Kyverna Therapeutics Aktie

Thanks. Good morning, and welcome to the Kyverna Therapeutics Conference Call. [Operator Instructions] Please note, this call is being recorded.

I would now like to introduce Jessica Serra, Head of Investor Relations.

Today's conference call will cover the positive top line 1-year data from our KYSA-8 Registrational Trial of mivocabtagene autoleucel or Miv-cel, formerly referred to as KYV-101 in Stiff-Person syndrome as well as top line longer-term follow-up data from our KYSA-6 Phase II trial in generalized myasthenia gravis. 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 our safe harbor statement in our press release and presentation materials and risk factors included in our SEC filings for additional information.

Joining us today are Warner Biddle, our Chief Executive Officer; and Naji Gehchan, our Chief Medical and Development Officer. Warner will start with brief remarks, followed by Naji, who will cover our data for Stiff-Person syndrome, or SPS, and generalized myasthenia gravis or gMG, after Warner will close on our commercial opportunity in Stiff-Person syndrome. Following our prepared remarks, Greg Martini, our Chief Financial Officer, will join for a Q&A session.

With that, I'll turn the call over to Warner. Warner?

Thank you, Jessica. Today, we are excited to share longer-term durability and safety data for our lead indications that further reinforce Kyverna's leadership in autoimmune CAR T and our near-term potential to deliver the first approved cell therapy in autoimmune disease in addition to be the first approved treatment for Stiff-Person syndrome. Overall, we continue to establish a new benchmark in both durability and safety for the entire field. Across both SPS and gMG, data demonstrated robust and durable efficacy for at least 1 year following a single dose of Miv-cel with nearly all patients remaining off chronic immunotherapies.

Importantly, Miv-cel's consistent safety profile was maintained in the 1-year follow-up with no high-grade CRS, no high-grade ICANS and no cases of IEC-HS. These are remarkable results that continue to define Miv-cel's unique construct and differentiated profile where deep B-cell depletion can support a broad immune reset and durable outcomes that have not been seen before with existing therapies and therapies under development. Today's data bring us one step closer to our mission to deliver transformative therapies with curative potential to free people from the burden of lifelong disease and chronic therapy. We remain on track to complete our rolling BLA submission in Q4 of this year, seeking priority review under our RMAT designation, supporting a potential first-in-class autoimmune CAR-T launch in 2027.

We expect this to be a compelling rare disease launch in a multibillion-dollar Stiff-Person syndrome market that not only establishes our first-to-market leadership, but also lays the foundation for expansion into additional neurologic autoimmune conditions such as gMG and Progressive MS. Further, as our Phase III gMG trial advances towards enrollment completion in mid-2027, unprecedented 18-month durability data continue to derisk the registrational path and strengthen miv-cel's differentiation in the large and growing MG market.

Turning to Slide 5. Miv-cel's potential first-in-class, best-in-class clinical profile is underpinned by its unique CAR construct, robust clinical data and a well-established manufacturing process, which I will touch on later. Miv-cel is a next-generation CAR exclusively licensed from the NIH for autoimmune diseases and specifically engineered for both potency and tolerability. Importantly, it's the only fully human CD19 targeted [ autologous ] CAR T cell therapy with a CD28 co-stimulatory domain, which enables rapid and potent T cell activation. This unique construct design continues to bear out in our clinical data across efficacy, safety and durability, demonstrating deep B-cell depletion, including in targeted tissues, supporting a broad immune reset and the potential for durable remissions. In fact, the first SPS in gMG patients treated with a single dose of Miv-cel under the compassionate use pathway have now achieved durable responses beyond 2 years without the need for chronic immunosuppressive therapies.

These outcomes are reinforced across our own clinical trials in Stiff-Person syndrome and gMG, where we're seeing this durability trend continue. To date, more than 100 patients have been treated with Miv-cel across multiple autoimmune indications, and we continue to observe consistent and manageable safety profile with no high-grade CRS or ICANS and no reported cases of IEC-HS. These data support the potential for outpatient administration, which is an important consideration for patients, physicians and health care systems. Overall, these outcomes highlight the potential for Miv-cel to fundamentally redefine the treatment paradigm for autoimmune diseases.

Now let's turn to manufacturing. Next slide. Miv-cel is manufactured using a well-established and validated process like those used for commercially available autologous CD19 CAR T cell therapies with a manufacturing success rate exceeding 98% across our clinical trials. Recently, we signed a commercial agreement with ElevateBio, our primary manufacturing partner for Miv-cel, providing the flexibility and scale to support both our commercial transition and ongoing clinical programs. Overall, our unique construct and well-established manufacturing process support a strong Miv-cel efficacy and tolerability data generated in now over 100 patients across indications to date.

With that, I'll turn the call over to Naji, who will now go over our top line data. Naji?

[Audio Gap] One year follow-up data in SPS, which represent one of the most mature durability data sets reported to date in an autoimmune CAR-T clinical trial. Let's go to Slide 8. As a reminder, our FDA- aligned KYSA-8 clinical trial is a single-arm, multicenter, open-label registrational Phase II trial. We have received both the RMAT and Orphan Drug designations for Miv-cel in SPS. The change from baseline in the Timed 25-Foot Walk test measured at 16 weeks in our primary endpoint, this is a validated test to assess walking ability as well as to evaluate stiffness and loss of mobility.

To put things into perspective, the time that it takes a healthy individual to walk 25 feet is about 4 to 5 seconds. For patients with SPS, that time can be twice as long or even longer depending on the severity of their disease. Our secondary endpoints for measuring disability and stiffness include the Modified Rankin Scale, or mRS, the Distribution of Stiffness Index, or DSI, and lastly, the Heightened Sensitivity Scale. The trial included 26 patients with follow-up through 1 year. Importantly, all patients discontinued their immunotherapies prior to a single dose of Miv-cel.

Let's turn to the data on Slide 9. As you recall, we reported positive primary analysis of our KYSA-8 Registrational trial at AAN earlier this year, demonstrating statistically significant durable clinical benefit across all primary and secondary endpoints with reversal of disability scores. In addition, all 26 patients remained off immunotherapies at the 16-week primary endpoint measurement and Miv-cel was well tolerated. These outcomes achieved with a single dose of Miv-cel alone are unprecedented in SPS, a highly debilitating and progressive disease with no approved therapies. Today, we are reporting data on all 26 patients who have reached the 1-year follow-up. As you can see on the chart on the left-hand side, improvement in mobility as measured by the Timed 25-Foot Walk test supporting reversal of disability was sustained through 1 year. Recall in the primary endpoint measured at 16 weeks, we saw 81% of patients achieved a clinically meaningful improvement in the Timed 25-Foot Walk.

At the 1-year follow-up, 95% of patients maintained their benefit with nearly all patients or 24 out of 26 remaining [ off ] immunomodulatory or immunosuppressant therapies for SPS. At baseline, the median Timed 25-Foot Walk was 11.1 seconds. At this 16-week primary endpoint, the median reduction in Timed 25-Foot Walk was 46%, and this was further improved to a 49% reduction from baseline at 1 year, representing an over twofold improvement of what is considered a clinically meaningful improvement of at least 20%.

These improvements translate to more than 1/3 of patients achieving a Timed 25-Foot Walk of less than 5 seconds, which is consistent with a healthy adult walking speed. Importantly, of the 12 patients who required a walking aid prior to treatment, 67% continued to walk unassisted at 1 year, further highlighting Miv-cel's durable efficacy and potential to reverse disability. The magnitude of improvement and the durability of outcomes are unlike anything else that has been observed in SPS and marks an important milestone for patients who are desperate for an approved therapy that has the potential to reverse the course of their disease.

Let's turn to Slide 10. To further highlight the consistency and strength of the data, we wanted to share with you the p-values of the primary and secondary endpoints, both at 16-week primary endpoint measurement and at 1-year follow-up. As you can see from the slide, statistically significant improvements were sustained through 1 year across the Timed 25-Foot Walk test and all secondary endpoints that measure the extent of disability and SPS-specific symptoms, including mRS, DSI, Hauser Ambulation Index and the Heightened Sensitivity Scale.

Let's turn to safety on Slide 11. At the 1-year follow-up for SPS patients, Miv-cel continues to be well tolerated with no high-grade CRS or ICANS. In addition, there were no IEC-HS observed. 5 patients developed grade 3 or 4 neutropenia, which is a known adverse event associated with CAR-T treatments. All cases were manageable. 4 out of the 5 patients have fully resolved, while 1 patient continued to have a residual grade 1 neutropenia at the end of the study. Importantly, there were no serious infections associated with neutropenia. Further, all treatment-related serious adverse events in 3 patients have been resolved. Overall, a single dose of Miv-cel has demonstrated sustained improvements across all primary and secondary endpoints out to 1 year with continued reversal of disability and nearly all patients remaining off chronic immunotherapies for SPS.

These results are in stark contrast to what have been observed in the natural history of the disease, where most patients see minimal to no improvement in the Timed 25-Foot Walk test despite being on off-label treatments with the majority increasing walking aid usage over time. We're excited to include these 1-year results in our BLA submission, which further increases our confidence in our filing and path to approval. Before we turn to our data in generalized myasthenia gravis, I'd like to conclude with a few videos of our SPS patients performing the Timed 25-Foot Walk at their 1-year follow-up visit.

The first video is of a 39-year-old male patient who we showed at AAN, where he performed the Timed 25-Foot Walk test at the 16-week primary endpoint. Let's play the video. Prior to receiving Miv-cel, the patient requires a walker to ambulate. And despite the walking aid, you can see his walk is still slow and unstable. Here is the video after just 16 weeks and a single dose of Miv-cel. And here it is at 1-year follow-up where improvement is sustained. As you can see, a remarkable transformation with improvement sustained through 1 year. His time to complete the walk went from 17.3 seconds to 5.4 seconds at 16 weeks and 5.3 seconds at 1 year comparable to a healthy adult. Importantly, he continues to walk without a walker.

We want to share another case of a female patient who also required walking aid assistance prior to Miv-cel and her results following a single dose of Miv-cel. Let's play the video. Here, we have a 73-old female patient diagnosed with SPS in 2024 with symptoms for about 2 years prior to diagnosis. The video shows her performing the Timed 25-Foot Walk test prior to treatment. And here she is at 16-week post treatment walking without a cane. And here she is at her 1-year follow-up, continuing to maintain her improvement. As you can see, another transformative outcome following a single dose of Miv-cel.

Not only was the patient able to walk without her cane, but her walk time also improved from 14.8 seconds to 7.2 seconds at 16 weeks and to 6.8 seconds at 1 year. Now let's turn to our positive longer-term Phase II data in gMG. Slide 14. As a reminder, the KYSA-6 Phase II trial included 7 patients who had failed prior immunotherapies. It is important to note that all patients discontinued their MG immunotherapies prior to receiving a single dose of Miv-cel. The primary endpoints in Phase II of this trial were the reduction from baseline in MG-ADL score at 24 weeks and tolerability. We continue to follow these and other secondary measures on this slide, including QMG and MGC throughout the 18-month follow-up period, which is ongoing.

Next slide, please. In this longer-term follow-up data with data cutoff as of June 2026, all 7 patients in our trial have reached the 24-week primary endpoint measurement. 5 patients reached the 52-week follow-up and 2 patients reached 76 weeks. As you can see from the chart, a single dose of Miv-cel delivered rapid and robust improvements in MG-ADL and QMG that were sustained for at least 1 year. Mean improvements from baseline were seen as early as 2 weeks of 6.9 points with responses deepening through 24 weeks at 8.3 points as sustained through 52 weeks and at 8.2 points. Similar durable results were seen in QMG with mean improvements from baseline seen as early as 2 weeks at 8.6 points and further deepening through 24 and 52 weeks at 11.7 and 12.8 points, respectively.

Moreover, results remain durable out to 18 months in patients who have reached that time point. It is also important to note that MG-ADL and QMG are both the co-primary endpoints of our ongoing Phase III trial. Given the sustained magnitude of response achieved by Miv-cel in both measurements, we continue to feel confident in the probability of success of our registrational trial.

Next slide, Slide 16. In addition to the durability of response, we continue to see 100% of patients achieving clinically meaningful responses in MG-ADL, QMG and MGC as of last follow-up. This is defined as greater than or equal to 2 points improvement in MG-ADL and a greater than or equal to 3-point improvement in QMG and MGC.

Moreover, we continue to see a 100% response rate for our primary endpoint, MG-ADL, which is defined as the proportion of patients achieving a greater than or equal to a 3-point reduction. Importantly, 57% of patients continue to maintain a minimal symptom expression, or MSE, as of the last follow-up and nearly all patients, 6 out of 7 remained free of immunotherapies, including nonsteroidal immunosuppressive therapies, high-dose steroids, FcRn and complement inhibitors. I want to highlight the importance of these 2 data points. When we think about the potential for miv-cel in gMG, our mission is to provide hope for a drug-free, disease-free remission for patients which will fundamentally change the treatment paradigm.

Today, even with advances in targeted therapies, many patients continue to experience residual disease despite being on chronic treatment. We believe the goal should be to help more patients achieve MSE because that is what is matter most to patients, which is living with little to no functional impact from their disease.

