Good afternoon, everyone. Thanks for joining us here at the Leerink Partners Global Healthcare Conference. My name is Tom Smith. I'm one of the senior biotech analysts here at Leerink, and very happy to be welcoming our next company to the stage, Kyverna Therapeutics. With us from Kyverna, we have CEO Warner Biddle. Warner, thanks for being with us. This will be a little bit of a hybrid session. We're going to kick off with a bit of a presentation, and then we'll move right into Q&A. Warner, why don't you go ahead and take it away?
Thanks. Thanks, Tom. Thanks, everybody, for joining us. Thanks to the Leerink team for setting this up this afternoon. Yeah, I'm going to give a brief presentation, just giving a summary and highlights of our 2025 strategy and the progress that we're making against our goals. We're going to turn it over and have a little bit of a Q&A. This is our standard forward-looking statement, and safe harbor. We'll start with this, though. This is why we're in business. Kyverna is a leader at this point and pioneering the way forward with the opportunity to be the first CAR-T company to launch in the autoimmune space. We have a unique CAR-T construct.
We're the only one with a CD19, CD28, costimulatory domain, fully humanized construct with the opportunity to bring a differentiated profile, both in terms of efficacy and safety, with no high-grade CRS and no high-grade ICANS. You can see our leading indication is stiff person syndrome. This is an opportunity for us to move quickly and establish a presence in this market with two fast-follower indications, with myasthenia gravis, as well as lupus nephritis.
We've got a follow-on construct we're calling KYV-102. This is a whole-blood rapid manufacturing construct that will provide numerous benefits for patients in terms of speed and access and lower cost of goods. In addition, we're continuing to leverage our ongoing IITs, clinical studies, and the wealth of data that we've already established in our compassionate use program to indicate where we're going to go next in terms of our new indications.
As you've probably seen, we've built on our leadership team over the last few months that I've been at the company, bringing in people with late-stage development, CAR-T experience, commercialization experience. That, with the cash runway that we have taking us into 2027, we feel really confident about our ability to deliver on these milestones, deliver value for our patients, and deliver value for our investors. This is ultimately why we're treating these patients.
The results from our first three CAR-T patients in the three priority indications are on this slide right here, all of them now seeing transformative and durable results beyond one year. I talked a little bit about our middle patient, Denise, who's a myasthenia gravis patient back at J.P. Morgan. She's now at 19 months and counting.
This is a transformative result that we haven't seen across any kind of therapy, whether it's CAR-T or anything in this space. All of these patients, off of background immunosuppressants, off of background glucocorticosteroids, we're truly transforming the lives of these patients in really meaningful ways. We like to say that we're taking these patients and turning them back into people again, which I think is really an important mission and goal for us here at Kyverna. We believe we're doing this because we have a differentiated construct.
As I said earlier, this has been really differentiated for potency and for safety. We have the only CD19, CD28, costimulatory domain, fully human construct within the autoimmune space, which means we're seeing deep B-cell depletions, a chance for giving patients a deep immune reset. I think it's contributing to these long-term results that we're seeing in the patients.
In addition, because we're fully human, we actually have no grade high CRS and ICANS, and we have a very manageable safety profile across the 50+ patients that we've treated today. In addition, we have to remember this is a one-and-done therapy. We're changing the paradigm for the way these patients are being managed. In addition, because of the safety profile we're seeing, I believe by the time we get to market, this will be administered as an outpatient setting product, which will make it even more convenient and increase access for these patients moving forward. We believe that CD19 is actually the best target for autoimmune diseases.
You can see the broad breadth that a CD19 CAR-T can tackle from the early B- cells, the pro-B cells, pre-B cells, all the way to plasma blasts, but sparing the plasma cells, which are obviously important for patients' humoral immunity and ensuring that the long-term safety of patients remains intact. In addition, it's not just the breadth of coverage on the right targets. It's the depth of B-cell depletion, which is becoming increasingly important as we look for these long-term durations. This is some data, early data that was generated with our academic collaborators. It was presented last year. You can see this is measuring B-cell depletions in lymph node biopsies.
You can see in the CAR-T treated patients, we can see deep B-cell depletions, elimination of B- cells in both the blood and the targeted tissues, whereas with the CD20 monoclonal antibodies like Rituxan, we're seeing a partial impact on B- cells, but we're certainly not seeing a complete impact on B cells and not getting at the tissue penetration like we're seeing with CAR-Ts.
