Jefferies Global Healthcare Conference

Thanks, Natasha, and to the Jefferies team for hosting this great event. Really excited to share with you the progress we're making here at Caiverna as we continue to pioneer our way forward, bringing autologous therapies to autoimmune disease patients. At Caiverna, we're uniquely positioned in both a differentiated as well as a leadership position to actually bring these autoimmune therapies to CAR-T patients, starting with our unique CAR-T construct and this proven durability of effect across a variety of different autoimmune patients and we've actually been focusing our strategy to ensure that we actually bring this to patients in a quick manner starting with stiff person syndrome as our lead indication and then leveraging that to a broader aperture of indications over time as we continue to move forward and bring this to patients over the course of our life cycle but stiff person syndrome is just the beginning we've generated some very very interesting data and other neuro immunology diseases, including myosinia gravis and progressive MS. And we're using and leveraging our first mover advantage to initiate a position in this marketplace and then leverage that position to advance into other indications, as well as working in parallel to advance our manufacturing capabilities with improved cost of goods and more rapid manufacturing so that we can bring this to patients faster and cheaper and at greater scale. At the heartbeat of what drives Caverna is our unique construct and MivCell or what was formerly known as KYV-101 is the only CD19 targeted CAR-T therapy with a CD28 co-stimulatory domain. It's also fully humanized with some improved transmembrane and hinge components which actually means it's been designed for potency as well as improved safety and in fact over the hundred patients we've now treated to date we still see no high-grade CRS or ICANs and because of this improved potency we're now seeing durable impact in our first treated patients in both SPS and MG beyond 24 months. Behind all of this is what we're now seeing is an emerging translational medicine data set that's supporting why we're seeing these transformative results in this clinical setting. On the left, you see the ability for MIV cell to actually penetrate into targeted tissues like the CNS in progressive MS patients and do so consistently across all the patients that we've been dosing to date. and on the right you see that as we provide this deep and broad immune reset and b-cell elimination we're actually seeing the b-cells repopulate in a more naive profile as well as seeing the regulatory t-cells upregulated in the sps patients as well as a normalization of the cytokine profiles all this is indicating that we're actually doing something fundamentally different from other traditional therapies both in terms of the depth of b-cell depletion but this broad immune reset. What this translates to is incredible commercial opportunities for our first two indications starting with stiff person syndrome and then also with generalized myasthenia gravis. Both of these indications have tremendous market opportunities because of the unmet market needs that are there, the high cost of burden of therapy that these patients are undergoing, and this ability for MivCell to rapidly advance to marketplace at a premium price to current CAR-T therapies and actually entering the market with biologics like margins. As you can see here, we have a number of catalysts to look forward to in the second half of this year, actually reporting out longer-term data and follow-up across all of our key indications, including stiff-person syndrome and myasthenia gravis, but also additional longer-term follow-up data in other pipeline opportunities like progressive multiple sclerosis and rheumatoid arthritis. The exciting piece of news that we announced just recently is the alignment that we now have with the FDA after our pre-BLA meeting and the initiation of our rolling BLA submission. We have alignment with the FDA on the core components of our package, including the CMC package and the single-arm trial design for Stiff Person Syndrome, and we're well on track now initiating that rolling submission with a target to complete it in Q4 this year. This puts us on track to be the first company to launch an autologous CAR-T therapy into the autoimmune space, and certainly the first company to have an approved therapy in stiff person syndrome. I'd now like to take a little bit of time to dive into stiff person syndrome in a little bit more detail, but before I do, I think nothing puts into perspective the impact that we're having on patients like showing you a patient video. So I'd like to roll a patient video. This is one of the patients from our Kaiser 8 pivotal study, and you can see this patient before MivCell displaying the classic symptoms of stiff person syndrome. She's hunched over, she's holding herself up with her hands because she's afraid of falling, and she has a very unsteady gait. After a single dose of MivCell, 16 weeks later, you can see that not only is she walking faster, but her gait is normalized and she's actually walking with a tremendous amount of confidence. So you can see that this video demonstrates that we're doing something fundamentally different here than just treating the clinical symptom of this disease, but actually reversing the course of disability as well. We know stiff person syndrome is a debilitating autoimmune disease, and we know that over 80% of these patients will progress to disability over the course of time, including the need of walkers, wheelchairs, and even some become bedbound. What's also really important is that these patients tend to be younger and of a working age, and we know that 19% of them are only working after four years from their initial diagnosis. What we do know as well is that there's no approved therapies in this space, and patients treat their disease