For Miv-cel, we have demonstrated the potential to achieve this higher standard. With currently available therapies, patients can also face years of immunosuppression, repeated infusions of or injections, monitoring and the cumulative burden of both therapy and disease. Furthermore, there can be serious and longer-term side effects associated with chronic immunotherapies. The compelling value proposition for Miv-cel is, therefore, not simply symptom improvement, but offering the potential to free patients from disease while removing background immunotherapies with a one-time treatment.

Let's turn to safety on Slide 17. Consistent with our SPS data, Miv-cel remains well tolerated in MG in this longer-term follow-up. There were no high-grade CRS and no instances of ICANS observed. In addition, there were no cases of IEC-HS observed. There were a total of 3 patients that had Grade 3, 4 expected adverse events associated with CAR T cell therapy and lymphodepletion that included neutropenia and lymphopenia. All were not associated with infections and were manageable and fully resolved. Overall, we remain very encouraged by the consistent and well-tolerated safety profile of Miv-cel.

Let's turn to Slide 18. Before I turn the call over to Warner, I want to conclude an important slide that highlights Miv-cel's differentiated profile and competitive positioning. While cross-trial comparisons are not based on head-to-head studies, you can see that across all primary endpoint measurements for these approved and investigational therapies, Miv-cel is the only product candidate that has demonstrated the greatest depth of response while freeing patients from chronic background immunotherapies with a single dose.

With that, I will turn the call back over to Warner.

In summary, today's results further reinforce that we are doing something fundamentally different here at Kyverna for patients with neurologic autoimmune diseases, positioning us for a strong commercial trajectory. Compared to current treatment landscape for both SPS and gMG, which largely entails ongoing disease management and inadequate treatment outcomes, Miv-cel's compelling value proposition to both patients and payers is very clear. For the first time, we are moving patients from chronic therapy to a single-dose treatment that has the potential to deliver durable, drug-free, disease-free remissions.

Rather than chronic immunosuppression of the immune system, Miv-cel is designed to reset the immune system, enabling lasting results. Beyond efficacy and durability, Miv-cel's consistent safety profile increasingly differentiates the therapy in the competitive landscape. Data presented today reinforce the real-world potential of Miv-cel to address patient and provider needs, and we believe adoption will expand with growing awareness and experience. In summary, our goal isn't to achieve incremental improvement, but rather fundamentally changing the trajectory of the disease for people living with neurologic autoimmune conditions. Today, Kyverna is defining what is possible for both patients and physicians.

Finally, as we execute on our strategy, we're increasingly confident in the regulatory path forward for Miv-cel, particularly in SPS, where we're encouraged that the FDA and new [ CBER ] leadership continue to prioritize regulatory efficiency, innovation and an urgency to accelerate transformative therapies in diseases with high unmet needs and no approved treatment options. I'd now like to turn to our valuable commercial opportunity in SPS. Turning to Slide 21. As the only company with a late-stage asset in this disease and no approved therapies, we believe we are well positioned for a compelling rare disease launch into the multibillion-dollar SPS market in the U.S.

The market dynamics are particularly attractive with approximately 6,000 diagnosed patients in the U.S. and treatment concentrated in key academic centers. In addition to a high disease burden, SPS also carries substantial economic burden to patients and society, driven by high cost of care, which can range from $700,000 to over $1.5 million over a 3-year period. On top of these, there are additional costs related to disability and job losses. We believe Miv-cel's strong value proposition supports pricing that is a significant premium to oncology CAR-Ts, which currently have a U.S. [ WAC ] price range between $500,000 to $600,000 per treatment.

Given the significant unmet patient needs in this disease, our market research shows that 90% of top SPS treaters view Miv-cel's profile as highly compelling versus current treatment options and 85% of them will use Miv-cel for their moderate to severe patients at launch. Our initial priority will be the 2,000 to 2,500 patients who have had an inadequate response to off-label immunotherapies with a meaningful proportion of these patients concentrated in approximately 10 academic treatment centers, which we are targeting at launch. These centers have the necessary CAR-T expertise and infrastructure, a strong neurology partnership and positive site economics with the potential to adopt and increase uptake.

Over time, we believe Miv-cel has the potential to address the majority of the total diagnosed patients given that most patients progress with this disease. All of these market dynamics set us up for a strong execution on a targeted, efficient and valuable launch in SPS. Next slide, Slide 22. Before we move to Q&A, I would like to summarize our excitement around the promising path forward. We look forward to providing updates on several upcoming key milestones, including expected completion of our SPS BLA submission in Q4, reporting additional MS IIT data in Q4 of this year and sharing our clinical development plans for progressive MS in early '27. In addition, we are targeting to complete enrollment of our ongoing MG Phase III trial by mid-2027.

Our focused neuroimmunology strategy positions us to enter the attractive Stiff-Person syndrome market, representing a high-value commercial opportunity that provides a strong foundation for expansion into generalized myasthenia gravis and additional indications, including progressive MS as well as pipeline innovations, including new delivery mechanisms and manufacturing enhancements for expanding access. This all starts with Miv-cel and its potential to become the first approved CAR-T therapy in autoimmune diseases and the first approved therapy in SPS, supported by its unique CAR construct and best-in-class clinical profile. At Kyverna, we are executing our mission to deliver differentiated therapies with curative potential to free people from lifelong autoimmune diseases and chronic therapies.

And with that, I'll turn the call over to our operator for the Q&A.

[Operator Instructions] Our first question comes from Thomas Smith with Leerink Partners.

Congrats on these really strong data updates. It's always great to see the consistency here as the data continue to mature. Three questions actually, if I could. First on the clinical side. In these SPS and MG data sets, nearly all the patients remained off immunosuppressive therapy at 1 year, truly remarkable efficacy. Can you just talk about how that compares versus your initial expectations and maybe give us an update on your current expectations with respect to the durability of response going forward?

And then second, just as we continue to see this durability play out with the longer-term data, could you elaborate a bit on how you're thinking about some of the commercial levers and your potential to price miv-cel in both SPS and MG? And then lastly, just on the regulatory front, you're making progress here on the rolling BLA submission. Wondering if you could provide an update on that submission. Just remind us what's been submitted.

Do you have any sense of whether FDA has maybe started to review any of the submitted modules? And are there any gating factors to completing that submission? Just remind us of the gating factors for completion next quarter? Thanks so much for the questions.

I'll start with just saying I think these results exceeded even our expectations and what anybody would have expected for a one-time treatment in both stiff person syndrome and myasthenia gravis. But Naji, maybe I'll let you speak and add a little bit more color on the patients and their use of immunosuppressants and how that transpired and moved over the course of the trial.

As you said, this is truly a remarkable data set that we're seeing. Already with the primary endpoint at 16 weeks, we've seen this really strong reversal of disability and impact on all primary and secondary endpoints and exploratory endpoints. So we are very excited to see here that all of those are maintained for the vast majority of patients at 1 year. That's really a key piece. It's, as we said, some of it probably we can say it exceeded even expectations, but we were expecting this one when we look at also some of the data from the compassionate use patients that is now beyond 2 years.

Here, we're seeing the strength of data being maintained for the majority, vast majority of patients at 1 year. The use of immunosuppressants, to your point, all patients by design stopped their immunosuppressants, and we're seeing the vast majority of patients remaining off immunosuppressants while having this profound clinical benefit in both of the diseases at 1 year and even at 18 months for the patients who reached 18 months in MG.

That's great, Naji. And just following up on your second question, Tom, regarding price. We believe there's a strong value proposition here for both payers and patients because of the cost to the system and the cost to these patients and families of these diseases. Stiff person syndrome is usually treated with these patients with multiple doses of IVIg, sometimes biweekly, monthly doses.

These cost the system and cost patients hundreds of thousands of dollars a year alone, and we see that they don't work. You can see in the natural history data that the patients continue to progress over time, requiring increasing use of immunosuppressants and increased use of assisted walking devices, and we do know that less than 20% of patients will remain employed after 4 years after their initial diagnosis.

So this disease has a devastating effect on these patients and their families. And that's why we believe that the value proposition for miv-cel is extremely high and justifies a price at a significant premium over current CAR-Ts and pricing, which is currently in the $500,000 to $600,000 range, but we believe that this will justify a significant price premium over that point.

Turning to your last question on the status of the FDA BLA filing, we remain on track to complete the filing in Q4 of this year. Naji, maybe you want to provide a little bit of color on what the team is doing right now to finalize that submission.

As Warner said, to finalize the submission by end of this year, we did already -- we started the rolling submission, as we disclosed earlier half of this year, and we did finalize the CMC section, actually was submitted, as we also shared last month. So now with this 1-year data, we will add this to our BLA, and we're preparing the final analysis on the natural history for it to get into the BLA submission, and we're well on track to get it in Q4 and confident, as we shared, with this additional data of our path to approval fully.

We'll be seeking a priority review. And if achieved, we'll be launch ready by mid-'27. So this is coming soon and patients are waiting for a new therapy that actually works for them in this disease. So we're excited to continue to advance this program forward.

Our next question comes from Derek Archila with Wells Fargo.

Let me add my congrats on the data. Just a few questions from us. I was wondering if you could share some color on the 2 patients that maybe went back on immunotherapy in the SPS update. And just trying to understand maybe some of the things that are happening and ultimately, would there be a potential to redose at some point?

And then the other question, just as you think about the launch in SPS, I know you guys have talked about the potential for outpatient therapy. So I guess how are you thinking about the logistics of that? And is that something that would be ready at launch or sometime slightly after launch?

Naji, do you want to start with the first question, and then I'll take the next one on the launch and the outpatient usage.

Vast majority of patients, as we discussed today, remain off chronic immunotherapies for SPS at 1 year, while maintaining their clinical benefit. So this is -- I want to start with this because this is really unprecedented in SPS and a drastic difference from what we see in the natural history. The 2 patients who went back on IVIg after 8 months, one of them did not achieve clinical benefit of miv-cel. So this is the one patient that did not achieve this, and we shared it at AAN earlier this year.

We had 25 out of 26 patients achieving clinical improvement, at least on the primary or secondary endpoint. And this patient went back. This is the one who didn't achieve after 8 months. The second patient actually elected to restart IVIg, though at a lower dose and frequency, despite continued clinical benefit.

The really key piece here, Derek, that is important to go back to is the stark difference between natural history, where patients do not improve or at best, do not improve, but usually progress, unfortunately, over time, with no FDA-approved therapies. Here, we're seeing something remarkably different, while freeing the vast majority of patients from their immunosuppressants.

And just building on your second question, Derek, we believe that miv-cel will be an outpatient-administered CAR-T therapy at launch. And that's based on the very predictable and well-managed safety profile that we have, and it's now being established in over the 100 patients we've treated.

What these sites and physicians are looking for is not only low-grade AEs like CRS and ICANS, which miv-cel has now demonstrated a consistent pattern of that, but they're also looking at the consistency and the timing of when these low-grade AEs would come. So if you have a low-grade CRS, for example, with essentially a fever, we essentially know it will occur sometime between day 5 and day 10.

This makes it very predictable and easy for these centers to set up their outpatient protocols, and all of the centers that we're targeting are now utilizing existing CAR-T therapies in the outpatient setting, so we can utilize and draft off these existing protocols to establish those protocols now for miv-cel.

And this is the work that's ongoing. Even as we progress ahead of launch, we are working with the centers to have them site ready and including these protocols around outpatient usage, but all the other important mechanisms that we need to put in place in order to have the transfer of patient cells and also manage patients through their patient journey.

Next question comes from Brian Cheng with JPMorgan.

Congrats on the impressive longer-term data updates here. First, I'm curious if you can talk a little bit about the impact that miv-cel has on these attacks that you see in stiff person syndrome. I know that these attacks or muscle spasms are very much a feature of the disease. So I'm curious if you can give us some color on the impact on the number of attacks or the frequency of these attacks. And just on the regulatory front, curious also if you have any feedback from the agency so far on this longer-term data set that you reported today?

Naji, do you want to provide a little color on the impact on the patient symptoms because it goes beyond the timed 25-Foot Walk Test, as you've indicated in the presentation.

What is, as we shared at the 16 weeks and what we're looking in this trial is this primary endpoint of timed 25-Foot, which is mobility. But as you know, we have secondary endpoints, key secondary endpoints that do measure specific symptoms of SPS, and this is the Distribution of Stiffness Index, but also the Heightened Sensitivity Scale, which one actually measures the triggers for this disease.

And the other one, as you're saying, like the distribution of the stiffness in different parts of the body. And we've seen at 16 weeks this remarkable improvement in all primary, secondary endpoints and also exploratory endpoints that we see -- and we have this also demonstrated at 1 year.

We showed here the P value where we see this strong consistency across all primary, secondary endpoints, and we will be sharing more of the data and more granularity at AANEM, as we disclosed. So stay tuned for additional granularity on those endpoints at that conference.

