disability or specific scores, as Amanda was sharing, for the disease itself, which is truly remarkable and not seen with this consistency across all those primary and secondary endpoints. This is, you know, another thing to put into perspective. Those patients who are now walking without aid. The majority of patients now, 67% of patients who needed walking aid, just threw them away. This is truly remarkable and never seen. I don't know if Amanda, you want to comment on this, obviously, with the experience you've had with your patients on those data.
Yeah, I think just looking at the aggregate data, I mean, you're just seeing a remarkable benefit in that 25-foot walk along with all those secondary outcomes.
I do want to emphasize those secondary outcomes, particularly the stiffness and that sensitivity score to measure the triggers of the muscle spasms are very specific to this disease. To see that kind of benefit, again, we do not see that with our current unapproved therapeutics.
Yeah. Very helpful. Thanks. Congratulations again.
Thank you, Mike.
Thank you. Our next question comes from Derek Archila with Wells Fargo. Your line is open.
Hey, good morning, and congrats on the data. Thanks for taking the questions. Maybe just first, you know, as you look at the baseline characteristics from the trial, how do you think they reflect the patients that you see or, you know, some of the physicians see in the real world? So that's question number one. Then I just wanted to confirm on the neutropenia. I presume this is largely attributed to the preconditioning regimen.
I just wanted to confirm that. And then I have a follow up as well. Thanks.
Sure. Naji, do you want to start a little bit on the patient profiles? And then Amanda, you may want to comment a little bit on that. Then we'll come back to the second one on neutropenia.
Yeah. The patient profile we're seeing in the study is really representative of what we will see in the real world. And I'm sure Amanda can comment on this more. The median here we're seeing is 11.2 seconds for patients. And you saw the range, which is really real world and also from their disease severity. We really, in this trial, tried to be close to what the real world of SPS patient is. Amanda, do you want to comment on this?
Yeah, I would agree with the inclusion criteria used.
This is pretty standard for what we would expect to see with your typical classic SPS patient, so I think it does a great job capturing kind of what we see in clinic, and you have the similar kind of breakdown, which you presented in the breakdown of GAD65 to glycine patients, which is pretty representative of what we see in epidemiology studies,
and for your,
go ahead, Naji. Do you want to comment a little bit about the second part there about the neutropenia?
Sure, so for the neutropenia, as you said, it's a known adverse event with CAR-T regimens, and what's important here is, obviously, patients experienced this within 28 days and was fully resolved, so nothing that is unexpected or that was not seen before, so very manageable.
And we're really very pleased with the safety profile, actually, that has been confirmed as consistent as we've shared with a manageable safety profile.
Very helpful. And then I just wanted to follow up on the prior comments in terms of, like, BLA submission. I just wanted to know, in terms of CMC, where you stand there, and, you know, is that kind of a potential factor or gating factor on the BLA submission? Thank you.
Thanks, Derek. No, not at all. I think, as we previously commented, we are well down the path with the CMC package and module three preparations. The conversations we've had with the FDA up to now have been very, very positive.
We have, you know, been answering minor questions up to this point, but feel really, really confident that the BLA package we have to support the CMC will not only support the SPS filing, but will lay the foundation for future indications like myasthenia gravis as well, which is a big win for us as a young company here moving into the space.
Great. Thanks, Warner. Congrats again.
Thank you very much.
Thank you. Our next question comes from Sami Corwin with William Blair. Your line is open.
Good morning. Congrats on the data, and thanks for taking my questions. I noticed that over half of the patients have follow-up beyond 24 weeks. So I guess I was curious if you continue to see stability or continued improvements in the 25-foot walk test beyond that time point. And then for Dr.
Piquet, how important is durability of response, and how long would you want to see improvement sustained for?
Sure. Naji, do you want to comment a little bit on the data we've got? You got some patients going beyond 24 weeks, but that data set is not mature yet. But do you want to give us your perspective on that?
Yeah, of course. So what you've seen here is obviously we're sharing our primary endpoint at week 16, which is the agreed time point for our endpoints with the agency. And we've seen this remarkable improvement versus baseline and the p-value of 0.0002. We are also, as you've seen on the plot, we have the 24-week data for 16 patients. So that's an important point to reiterate. Those are patients who are at this cutoff at week 24. So there are 10 patients who didn't reach yet this time point.