with a cadre of off-label therapies, including IVIG and muscle relaxants. Nothing treats the underlying course of the disease, nothing gets at the cause of the disease, and nothing actually has a significant clinical improvement in patients over time. Which is why the results that we saw from MivCell in our pivotal clinical study, the Kaiser 8 study, are so remarkable. You can see here in terms of the time 25-foot walk test, which was the primary endpoint, we can see a significant reduction as early as 16 weeks. And in fact, a clinically meaningful reduction is 20%. What we're seeing at 16 weeks is a 46% reduction. So this more than doubles what is clinically meaningful. In addition, of the 12 patients that started the study that required walking aids, a walking cane or walking materials, two-thirds of those were able to eliminate those walking aids by the end of the study, which tells us that we're not just improving this disease clinically and having a marginal impact on clinical symptoms, but transforming this and actually reversing disability for the first time. These results also played forward in terms of the secondary endpoints, including the modified Rankin-Scale and Hauser Ambulation Index, which you can see here, a significant shift towards improved mobility. And we also saw improvements in terms of the DSI, the distribution of stiffness index, as well as the HSS, which is the heightened sensitivity index. These are indices that are specifically designed for SPS patients, and in both cases, we're seeing statistically and clinically meaningful improvements across all of these secondary endpoints. MivCell also demonstrated a very tolerable safety profile with no high-grade CRS or ICANs. Of the AEs that patients did report, they were manageable with regular and traditional therapies and fully resolved through the course of the actual trial. What's really interesting now is comparing the Kaiser 8 study results with what we were actually seeing in the natural history study, and we shared a natural history study of data at the American Academy of Neurology just a few weeks ago, and in this study, we actually were tracking over 150 patients over the course of 10 years, and what we're actually seeing in this patient group that's actually being treated with a number of these off-label therapies is that patients still progress. They see no or minimal improvement in terms of their time, 25-week walk. over the course of their lifetime they actually increased their need for walking aids and actually significantly increased their immunotherapy use as well this contrasts very very nicely with the results that we saw in kaiza 8 where we saw 46 improvement in the time 25 walk test we actually saw significant improvement in terms of the reduction in walking aid use and all patients by the nature of the way mivcell is actually works and is administered to patients are able to eliminate the background immunosuppressants and high-dose steroids that these patients are chronically burdened from. So in a sense, we're showing and demonstrating here a paradigm shift in how to treat autoimmune diseases like stiff person syndrome. We also know there's a very viable and attractive commercial marketplace for MIPSEL. This is a disease that has no approved therapies, and we know there's 6,000 diagnosed patients waiting in the U.S. right now for an approved therapy, of which we've now identified between 2,000 and 2,500 that are already refractory to off-label immunotherapies. These are the patients that are the low-hanging fruit, if you will, that are desperate for a new therapy like MivCell, and ones that we'll be addressing through a focused commercial launch strategy when we get to launch. At launch, we'll be targeting 10 initial centers. We know that these patients are highly concentrated in these 10 centers, and these 10 centers represent not only centers of excellence from an SPS perspective, but they're also high uses of CAR-T and established uses of CAR-T centers and have expertise in treating patients across a number of different reimbursement scenarios. All of these put together underscore the fact we have a very meaningful and commercially viable initial opportunity for us that we can continue to grow and expand from over time. We've also conducted market research with stiff-person syndrome treaters. And you can see from this that they have a high response to the actual clinical profile that we were showing you here a few minutes ago. Over 90% view this profile as being compelling for patients, and 85% of them would use this immediately at launch for their modern-to-sphere patients. We're leveraging this commercial scenario to actually translate and use our manufacturing model to bring this to patients at scale. We're currently using a dual-source manufacturing of both Elevate Bio and Menaris Advanced Therapeutics and we've been able to demonstrate through our clinical trial program over 98% manufacturing success rate and a low cost of goods, which means that we're going to be able to scale this for launch and actually deliver biologics like margins at the time of launch. I'd now like to take a look at our second indication, generalized myasthenia gravis, provide a little bit more context about why we're so excited about bringing this to patients as well. This is another disease with a high disease burden, although there's a lot of therapies available in the marketplace right now. The therapies are lacking in many, many important ways. First, they do provide some moderate symptom control, but many of them are inadequate for many patients. few patients actually reach MSC or minimal symptom expression and a majority of patients still require ongoing immunotherapy and high-dose steroids in order to manage their disease. This means that this is costly, it's burdensome to the patient and it's highly burdensome to the system as well. Which again, why we're seeing this dramatic impact on our first patients