Your question, Brian, on the FDA reaction on the data. You're seeing the data in real time. This is the work that Naji and his team are doing now to prepare to submit this longer-term follow-up data as a part of our BLA submission. So more to come on this. But we believe, overall, this data continues to reinforce the durability and sustained durability that miv-cel can provide for these patients and strengthens our file and strengthens our regulatory probability of success.

Our next question comes from Michael Ulz with Morgan Stanley. Your line is open.

This is Avi Novack on for Mike. Congratulations on the data. I'd actually like to shift to gMG, I guess. Seeing as the Phase III trial's open label, I was wondering if maybe you could give us some commentary on early safety and so far, do you think in terms of ICANS and CRS, is it consistent with the data that we're seeing in the Phase II trial?

And then also maybe it's a similar question as before. I thought there's now 1 patient who resumed prior immunotherapy. I was wondering if you can maybe provide some color on that from the Phase II gMG trial.

As it relates to the results that are happening in the Phase III trial. And Naji, maybe you could add a little bit more color to that, but we're not seeing the results in real time from that trial, and they'll be read out when we complete enrollment. And Naji, maybe you can comment on that and also the 1 patient in the gMG trial, which we had reported on earlier, maybe you can add a little bit of color there as well.

It's a Phase III trial, obviously, randomized. So we're blinded on the data. Your question was hinting on safety. Of course, we take safety very seriously, and aggregate data is consistently seen by our safety teams, but also the DSMB, and there's nothing, as we would expect, actually -- the important piece here is, as Warner said, and I shared today, we have now more than 100 patients dosed, no high-grade CRS, no high-grade ICANS, no IEC-HS reported cases observed. So the consistency and predictability of our safety profile, we expect it to continue through the trials that we have.

To your question on the one patient about immunotherapy. So this is actually the patient we did share end of last year. So there was 1 patient on a patient-initiated request who went back to 1 of their immunotherapies and is still at MSE. So this patient actually had 3 immunotherapies before getting on our trial. Their MG-ADL was double digit, and that's why they got on the trial. They went to MSE. They had some minor symptoms and, at their request, they went back to 1 of the immunosuppressants, and they are still at MSE. So what's remarkable is this patient is beyond 1 year now and still achieving MSE.

Our next question comes from Matthew Phipps with William Blair.

Congrats on this very strong durability data here. I was wondering if at this point, can you infer anything about an SPS patient's, like, length of disease duration and potential outcomes with miv-cel treatment. Just wondering if there's any data to suggest that treating patients earlier in their disease could lead to better outcomes, maybe giving incentive to not limit this therapy to patients who failed things like IVIg and rituximab.

And then I'm just curious if you've had any discussions with the FDA since the news came out about Novartis and Bristol's issues with safety and just around the total safety database that they will want to see -- I know you guys have treated 100 patients. That sounds pretty good. Just wondering if this has had any update or discussion with the FDA.

Yes. I'll start with the first one. All patients that were enrolled in the KYSA-8 trial had failed 1 immunosuppressant. And in this case, a majority of them have been on IVIg, and you saw the impressive results that we were reading out and reconfirming with the 1-year follow-up here today. But I think you're raising a really important point, Matt, about the unmet needs of this disease.

Patients know their prognosis and see their friends and other people with this disease progressing over time, and we know through our interactions with the Stiff Person Syndrome Research Foundation, for example, which is the leading U.S. advocacy group here, that there's a high demand and high interest in the trial and a high interest in getting access to miv-cel.

These patients are very well aware of their prognosis. They do not want to progress and see themselves needing a walker or being in a wheelchair or worse. And we've had a high level of interest in getting access to miv-cel even as we were reading out these trial results. Naji, maybe you could add a little bit more color to that, but you can maybe just comment a little bit on the safety data overall and the interactions we continue to have with the FDA.

Yes. So on your question specifically on this event, I would say, as we shared today and we've been sharing, our construct actually has been built for safety since the beginning. When we licensed this construct, the construct has shown tenfold less neurotoxicity, and we took it and developed it, and our manufacturing is also a conventional manufacturing that has been proven now with more than 100 patients.

So in the pre-BLA meeting, as we disclosed earlier, we had alignment on our safety data set and the integrated safety database that we have with more than 100 patients, and we did not see any high-grade CRS, ICANS and no observed cases of IEC-HS. So we're not expecting any change to what was aligned with the agency so far.

Yes. Matt, we're not pausing anything at this point. We're continuing with the submission. We're continuing with our full development program. And as Naji says, I think the data that we're reading out today, particularly with this longer-term follow-up, underscores the manageable and predictable safety profile that we have with miv-cel.

[Operator Instructions] Our next question comes from Mitchell Kapoor with H.C. Wainwright.

This is Ahmed on for Mitchell. Congrats on the data. So just on gMG. So the Phase II population had a starting MG-ADL of 11. How does the baseline severity in Phase III compare, and do you think if patients enter with lower symptom score, do you expect a smaller absolute treatment effect but a higher probability of MSE?

And have you accounted for that distinction in the trial assumptions? And then a second question in gMG. I was wondering if patients require rescue IVIg, PLEX or steroid escalation before week 24, do subsequent MG-ADL and QMG scores remain in the primary analysis? And can that patient still count as an MSE responder?

Yes. Naji, do you want to touch on the relative MG-ADL scores and the use of rescue therapies and how we're accounting for that in the trial?

Yes. So the patients we're seeing, obviously, MG-ADL more than 6, mean 11, as an inclusion. And we've seen, I think, to your point, when you look at the 7 patients, we've seen really this robust response on all patients. So we're reporting 100% response rate on MG-ADL. And then we've seen this robust improvement on both endpoints, MG-ADL and QMG, that is sustained now for those who have reached 18 months, up to that point. So that's really a key point. And we believe that we will see this efficacy on all this population.

Our Phase III is very similar to the Phase II. So we're expecting an even stronger probability of success actually in the Phase III based on this data from the Phase II. To your second question was on how we're going to treat in the Phase III IVIg or other treatments. Any rescue therapy that is happening within the 6 months of primary endpoint is considered a rescue therapy.

So they will be counted as such in the Phase III trial. What is key in the Phase II, there was no flare of disease, and there was no rescue therapy. So even that patient we talked about was minor symptoms when they came back, and it was beyond 6 months. It happened after 8 months.

Yes. And I think the other -- yes. And I think the other important takeaway here is that the results that we're seeing in the Phase II study and then this extended longer-term follow-up that we're reporting out today, with MG-ADL score reductions of 8.3 and QMG reductions of 11.7 at 24 weeks, highly derisked our Phase III study. We believe this adds additional confidence that we cannot only recruit this study with the right patients, but we can actually see these transformative results being replicated in our Phase III trial.

I'm showing no further questions at this time. I'd like to turn the call over to Warner Biddle for closing remarks.

Thank you, operator, and thank you all for joining us today. On behalf of the entire leadership team, I want to express our gratitude to the patients and families who participated in the KYSA-6 and KYSA-8 trials and to our investigators and clinical site teams. I also want to acknowledge the entire Kyverna organization for their hard work and dedication on behalf of our patients. We look forward to updating you on our progress ahead. Thank you.

This does conclude the program. You may now disconnect. Good day.

All right. Good afternoon, everyone, and thanks for joining us at the Morgan Stanley Global Healthcare Conference. I'm Mike Ulz, one of the biotech analysts, and it's my pleasure to introduce Warner Biddle, CEO of Kyverna Therapeutics. And just as a quick reminder, the format for today is a fireside chat, so if anyone in the audience has a question, please raise your hand and we'll get it looped into our discussion here. But before we get started, I just need to read a quick disclosure. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures.

If you have any questions, please reach out to your Morgan Stanley sales representative. And with that, I'll turn it over to Warner and if you want to make some introductory comments, and then we can hop into the Q&A.

Sure, Mike. Thanks very much for hosting us. It's been a great day so far. And yes, I'd like to just start off by saying Kyverna is really excited about the tremendous progress we're making. We're leading the world in bringing cell therapy to autoimmune patients, starting with our first indication with Stiff Person syndrome, but we're on track to finish filing our BLA as of Q4 of this year, which would put us on track to be the first approved therapy in this terrible condition that has no approved therapies. But more importantly, it puts us on track to be the first cell therapy company anywhere in the world with an approved therapy in autoimmune diseases.

So really excited about that tremendous progress there. But this really opens up the aperture for the rest of our neuroimmunology strategy and portfolio that we're building here and looking at additional indications with myasthenia gravis and progressive MS and other things that will continue to build and grow our company as we continue to navigate this space, but more importantly, help these patients that desperately need something new in terms of a new therapy that can transform their lives.

Great, and thanks for that introduction. And I thought maybe we could start with a couple big picture questions here, just maybe why autologous CAR T cell therapy and specifically, miv-cel has been so promising for autoimmune indications.

I think what's really important here is that miv-cel, unlike other CAR T therapies, has been specifically designed for autoimmune diseases. This construct was in-licensed from the NIH as a next-generation construct for potency in these conditions, but more importantly, significantly improved safety. We're the only CD19 with a CD28 costimulatory domain in the autoimmune space with a fully human design as well and other changes to the CAR construct that provide this improved safety profile. And we're now seeing that bear out in the over 100 patients that we've now treated.

We're seeing these remarkable clinical results, but at the same time, no high-grade CRS, no high-grade ICANS, no incidences or reported cases of IEC-HS. All these things are really important when you're looking at developing a construct that's going to help patients more broadly across these conditions.

So you're seeing very promising results, not only on efficacy, but safety across a lot of different indications and quite a few number of patients there. So maybe talk about the impact of the recent news from Novartis and BMS and kind of what that means for your program or doesn't mean?

Yes, first of all, I think it's really unfortunate that these cases were announced and the impact that it has on these patients and these programs. But I do think it really underscores what we're doing at Kyverna is very different, and very different on 2 important ways. First, the construct itself, and I touched on that a little bit in my opening, but miv-cel has been uniquely designed for use in autoimmune patients and it's been designed for significantly improved safety and like I said, this has been bearing itself out in the clinical profile that we've now seen in over 100 patients treated.

So again, no high-grade CRS, no high-grade ICANS, no cases of the IEC-HS, which some of these other constructs have been associated with. And I think that's critically important to keep in mind that we're dealing with a construct like miv-cel that has this prominent safety profile, improving safety profile. In addition, what's also really important is the manufacturing. We're not using a rapid manufacturing process. In fact, we're using a traditional, well-established, tried-and-true manufacturing process that has been, again, well-validated and established in the over 100 patients we've now treated. We see 98% manufacturing success rate. And we believe this combination of the construct and the manufacturing is what's contributing to the overall promising safety profile that we're now seeing.

Yes. And just on the manufacturing side, like what do you think is contributing to the sort of risk around that, particularly in autoimmune disease?

Well, it's difficult to speculate about other manufacturing programs and other companies. Some would say you're introducing more naive T-cells and that has a different clinical profile in patients and one that needs to be elucidated through their own development program. But again, coming back to Kyverna, what is really critically important here is we know what we've got and we've got a really well-established manufacturing process that's been well validated and this is bearing itself out in the safety profile that we're seeing across all these patients.

Yes. Makes sense. And if we focus on Stiff Person syndrome, you mentioned this in your prepared remarks, it's your sort of first-to-market strategy here. Maybe discuss the unmet need there and give us a sense of the potential market opportunity, patient numbers, et cetera.

Sure. Well, Stiff Person syndrome is a really underappreciated disease. It is a rare condition. It has no approved therapies up to this point, and nothing that these patients are actually using actually works for them. So if you look at the natural history of Stiff Person syndrome, over 80 percent of these patients will progress throughout the course of their disease to significant disability, where they'll either need a walker, a wheelchair, or be bed bound. Less than 20% of them will actually be employed 4 years after their initial diagnosis. So the impact on these patients and their families is horrendous, which puts into context what we're seeing with miv-cel in the clinical pivotal program that we just announced earlier this year, so remarkable in -- what we're doing here is so remarkable.

For the first time ever, not only seeing clinical improvements in these patients, but for the first time ever, actually seeing a reversal of disease and a reversal of disability. So patients that in the trial we had 12 patients in the trial that required walking and assisted devices. Over 2/3 of these patients actually didn't need those walking devices by the end of the trial. So you're able to reverse the course of disability in these patients and do so with the one-time therapy that also allows these patients to come off background therapies that they've been chronically burdened with. So high doses of steroids, high doses of IVIG, things that have their own safety impact on patients, these patients are able to come off of that and live this, you know, drug-free, disease-free remission, which is actually quite remarkable.

Yes. Quite dramatic effect there. I guess maybe just talk a little bit about how you identify these patients or diagnose them and kind of what percentage are currently diagnosed.

Well, we know in the U.S. there's 6,000 diagnosed patients, and we know this through epidemiological studies as well as through additional work that we've done on claims analysis. And patients are diagnosed in 2 ways. They need the clinical symptomology. So there's a battery of tests that these patients take with stiffness scores and mobility scores and that plus a combination with their diagnostic testing. So they are also tested for antibodies like GAD65 being the predominant one.

