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

Good morning, and welcome to the Caverna Therapeutics Conference Call. At this time, all participants are in a listen-only mode. A Q&A session will follow the prepared remarks. Please note this call is being recorded. I would now like to introduce Jessica Serra, Head of Investor Relations.

Good morning, and thank you for joining us today. Today's conference call will cover the positive top-line one-year data from our Kaizen 8 registrational trial of mevocaptogene autolusel, or MIFCEL, formerly referred to as KYV-101 in stiff person syndrome, as well as top-line longer-term follow-up data for our Mount Kaiser VI phase II trial and 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 defer 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 Najee Ghishan, our Chief Medical and Development Officer. Warner will start with brief remarks, followed by Najee, 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 for 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 Kyberna'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 one year following a single dose of MIB-Cell with nearly all patients remaining off chronic immunotherapies. Importantly, MIV cell's consistent safety profile was maintained in the one-year follow-up with no high-grade CRS, no high-grade ICANs, and no cases of IACHS. These are remarkable results that continue to define MIV cell'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 a rolling BLA submission in Q4 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 multi-billion 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 3 GMG trial advances towards enrollment completion in mid-2027, unprecedented 18-month durability data continue to de-risk the registrational path and strengthen MIVCELL's differentiation in the large and growing MG market. Turning to slide five. MIVCELL'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. MivCell 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 cell under the compassionate use pathway have now achieved durable responses beyond two 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 cell across multiple autoimmune indications, and we continue to observe consistent and manageable safety profile with no high-grade CRS or ICANs and no recorded cases of IEC-HS. These data support the potential for outpatient administration, which is an important consideration for patients, physicians, and healthcare systems. Overall, these outcomes highlight the potential for MivCell to fundamentally redefine the treatment paradigm for autoimmune diseases. Now let's turn to manufacturing. MivCell 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 Elevate Bio, our primary manufacturing partner for MivCell, 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 MivCell efficacy and tolerability data generated in now over 100 patients across indications to date. With that, I'll turn the call over to Najee, who will now go over our top-line data. Najee.

Thank you, Werner.

I'm very excited to share our one-year follow-up data in SPS, which represent one of the most mature durability datasets reported to date in an autoimmune CAR-T clinical trial. Let's go to slide eight. As a reminder, our FDA-aligned CAISA-8 clinical trial is a single-arm multi-center open-label registrational phase 2 trial. We have received both the RMAT and orphan drug designations for MIFCEL and SPS. The change from baseline and the time 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 one year. Importantly, all patients discontinued their immunotherapies prior to a single dose of MefCell.

Let's turn to the data on slide 9.

As you recall, we reported positive primary analysis of our Kaiser-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 MIFCEL was well-tolerated. These outcomes achieved with a single dose of MIFCEL alone are unprecedented in SDS, a highly debilitating and progressive disease with no approved therapies. Today, we are reporting data on all 26 patients who have reached the one-year follow-up. As you can see on the chart on the left-hand side, improvement in mobility as measured by the time 25 footwalk test supporting reversal of disability was sustained through one year. Recall in the primary endpoint measured at 16 weeks, we saw 81% of patients achieve a clinically meaningful improvement in the time 25 foot walk test. At the one-year follow-up, 95% of patients maintained their benefit with nearly all patients, or 24 out of 26, remaining off immunomoderatory or immunosuppressant therapies for SPS. At baseline, the median time 25 foot walk was 11.1 seconds. At the 16-week primary endpoint, the median reduction in time 25 foot walk was 46%, and this was further improved to a 49% reduction from baseline at one year, representing an over twofold improvement of what is considered a clinically meaningful improvement of at least 20%. These improvements translate to more than one-third of patients achieving a time 25 foot walk of less than five 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 one year, further highlighting MIPSEL'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 SDS 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 one-year follow-up. As you can see from the slide, statistically significant improvements were sustained through one year across the TIME25 footwalk 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 one-year follow-up for SPS patients, MIFCEL continues to be well-tolerated with no high-grade CRS or ICANs. In addition, there were no IEC-HS observed. Five patients developed grade 3 or 4 neutropenia, which is a known adverse event associated with CAR-T treatments. All cases were manageable. Four out of the five patients have fully resolved, while one 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 three patients have been results. Overall, a single dose of MIRCEL has demonstrated sustained improvements across all primary and secondary endpoints out to one year with continued reversal of disability and nearly all patients remaining off chronic immunotherapies for SDS. 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 Time25 footwalk test, despite being on off-label treatments, with a majority increasing walking aid usage over time. We're excited to include these one-year results in our BLA submission, which further increases our confidence in our filing and path to approval. Before we turn to our data and generalize myasthenia gravis, I'd like to conclude with a few videos of our SPS patients performing the Time25 footwalk at their one-year follow-up visit. The first video is of a 39-year-old male patient who we showed at AAN, where he performed the time 25 foot walk test at the 16-week primary endpoint.

