Hello everyone, my name is Mitchell Kapoor. I'm a Senior Biotech Analyst at HC Wainwright. It is my pleasure to welcome Kyverna Therapeutics today. From the company, I have the CEO, Warner Biddle. Warner, thank you for joining us today.
Thanks for hosting us. I really appreciate to see you again, Mitchell. Yeah, thanks for inviting us.
Absolutely, anytime. We have an exciting discussion coming up, but maybe to set the stage, you could just give an overview of where Kyverna is at today, and what are the key initiatives for the company?
Sure. For those of you who are not following the company closely, Kyverna is a late-stage development company focused in on autologous CAR-T cell therapies. It is focused on the, in the autoimmune space. We're in a leading position right now, having treated our 100th patient across a variety of different indications, but we're actually in late-stage development on two specific indications: Stiff Person Syndrome, as well as Myasthenia Gravis, which are allowing us to provide a first-mover advantage in terms of bringing CAR-T cell therapies into the autoimmune space, specifically in the neuroimmunology field. Really, really excited about the progress that we've been making over the last few months in terms of executing these clinical trials and moving these towards eventual BLA filings and eventual submissions and eventual commercialization.
Great. You're on the cusp of delivering the first CAR-T in autoimmune disease. Can you tell investors what's significant about that milestone?
First of all, it's really significant for patients. The first indication, Stiff Person Syndrome, is a devastating disease. There's no approved therapies for this condition. Although it's a rare condition, we believe it's actually larger in terms of the prevalent patient population than initially thought. There's a number of patients out there that are struggling with this disease. It's a disease of the neuromuscular junction that causes a breakdown in the GABAergic system where stiffness in the muscles tends to occur in spasms at least initially, but then progresses over time where patients lose mobility, particularly in the truncal regions and lower regions. Many of these patients lose their ability to walk or walk effectively. A lot of them will need walkers, eventually wheelchairs, and many of them end up bedbound. The natural history of progression of this disease just gets progressively worse over time.
Because there's no approved therapies right now, patients are really looking for something completely new. What KYV-101 does, which is our lead construct, in addition to providing significant clinical relief, it actually has an opportunity to reset the immune system in these patients and give them this opportunity for a long-lasting, durable remission from their disease, which is really remarkable, given what these patients are faced with day to day. The opportunity to do this first and come to market first and provide this real strong clinical impact, but also lead the way, really sets the bar for Kyverna to capitalize in terms of this first-mover advantage in terms of setting up from a market access and commercialization perspective, which we believe is going to create a lot of opportunity for us as we launch second and third indications into this space.
Great. Before we dive further into the details, could you talk about the construct with CD19, CD28, and the design advantage, why it's optimal for autoimmune disease versus FcRn complement inhibitors and CD19 antibodies?
Sure. I mean, you're alluding to the fact that there's a lot of new treatments, particularly in the MG space, that have been coming forward for patients. I think this is great, but I think the issue or the thing that's still on the table with these new therapies that are coming to the market is that although they provide some symptomatic relief for patients, nothing is doing for these patients what we're seeing in the first initial patients with KYV-101 being treated. It's fundamentally different, obviously, in terms of the mechanism of action. We're a CD19, and a lot of the CAR-Ts being studied in the autoimmune space are CD19s, but we're the only one that has a CD28 co-stimulatory domain, also fully human, which we believe is really important.
It was actually designed as an improvement over the foundational Yescarta construct, and licensed in from the NIH back in 2020. We really designed for improved safety profile while still maintaining this potency and efficacy that we were seeing with the original Yescarta construct. This is actually starting to bear itself out in the 100+ patients that we've treated to date. We're not seeing any high-grade CRS or ICANS, but we're starting to see these long-term durable potent effects across SPS, as well as Myasthenia Gravis and other indications that we're studying. We believe we really have something that's fundamentally different here that works on removing the pathogenic B cells from these deep tissue compartments where a lot of these neuroimmunology conditions are, patients are struggling with and giving patients this chance at this autoimmune reset and this chance at this long-term, durable effect that we're seeing clinically.
Great. Durability is certainly a defining characteristic whenever you look at the competitive landscape. Is there any particular feature of KYV-101 construct that you think is most responsible for driving durability? We've seen the MG data, which has been very impressive, the compassionate use data of patients out 24 months, 22 months, 15 months. That's very long to have durable remissions. What's driving that?
I think the construct is unique. The CD28 co-stimulatory domain, we speculate, may be driving some of that as well. As you know, the co-stimulatory domain is just one part. We think it's the totality of the construct itself that is actually driving this opportunity for patients to have this durable remission. I think what you're hitting on is really an important point. For many of these patients, particularly with Myasthenia Gravis, the opportunity to come off of their other background therapies, which a lot of them are being administered chronically over the course of many years, is significant. Many of them, even with these chronic therapies, are still struggling with their disease. They have MGADL scores of 3, 4, 5. They're ending up with intermittent Myasthenia crisis where they're in the hospital, in the ICU, many of them intubated or, you know, or worse.