With patients who have both of those, that becomes a confirmed diagnosis for an SPS patient. And as I said, there are 6,000 patients in the U.S. These are well-identified patients. And in fact, we do know there's between 2,000 and 2,500 that are also refractory to existing therapies, and these are highly concentrated in a number of key academic centers. So this makes this a very important disease, but also one that's easily identifiable and we can tackle here at Kyverna in terms of addressing.

Yes. Makes sense. You talked a little bit about the data you've seen so far, and I think near term you're going to have another update with some longer term data out to 12 months, I believe, and later this quarter, so probably fairly soon here. I guess, how should we think about durability of the effect? Is it something that's kind of, you know, can it continue to improve? Is it something that is kind of -- you have a nice impact early and you kind of stabilize it at the same place, or just maybe talk about what to expect there or how to think about that?

Well, if you look at the pivotal data readout that we announced earlier this year, the primary endpoint being the timed 25-foot walk test, we saw a 46% improvement in patients and this is statistically significant, but also highly clinically relevant because a 20% improvement is considered clinically important. So we are seeing that from the primary endpoint but we also saw high statistical significance across all the secondary and exploratory endpoints as well, which is quite remarkable.

What we are looking for in longer-term follow-up is, can we see a majority of these patients continue to see a durability effect? Can we actually see a majority of these patients also remain off their background IVIG and background immunosuppressants that they've been chronically burdened with? Again, if you put this in perspective with the natural history of the disease, again, these are patients that progressively get worse over time. Patients never get better. At best, they'll stay constant, but most will progress. And if we can actually continue to show that a majority of these patients can have this significant clinical improvement, again, with the one-time therapy that allows them to come off all these other background chronic therapies that they've been burdened with, we are truly introducing a paradigm shift here that will have never been seen before.

Yes. Can you talk about durability and what you've seen with the longest patient out there? I think it might be the MG patient, but just generally what you've seen with -- over the longer term after treatment.

Well, prior to the initiation of our clinical studies here at Kyverna, we had done some work through a compassionate use and IIT programs, and some of our first patients treated with both Stiff Person syndrome and myasthenia gravis are now well past the 2-year mark, and free of disease, but also off their background immunosuppressants and chronic therapy.

So the early patients are really giving us an indication of what the longer-term durability of miv-cel can be and that's why we're so excited by the longer term follow-up of the Stiff Person syndrome, KYSA-8 trial, which we will provide an update here in the coming weeks, as well as a longer-term follow-up on our KYSA-6, which is our MG Phase II study. And again, if we can continue to demonstrate a durability effect in a majority of these patients, we are truly doing something transformative here.

Yes. Great. And you began your rolling submission for Stiff Person earlier this year. You expect to complete that, I think, by the end of this year. So maybe just talk about what's been submitted so far and what kind of remains to be submitted to sort of complete that process?

Well, through the RMAT designation that we have for Stiff Person syndrome, we've had some very positive dialogues with the FDA and started our rolling BLA submission earlier this year after our pre-BLA meeting. And we're on track, we've announced this earlier, but we're reiterating our guidance to finish this BLA submission in Q4 of this year. We have submitted all of the modules, except for the clinical module. So the CMC module we just announced in our Q2 earnings has been submitted and as I think everybody knows, this is a critical module for cell and gene therapies to have completed and gives us a lot of confidence that we're derisking the rest of the file.

And in terms of the clinical package itself, we are finishing the completion of that documentation, including adding in the 1-year follow-up data, which we just mentioned a few minutes ago, as well as some additional analyses on the natural history study, which will provide some context as to what we're seeing in the KYSA-8 study. These things are coming together and we're well on track. So as I said, we're going to be on track to finish filing in Q4.

Yes. Great. Can you talk about interactions that you've had with the FDA? Is this sort of the same team you've been working with for a while for this Stiff Person syndrome? And there's been some, obviously, changes in leadership. Has that had any impact at all on your interactions?

At this point, no. We've had no major deviations at all from the conversations we've been having with the FDA. In fact, throughout the whole development process, and again, tapping into the RMAT designation that we do have with the FDA, we've had constant conversations with them, and they've been highly supportive of what we're doing here at Kyverna, and highly supportive of this program with the recognition that, again, there's no approved therapies and what we're doing here is highly transformative with the clinical results that we're generating.

And just given the profile and the dramatic impact you've had in Stiff Person, is it fair to assume you'll request priority review for an accelerated timeline?

Definitely. The high unmet need here, the transformative results that we have, the RMAT designation, all these things will allow us to request a priority review. We think there's a high probability that the FDA will grant that.

And considering you're sort of -- I think I've mentioned you're in the process of preparing for the launch and kind of being ready by the end of this year, maybe just talk a little bit about what you've done so far and what remains and maybe early thoughts on strategy.

Yes. Stiff Person syndrome is an excellent first launch for us at Kyverna. It allows us to be really focused in terms of our strategy and generate some really a valuable opportunity commercially. We've been working behind the scenes on a number of fronts to prepare for launch. First, in terms of manufacturing, we're working with our manufacturing suppliers, continue to prepare for scaling for commercialization, and we're well on track and feel confident that we're doing the right things there.

In addition, site activation becomes critically important. And we're targeting 10 centers to start because of the concentrated nature of these patients and where they're actually seeking and accessing treatments up to this point. And we're working with these centers now to prepare them for commercialization, including getting the necessary contracts and processes in place to deliver miv-cel on time and consistently for them in a commercial setting.

In addition, we're doing a lot of work with payers, spending time with them working through the value proposition. We've now got the data set from our pivotal readout. We'll have some longer-term follow-up here in a few weeks. We're sharing that with payers and we have a very, very strong value proposition in support of miv-cel in a strong payer position, which has been positively moving forward well.

In addition, we're spending a lot of time working with patient advocacy groups. This is a very tight-knit community. These patients are well aware of their own personal diagnosis, but also by looking at their peers and their friends, they know what the prognosis of this disease will happen to them over time. And so there's a lot of anxiousness and hope in the community right now with what we're doing here at Kyverna and a lot of support for helping us bring this to patients more broadly.

Can you talk about maybe some of the market research you've done so far and kind of the level of enthusiasm among maybe the physicians and patients as well?

Well, physicians and patients are waiting. We've seen clearly from the market research that over 90% of physicians are strongly supportive of the TPP that we have and the value proposition that miv-cel can bring for patients. And we know that 85% of physicians would use miv-cel consistently in their moderate-to-severe patient population. So that's a very, very strong initial market research read and we believe that will only improve as we get closer to launch if we can continue to show a durability of impact, if we continue to show that a majority of patients can remain drug-free, disease-free, post the miv-cel treatment, we believe the adoption rate and the willingness to try and use miv-cel will only go up over time.

Yes. Makes sense. I don't know how much you can say about this, but just in terms of your current thinking on pricing, I know you mentioned you're doing a lot of work with payers there to try and figure that out, but any thoughts on how we should think about pricing? Are there good sort of analogs out there? Just any thoughts you can share?

Well, we come back to the value proposition that miv-cel is bringing for these patients and looking specifically at these diseases. And the case of both Stiff Person syndrome and myasthenia gravis, which would be our second indication, there's a high cost to managing these patients. In Stiff Person syndrome alone, the cost of IVIG costs the system and patients hundreds of thousands of dollars a year. And then you layer on top of that caregiver costs, lost time from work. There's a lot of emergency costs because these patients unfortunately have these stiffness attacks where they freeze up and fall and have significant injuries.

There's a psychological burden as well with these diseases. Overall, it costs the system and the patients hundreds of thousands of dollars a year to manage. So we believe there's a strong value proposition for miv-cel if you can come and treat these patients once and not only have this transformative clinical impact but also get these patients off the background chronic therapies and chronic burden on the healthcare system that these patients have been enduring.

So we're actually targeting, if you take a look at the cost of CAR T therapies now, which is roughly $500,000 to $600,000 for a CAR T treatment, we're targeting a significant premium to that for miv-cel, and we believe it's justified, given the high value proposition that we're bringing for these patients in both of these initial indications.

Yes. Makes sense. So a lot to look forward to in Stiff Person syndrome, but you also have myasthenia gravis studies ongoing, the KYSA-6, the phase II study, maybe highlight some of the key takeaways from that data that you've shared so far.

Well, again, miv-cel is setting a new standard for myasthenia gravis patients. No one is doing what we're doing in terms of the clinical impact. We're seeing dramatic reductions in MG-ADL scores and QMG, which are the primary endpoints that are used in a number of these trials. Again, no one is delivering reductions of 8.5 for MG-ADL and 11.3 reduction in QMG, any of the other current therapies or ones that are being studied.

So we're doing something dramatically different from a clinical perspective. But in addition, we're also allowing more patients to get to MSE, which is minimal symptom expression. If you ask patients and physicians what they ultimately want, they want to feel like they're free of their disease and MSE is an attribution to that. And we're getting a majority of our patients in the early data to an MSE level, which is remarkable. And again, we're doing with a one-time therapy that also allows them to come off their background FcRns and complement inhibitors, which are usually layered on top of high-dose steroids or other immunosuppressants that these patients are burdened with, which you take a look at the burden of therapy for these MG patients and the fact that it's not always working for them, it really opens up the door for why miv-cel is so remarkable and what we're doing here is so transformational.

Yes. And you mentioned this earlier, but you'll also be sharing longer-term update from that study as well. And I guess, maybe a similar question, is it possible for those responses to deepen over time with longer treatment or how should we think about that?

Well, between the initial top line readout and additional follow-up from the MG patients, we did see some of the deepening of effect. So we'll be looking for that in the future in the readout of this data. But again, we're talking about 7 patients. At this longer-term follow-up, we'll have all 7 patients at the 24-week primary endpoint time frame as well as 5 patients that will be at 1 year or beyond. So, again, we're going to be seeing if there's a continued effect in a majority of these patients. And can we also continue to see a positive safety profile in these patients. And again, this will be part of the overall readout.

Yes. Got it. Also, maybe MG is a pretty competitive space right now, maybe talk about where you think miv-cel could fit in and what the market opportunity might be there?

Well, there's a significant space for miv-cel in this disease. If you take a look at MG patients and again there's a lot of treatment options for these patients but none of these treatments are doing what miv-cel is doing, again not just in terms of the clinical responses but this ability to provide this deep B-cell depletion and give an autoimmune reset in these patients, which gives them a chance at a drug-free, disease-free remission. We haven't had to re-dose any of our patients with miv-cel in myasthenia gravis.

This includes the patients in the compassionate use program as well as in the clinical trial, which gives us a lot of hope that we're actually seeing a durable remission in patients that is highly differentiating versus existing therapies. So if you take a look at the overall market for MG, here in the U.S. there's roughly 80,000 patients with generalized myasthenia gravis. We know there's at least 12,000 that are already refractory to existing therapies.

This will be an initial target for us with miv-cel where we know we can provide immediately improved value because these patients aren't getting full clinical relief from the existing therapies that they're taking. But we also know from market research that patients are looking for therapies that also simplify their treatment. And only miv-cel allows these patients to come off their other background therapies and do so with a one-time dose. So we believe the opportunity for miv-cel is even greater than this initial 12,000 patients.

Yes, do you think initial use may be sort of later line patients that have been on all these other treatments first? Or -- and then over time, you think you move upstream just given the profile?

I think there's going to be a broad adoption for miv-cel, not only in patients that are refractory to existing therapies, but we even know from our clinical trial, we're getting patients approaching our physicians wanting to be in the clinical trial that are at earlier stages of their disease and simply because they don't want to be taking chronic FcRns and complement inhibitors that just don't work for them and that's why I think there's going to be a large opportunity for miv-cel beyond just refractory patients.

Yes. Makes sense. Maybe since you'll be launching Stiff Person syndrome first and MG technically second, I would assume. But just any -- can you leverage the sales force? Can you leverage the infrastructure when you kind of get the MG or how do you think about that or how much build out is needed?

This is why we chose the strategy we did and why we're starting with Stiff Person syndrome. This allows us to go to market in a commercialization setting in a very focused way and start with a very valuable opportunity like Stiff Person syndrome, which is going to provide real value -- valuable revenue opportunity for us as a company. But then we can continue to build on that.

So there's a lot of synergy between the physicians and the academic centers that are treating Stiff Person syndrome, that those are also treating myasthenia gravis. And if you even look ahead to other neuroimmunology conditions that we're generating early data in like progressive MS, all these things fit together really nicely in terms of a portfolio that we can leverage and synergize together as we continue to advance our commercialization strategies.

Yes. You mentioned PMS, right? So maybe you could talk a little bit about that. What are the early findings there? And what additional data might you share later this year?

We've been very encouraged by the results that we've seen in progressive MS, and we're treating patients in an IIT setting right now, but these initial patients that we've treated, again, it's progressive MS, so there's not a lot of treatment options for these patients and we're seeing for the first time ever in a disease that naturally just progresses over time. We're seeing for the first time ever stabilization of EDSS in all of the patients that we've treated and in a majority of the patients we're seeing a significant improvement in EDSS, which is again something that's never been seen before.