Ultimately, we believe this is the reason why you're going to be treating with CAR-Ts, to have this kind of a deep B-cell depletion and giving patients a chance at a long-term remission. We've taken all of this because the data that we've seen so far across 15 different indications, across 15 different patients, we could have moved in a number of different directions.
What I've been doing with my leadership team over the past four to five months is actually focusing our strategy in a very thoughtful and strategic way, looking for the indications where we can create early value for the company, create the biggest impact on patients, and ones that we can deliver on the cash runway that we have.
This is why we've chosen the strategy that we have, starting with stiff person syndrome or SPS, which is an area of high unmet need and where we're already 40% enrolled on our pivotal clinical study, myasthenia gravis, which is going to be a fast-follower indication and allow us to leverage and build a neuroinflammation franchise, and then lupus nephritis, which is obviously a core indication for us in the rheumatology space and one that we continue to roll our phase one study in as well.
In addition, we're going to be taking a really thoughtful and strategic approach, looking at the IITs and ongoing clinical studies, this wealth of data that we've generated as well with our compassionate use program in terms of where we go next and the next indications, because clearly the opportunity in the autoimmune space is huge, and we're going to use these foundational indications to help us build a bridge to get there.
I want to take a couple of minutes and just dive deep into SPS or stiff person syndrome. We're getting a lot of questions about this because this is a relatively new indication that people don't know a lot about. This is an autoimmune B-cell mediated disease, primarily impacting antibodies like GAD65 and glycine receptor. What happens is that patients' muscular system impacts their inhibitory system or the braking system on their muscles.
Patients end up having these spasms and muscle stiffnesses. A lot of patients describe them as like a charley horse that you feel all over your body. Patients actually get these increasing number of spasms over time. They get progressively worse. They have trouble walking in the beginning, then eventually they cannot walk at all. They are in wheelchairs. Most patients end up bedbound, which is horrible, and they have a horrible prognosis and end-of-life prognosis.
In fact, the natural history, which has been documented now and published over the last couple of years, shows that patients do not get better. They just either stay the same or eventually get worse. What ends up happening is patients end up trying to do a number of things in terms of treating the disease, but there is no proven therapy or no approved therapy either.
IVIg off-label is often used, as well as background immunosuppressants. They often use symptomatic treatments like muscle relaxants and pain relievers and so forth, but nothing actually underscores or affects the underlying course of the disease and changes the course of the disease. These patients just get progressively worse over time, which is why the results that we're seeing in the first three patients through our compassionate use program are so remarkable.
We're not only seeing reduction in the key antibody titers, GAD65 being the main one here, but also one of these patients had glycine receptor as well, reduction in their antibodies. If I draw your attention to the middle panel, this is the improvement in mobility, which is what ultimately patients want. This is the measure of Timed 25-Foot Walk test, which is a validated clinical endpoint.
It's the primary endpoint that we're going to be using in our clinical study. You can see a significant reduction in a matter of weeks with the patients that are treated with KYV-101. You're seeing reductions. These patients start out in the double digits and actually going down into single digits within, again, a matter of weeks.
All of this without the need for background immunosuppressants anymore, without the need for glucocorticosteroids. They're removing the supportive care and actually moving towards a normal life, which is an incredible achievement to see versus their natural history prognosis. This has led us to the design of our pivotal clinical study, which we're in close contact with the FDA.
I think all of you know that we have an RMAT designation in this space, and this has allowed us to have a really close collaboration in terms of the design of the study. We feel very confident with the Timed 25-Foot Walk test as being the primary endpoint, as well as a number of secondary endpoints here around muscle stiffness.
We are looking at 25 patients with a single-arm study, open label, but using a natural history comparator that we can actually enroll this trial. In fact, we are over 40% enrolled in this study and expect to be enrolled by mid of this year. You can see that we have really focused ourselves around a few key priorities: stiff person syndrome, myasthenia gravis, lupus nephritis, and this rapid whole blood process we are calling KYV-102.
I neglected to say a couple of minutes ago that although I presented the data on stiff person syndrome and the transformative impact we're having there, in the interest of time, and I know we wanted to get to a few questions, I didn't show you the data for myasthenia gravis and lupus nephritis. This is on our website right now.