Let's play the video.

Prior to receiving MIFCEL, 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 MepCell.

And here it is at one year follow-up where improvement is sustained. As you can see, a remarkable transformation with improvement sustained through one 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 MIFCEL and her results following a single dose of MepCell.

Let's play the video.

Here we have a 73-year-old female patient diagnosed with SPS in 2024 with symptoms for about two years prior to diagnosis. The video shows her performing the Time 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 one-year follow-up continuing to maintain her improvement.

As you can see, another transformative outcome following a single dose of MIFSA. 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 one year.

Now let's turn to our positive longer-term phase 2 data in GMG. Slide 14.

As a reminder, the CAISA-6 Phase II trial included seven 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 MIF-Cell. 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 the 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 seven patients in our trial have reached the 24-week primary and point measurement. Five patients reached the 52-week follow-up, and two patients reached 76 weeks. As you can see from the charts, a single dose of meth cell delivered rapid and robust improvements in MG-ADL and QMG that were sustained for at least one year. Mean improvements from baseline were seen as early as two weeks of 6.9 points, with responses deepening through 24 weeks at 8.3 points as sustained through 52 weeks at 8.2 points. Similar durable results were seen in QMG, with mean improvements from baseline seen as early as two 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 3 trial. Given the sustained magnitude of response achieved by MEF-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 MGADL, QMG, and MGC as of last follow-up. This is defined as greater than or equal to two points improvement in MGADL and a greater than or equal to three-point improvement in QMG and MGC. Moreover, we continue to see a 100% response rate for our primary endpoint, MGADL, which is defined as the proportion of patients achieving a greater than or equal to a three-point reduction. Importantly, 57% of patients continue to maintain a minimal symptom expression, or MSC, as of the last follow-up, and nearly all patients, six out of seven remained free of immunotherapies, including non-steroidal immunosuppressive therapies, high-dose steroids, FCRN, and complement inhibitors. I want to highlight the importance of these two data points. When we think about the potential for MIPSET and 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 MSC because that is what is most important to patients, which is living with little to no functional impact from their disease. For MIFCEL, 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 Mifcel 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, MIFCEL remains well-tolerated in MG in this longer-term follow-up. There were no high-grade CRS and no instances of ICANNs observed. In addition, there were no cases of ICHS observed. There were a total of three 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 MIF-cell.

Let's turn to slide 18.

Before I turn the call over to Werner, I want to conclude an important slide that highlights MIF-cell'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, MIFCEL 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 thank you nazi and turning to slide 20. in summary today's results further reinforce that we are doing something fundamentally different here at caverna 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, MIB-Cell's compelling value proposition to both patients and payers is very clear. For the first time, we're 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, MIB-Cell is designed to reset immune system, enabling lasting results. Beyond efficacy and durability, MivCell's consistent safety profile increasingly differentiates the therapy in the competitive landscape. Data presented today reinforced the real-world potential of MivCell 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, Caverna 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 MIVCELL, 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 and met 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 multi-billion 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 the society, driven by high costs of care, which can range from $700,000 to over $1.5 million over a three-year period. On top of these, there are additional costs related to disability and job losses. We believe MivCell'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 MivCell's profile as highly compelling versus concurrent treatment options, and 85% of them would use MIB-Cell 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 NefCell 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 MIB-Cell 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 Caverna, 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 thank you warner i will now open the call up to a question and answer session if you'd like to ask a question please press star one one if your question has been answered and you'd like to remove yourself from the queue press star one one again our first question comes from thomas smith with lyric partners your line is open hey guys good morning thanks for taking our questions and 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 SDS and MG datasets, nearly all the patients were made off immunosuppressive therapy at one year. Truly remarkable advocacy. 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 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 VivCell in both SPS and MG? And then lastly, just on the regulatory front, you're making progress here on the rolling BLA submission. I'm 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.