So this has generated a lot of excitement with us, it's generated a lot of excitement with the KOL community and as a result we've submitted this data and had really positive dialogue with the FDA. In fact, we were just granted our third RMAT designation, and we now have 3 RMATs. And this is going to allow us to have a real positive dialogue with the FDA on the next steps of what that development program will look like for progressive MS.

Can you maybe talk about why progressive MS versus maybe some -- I know you were looking at other indications too, I believe, but maybe talk about the why.

Well, progressive MS has some high unmet needs. And in fact, the RMAT designation is specifically in the non-active secondary progressive MS. This is the largest proportion of that patient population, and one where there are no approved therapies and one where anti-CD20 therapies just simply don't work. And again, we're seeing these remarkable clinical results, which then gives us a really important window into how we can accelerate and bring this to patients really, really quickly.

And maybe one point I'd add here is in addition to the clinical results that we're seeing, this dovetails very nicely with the mechanism of action and how miv-cel actually works because, miv-cel actually has this ability, because of its mechanism of action, to actually cross the CSF, getting past the blood-brain barrier. So we know we are having this deep and broader B-cell depletion in targeted tissues and these pathogenic B-cells which a number of the opinion leaders are saying are responsible for the fundamental clinical involvement that these patients are experiencing. Miv-cel has a way of attacking those and attacking those at the source, which is probably why we're seeing these clinical results that we're seeing in such a transformative way.

Yes. Can you talk a little bit about just manufacturing scalability? Your strategy makes a lot of sense. You start with Stiff Person syndrome, kind of smaller, and then keep going much much larger over time. So maybe just talk about the ability to scale later down the road, kind of, when you get there. It seems like there's lots of opportunity in places to go and treat a lot of patients. So how do you make sure that you can scale this and kind of get it to the patients that need it?

Yes. Well, we're taking advantage of high-quality CDMOs that are able to support not only our clinical program right now, but our path to commercialization. We're working with 2, ElevateBio out of Boston and Minaris Advanced Therapeutics out of Philadelphia. This allows us to, as you indicated, scale and support our commercial program as well as our clinical development program.

In fact, with Elevate, we just signed our commercial contract with them. We now have a pathway to support not only the SPS launch but the initial launches of myasthenia gravis as well. And we won't stand pat with this. We're continuing to evaluate our manufacturing processes to look for improvements in automation, improvements of how we can bring innovations like whole blood to make it easier for patients to access these cell therapies. And we're going to continue to look at alternative manufacturing platforms that will allow us to scale because you know as we continue to move from Stiff Person syndrome to myasthenia gravis and other larger indications like progressive MS, we're going to continue to tap into the technologies that continues to evolve.

I just wanted to flip back to progressive MS and kind of next steps and how you're thinking about it. I know you're kind of working on a development plan with the FDA, and you're going to maybe share it sometime next year. But just what are the things you need to sort of iron out kind of in the development plan from here?

Well, I mean, we've just received the RMAT designation, so this will be part of the dialogue that we have with the FDA. But if I can put it to you a different way, when you look at other therapies that have been studied in MS for many years now, many of them actually had an explicit goal of just trying to slow the progression.

And if we're coming to the market with a potential opportunity to not just slow progression, but stabilize EDSS or even improve EDSS in the majority of patients, that changed the mindset of how you think about designing a clinical study, how you think about the size of that what that clinical study would be. And we believe we might have an opportunity here at Kyverna to really accelerate and bring that to patients faster. So more to come. We've got, again, a real positive dialogue with the FDA on a number of fronts and this will be another one and we'll share the details of this coming up in 2027.

Okay, very exciting. Maybe in the last few minutes we can flip to some of these survey questions on key themes in the space. We're asking all the biotech teams, asking all our companies on these themes. So I'll start with the first one here. It's, you know, how has the rise of China origin innovation sort of changing your competitive positioning and your R&D versus sort of BD playbook?

Yes. Overall, I think the innovation that's being developed in China right now is exciting. It's exciting for patients and it's exciting for the entire field because I think it's accelerating and making us all more competitive and stronger. In fact, I think back to looking here at the U.S. I'm hoping that it continues to accelerate the dialogue here on how we can continue to improve innovation, things on the advances and the discussions around how to accelerate first-in-human studies, the work that's being done at NIH now to translate that and bring that to patients faster, the work that's being done with key academic centers to accelerate these early trials.

I think all of that is really, really positive, and Kyverna is taking advantage of that, and all of us will be taking advantage of that in the space. But overall if you look at what's going on in China, I think we've got to keep in mind here is that Kyverna is leading the world. We're leading the world in bringing miv-cel and B-cell therapies to autoimmune diseases and we're really excited about the progress and I think we'll be setting a bar for any company whether they're from China or from the U.S. in terms of what great looks like in terms of bringing these therapies to patients.

Makes sense. Second question, this is a hot topic that seems to be getting hotter by the day. I guess in terms of implementing AI adoption, where has it -- I guess, where are you implementing it? Where has it already changed the decision or timelines or cost or probability of success? And what measurable evidence should we expect over the next, say, 2 years or something like that?

Well, I think 2 years is even too long with how quickly everything's moving. And obviously, like every company, we're assessing AI and how we can apply it into our own development programs. We are looking specifically and using it to enhance our manufacturing program and the processes of how we can continue to streamline that, reduce deviations and improve the turnaround time for -- and success rate for patients, so that's one key area.

We're also leveraging AI for patient identification in clinical trials and also from a competitive intelligence perspective, it's becoming extremely valuable to monitor what's going on out there. But I think there's more to come, I think this is just the tip of the iceberg and I think it's going to impact in a very meaningful way many aspects of how we do business here and develop drugs.

Okay, great. And maybe third and last question here, just which policy variable, whether it's FDA, Medicare negotiations, MFN tariffs or global pricing matters the most to your economics, and what have you changed, if anything, because of it?

Well, I think just given where we are in our life cycle and our journey, it's the FDA is probably the thing that's front and center for us. And as I commented on earlier, the dialogue with the FDA has been very, very positive and constructive. In fact, the review team has been very, very consistent as well, as we talked about earlier. So we're really confident with the progress we are making and the group that we're working with at the FDA.

In addition, I think some of the policies the FDA has publicly announced that will help improve access for rare diseases and rare disease medicines as well as accelerating those development programs I think are going to become really extremely important. And I'm encouraged by some of the positive dialogue because it'll help improve our ability at Kyverna to bring these therapies to patients, but help the class overall.

Yes. Okay. Great. Looks like we're just about out of time, so why don't we end it there. Warner, thanks so much for your time. We appreciate it.

Really appreciate it, Mike. Thanks for hosting us.

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

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

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

Sure. Thank you, Tom. It's really great to be here. As you know, my leadership team and I did a transformative amount of work over the last 18 months to put us in a leadership position, but also differentiate us from the other companies that are operating in this space. And we're doing this in 3 important ways.

First starting with our construct. miv-cel is a unique construct. It's been specifically designed as a second-generation CAR-T for potency and efficacy as well as significantly improved safety profile. And we're actually in terms of the second point of differentiation, bringing this transformative therapy to patients first.

We're starting with syndrome, as you indicated. This is a rare disease, but one that has high unmet medical needs and is highly debilitating for patients. And what we've seen and read out at the end of last year was simply transformative results in these patients, not only improving the clinical symptoms, but for the first time ever showing that we can reverse the course of this disease. And so we're heads down on track for filing our BLA in the first half of this year, which leads me to the third point of differentiation, which is our pipeline.

Stiff Person Syndrome is a valuable commercial opportunity on its own -- but in addition, we're looking forward to actually building a neuroimmunology portfolio and franchise -- moving to myasthenia gravis, where there are significant unmet needs for patients despite available treatments, and we're on track in enrolling our pivotal Phase III trial in that indication. And we're also seeing some really promising early data in other indications like progressive MS, where we're seeing transformative data for the first time with this indication. So we're really excited about the progress we've made, really excited about the pipeline and what we have in front of us, and we're really excited about leading this and bringing this to patients first.

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

Yes. Well, it is a very unique construct. We in-licensed this construct from the NIH as a next-generation CAR-T. And it was specifically modified in a couple of key ways. First, it's a fully human design as well as some CD8a hinge and transmembrane has been replaced versus some of the older CAR-Ts. And what this means is that it actually is a safer profile.

We've actually seen in the head-to-head studies with traditional CAR-Ts a tenfold reduction in terms of ICANS and CRS, which is bearing itself out in the clinic in 10 treated patients as you've indicated, we have no high-grade CRS or ICANS, which is remark and really translates us and puts us in a position when we get to commercial stage that we can use this in an outpatient setting, which I think is going to be really important when we get to treat autoimmune diseases.

But in addition to that, one of the other differentiating factors for miv-cel is the fact that we're the only CD19 CAR-T in the autoimmune space that also has a CD28 costimulatory domain. And we believe this is really important because it gives potent B cell depletion and really giving patients a chance of an autoimmune reset, which is why I think we're seeing these transformative long-term durable results from the clinical patients that we've been treating so far.

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

Well, Stiff-Person syndrome is an important first indication for us and one that has no FDA-approved therapy and one where there's significant unmet needs. This is a highly debilitating disease that's progressive over time. 80% of patients will progress to needing walking aids or wheelchairs or be bed bound, which is a truly horrible prognosis.

And what we've been able to demonstrate with our pivotal data that we read out at the end of last year is not only a significant impact in terms of clinical response across a number of different endpoints, but this ability to actually, for the first time ever, reverse the course of the disease, which I think is something transformative and something that patients desperately want.

So this is a very significant patient population, and we're really excited about the fact that we get the chance to be first. We're accelerating, as I said, in terms of filing our BLA and we'll be prepared to launch this construct for these patients at the end of this year. And we could be the first to launch any autologous CAR-T into the autoimmune space for the first time.

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

Well, the time 25-foot walk test is a standard validated test that's used across a number of neuroimmunology and neuroinflammation diseases. And what we saw from our pivotal data with miv-cel that read out at the end of last year is not only a clinically significant response, but we saw that as early as 4 weeks and being sustained over time. And by the 16-week primary endpoint, we had a 46% reduction in the time 25-foot walk test. Just to put this into perspective, a clinically meaningful response in these patients is a 20% reduction in the time 25-foot walk.

So we're well beyond that. In fact, we're more than doubling that in our clinical trial. And to also put this in perspective with Stiff-Person syndrome, we know the natural history of this disease, at best, these patients will stay flat in terms of their time 25-foot walk and over time, will get progressively worse. So the fact that we're not only seeing a clinically meaningful response, but one that's actually deep and durable and enduring in these patients is actually really remarkable.

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

Well, there's a natural history that's been well documented in retrospective trials right now that, as I mentioned a few minutes ago, the fact that patients at best stay flat despite off-label treatments with a number of other therapies, the disease doesn't get better in these patients. And the natural history is that over time over a 80% of patients will progress to requiring walking aids or worse.

What we've seen from retrospective data, this is an analysis coming out of Denmark is that patients over the course of their prognosis with this disease is that they will have a 4x more likelihood of comorbidity. So this is a really impactful disease and it goes beyond just stiffness of the joints. This is highly painful for patients and one that really impacts their lives. So the fact we're bringing something here that can actually reverse the course of this disease is really remarkable.

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

Well, we've had some really positive interactions with the FDA, they've been continuous, and we're very confident with the pathway that we've established. In fact, as I said, we're on track for filing our BLA in the first half of this year, and we're doing all the necessary work in order to make that happen.

We've been actually working with the FDA through the RMAT designation and orphan drug designation. So we're in regular contact with them and seeing the transformative clinical data that we're seeing not only across the primary endpoint, but consistently across all of the secondary endpoints as well gives us confidence that we're doing something here that no other therapy can do and that this is something that patients desperately need.

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

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

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

Yes. Well, we believe the value proposition for miv-cel in Stiff Person Syndrome and in myasthenia gravis is very high. We've got a very, very strong value proposition. So although we're not guiding to specific pricing, if you look at the impact that this disease has on patients, not just in terms of the clinical symptoms, but the chronic use of therapies like IVIg, which cost the system hundreds of thousands of dollars a year. You talk about lost time off work, you talk about impact on families and caregivers.

There's a real health economic burden that both of these diseases have on patients and one where we can treat these patients with a onetime therapy like miv-cel and not just have this significant improvement in clinical symptoms, but this chance to actually remove and eliminate all the background therapies that patients are on. So when you factor that into a health economic argument when we go in front of payers, we've got a real justification for charging a premium to current CAR-T pricing, and we're going to continue to work on that. In fact, the feedback from the payers up to this point in our research has been extremely positive about the value proposition that miv-cel is bringing.

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

Yes. Well, we know from epidemiological studies that are emerging as well as our own ICD-10 claims analysis, the population for Stiff-Person Syndrome in the U.S. is larger than what was initially thought. We know this patient population is roughly about 6,000 patients. And of those, we know there's about 2,000 to 2,500 of these patients that are already refractory to existing off-label treatments. And these are the patients that are in desperate need of a new therapy like miv-cel.