You can reference that after the meeting. In both cases, we're seeing very, very similar results in terms of a pattern, in terms of really deep B-cell depletion, potency and efficacy in these patients, very durable responses in terms of efficacy over time. We're really, really comfortable and confident with these as the first three indications. The whole blood rapid manufacturing process we call KYV-102 is going to allow us to expand our access.
This is going to allow us to remove the apheresis step for patients, actually shrink the manufacturing time, shorten or reduce overall cost of goods. This should actually help us increase overall access and reduce impact and capacity in the system, which is going to be important as we continue to pursue other indications and broader indications in this space. Our future opportunities that we still have in our pipeline are around MS, systemic sclerosis, and other indications that are there.
We still have these aspirations and are looking for these opportunities moving forward, but we are focused on these top priorities in order to unlock value for the company so that we can invest in these indications at a future point. These are our near-term catalysts, and we've talked about these before at J.P. Morgan. It's stiff person syndrome.
We're looking to complete the pivotal phase two study, as I said, here by mid of this year. We're well on track for making that happen. We're going to report the top-line results in stiff person syndrome in the first half of 2026 and also file the BLA in 2026. We believe we'll be the first to file a BLA, not just in stiff person syndrome, but the first to file a BLA for an autoimmune disease across the CAR-T space. For myasthenia gravis, we also have an RMAT designation in this space. This is really exciting for us. We're in conversations with the FDA right now, confirming the regulatory pathway.
Given the really high effect size that we're seeing in myasthenia gravis and the impact that we're having on patients, we believe we can design a different clinical study than we're seeing from other competitors in this space and have a rapid path to market here too. We are working on that, and we will read out the discussions with the regulators in due course.
We will also be reporting out our interim results for our phase two study in myasthenia gravis in the second half of this year. Lupus nephritis is still an important indication for us. We are finishing enrollment in our phase one study right now, and we will be also reading out those results in the second half of this year as well. As I talked about before, the KYV-102 is an important part of our pipeline.
We're working right now on the CMC package and the preclinical and the non-clinical work, rather. All of this is coming together, and we expect to file our IND in the second half of this year. I want to underscore again that we've got the cash runway that takes us well into 2027. We feel very confident with the leadership team around us and these resources that we'll be able to deliver on all of these catalysts. I'll end here, just by saying we're really, really excited about the progress we're making, really excited to be in this position and really honored to be working with all of these individuals to make this transformative impact on these patients.
We've got a pathway to be first, be first with a CAR-T autoimmune construct and one that we think we can have a demonstrable effect on patients that desperately need it, quickly following that up with new indications in myasthenia gravis and lupus nephritis, as well as this follow-on construct that will help us expand the market with KYV-102. Again, we've got the cash runway and the leadership team around me, and I'm really looking forward to updating you more at the future junctures over the course of this year about the progress we're making to make a dent in these autoimmune diseases for patients around the world. Thank you.
That's great. Yeah. Great overview. Certainly a lot of data points coming in the next 12 months. I guess I want to take a step back and just maybe ask you to kind of double-click into differentiation, right? We've seen an explosion of therapeutic advancements, auto allo CAR-T, bispecifics, T-cell engagers, etc. Just when you think about KYV-101, if you could just really, I guess, dial into what sets you apart and differentiates you from what has become, I think, an increasingly noisy, if not crowded, field.
Yeah. I touched on some of it in my talk, but the differentiated construct is where I would start with. We're the only ones, again, with the CD19, CD28 co-stimulatory domain, fully human construct. We believe this is an advantage. I know a lot of the autoimmune companies are moving with 4-1BB, but we believe the CD28 co-stimulatory domain has proven in the hematological space to have this deep depletion of B- cells.
We believe this is an advantage. We believe this is why we're seeing some of the transformative results that we're seeing in these early patients. In addition, the results that we are seeing, particularly if you talk myasthenia gravis, which is I didn't get to present that data, a lot of the competitors in this space are getting approved with a two, three-point change in reduction of MG-ADL scores.