treated in our Phase 2 study with MibCell that we're so excited to bring this to patients at scale. You can see here in this Phase 2 readout, We saw both in terms of the MG-ADL score and the QMG score a significant reduction in these scores as early as four weeks that deepened and progressed over time to even better responses. By 24 weeks, which is the primary endpoint, we see reductions of 8.5 from an MG-ADL score and a reduction of 11.3 with QMG. These results are unprecedented and demonstrate that we're doing something here fundamentally better and different from other therapies that are being used in this space. In addition, 100% of our patients responded, and they all had a clinically meaningful response on both of these key endpoints. And we were also able to achieve 57% of patients getting to MSC. This is ultimately what patients want in this disease. They want to live in a drug-free, disease-free state, and MivCell provides them the best opportunity of achieving that. Again, we're able to demonstrate a really strong safety profile in these patients as well, with no high-grade CRS or ICANTS observed, and manageable safety events that we're resolving through the clinical trial and regular standard support of care. In addition, because of the low levels of side effects and adverse events with MivCell and the predictability of when these adverse events occur, we're actually very confident that this will be used in an outpatient setting at the time of launch. When you compare MivCell to other standards of care or other therapies that are being studied and recently approved in this space, you can see the dramatic impact that MivCell brings that nobody else can touch. These dramatic impacts in terms of the depth of response, both in terms of the MGADL score reductions and QMG score reductions are unmatched. In fact, we more than double what we see from other competitors in this space. In addition, all of our patients are responding, and we're getting more patients to MSC. What's critically important to mention that's not written on this slide is that all these other therapies on the left-hand side are actually being used in addition to other chronic immunosuppressants and other high doses of steroids. Only MivCell allows you to have this dramatic clinical impact while also removing the other background immunotherapies and steroids that patients are chronically burdened from. Again, we're demonstrating a paradigm shift in terms of how to treat this autoimmune disease. This is an outline of our phase three clinical study, and based on these phase two results, we've pivoted and now started enrolling patients into our head-to-head phase three clinical design. We're comparing MIV cell versus standard of care and we'll demonstrate superiority over standard of care on both primary endpoints, the MGEDL score and the QMG. The primary endpoints at 24 weeks, but we're going to continue to follow these patients to show and demonstrate durability as well as a crossover from the standard of care onto MIV cell if patients choose to do so. Overall, there's a strong interest in this trial given how differentiated MIV cell is. We've started enrolling our first patients at the end of last year and we're now at 15 centers globally with a huge interest from patients and physicians. In terms of commercial opportunity, we also see a tremendous opportunity here for MivCell when we get to the commercial stage of this launch. Of the 80,000 diagnosed generalized myasthenia gravis patients here in the U.S., we believe that about half of them will be eventually addressable with CAR-T therapy. But we know as an initial priority there's 12,000 patients that are already refractory to existing biologic therapies. These are the patients that we are enrolling in our study, and this is a significant patient pool, significantly larger than SPS, but one that we can tap into. And given the fact that we are the only company with a Phase III study, we believe that we will be first to market to bring ontologous CAR-T therapy to generalized myosinia gravis patients. Looking ahead to additional opportunities, we're really excited about the emerging data in progressive MS. We've now shared, through our IT studies at both Stanford and UCSF, some very, very exciting data with MivCell in progressive MS. What we've seen, actually, is not only a stabilization, but in a majority of patients, an improvement in the ESS. This has never been seen before. In addition, we're actually now seeing these patients off background immunosuppressants and significant improvement in fatigue scores. All of this could represent a new standard of care for progressive MS patients, particularly those who have already failed anti-CD20 therapies. We'll be actually looking to read out additional data on these IITs in the second half of this year, and that will help indicate and point the way for our future indications of how we're going to continue to progress our story as a company. Overall, Caverna is uniquely positioned to be the leader, and also from a differentiated perspective as we continue to advance and pioneer the way forward for autologous CAR-T therapies in autoimmune diseases. We have a unique CAR-T construct that's been designed for autoimmune diseases, suitable for use in an outpatient basis, and with a really, really strong safety profile. We've now treated over 100 patients, and we've actually de-risked our clinical trial programs with really, really positive data in our Phase 2 and Phase 1 studies. We have the potential and will be on track to be the first autologous CAR-T therapies to bring this to not only stiff person syndrome but also myasthenia gravis and looking forward to future indications as well and i've been assembling a very strong leadership team around me with not only strong cell therapy experience but rare disease and neuroimmunology experience as well that will carry this forward and bring this to patients at scale thank you very much