And those are the patients that we'll be targeting first these are the patients that are known academic centers and ones that we can actually accelerate and move into a launch phase very quickly. But we do know with any disease where there hasn't been an approved therapy and where the existing treatments are not managing these patients very well, we believe once miv-cel gets on the market and we actually can work with physicians and patients to increase education, we believe that larger patient pool will be addressable over time as well.

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

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

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

Well, with a really focused initial launch center like these 10 centers that I was referring to, we can have a very efficient commercial launch strategy, which is a big reason why we chose Stiff-Person Syndrome, not only are these high unmet needs and allowed us to accelerate our clinical development program in a rapid way, we can go to market in a very efficient way with this initial indication. So we won't need a large commercial team in order to service these 10 initial centers, but they will be important centers that we can go deep in and establish deep relationships and the infrastructure in order to support and manage these patients.

And then what's really important with these 10 centers is it allows us to bridge and move on from there because if you think about our next indication is myasthenia gravis. And there's a huge amount of synergy between these academic centers that are treating Stiff-Person Syndrome and myasthenia gravis. We can continue to build on those, adding more centers in preparation for the myasthenia gravis launch. But each new center that we're adding can also treat more Stiff-Person Syndrome patients, too. So there's a huge synergy between these indications that we're going to leverage as we continue to advance the launch program.

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

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

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

Yes. Well, myasthenia gravis is a very valuable market opportunity for us and a great second indication because of the synergies that you just indicated. And when you look at the interim Phase II data that we read out at the end of last year, miv-cel doing something completely different from the existing therapies that are in this space. So there are existing treatments. Many of them are treating the symptoms of the disease or trying to manage the antibodies in a partial way.

But for the first time ever, we're seeing with miv-cel treated patients, this opportunity to give patients this deep B-cell depletion, this autoimmune reset, if you will, and this chance of this long-term durable remission in patients with one single treatment of miv-cel. In fact, our first patients that have been treated with miv-cel are still doing very, very well, not needing any follow-up therapies or background supportive care. And they've done this with one single treatment in miv-cel and they're now lasting out to 2 years plus. So we know we're doing something remarkably different with these patients, and this is why we're really excited about advancing our pivotal Phase III study, which we're now moving into and actively enrolling.

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

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

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

Sure. Well, just starting with the Phase II, which we read out an interim analysis on that at the end of last year, and we'll have a full analysis actually coming at AAN as well. So that will be an additional presentation for us. But what we saw in that interim readout is remarkable. We saw MG-ADL score reduction of 8, QMG reductions of 7.7. No therapy in the treatment of MG has shown this dramatic impact in terms of these key clinical endpoints.

But in addition, we were actually able to see more patients actually reach MSE, which is minimal symptom expression. This is ultimately what patients want. They want to live without the burden of their disease and they want an MGA score of 0 or 1, which is MSE. And we're seeing more of our patients actually reach that level. And again, doing so with a onetime treatment that allows you to actually remove the background therapies that patients are chronically on. You look at FcRn trials or complement trials or any of these other trials in MG, these are all additive.

These therapies are being added on to a backbone of immunosuppressants hydrosteroids, which we don't have once they enter our trial with miv-cel, which again, tells you the paradigm shifting work that we're doing here in terms of not just the clinical impact, but also reducing the overall burden of care. Based on those results, we actually got the nod from the FDA to truncate that Phase II trial early. So we actually now are moving into the Phase III portion of the trial. We're actively enrolling those patients. And if you look at the outcome and the efficacy impact that we were having in the Phase II, we're in a sense derisking the Phase III because we know that the clinical results and how we powered that study will allow us to show a really transform result for these patients as well.

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

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

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

Well, first of all, the MG market is a significantly larger market than SPS. So there's a huge market opportunity more broadly. And if you take a look and you subseg that market a little bit further out of the 80,000 patients that are there, 40,000 of them are readily addressable that we believe could be CAR-T illegible patients. And of those, we know there's about 12,000 to 13,000 patients that are already refractory to existing therapies.

We think this is an initial starting point for miv-cel in that there's -- if you look at FcRns alone, 1/3 of patients are not doing well and have high MG-ADL scores of 6 or greater. This will be a readily addressable patient population for us coming right out of the gate. But again, with increased education, with increased durability of effect, and we've seen more patients like Denise get out to the 2 years and beyond, we believe this will be more applicable to a broader patient population.

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

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

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

Yes. Well, I think there's going to be 3 components to scaling up and being ready for launch. We talked about the first one we're manufacturing and then again we're confident we can scale up with this initial launch with Stiff-Person Syndrome and beyond with the manufacturing suppliers we have. The second component is the cell orchestration and the delivery of the cells to the patients. We've obviously put in place to service our clinical trials, and we're busy modifying that including adding additional patient support services, reimbursement support, travel and lodging, things that are going to be critically important for supporting patients from a commercial perspective. And then the third key element that we're working on and putting in place, of course, is the reimbursement strategy.

So we're engaging with payers now. We're doing research. We're developing the value proposition for miv-cel for this initial indication, and things are progressing along very, very well on that front. In terms of capacity, we know all these academic centers are starting to shift and they're building up their capacity. They're moving from just being a pure CAR-T-focused academic centers for oncology only, and they see the scientific and academic desire of doing this, but also from a patient treatment perspective moving into autoimmune diseases.

And this is a real advantage for us at Kyverna being the first mover here and being first to the market. This not only allows us to set the price and set the reimbursement guidelines, but allows us to establish those relationships in these key centers, which is what we're doing now in order to prepare and then we can expand on in terms of future launches. So all of that is going very well.

The other point I would add is that because of our safety profile and the fact that we have what we believe is an outpatient administered drug, we believe that the ability to optimize the existing capacity that's in these centers will be a huge advantage for us because we can have a less burden of a footprint on every treated patients that we administer miv-cel.

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

Yes. Well, I think as I said at the beginning, one of the key differentiators for Kyverna at this stage is our pipeline. And we're looking beyond Stiff Person Syndrome and myasthenia gravis to building longer term a neuroimmunology franchise. And when you start looking at some of the early data coming in progressive MS, for example, we've got centers in Stanford and UCSF that have been treating patients. And if you ask the experts of these institutions what they're seeing with miv-cel. They will comment, but they haven't seen anything like this in 30 years that they've been treating and managing these progressive MS patients.

As you know, there's a few treatment options for these patients. And once they start failing, the patients just do progressively worse in terms of their overall prognosis. And for the first time ever, we're not only seeing stabilization of EDSS in PMS, for example, we're actually seeing significant improvements in these patients as well as improvements in disability and fatigue score. So really remarkable early data. We're really excited about that, and this gives us an opportunity to open up the aperture, if you will, to treat even larger patient populations and bring something transformative like miv-cel to even more patients.

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

Yes, exactly. We filed our IND for KYV-102 at the end of last year. And this is building off the backbone of KYV-101 or m-cell. So it's got the same CAR construct, but it's on a different manufacturing platform that allows a couple of things. First of all, we can start with whole blood rather than patients, which is a real important advance for improving patient access and will allow us to start the CAR-T journey for patients even closer to their homes, which we believe will improve access for patients over time.

In addition, because it's a rapid manufacturing process, we're speeding up the turnaround time, obviously. But more importantly, we're actually significantly reducing cost of goods for patients, which, again, as we start thinking about larger indications and how we expand the portfolio over time, this is going to provide a lot more opportunities and flexibility for how we commercialize this and bring this to more patients.

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

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

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

A pleasure.

An exciting 2026.

Good morning. Thank you so much for joining us for another session at the 44th J.P. Morgan Healthcare Conference. I'm Brian Cheng, one of the senior biotech analyst here at the firm. On stage, we have Kyverna Therapeutics. I'll now pass the mic to their CEO, Warner Biddle, for a short presentation, followed by a live audience Q&A. Warner, the stage is yours.

Thank you, Brian. Thanks for the invite, and great to be back here at J.P. Morgan. Really excited to be sharing with you the exciting progress we're making at Kyverna. As we continue to pioneer the way forward for CAR T therapies in the field of autoimmune diseases. These are our forward-looking statements. You can find them in more detail on our website. Now I was standing here a year ago laying out the vision and strategic priorities for our organization. And I'm really, really pleased to come back here and report that 2025 was a fantastic year. It was really an incredible year and transformative year for our company. And I'm going to walk you through over the next 20 minutes or so, the progress we're making, how we're demonstrating transformational clinical data in our 2 leading indications with Stiff Person Syndrome, myasthenia gravis.

How we've established a clear regulatory pathway for both of these indications, how we're thinking ahead from a commercialization perspective, leveraging our first-mover advantage to come to this market, start serving these patients and start growing our young organization to greater heights and how we've also been progressing, particularly at the back part of the year to strengthen our financial position, putting us on a cash runway that takes us well into 2028 and allowing us to execute on this milestone in these visions.

Now our mission at Kyverna is to transform the lives of CAR T patients through the transformative and curative intent of CAR T therapy. And I think nothing displays this more than actually looking at patient videos. So I'm going to show you 2 patient videos now that are on our website, but these are actual patients from our Stiff Person Syndrome registrational trial. The first patient is a 62-year-old female. She's been living with the disease for many, many years. And you can see once the video starts that she's actually got all the classic hallmark symptoms of Stiff Person Syndrome. She's got this hunched-over posture, a really slow walking gait.

She doesn't want to swing her arms because she's extremely fearful of falling. Now after one single treatment with miv-cel and 16 weeks later, you're seeing the confidence of this patient dramatically improve. The gait and speed and arm swing are all there. In fact, her time 25-foot walk test was reduced from 17.3 seconds down to 4.5 seconds. That's a 74% reduction and she's basically effectively walking like you and I would taking this test.

The second patient is a 52-year-old male he is also suffering with Stiff Person Syndrome, but he's been suffering with this disease for over 20 years. In fact, he needs a walker to walk normally. And you can see here as he's taking the test, he's walking sideways because he has this intense fear of falling and he's trying to use the wall as a gauge to help him prevent falling. He's refractory to IVIg and is on daily and multiple doses of supportive medications and [ valine ], et cetera. Now you can see again, after one treatment with miv-cel 16 weeks later, the confidence of this patient moving, the ability and ambulation is dramatically improved. And we saw a significant reduction in the time 25-foot walk test from 18 seconds down to 5 seconds.

So again, really, really revolutionary impact on these patients that has never been seen before in this disease. What's really important to keep in mind when you're thinking about Stiff Person Syndrome is this is a progressive disease. Patients don't get better. The prognosis in natural history is that patients get progressively worse over time. The muscles continue to stiffen and actually patients end up in wheelchairs or bed bound over the course of their disease, which is truly a horrific prognosis for them.

What's also really important to keep in mind is there's no approved FDA therapies and all the off-label treatments that patients get access to and try don't actually impact the underlying cause of the disease, which is why the fact that we've now completed our first registrational trial, and we're not only seeing highly statistically significant results on key clinical endpoints, but we're actually seeing this reversal of disability is truly remarkable. And then if you think about it in the context of being able to eliminate the background immunosuppressants and other therapies that these patients are taking, so they don't have to be burdened with these other therapies that they've been trying before.

Again, this really indicates that we've got a paradigm shift in how to manage this disease and how to think about treating these patients moving forward. In addition, I do want to stress that we've now treated over 100 patients with miv-cel. And in this particular study, the safety profile that we're seeing confirms what we're seeing across these -- all these other patients with no high-grade CRS or ICANS, making this construct very amenable to commercialization, particularly using it in an outpatient setting.

This is the design of our pivotal clinical study that we have alignment with the FDA using and leveraging our Orphan Drug Designation and RMAT designations. What's really important to note here is that this trial was rapidly enrolled. We enrolled it in under 7 months, which indicates 2 things. One, we're very effective and focused at Kyverna and we're able to execute.

And second, there's a high unmet need here because patients were striving for something new and unique to treat their disease. These are the primary endpoints and secondary endpoints, and you can see the results are really remarkable, not just the -- our impact on the time 25-foot walk test, which was our primary endpoint, and you can see the significant P Value here, but this consistency and dramatic impact on secondary endpoints as well.

In fact, if you ask our leading investigators, one of them came up to us and said, in all of her decades of treating Stiff Person Syndrome patients, she's never seen this kind of an impact on patients before, particularly when you look at the secondary endpoints that are specifically designed to measure the impact of Stiff Person Syndrome, she's never seen any treatment improve this in patients. So we're really seeing something here revolutionary and game changing.

Taking a deeper look at the primary endpoint, which is the time 25-foot walk test. This chart documents the improvement in time 25-foot walk over the months post-treatment with miv-cel. I want to draw your attention to the green line. This is the validated clinically meaningful improvement line that's been validated through other diseases and where this test is used to measure the impact in other conditions. And you can see as early as 4 weeks, we're already seeing a clinically significant impact that continues to deepen and be sustained over time. And by the time you get to 16 weeks, which is the primary endpoint, we're seeing a 46% reduction in the time 25-foot walk test, which again is unprecedented, and this continues to be sustained for those patients we were able to measure up to 24 weeks.