Thanks, Tom. Appreciate those 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 myosinia gravis. But, Najee, 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.

Sure. Thanks, Werner. Yeah, Tom, as you said, this is truly 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 one year. That's really a key piece. As Werner said, some of it probably we can say it exceeded even expectations, but we were expecting this when we look at also some of the data from the compassionate use patients that is now beyond two years. Here we're seeing this strength of data being maintained for the majority, vast majority of patients at one year. On the use of immunosuppressants, to your point, all patients by design stop their immunosuppressants, and we're seeing the vast majority of patients remaining of immunosuppressants while having this profound clinical benefit in both of the diseases at one year and even at 18 months for the patients who reach 18 months in JMG. it.

That's great, Najee. 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 of these patients and families of these diseases. Stiff person syndrome is usually treated with these patients with multiple doses of IDIG, 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 four 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 MivCell is extremely high and justifies a price at a significant premium over current CAR-T 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. Najee, maybe you want to provide a little bit of color on what the team is doing right now to finalize that submission.

Sure. So we are on track, as Werner 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 one 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.

Yeah. And just adding on that, Tom, 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.

Thank you. Our next question comes from Derek Arkilla with Wells Fargo. Your line is open.

Hey, good morning. And 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 two patients that maybe went back on immunotherapy in the SPS update and just trying to understand, you know, 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, you know, the potential for, you know, outpatient, you know, 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, you know, slightly after launch?

Thanks, Derek. Appreciate it. Najee, do you want to start with the first question, and then I'll take the next one on the launch and the outpatient usage?

Of course. Thanks, Eric. The vast majority of patients, as we discussed today, remain off chronic immunotherapies for SPS at one year. while maintaining their clinical benefits. So this is, I want to start with this because this is really unprecedented in SDS and a drastic difference from what we see in the natural history. The two patients who went back on IVIG after eight months, one of them did not achieve clinical benefit of MIF cells. 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 eight 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, you know, not FDA approved therapies. Here we're seeing something remarkably different while freeing the vast majority of patients from their immunosuppressants.

Thank you, Najee. And just building on your second question, Derek, we believe that MivCell 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 MivCell 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 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 MIF-CELL. 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, 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.

Very helpful. Thanks, guys.

Thank you. Our next question comes from Brian Chang with J.P. Morgan. Your line is open.

Hey, guys. Thanks for taking our questions this morning, and congrats on the impressive longer-term data updates here. You know, first, I'm curious if you can talk a little bit about the impact that Nipsel has on these attacks that you see in sick person syndrome. I know that these attacks are, you know, not muscle spasm. It's very much the signature of the disease, So I'm curious if you can give us some color on, you know, the impact on the number of attacks or the frequency of these attacks. And just on the regulatory front, I'm curious also if you have any feedback from the agency so far on this longer-term data set that you reported today.

Thank you, Brian.

Najee, do you want to provide a little color on the impact on the patient's symptoms? because it goes beyond the time 25-foot walk test, as you've indicated in the presentation.

Yes. So, Brian, as we shared at the 16 weeks and what we're looking in this trial is this primary endpoint of time 25-foot walk, 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 the spasm 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 one 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 MS Toronto as we disclosed. So stay tuned for additional granularity on those endpoints at that conference.

Yeah, thank you, Najee. And with regards to your question, Brian, on the FDA reaction on the data, you are seeing the data in real time. This is the work that Najee 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 sustain durability that MIF-CELT can provide for these patients and strengthens our file and strengthens our regulatory probability of success.

Okay, thank you. Thank you. Our next question comes from Mike Oles with Morgan Stanley. Your line is open.

Hey, good morning, guys. It's Avi Novak. I'm on for Mike. Thank you for taking your questions, and congratulations on the data. I'd actually like to shift to GMG, I guess, you know, seeing as the phase three trials open label, I was wondering if maybe you could give us some commentary on, you know, early safety and, you know, if so far you're thinking in terms of ICANN and CRS, you know, is it, you know, consistent with, you know, the nice data that we're seeing in the phase two trials? And then also maybe, you know, it's a similar question As before, I saw there's, you know, now one patient who, you know, who resumed, you know, prior immunotherapy. I was wondering if you can maybe provide some color on that from the Phase II GMG trial.

Sure, Abby. We're blinded, actually, to the results that are happening in the Phase III trial. And, Najee, maybe you can 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 Najee, maybe you could comment on that and also the one patient in the GMG trial, which we had reported on earlier. Maybe you could add a little bit of color there as well.