So it's not patients, you know, who drop out. We have no dropouts and no rescue therapy in this data set. So as more patients actually will be reaching these time points, we will be sharing more of those. But as you've seen, we are seeing this consistency of results and durability of results for patients beyond those 16 weeks. Amanda, do you want to comment more on that?
Yeah. Like you said, the data is still maturing. And I'm really looking forward to working with Kyverna on the future updates to understand how patients do with the longer follow-up. I think it's going to be very exciting to see, you know, up to the 12-month data as this trial comes to a close.
And again, you know, what has already been demonstrated with this significantly meaningful benefit for the entire cohort. I've just not seen this level of response with any off-label therapies that we use. So I'm really excited to see that 12-month data.
Yeah. And just maybe,
thank you.
Yeah. Thanks, Sami. And maybe just addressing your second part of that question a little bit more. We know from our market research that getting patients to one year or beyond one year is a watershed moment to them. So we'll obviously be watching the maturity of this data set to see whether we can bring a majority of these patients over that line. But as you know, and as we've talked about, our first two patients that we've dosed with miv-cel, our first patients are now getting beyond the 24-month mark, which is truly remarkable.
And I think really shows how transformative and impactful this is going to be for patients, particularly when you think about this as a one-time therapy where you can also remove all the other background immunosuppressants and other immunomodulatory therapies that these patients have been burdened with over the years.
Thank you. As a reminder to ask a question, please press star 11. Our next question comes from Mitchell Kapoor with HC Wainwright. Your line is open.
Hi. Good morning. This is Katie on for Mitchell. Fantastic presentation. And thank you for answering questions today. Have you guys considered a dose-ranging study in the future for either SPS or other autoimmune indications? Is that something you guys are looking at or might find valuable?
Naji, you could add a little bit more here, but we did some of the dose-ranging work and some of the earlier clinical trials and IIT work. We have now landed on a final target dose of 100 million cells that we are using in SPS as well as MG. That is the go-forward indication up to this point for other future indications that we are exploring as well. Naji, do you want to comment any further on that?
No, you summed it up perfectly, Warner. 100 million dose is our therapeutic dose that we are for miv-cel dosing patients across multiple indications.
Yeah.
But maybe what you're referring to, Katie, is something exciting that we're really excited about, is the emerging data from the IITs, particularly some of the more recently presented data in multiple sclerosis as well as rheumatoid arthritis that really show the transformative impact of miv-cel across these other larger indications. So as we continue to advance our strategy, starting with SPS, and myasthenia gravis will be our second indication. We're looking at larger indications where we know the impact of this therapy can have a tremendous impact on patients.
Great. Thank you.
Thank you. I'm showing no further questions at this time. I'd like to turn the call back over to Warner Biddle for closing remarks.
Thank you, Operator. And thank you all for joining us today. Today marks a significant milestone for SPS patients, for Kyverna, and for the autoimmune CAR-T field.
KYSA-8 is the first completed registration-enabling autoimmune CAR-T trial. And we're uniquely positioned to deliver the first approved CAR-T therapy for autoimmune diseases and also the first FDA-approved therapy for SPS, a debilitating and progressive autoimmune disease impacting several thousands of patients. Importantly, today's data supports our ability to establish our first mover advantage in autoimmune CAR-T and lays the important groundwork for future indications such as myasthenia gravis and others, further solidifying our leadership in this space. And finally, we remain confident on the valuable commercial opportunity in SPS, which is underpinned by our focused go-to-market strategy and deep CAR-T commercialization experience. Lastly, before we conclude, and on behalf of my entire leadership team, I want to express our gratitude to the patients and families who participated in the KYSA-8 study and our investigators, clinical site teams, including Dr.
Piquet, who's graciously shared her time today and her expert perspectives with us on this call. I also want to acknowledge the entire Kyverna organization for their hard work and dedication on behalf of our patients. Thank you.
Thank you for your participation. You may now disconnect. Everyone, have a great day.