All in all, 80% or more than 80% of patients have this clinically meaningful response to therapy, which is truly remarkable. And another thing of note, at the beginning of the study, 12 patients actually required walking devices, either a cane or a walker or a wheelchair. And at the end of the study, 67% of these patients were able to get rid of their walking devices and walk normally like we saw in the videos, which I think, again, is a truly remarkable undertaking and a truly remarkable result that we're seeing in a patient group that typically doesn't have any hope at all in terms of their long-term prognosis.

Now I want to take a couple of minutes and talk about myasthenia gravis. We've talked about Denise before, but I want to show her case study again. She's now 24 months, 2 years past her miv-cel treatment and still going strong. She's not on background immunosuppressants or any other background treatments. And you can see from this video, she's living a remarkably normal life for somebody who's been burdened by this disease for over 12 years. She is a German patient. I just noted there are subtitles here to the video.

[Presentation]

Again, a really remarkable and transformational impact on these early patients that we were treating through the compassionate use program. And this really propelled our organization forward, and we rapidly started a Phase 2 program, which we read out interim results in the back half of last year. And again, what we were seeing through this clinical trial these unprecedented disease control across multiple primary and secondary endpoints that are used in the myasthenia gravis disease.

And even more importantly, we're seeing a majority of patients either at or trending towards MSC or minimal symptom expression. This is ultimately what patients want. They want to live without the knowledge or this daily reminder that they have their condition and MSC is that ultimate target and what patients are working towards. And with miv-cel, we get more patients to that clinical endpoint. And again, we're doing this while also transforming how patients are being managed. In many cases, patients like Denise and others are on chronic immunosuppressants when they're taking the FcRns or complement inhibitors, this is on top of these background immunosuppressants and other therapies that these patients have.

The daily burden and chronic treatment burden that these patients are undergoing is tremendous. And the fact that we can actually see these transformational clinical results while also removing all these background therapies, again, is a paradigm-shifting way of managing this disease. And we're doing this with a really well-tolerated and safety and manageable safety profile again, which again is conducive for using these therapies in a commercial setting in an outpatient setting.

Looking more closely at the primary endpoints. This is the MG-ADL score and QMG score. And again, the green line represents a clinically significant improvement in terms of these 2 endpoints. And you can see on both counts, we're actually achieving significant clinical improvement as early as 4 weeks. And again, this is sustained and even improved over time. And I do want to draw your attention to the absolute reduction in MG-ADL & QMG. A reduction of 8 points and 7.7 points are truly unprecedented. And no other therapies in myasthenia gravis have demonstrated this kind of an impact in terms of these key endpoints on patients.

This is our Phase 3 registrational trial. And based on the results we were seeing from the Phase 2, we quickly pivoted into the Phase 3 trial design. This is a really bold and unique design. We're comparing miv-cel to a standard of care, and we're going to demonstrate superiority to standard of care in this clinical setting. We've already received a lot of inquiries from physicians and patients, a lot of interest on this based on the data they were seeing in the Phase 2 study, and we've already enrolled our first patients. And I'm looking forward to updating you on the progress of this trial and the enrollment over the course of 2026.

Through all this, we've also been working with the FDA on establishing our clear regulatory path for miv-cel for both SPS and MG, and we've got alignment on both of these fronts. We've had regular and consistent conversations with the FDA that have been very positive and constructive, and we're actually on track to file our first BLA for Stiff Person Syndrome in the first half of this year. So we have the clinical development program in place. We've got the regulatory strategy moving forward. We're already now starting to look forward and think about commercialization.

And I can tell you, I've been working in the CAR T space now for over 5 years. And what's really exciting to see is this advance in the environment, in the ecosystem for CAR T therapies. There's been a number of positive developments that are only going to help us and other companies as we bring these therapies to market. There's increased capacity in all the key academic centers, and they're particularly of interest of their converting the purely oncology hematological CAR T centers into broader use, including use for autoimmune patients.

We're seeing improved access with this really dramatic shift to outpatient usage and being able to use these therapies in an outpatient setting. We're seeing more favorable site economics and the payer dynamics are working themselves through. We're also seeing simplified regulatory frameworks as well as simplified treatment paradigms through improved REMS programs and updated fact standards. All these things are coming together at a very, very important time because their open up the aperture for these academic centers to treat more patients and for patients to have easier access to therapy. So this is going to positively impact all CAR T therapies. But as the leader and first-mover advantage in the autoimmune space, we're going to be able to take advantage of this so we can propel ourselves forward and have a very, very successful launch.

And we are thinking about our commercialization strategy in more detail. We're already activating new centers while taking the clinical sites and converting them to commercial centers. That work is ongoing now. We're also spending a lot of time with the patient advocacy groups. There's a huge amount of interest from the patient advocacy groups. The Stiff Person Syndrome Research Foundation, in particular, has been a strong voice for the need for new treatments.

They were very, very vocal when the new data came out, as I just presented to you. And they're very, very excited because these patients are desperate for therapy and the Stiff Person Syndrome Research Foundation is connecting these patients with physicians so they can get access to therapy as soon as we actually get approved. Of course, we're also working with our commercial manufacturing suppliers, and we're scaling up, not just to make sure we continue to address the ongoing clinical study work that we're doing, but that we're ramping up to meet the commercial demand as well for Stiff Person Syndrome.

Overall, there's a very attractive market for Stiff Person Syndrome that I think a number of people are underappreciating at this point. There are 6,000 patients that are already diagnosed with the disease, which we believe a majority are CAR T eligible. But there's a specific subsegment between 2,000 and 2,500 that are particularly are at need of a new therapy. These are the ones that are already refractory to existing therapies.

These are the ones that are desperate for therapy, the ones that are well known to us as well and well known to the academic centers. These are the ones that we're going to be focusing in on from a launch perspective so that we can get off to an early and fast launch trajectory.

In addition, these patients are predominantly of working age, and this is really important because the impact that this disease has on a patient life extends beyond them. They're unable to work. They're unable to have an impact with the families, which means there's a sense of urgency to treat these patients and do something transformational so they can have their life back. In addition, the off-label treatments that patients are often using in this setting are costly. IVIg alone cost patients in the system hundreds of thousands of dollars a year. It doesn't really work. Patients get progressively worse over time, but there's a really strong value argument here from both the payer perspective as well as a health economic perspective on a new treatment that can transform patients' lives and remove these chronic therapies and actually deliver something completely new for this patient population.

Because of these patients are concentrated and well known to physicians, we've got a very efficient commercialization strategy in mind, starting with approximately 10 authorized treatment centers, and we'll refine that numbers as we get closer to launch. But we know these are the centers that have high volume in terms of an SPS treaters where the patients are known and either being managed directly or being referred to on a regular basis.

This is where we're going to start, but we won't stop there. We're going to continue to onboard additional authorized treatment centers over time because we're going to be preparing for myasthenia gravis. And there's a huge synergy between these 2 indications. So as we add new centers for MG, these centers can also be treating SPS as well and continue to accelerate that launch. Looking at the progress we made as this organization over this past year, I think you can agree with me that we've just come a tremendously long way. When I was standing here last year, we were really sitting on this really interesting and intriguing early set of data across multiple indications.

But through our strategy and focused execution, we've now transformed this company. So with a strong focus on our 2 lead indications with Stiff Person Syndrome and myasthenia gravis and a clear pathway forward to bring these to patients in a commercial setting. But we're not stopping there. We're looking forward. We have some very promising data in other larger indications like MS, RA, lupus nephritis.

We're also working on a second-generation platform that will simplify access for patients by removing the apheresis step as well as speeding up manufacturing and reducing cost of goods. We're calling this KYV-102, and we filed our IND, and we are going to disclose more around the development program over the course of 2026. We've also bolstered our cash position. We ended the year with $279 million, and this was bolstered by the equity financing that we put in place towards the end of the year as well as the debt facility that happened back in Q4 as well. All in all, this puts us on a cash runway well into 2028, and it fully funds the plans we have around Stiff Person Syndrome, the BLA filing, the commercial launch as well as the myasthenia gravis Phase 3 trial.

2026 is starting with a bang, and we're really, really looking forward to a number of key catalysts in the exciting year ahead. We talked a little bit about Stiff Person Syndrome and the key catalyst here being filing the BLA in the first half of this year and preparing for commercialization. From an MG perspective, we're going to read out maturing data on the Phase 2, as well as heads down on the Phase 3 program and continuing enrolling that.

And we're also going to be looking at the additional pipeline opportunities because we have maturing a new data with MS, RA and lupus nephritis. And we're going to think about this in a very strategic and focused way on what the next possible indications could be for miv-cel, but we know that the opportunity to change patients' lives in a larger and greater sense is in front of us, and we have an opportunity to do that first here at Kyverna. Overall, I think you can feel my excitement and feel the excitement that we're generating around this space. We've had an amazing 2025. We've delivered on the clinical outcomes that we wanted to see from these first 2 key indications. We've established a clear regulatory pathway.

We're already thinking about and implementing a commercialization strategy, and we strengthened our financial position. I'm really proud to be working with my leadership team and the entire Kyverna team on this tremendous progress that we're making for patients, and we're really excited to keep you informed about the progress that we're making over the coming months. We believe we're putting ourselves in a leadership position in a first-mover advantage to really transform the lives for patients in autoimmune diseases. Thank you.

Let's begin the Q&A session. For those of you who are in the audience, if you have any questions, feel free to raise your hand. And for those joining us virtually, you can also submit questions on the portal. I guess just to -- before we talk about some of the details around the SPS, can you talk about the unmet needs in SPS? I think a lot of us who are in the audience, they haven't heard of the SPS indication.

So can you talk about the unmet needs here? And I think it will be interesting to hear what you're hearing from the ground as well. You talked to -- you engage with a lot of the physicians who manage a lot of these SPS patients. What is their first take? What is the feedback that you're hearing on the pivotal data that you have presented last month?

Well, the first take is like I was indicating this is truly remarkable. These physicians that have been treating and following these patients for many, many years never see an improvement in the patients. The prognosis and the natural history, which is now well documented has been published to the University of Colorado and others have published on the natural history of this condition. Only shows that the patients get worse over time. They might be stable for a while, but eventually, they get progressively worse. And 80% to 85% of patients will require walking aids or become bed bound over time.

We also know that these patients have a prognosis of a higher rate of mortality. There's been a [ NordICC ] study as well that's been validating that. So the prognosis for these patients is horrible and the initial reaction that we got from the physicians that were treating these patients in the clinical trial settings was just surprise. They were expecting that we would hit on the primary endpoint, but the ability to actually impact these secondary endpoints and do so in a really meaningful way and transformative way, I think, was really remarkable.

They were actually commenting as well when the patients saw the data they were coming back into their offices and hugging the physicians and saying, finally, we have something that can treat this disease, which I think really underscores what we're doing here.

Just in terms of the preparation towards filing, it's very clear that you have started mapping out the payer side, how many centers you're targeting and all the good stuff. How do you think about just the gating factors towards the BLA filing milestone? What else is left in terms of your -- on your road towards the filing?

Well, there's no gating factors. We've just read out the data just before Christmas. And my CMO is in the front row here, and their team is hard at work right now in terms of preparing the BLA filing. Obviously, we've got TFLs that we need to double check and make sure those are ready to insert into the modules, but we've also been preworking on the modules. So we've shown that we've been able to execute and move it speed in terms of the recruitment of the clinical trials.

We're going to apply the same discipline around our focus to get the BLA filing in place. And like I said, we're on track to file in the first half of this year, and we'll update you guys more on specifics around that timing as things progress.

Okay. Any questions on the audience?

Good question for you. We respect your commercial launch strategy, how do you think about launch at U.S.? And what's the size of the market for SPS at U.S.

Yes. We're considering that. But just to be clear, we really believe the initial opportunity and where our focus as an organization is going to be is initially here in the U.S. So we're mapping that out and have a really clear pathway forward. But of course, Stiff Person Syndrome and myasthenia gravis, the epidemiology is very similar when you look at Europe and look at some of these other countries around the world. So we're assessing what those opportunities are, and we'll be looking at that as we continue to advance our program.

I have 2 questions. One, in your longer-term follow-ups, have you seen any reversion at all? And the second question is, what do you predict that your price will be for a single dose?

Right. Well, what's been amazing is in these target indications, we haven't seen any need to retreat patients. And patients are off their background immunosuppressants and other therapies that they've been burdened with us, as I said. So we're going to continue to track this over time. But obviously, examples like Denise really underscore this durability impact, which I think is really, really important for patients. And the trials go out to 1 year and 18 months for MG, but we're going to be enrolling these patients in long-term follow-up studies. So we're going to continue to monitor their efficacy over time.

We know from physicians and patients that 1 year is definitely a bellwether. You get a majority or most patients past 1 year, that is already transformative. But now we're seeing multiple patients getting out to 18 months and 2 years, and that becomes a game changer in terms of how you think about treating this disease. So maybe to dovetail that into the second part of your question, you look at the chronic, again, treatment burden that these patients are under, which is not inconsequential.

