Kyverna Therapeutics, Inc. (KYTX) Earnings Call Transcript

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 Kaizen registrational trial of navocaptigene Autolus or Mitel formerly referred to as KLV101 and StiffBerson syndrome as well as top line longer-term follow-up data for a MCIs6 Phase II trial in generalized myosin and 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 dial information. Joining us today are Warner Biddle, our Chief Executive Officer; and Naji Ashan, our Chief Medical and Development Officer. Werner will start with brief remarks followed by Nausea, who will cover our data for Stivers on syndrome or SPS and generalized myasthenia gravis or GMG, after Warner will close on our commercial opportunity in titers syndrome. Following our prepared remarks, Greg Martini, our Chief Financial Officer, will join for 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 Cavena'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 stifferson syndrome. Overall, we continue to establish a new benchmark in both durability and safety for the entire field across both SBS and GM and data demonstrated robust and durable efficacy for at least 1 year following a single dose of Mibcell with nearly all patients remaining off chronic immunotherapies. Importantly, Mebel'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 IECHS. These are remarkable results that continue to define Mittal's unique construct and differentiated profile where 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 1 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 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 enrolling completion in mid-2027, unprecedented 18-month durability data continue to derisk the registrational path and strengthen Misale differentiation in the large and growing MG market. Turning to Slide 5. We Mib cell'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. Mice 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 costimulatory 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 mis-sell 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 Mivcell 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 CHS. 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 Marcell to fundamentally redefine the treatment paradigm for autoimmune diseases. Now let's turn to manufacturing. Next slide. Medcel 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 Medcel 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 mix 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?

One year follow-up data in SPS, which represents 1 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 CISA 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 Mertens. The change from baseline and the time 25-foot walk test measured at 16 weeks in our primary end point. This is a validated test to assess working ability as well as to evaluate stiffness and loss of mobility. To put things into perspective, the time that it takes a health 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, RDSI 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 metal. Let's turn to the data on Slide 9. As you recall, we reported positive primary analysis of our CISA a 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 of immunotherapies at the 16-week primary endpoint measurement and MIP cell was well tolerated. These outcomes achieved with a single dose of Marcell alone are unprecedented in SBS, 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 TIM25-footwalk 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 time 25-foot walk test. And the 1-year follow-up 95% of patients maintained their benefit with nearly all patients or 24 out of 26 remaining of immunomodulatory or immunosuppressant therapies for SPS. At baseline, the medium time 25-foot walk was 11.1 seconds. At this 16-week primary and point emedia reduction in time 25 footwall 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%. We these improvements translate to more than 1/3 of patients achieving a time 25-foot walk of less than 5 seconds, which is consistent with a healthy adult walking speed. Importantly, of the 12 patients who acquired the walking prior to treatment, 67% continue to walk unassisted at 1 year. further highlighting Mitel'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 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. We 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 time 25-foot walk test, and all secondary endpoints that measure the extent of disability and SPS specific symptoms, including MRS, DSI, Houser ambulation Index and the heightened sensitivity scale. Let's turn to safety on Slide 11. As the 1-year follow-up for SPS patients, mill cell continues to be well tolerated with no high-grade CRS or icons. In addition, there were no ICHs observed. Five 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 on 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 me cell has demonstrated sustained improvements across all primary and secondary end points out to 1 year with continued reversal of disability and nearly all patients remaining off chronic immunotherapies for SBS. These results are in stark contrast to what has been observed in the natural history of the disease, where most patients see minimal to no improvement in the time 25-foot Waktest despite being on off-label treatments with the majority increasing walking aid usage over time. We are excited to include these 1-year results in RBLA submission, which further increases our confidence in our filing and path to approval. Before we turn to our data and generalized myasthenia gravis, I'd like to conclude with a few videos of our SPS patients performing the time 25-foot walk at their 1-year follow-up visit. The first video is of a 39-year-old man patients 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 Metal, the patient requires a walker to ambulate. And despite the walking aid, you can see his work is still slow and unstable here is the video after just 16 weeks and a single dose of my cell. And here it is a 1-year follow-up where improvement is sustained. As you can see, a remarkable transformation with improvement sustained through 1 year. is 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 adults. 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 Medcel and her results following a single dose of net cell. Let's play the video. Here we have the 73 old female patient diagnosed with SPS in 2024 with symptoms for about 2 years prior to diagnosis. The video shows are 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 1-year follow-up continuing to maintain her improvement. As you can see, another transformative outcome following a single dose of my cell. Not only was the patient able to walk without hurricane, but her work 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 CISA 6 Phase II trial included 7 patients who have traded prior immunotherapies. It is important to note that all patients discontinued their engine immunotherapies prior to receiving a single dose of my 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 7 patients in our trial have reached the 24-week primary endpoint measurement. Five patients reached a 52-week follow-up and 2 patients reached 76 weeks. As you can see from the chart, A single dose of Mitel deliver rapid and robust improvement 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 and 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 metal 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 MGL, 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 a 3-point improvement in QMG and MGC. Moreover, we continue to see 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 MSC as of the last follow-up at nearly all patients, 6 out of 7 remained free of immunotherapies, including nonceredal 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 Meta -- 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 matter most to patients, which is living with little to no functional impact from their disease. For rest cell, 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 Mesel is, therefore, not simply symptom improvement, but offering the potential to 3 patients from disease while removing background immunotherapies with a onetime treatment. Let's turn to safety on Slide 17. Consistent with our SPS data, Mitel remains well tolerated in MG in this longer-term follow-up. There were no high-grade CRS and no instances of icons observed. In addition, there were no cases of ICH as observed. There were a total of 3 patients that had Grade 3/4 expected adverse events associated with CAR-T cell therapy and apodepletion that included neutropenia and neuphopenia. 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 Medcel. Let's turn to Slide 18 before I turn the call over to Werner, I want to conclude an important slide that highlights Mitel'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, Mitzel is the only product candidate that has demonstrated the greatest depth of response while freeing patients from chronic patron 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 Kavarna 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 comes, Mibcell'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, MICE is designed to reset the immune system, enabling lasting results. Beyond efficacy and durability Mi cells consistent safety profile increasingly differentiates the therapy in the competitive landscape. Data presented today reinforce the real-world potential of MIPS 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, Kiverna 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 Medcel particularly in SPS, where we're encouraged that the FDA and new CBR 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. We 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, 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 were 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 Mivcells profile is highly compelling versus current treatment options and 85% of them would use Mibcell 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 in infrastructure, a strong neurology partnership and positive site economics with the potential to adopt an increase uptake. Over time, we believe Novocell 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 2017. 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 NICE 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 Kiverna, 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 FPSM data sets, nearly all the patients were made off immunosupressive 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 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 the sell 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 questions.

I'll start with just saying I think these results exceeded even our expectations and what anybody would have expected for a onetime 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 visibility 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 1 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, 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 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 of these patients and families of these diseases. StiffPerson 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 Mice is extremely high and justifies a price at a significant premium over current cars 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 this mission 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 up 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, will 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.

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 sometimes slightly after launch.

Naji, do you want to start with the first question, and then I'll take the next 1 on the launch in the outpatient usage.

Vast majority of patients, as we discussed today remain of 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 SBS and a drastic difference from what we see in the natural history. The 2 patients who went back on IVIG after 8 months, 1 of them did not achieve clinical benefit of met cell. So this is the 1 patient that did not achieve this, and we shared it at the end 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 1 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 NICE 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 MIFCellhas 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 MICE. 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 Mitel has on these attacks that you see in person syndrome. I know that these attacks are muscle statin is very much to finish rote 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?

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