We're seeing in our initial patients reductions of six and seven. Not only that delta, but we're actually seeing the MG-ADL scores go down to zero and stay at zero. We're changing the course of the disease for these patients while also eliminating all their need for background therapies and background immunosuppressants. We think there's a real opportunity from a theoretical perspective, I guess, when you look at the construct itself and why we believe it's better, but it's starting to bear itself out in terms of the clinical results that we're seeing here too.
Got it. That makes sense. Obviously SPS, you've described and continue to describe as kind of like tip of the spear. You laid out, I think, a pretty ambitious goal of having completed enrollment in the middle of this year. You said at J.P. Morgan, I think 40% enrolled into that study. Any additional update you can provide on how enrollment's going there, I guess, level of confidence that you're going to hit that mid-2025 enrollment target, and then maybe just start to sort of frame expectations for that data readout in 2026?
Yeah. I mean, like I said, we're very confident. The great thing about Kyverna and working with the group that we have is this is all we're doing. This is what we're focused on. We have really strong relationships with the key sites that are enrolling these patients. We're not throwing this over the fence to a CRO and telling them to solve it. We know where these patients are. Yeah, we're going to update the official number. We said 40% at J.P. Morgan, but I can tell you we're in excess of 40% now, and I'm very confident about our ability to actually reach the enrollment target by mid of this year for sure.
Great.
The data readout will be like we targeted in the first half of 2026. Of course, we'll be reading out on the Timed 25-Foot Walk test, but we'll read out a complete safety data set on these patients as well, as well as the secondary endpoints. This will become the basis for our BLA submission and what we want to move forward with there.
Understood. You mentioned the RMAT designation, working closely with FDA. You also mentioned strong confidence in the Timed 25-Foot Walk test as a registrational endpoint. Maybe you just elaborate a little bit on some of the regulatory dialogue there. I mean, you truly are trailblazing in this indication. I guess what has gone into those conversations and what gives you that level of confidence that showing a good delta there on Timed 25-Foot Walk test is going to be registrational?
Yeah. I mean, it is a validated endpoint. It's used across a number of different neurological conditions, including multiple sclerosis, where medications are getting approved with a 20% delta in the Timed 25-Foot Walk test. We're seeing in these initial patients 40%-60% delta in terms of Timed 25-Foot Walk test. So we're having an even bigger impact than what we believe is registrational.
And this, frankly, in the conversations with the FDA, they've also seen the videos of our patients. Some of these patients haven't been able to walk, and now they walk. This, in conjunction with what I think is a really well-thought-out design in terms of the trial, has really facilitated a really strong conversation with the FDA. This is giving us confidence that we're heading in the right direction.
Got it. That makes sense. As part of this registrational path, my understanding is you're generating some natural history data that will kind of serve as the comparator. Can you just talk to, I guess, what goes into the generation of that data set? What have we seen historically in this patient population on that registrational endpoint?
Yeah, that's important. I mean, there are published data right now that show the progression of this disease on the stiffness index and Hauser index, some of these other secondary endpoints. That's published now and shows that patients only get progressively worse over time. What we're working on, as you indicated, is a natural history on the Timed 25-Foot Walk test.
We've already identified the centers. Some of them are in our clinical studies. There's some that are outside of our clinical studies, which will be a great validation point for ourselves. We're pulling all that data together. It will work in parallel with the data generation that we're doing in the pivotal study.
Understood. Okay. The expectation is you would have that available at the time of top line?
Yeah.
Yep. We get a lot of investor inbounds around the commercial opportunity here. I think you guys, I know you've done a lot of work in terms of identifying patients, patient segmenting. Maybe you just elaborate on some of the work that you've done. I think historically, you've kind of talked about maybe the low-hanging fruit being this 400-700 patients who are not well controlled via IVIG. Maybe just talk to kind of like the evolution of thinking there. Is that sort of still your initial target population or just how are you thinking about that today?
Yeah. We're going back, and there's more additional research that we're doing all the time here, but we actually think the relevant addressable patient population is larger than that right now. It's probably somewhere between 1,500 and 2,500 patients. 85% of patients fail on IVIg. Like they tried, there's some sort of symptomatic relief on patients for a short while, but then they continue to get worse.
Really that whole pool is going to be CAR-T eligible the way we're viewing it. Again, it's a very focused market. We know where these patients are from a commercial footprint perspective and what we're going to need in order to scale up, quote unquote, and get ready for launch. We can do this in a very, very focused manner because we're not going to have to try to find these patients in the community.