The opportunity to have this one-time therapy or treatment that gives these patients this long-term durable remission is remarkable. To your point, our first patient now, her name is Denise. I've spoken about her in a number of different forums. She's now out at 24 months plus off of her background immunosuppressants, off of her background steroids, and living really a disease-free, drug-free remission and drug-free life, which is really remarkable and something that all these other therapies that are being studied right now and being brought to market in the Myasthenia Gravis space can't offer patients. We really think we're doing something unique here.
Absolutely. Again, you know, with these compassionate use patients out 15 plus months, a lot of folks are focused on the one-year mark of durability. Can you help educate us on why that one-year mark is so significant for cell therapy?
We just held an investor relations day a couple of weeks ago, and Dr. Mappetti from Stanford, who's a Myasthenia Gravis expert and a neuromuscular disease expert, spoke on this specifically. He said these patients, given the chronic nature of their disease and the chronic nature of the fact that not only are they taking a lot of these FcRn inhibitors and complement inhibitors, but they're still having to be supported with background immunosuppressants as well in terms of managing their disease. That's a huge burden. Many of these patients are middle-aged women, for example, and to have that burden of disease on those patients in their childbearing years is quite significant. For him, and he stated this during our IR call, to have this opportunity at a drug-free holiday where patients are also experiencing a remission of their disease up to one year, he believes is really, really transformative.
As we just touched on, we're starting to see our first patients now reach the two-year mark and go beyond, which we believe is going to provide some fundamental differences here in terms of what we can offer patients over the long term.
If you consistently have patients that are out to this 15-month, two-year mark, where do you see your therapy being sequenced in the treatment continuum relative to the chronic biologics?
The interesting thing is we're now moving into a Phase 3 pivotal, registrational study that we have agreement on with the FDA through our RMAT designation. We'll be studying a variety of patients with varying backgrounds and different therapies coming into the study. The inclusion criteria will require patients to be on two previous immunosuppressants, and that could be a traditional immunosuppressant or one of the newer biologics, or one immunosuppressant and have had chronic exposure to plasmapheresis or IVIG. There's a wide variety of patients that we're including in this study, which I think will actually show and allow us to demonstrate superiority of KYV-101 versus one of these standards of care and actually then open up the door for using KYV both in the third line setting, but also over time into the second line setting as well.
Great. One of the things we just learned is your KYSA 6, 60 patient trial. Can you talk about the design there and how confident you are in the powering assumptions at 24 weeks and what risks are associated with a short primary endpoint?
We believe the 24-week endpoint is actually an excellent endpoint that will allow us to really see the results of KYV-101 from an efficacy perspective. If you take a look at the results that we are seeing in these initial compassionate use patients, we're seeing a pretty dramatic effect in terms of reduction in MGADL scores in as soon as 30 days to 60 days. We believe going out to 24 weeks, we're going to see a remarkable impact across many of the patients. Overall, we feel really confident about this design. It's a very unique design. It's a very thoughtful design.
We're actually going to be enrolling 60 patients into the study, randomizing them one-to-one into KYV-101 or a standard of care, which is, again, as I mentioned earlier, allowing us to demonstrate superiority over standard of care, which I think is a really bold design for us moving forward. The 24-week endpoint you've mentioned is where the key primary endpoint is going to be measured. We're going to be looking at MGADL score reduction as well as QMG reduction as well in these patients. These are co-primary endpoints, and will be assessed through an independent assessor. We'll get a really strong, prospective view of what KYV-101 can do in a clinical setting. Actually, as I said, we're going to be enrolling a number of different patients with various background therapies.
This is going to allow us to demonstrate the importance of the KYV-101 therapy in a variety of different patient types, which we think is going to be clinically relevant for a number of physicians and patients.
Right. Could you just talk about the potential for crossover, and how you expect regulators to view durability in longer-term follow-up?
Yeah. The other interesting thing of the design is that at that 24-week primary endpoint, the patients that are in the standard of care arm, we're going to allow them to cross over and get KYV-101, which I think is remarkable. It's also going to help us enroll patients in the study because all patients will have the opportunity to get KYV-101 at some point in their treatment journey. Then we'll be following patients up. The 24 weeks is the primary endpoint, but the official study reads out after 18 months. Of course, we'll be looking and measuring these patients over time and following them for many years afterwards. Of course, the long-term durable impact of what we're doing here with KYV-101 is so important to the long-term clinical benefit. We're going to continue to invest in that and make sure that we're measuring that over time.
Great. Could you talk about the dynamic of if this therapy is successful, physicians have patients that are stable on Bivgard or Uplinza, you know, how do you see the dynamic of converting those patients to CAR-T, or do you see it segmented a bit differently?
I think even with these new therapies, the FcRn inhibitors and the new CD19 antibodies, there's still significant unmet needs. Depending on the opinion leaders you speak to or some of the research that you're viewing, a third or more of these patients are maybe stable, but still walking around with MGADL scores of three, four, five, six. These are patients that need something else. Many of them also are requiring other background immunosuppressants in order to try to control their disease. I think we have the opportunity here to offer patients something completely different. If you can have a one-time therapy with KYV-101, not just eliminate the FcRn inhibitors and other therapies they're taking, but also remove background immunosuppressants, remove background steroids, do this with a one-time therapy, and then give them this long-term remission, I think this is a totally different value proposition for patients.