Sure. So, yeah, as Werner said, it's a phase three trial, obviously randomized. So we're we're blinded on the trial 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 SMB. and there's nothing as we would expect, actually. The important piece here is, as Werner said and I shared today, we have now more than 100 patient dose, no high-grade CRS, no high-grade ICANs, no ICHS 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 immunotherapy, immunotherapy. So this is actually the patient we did share end of last year. So there was one patient on a patient-initiated request who went back to one of their immunotherapies and is still at MSE. So this patient actually had three immunotherapies before getting on our trial. Their MGATL 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 one of the immunosuppressants and they are still at MSE. So what's remarkable is this patient is beyond one year now and still achieving MSE.

All right. Awesome. Thank you so much for taking our questions and congratulations on the data.

Thank you. Our next question comes from Matthew Phipps with Blair. Your line is open.

Good morning. Congrats on this very strong durability data here. You know, I was wondering if at this point, can you infer anything about an SPS patient's length of disease duration and potential outcomes with MIV cell treatment? Just wondering if there's any data to suggest that treating patients earlier in their disease course could lead to better outcomes, maybe giving incentive to not limit this therapy to patients who have 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. I'm just wondering if this has had any updated discussions with the FDA. Thank you.

Yeah, I'll start with the first one. All patients that were enrolled in the QAIS-8 trial had failed one immunosuppressant. And in this case, majority of them had been on IVIG. And you saw the impressive results that we were reading out and reconfirming what the one-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 high interest in getting access to MIPSEL. 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 SPS, even as we were reading out these trial results.

Najee, 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. yeah so the fda um they're interested out specifically on this event and i would say as as we shared today and we've been sharing our construct actually has been built for safety you know since the beginning when we licensed this construct the constructs that have shown a tenfold less neurotoxicity and we took it and developed it in immunology our manufacturing is also a conventional manufacturing that has been proven now with more than 100 patients So in the PVLA meeting, as we discussed 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 icons and no observed cases of ICHS. So we're not expecting any change to what was aligned with the agency so far.

Yeah, 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 Najee 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 MivCell.

Thank you. As a reminder, if you'd like to ask a question, please press star 11. Our next question comes from Mitchell Kapoor with HC Wainwright. Your line is open.

Hey, this is Ahmed from Mitchell. Thank you for taking your question, and congrats on the excellent data. So just on GMG, so the phase 2 population had started a mean MG, ADL of 11. How does the baseline severity in phase 3 compare? And do you think if patients enter with lower symptom scores, do you expect a smaller absolute treatment effect but a higher probability of MCE? And have you accounted for that distinction in the trial assumptions? And then a second question still on GMG. I was wondering if patients require rescue IVIG, PLEX, or steroid escalation before week 24, do the subsequent MG, ADL, and QMG scores remain in the primary analysis, and can that patient still count as an MCA responder? Thank you.

Najee, do you want to touch on the relative MGDL scores and the use of rescue therapies and how we're counting for that in the trial?

Yeah, so the patients we're seeing, obviously, MGAZL more than six, QMG more than 11 as an inclusion. And we've seen, I think, to your point, when you look at the seven patients, we've seen really this robust response on all patients. So we're reporting 100% response rate on MGAZL. And then we've seen this robust improvement on both endpoints, MGAZL 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 three is very similar to the phase two. So we're expecting, you know, an even stronger probability of success, actually, in the phase three based on this data from the phase two. To your second question was on how we're going to treat in the phase three IVIG or other treatments, any rescue therapy that is happening within the six months of primary endpoint is considered a rescue therapy. So they will be counted as such in the phase three trial. What is key, though, in the phase two, 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 six months.

It happened after eight months. yeah and i think the other important um yeah and i think the other important takeaway here is that the results that we're seeing in the phase two study and then this extended longer term follow-up that we're reporting out today with mgadl score reductions of 8.3 um and qmg reductions of 11.7 at 24 weeks highly de-risk our phase three study um we we believe this adds additional confidence that we can not only recruit this study with the right patients, but we can actually see this transformative result being replicated in our phase three trial.

Perfect.

Thank you again.

Thank you. 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 Kaiser 6 and Kaiser 8 trials, and to our investigators and clinical site teams. I also want to acknowledge the entire Caverna 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.