As I've said to some of you, they are in these centers. We know where they are. There is a huge unmet need. The existing therapies are not working. We have a huge value proposition. We can eliminate this need for all these other therapies that patients have, maybe put some of them back walking again, give the chance for some of them to go back to work. There is a huge value proposition for these patients. We feel really good about that.
Right. This exercise of identifying target patient population, this is all being done through claims data or patient registry data, or how are we finding these patients? You mentioned the center of excellence aspect to this. What proportion of that initial target exists in the center of excellence, or is it essentially all of them?
All the patients that are failing their first therapies, which happens relatively quickly, are ending up in these academic centers. In most cases, these patients are officially getting diagnosed in these academic centers because the community does not know how to diagnose it. We know these patients are already in these centers to begin with, which I think gives us a head start.
It was also indicative that we are probably underdiagnosing this as well because some of these patients go on for a few years that are struggling with different types of symptomology and trying to relate to what it is. Until they maybe get the confirmatory GAD65 antibody test, for example, and then matching it up with this progressive stiffness, that is how you end up identifying where these patients are at.
To answer your question more directly, I mean, we believe most of these patients are in the academic centers, the ones that we're going to be targeting when we go for initial launch, which makes it easier from an initial commercial perspective on how we ramp up and scale our organization.
Got it. That makes sense. I know it's still early days, but the unmet need here is quite substantial, particularly in the IVIg failures. Maybe just frame or comment on how we should be thinking about pricing, especially as we think about SPS as a rare disease, like very targeted opportunity relative to some of the other opportunities you're pursuing in MG and LN, which are obviously very different patient populations.
Yeah. I mean, like we were talking, you just mentioned IVIg. A lot of these patients that will end up treating with KYV-101 have been trying IVIg or on IVIg. Most of them are taking it once a month. Many of them are taking it twice a month. This is costing on that particular medication alone hundreds of thousands of dollars a year for these patients.
Then you add on top of it the hospitalization costs, the physical therapy costs, the lost productivity costs, the other symptomatic medications that patients are taking. There's a significant value argument here that we can make, particularly if we're taking patients beyond a year into 18 months. Our initial first patient treated now is at 15 months and counting. There's a huge value proposition that we think we have for the system and for payers by focusing on SPS right now.
Then bridging that, I mean, even the patients that we're targeting now with myasthenia gravis, the patients on the FcRns and complement inhibitors, these also cost patients hundreds of thousands of dollars a year and never actually fully cure the patient or put them out of remission of their disease. We have really got an opportunity here again to change the game in myasthenia gravis. We believe there's a lot of room here for a fair price. We're not commenting on price, but a fair price, but one that also creates value in the system.
Yeah. That makes sense. Okay. Let's talk about MG. You're meeting regulators in the first half of the year. You talked about in your prepared comments perhaps some creative design elements to what you could do for a registrational study. I guess you are obviously seeking clarity on what that registrational path would look like. What are you going into that meeting? How are you thinking about it? What are you proposing? What would be a win, I guess, coming out of that meeting?
The win would be confirmation of what could be a pivotal study for myasthenia gravis. I mean, we're not going to share with you the specifics of what that trial design could look like, but we know we can't do a placebo-controlled study here. It's just going to be unethical to leukapheresis patients and not give them access to CAR-T therapy.
We also know that we're going to need to control the study. We're working on alternatives of what that might look like in this disease. Again, I'll double down on the point I said a few minutes ago. We've really got transformative efficacy, larger delta in terms of the MG-ADL reduction, this ability to get patients down to zero on the ADL score.
Even if we're doing that in a significant fraction of patients and seeing those effect sizes, we believe that we can design this study in a different way in partnership with the FDA. The great thing about the RMAT designation, and I've seen it firsthand on the SPS side, is that the FDA is very collaborative with us. They've seen these results that we're having. The tone of the meeting is, how can we help? I think that's actually been really, really important for us as we move forward.
That's great. You talked to interim data coming from KYSA- 6 in the second half of the year. This will be a new data set. This is patients coming from the company-sponsored study. Just help frame expectations there. Like what can we expect in terms of number of patients, length of follow-up? Like how are you thinking about that interim data cut?