IVIg alone, like I said, is hundreds of thousands dollars a year. If you look at myasthenia gravis, these FcRns and complement inhibitors cost $400,000, $500,000, $600,000 a year. And that's on top of other immunosuppressants that patients have to take. So the cost burden for these patients and for the system is very, very high. So when you think about pricing in this market, we definitely think that the CAR T pricing is the floor. We believe that there's a premium to current CAR T pricing that we can justify and provide really strong value to the system while also providing a huge benefit for patients and their families.

I wonder if you could elaborate a little bit on the myasthenia gravis. Market landscape. Obviously, huge number of patients, the anti-FcRns have made a significant difference. Many patients benefit, many patients do not. Do you imagine that this would potentially be a replacement for FcRn? Or are you looking at the subset of patients, as you showed on your -- on the video, there are a subset of patients who are intractable and really need the next generation, which is not an immunosuppressive or anything else?

Yes. Well, I think as these things naturally progress, I think they will continue to expand over time, particularly going back to the other question, we see the durability in these patients continue to build over time. We're going to have a more compelling story. But already, when you look at the MG market, despite all these therapies that are there, and it's been great for patients to have this choice and these options, but you look at FcRns, there's still patients walking around with MG-ADL scores of 3, 4, 5 and 6, which is not inconsequential, and they're having to take FcRns, like I said, on this backbone of immunosuppressants.

So the chronic burden of treatment while not getting to MSC is huge. And we know there's an immediately addressable MG patient population that is quite large. We are estimating at least 12,000 patients that are already in this refractory setting that will be immediately amenable to CAR T therapy. But we also know as this durability improves and the value proposition of what CAR T therapies can do, this one and done, remove your other therapies, have this opportunity to get to MSC and a sustained MSC, we believe that we'll be able to capture larger patient populations and move up into earlier lines of therapy over time.

And we just kind of layer on top of that question. I mean, I think there's questions around T-cell engager, right, over the course of the last couple of months -- years or so. How do you think about them as a competitor? Or are they not a competitor? How do you think about that space, right? And yes, so how do you think about the emergence of that versus where you sit and potentially you'll be commercial within the near term. So how are you going to disrupt the space?

Right. I think we're doing something fundamentally different than the other therapies, including TCEs, this ability to get this deep B cell depletion, and we're now demonstrating this through the translational medicine. You're getting into targeted tissues you're crossing the blood-brain barrier to [ CSF ] you're actually changing the underlying cause of this disease and resetting the immune system, not just from a B cell depletion perspective, we had an IR call earlier last year and the translational medicine expert was up speaking on this. And we're actually seeing a normalization of B cells and naive B cells coming back, repopulating in a normal way, but this is also positively impacting Tregs and T cells as well as impacting cytokines and reducing the inflammatory cytokine. So we're, in effect, resetting the immune system. This is something that other therapies, including TCEs, just can't do and haven't demonstrated at this point.

You have presented data not just in MG and SPS. I think one of the most interesting data for us is really the multiple sclerosis data. How do you think about just expansion opportunity for miv-cel? How do you tackle everything else outside of SPS and MG?

Yes. I think you're touching on something that's really exciting. I mean, again, when I was here a year ago, we had these 2 IITs ongoing in multiple sclerosis. And I think a lot of us were thinking this would maybe bear fruit or have some impact on patients over time. I think what surprised us, it also surprised the physicians treating these patients that they were able to see not just a stabilization of EDSS, but actually an improvement of EDSS as quickly as we're seeing.

Dr. Dunn from Stanford, one of the leading investigators said, I've been treating patients for 30 years. Primary progressive MS patients and never seen an impact like this. So I think this is really increasing our confidence that miv-cel has utility outside of these initial 2 indications and this ability, again, to have this deep B-cell depletion in targeted tissues probably gives us a huge advantage, particularly in neuromuscular conditions, and this is something we're going to continue to build on as we advance our strategy.

So we're going to see the maturing of the MS data over this coming year. And based on that, we're going to evaluate whether it's this or another indication that we want to progress as a company.

Where do you stand today? How do you view add modality, specifically the In-vivo CAR T that is emerging? How do you see yourselves standing against that modality?

Yes. I mean, while in In-vivo, CAR T could provide some benefits for patients, but they're still a long way off. I mean even the experts in this area are saying they're at least 8 to 10 years away from actually reaching patients in a clinical setting. And what we know we've got something proven now, what we're doing with autologous CAR T and what we're specifically doing with miv-cel and doing this from a leading position really allows us to get to market and start to addressing really high unmet needs in diseases that need new therapies and start doing that on a relatively short-term basis.

So we're going to focus on this. Of course, we'll be looking to the future and how we can continue to evolve our company in terms of other modalities. But really, the unmet needs are here. The CAR T ecosystem, like I was saying in my presentation, are evolving, making it easier to treat more patients and treat them closer to home and in the community. We're going to continue to leverage and build on that because there's a very foreseeable market that's addressable now and a very valuable one for us.

Any questions from the audience? Just on the manufacturing front, any updates on how prepared you are in terms of capacity? And any just -- how you're building that out just to prepare for the launch of SPS and then also MG launch following that?

We feel very confident about our manufacturing. We've got 2 manufacturing suppliers on board. Both of these have been validated, the comparability studies, the PPQ batches have all been completed. So we feel very, very strong about our CMC regulatory package. And we have also been working with them, of course, sharing our forward-looking forecast, not only thinking about the clinical demand we have for the clinical studies, but obviously, the commercial demand as well.

In addition, I think something that maybe hampered other CAR T companies earlier on when CAR Ts were first getting launched with this manufacturing success rate. We've been reporting 95% plus manufacturing success. And in fact, in our Stiff Person Syndrome trial, we had 100% manufacturing success. So we feel really good about the reproducibility of what we're doing and how we can scale for commercialization.

102. Your IND is filed. How does that fit into the big picture? Is this a strategy from a life cycle management strategy, how does that fit in? And I guess, ultimately, where do you see it tackling in terms of indications?

Yes. We're really excited that our IND was filed and actually the FDA accepted our IND, which is great, and we'll provide more details around our development strategy there. But what 102 does is, I think, really takes the core constructed of KYV-101 or miv-cel from the CAR perspective. It's the same CAR. So we know it works, and it's derisked from that perspective, but puts it on a new manufacturing platform that allows us to use whole blood.

So we can skip the apheresis step make it easier for patients to start their CAR T journey, maybe even do this first step closer to home, which I think it's going to be really important. And in addition, it speeds up the manufacturing process and also significantly reduces cost of goods.

So maybe one way of thinking about it is a few years ago, there was this promise of allogeneic CAR T therapies that would come to market and everybody is really excited about those therapies. I think they've really fallen to the wayside a little bit over the past couple of years. But this idea of making CAR T easier, less expensive, improving patient access is still there. And we believe KYV-101 actually bridges that. It takes the confidence and efficacy that we're actually delivering from KYV-101, the initial CAR and actually then transcends it on this new platform, making it easier for patients to get the therapies.

Great. Well, just to kind of wrap up our conversation here. I guess any questions from the audience before we wrap up? Just kind of maybe forward-looking, what are you most excited about as we think about having the same conversation, let's say, December 2026, where do you think investor focus should be?

Well, honestly, I think what we've shown over this past year is that when we're focused and we bring a highly dedicated and skilled team to the table, we can accomplish a lot. And I think we've surprised a lot of people with our ability to execute, not just on Stiff Person Syndrome, put us in a position to file the first BLA. We could be the first CAR T to launch in the autoimmune space, and we're really, really proud of that. And we're not just stopping there. We've got the next-generation construct. We could be the second indication to launch as well. So we feel really, really confident with what we can do.

And if you look at the year ahead, it's really heads down. It's an execution story. It's finishing the pivotal Phase 3 for myasthenia gravis. It's filing the BLA for Stiff Person Syndrome and getting ourselves ready for commercialization. But we're assembled a fantastic team with late-stage development, CAR T experience, launch experience. We know we've got this and we can do it. And we've actually laid out a strategy that's very, very capital efficient as well and focused that it's going to allow us to execute it.

Great. Well, thank you so much, Warner. Looking forward to year ahead.

Thank you.

Good morning, and welcome to the Kyverna Therapeutics Investor Conference Call. [Operator Instructions] 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 mivocabtagene autoleucel 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 mivocabtagene autoleucel 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. And 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 road map 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 Stiffness 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, the 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. During the disability 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 9. 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 4 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 4 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 in 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 inadequate response to prior immunomodulatory therapy in addition to a stiffness index score of at least 2 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 Heightened Sensitivity Scale or HSS. The follow-up period for patients in this trial is 1 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 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 4 to 5 seconds for a healthy adult.

The median distribution of stiffness Index score was 3 points with a range between 2 to 6 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 1 timed 25-foot walk, turn around and do a second timed 25-foot walk, then the average time of the 2 walks is taken.

To put things into perspective, the time that it takes a normal healthy individual to walk 25 feet is about 4 to 5 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 time 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 4.

The null hypothesis represented by the black dotted line at 0 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 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 Heightened 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 patient who had been diagnosed with SPS for about 8.5 years, but had been experiencing symptoms of disease for about 20 years. When he was first assessed, he clearly had diminishing patient benefits of IVIg and was demonstrating clear disease progression. He was also on valium 3 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 5 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 chunk, 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, the 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% to 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 in 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 are 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 prelaunch 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.

[Presentation]

And with that, I'll turn the call over to our operator for the Q&A.

[Operator Instructions] Our first question comes from Brian Cheng with JPMorgan.

Really congrats on the data. As we think through the phenotype of SPS, there's always these painful spasm that is 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 or any possible contraction in the patients? Can you talk about the influence that miv-cel has in those patients? And then I have a quick follow-up.

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 it's very powerful. So in those scores, we have, as we've shared, ambulation scores and also disease-specific scores that capture those spasms and there -- how the sensitivity of those to happen and also the stiffness index on all the different muscles. And we have seen a 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 plans too. Amanda?

Yes. So thank you. I just want to reemphasize that in my expert opinion, the results of this trial are just truly remarkable. And when you look at the stiffness index and the hypersensitivity scale, those account for those painful muscle spasms that we see in the patient. And obviously, with the data presented, we saw a significant reduction there.

Great. And then just back to your first filing in the first half next year. What are some gating factors remaining 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.

Our next question comes from Thomas Smith with Leerink Partners.

Congrats on the really stellar data here. Maybe I could just start with maybe two for Dr. Piquet. Can 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, 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? And 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, 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 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 multilevel 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. Yes. 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 got you. So 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. So even patients that are stable right now in our clinical practice likely won't be in the future. And so 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. Yes, I appreciate the insight. And 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 National Priority Vouchers?

Yes. Thanks, Tom. Yes, 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 CNPV 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. Congrats again on the data.

Thank you.

Our next question comes from Mike Ulz with Morgan Stanley.

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.

Yes. Thanks, Tom (sic) [ Mike ]. 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 clearly 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. Like we're seeing improvement in 81% of patients beyond what is clinically meaningful. And then you're seeing this respond 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.

So this is -- and another thing to put into perspective is those patients who are now walking without aid, majority of patients now, 67% of patients who needed walking aid just threw them away. So 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.

Yes. 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. And 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. And to see that kind of benefit, again, we do not see that with our current unapproved therapeutics.

Our next question comes from Derek Archila with Wells Fargo.

Congrats on the data. Maybe just first, as we look at the baseline characteristics from the trial, how do you think they reflect the patients that you see or some of the physicians see in the real world? So that's question number one. And then I just wanted to confirm on the neutropenia. I presume this is largely attributed to the preconditioning regimen. So I just wanted to confirm that. And then I have a follow-up as well.

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, and then we'll come back to the second one on neutropenia.

Yes. So 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. So 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. So 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?

Yes, I would agree. With the inclusion criteria used, this is pretty standard for what we would expect to see with your typical classic SPS patients. 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...

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 events with CAR T regimens. So -- 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 is that kind of a potential factor or a gating factor on the BLA submission?

Thanks, Derek. No, not at all. I think as we previously commented, we are well down the path with the CMC package and Module 3 preparations. The conversations we've had with the FDA up to now have been very, very positive. We have 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.

Our next question comes from Sami Corwin with William Blair.

Congrats on the data. 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 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?

Yes, 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 weeks 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 this time point. So it's not patients who drop out. We have no dropouts and no rescue therapy in this data set.

So as data -- 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. We will -- Amanda, do you want to comment more on that?

Yes. 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 up to the 12-month data as this trial comes to a close. And again, 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.

And just maybe -- Yes. 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 1 year or beyond 1 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 the majority of these patients over that line. But as you know and as we've talked about our first 2 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 onetime 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.

[Operator Instructions] Our next question comes from Mitchell Kapoor with H.C. Wainwright.

This is Katie on for Mitchell. Fantastic presentation. 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 can add a little bit more here, but we did some of the dose-ranging work in some of the earlier clinical trials and IIT work, and we've now landed on a final target dose of 100 million cells that we're using in SPS as well as MG, and that's the go-forward indication up to this point for other future indications that we're exploring as well.

Naji, do you want to comment any further on that?

You summed it up perfectly, Warner. 100 million dose is our therapeutic dose that we are for miv-cel dosing patients across multiple indications.

Yes. 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 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.

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 support 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 our 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.