Yeah. We're looking at 16 weeks, and we're looking at six patients. We'll see the readout of those patients. We'll look at MG-ADL score reduction, of course, as well as secondary endpoints. We'll read out the safety on these patients as well. We'll have a complete data set that will complement the conversations we're having with the FDA and will allow us to confirm the regulatory path moving forward.
Got it. This is an area investors are very close to. We've seen the FcRn antagonist do extremely well. If efgartigimod continues to launch extremely well. I guess when you think about the role for KYV-101 in an indication like MG today, where do you see that falling into the treatment paradigm? Is this for your sickest patients that have failed an FcRn, a complement, IVIg? Is it more that refractory salvage patient, or is there opportunity to move upfront? How much further up the treatment paradigm could we move?
I think some of these patients that are failing some of these initial therapies, then going on FcRns and complements, will be the eventual target patient population for us. Like I said a few minutes ago, when you got a chance to reset their immune system and actually take them off all these other medications and do so at a very cost-effective and value-effective way for the system, we believe we're going to have a really strong value proposition versus the FcRns and complements. They're going to require constant treatment over time and never get patients back to a normalization of their disease.
Understood. Okay. Let's shift gears and talk about your third prioritized indication, LN. We saw data updated at ACR. We're looking forward to additional data in the second half of this year coming from company-sponsored studies. Again, just help sort of level set, frame expectations. What can we expect to see with that update?
Yeah. This will be an updated data set from our KYSA- 1 and KYSA- 3 studies, which includes three patients that were dosed initially at the lower dose when we were looking for the signal-seeking dose at the 50 million cell level, and then the other six patients at the 100 million dose. We will have and show the complete data set. Patients will be followed up for six months.
We will be looking at all the endpoints that we have talked about at ACR. Normalization or stabilization of eGFR. Are we seeing significant reductions in proteinuria? Are we able to normalize complement? Are we seeing significant reductions in the antibody titers? As we have seen in those initial patients that we have presented at ACR, we are also able to remove their background immunosuppressants. Many of them eliminate or at least reduce significantly down to physiological levels, their glucocorticosteroid levels.
All of that will be an entire package on the key data sets that we have. Based on what we're hearing from the opinion leaders and also what we're seeing coming out of ACR and EULAR and all these conferences, these guidelines on how to manage these lupus nephritis patients, which in our case had really high disease chronicity scores, really high disease activity scores, fairly advanced in their disease, to see these kinds of results are transformative. We think that on the basis of that, we can go back to the FDA and have a really valid conversation on what makes sense in terms of a pivotal study moving forward.
Right. That makes sense. Okay. Let's talk quickly about your manufacturing. Historically, you've used WuXi. Last year, you signed an agreement with Elevate Bio, starting to kind of diversify your manufacturing and process. I guess what is the latest in terms of manufacturing and how you're thinking about scaling up both to tackle the, obviously, the clinical programs that are ongoing, but also the commercial aspect?
Yeah. I mean, you've covered a lot. Bringing on board Elevate was really important to have a second manufacturing source for us. We've been bringing them on over the course of the last nine months. In fact, we're just completing our comparability runs between the two organizations, and they're positive.
We feel really, really confident that we'll be able to start treating patients from Elevate in the coming months here in the first half of this year. Between the two organizations, we've been actually looking at the forecast, not just for the SPS launch itself, but actually for the rest of the clinical development program we have. We feel really confident that we can build and scale to match the demand both from clinical and from the commercial side.
Yeah. That's helpful. And just lastly, on KYV-102 and implementing the Ingenui-T process, you've got to the IND in the second half of the year. I guess what are the gating factors to getting that filed? What are the steps, the boxes left to check to getting that potentially transformative manufacturing process in place?
Yeah. I mean, like I said, there's really a whole battery of things that are happening right now, including the CMC package and working on the process enhancements that are going to get us ready for that filing, as well as some of the other non-clinical work that's going to put us in place. Again, we're tracking with that. We've got some experts that are working on that within our team, both from the clinical, early research rather, and our manufacturing side. We feel confident we can deliver on those objectives as well.
Great. All right. We're up against time. Warner, thank you for the presentation and the updates. We look forward to staying tuned to the Kyverna story.
Thanks for hosting us.
Thank you.
Yeah. Thank you.