I think it competes very, very well. I think the market opportunity and the unmet need for these patients is significantly large.
From a payer perspective, when they're considering whether to cover a therapy that has a chance of durable remission, with the one year benchmark plus being that bar against a chronic $400,000 to $500,000 a year FcRn therapy, how do payers look at the value proposition that KYV-101 could potentially provide?
I think you're partly answering the question with the way you've asked it. These new therapies are not insignificant in terms of their cost to the system, hundreds of thousands of dollars a year. Like I said, patients are still effectively walking around with MGADL scores that make them prime candidates for something else that they need in order to control their disease. The cost of therapy is just one aspect to take into consideration here, but many of these patients also have, like I said, breakthrough Myasthenia crises. There's a burden on the system. There's an impact to caregivers, an impact for them not being able to work. We believe from a health economic perspective, there's a larger value story here that I think we can bring into play with KYV-101 and this ability to, again, reset the immune system, give them a chance at this long-term durable remission.
Potentially, you know, obviously we're aiming to, you know, aim for a longer-term cure is a longer-term vision, but even in the short term, this durable remission, I think, is going to be really remarkable and have a huge value to the system as well as value to the patient.
SPS, a bit. That is potentially the first beachhead indication for KYV-101. What does it mean to strategically have that as a first-to-market bridge indication for other indications in CAR-T? What does that say about the strategy for regulators, payers, and physicians?
Stiff Person Syndrome, as I talked about at the beginning, is a really important disease with huge unmet needs. That was part of the rationale for choosing Stiff Person Syndrome, but it also, because of its nature and there's no approved therapies, is really allowing us as a young company to move very, very quickly and create this first-mover advantage where we can enroll this trial quickly. In fact, we've completely enrolled our pivotal, Phase 2 study, registrational study. We're now working, preparing for the data readout, which we've indicated will come in the first half of next year, as well as plan to file the BLA next year.
This will give us this first-mover advantage and allow us to set the table, if you will, with an indication with huge unmet needs, but also with the prevalent patient pool that's out there right now, really provide a significant opportunity for us as a young company in terms of a value that we can create as an organization for us in terms of commercial revenue. We believe this is really important because there's a lot of synergies between Stiff Person Syndrome and Myasthenia Gravis, which is our second indication, and, if you will, really allows us to create a lot of synergies and set a foundation for us in terms of a commercialization strategy where we can then advance to larger indications down the line.
Great. With SPS being that potential first indication and you potentially launching with a price, how do you weigh that, setting that versus the potential for adding additional indications like MG later?
We talked a little bit about the Myasthenia Gravis, the cost of therapies, but there's a huge cost of care in the Stiff Person Syndrome disease as well. A lot of these patients are on chronic IVIG, a lot of other chronic therapies. They have a huge impact in terms of the system, in terms of the need for additional care, emergency room visits, et cetera. There's a huge value argument for the value of CAR-T and a one-time therapy like KYV-101 in Stiff Person Syndrome as well, which I think really sets us up very nicely from a market access and pricing perspective.
We're not disclosing specifics around price right now, but I think there's a natural evolution here between Stiff Person Syndrome and Myasthenia Gravis in terms of how we set ourselves up, in terms of a value argument for payers and a value argument for the physicians and patients that really need these therapies.
Thinking about the competition of cell therapies in the autoimmune space, particularly with entrants that are in the MG class, including mRNA CAR-Ts, it doesn't seem like it's a zero-sum game. Could you help us understand, is this the start of a new class and how do these coexist if they're all successful?
We want more therapies for patients. That ultimately is better if patients have options. We believe KYV-101 and in the autologous CAR-T class are really offering something different for patients, even versus the mRNA CARs, which we believe provide some benefit for patients but are very transient. We're seeing a lot of need in these early patients being treated with those modalities needing to be retreated. We believe that there's just a transient efficacy nature there that KYV-101, because of its ability to have this deep B cell depletion in the targeted tissues, really gives patients this chance of this long-term durable effect. All three of our initially treated patients in the compassionate use program are well beyond now the one-year mark, and our lead patient, of course, now well past two years.
I think this is actually something really transformative that sets us apart from not just the mRNAs but the other competitive therapies in this class.
Great. With MS and RA being larger indications that you could potentially pursue, what criteria guide the decision to advance that internally versus partner those out?
You're touching on, after establishing our company in Stiff Person Syndrome and Myasthenia Gravis, I think this is going to create an excellent foundation for us to generate an initial commercial presence. We are looking down the line. I think some of the really exciting early data that we saw in multiple sclerosis has even taken some of us internally by surprise. We had some discussions with Stanford, and Jeff Dunn is one of the leading world specialists there, and he's publicly stated on a number of occasions that in his 25+ years of treating MS patients, he has not seen the kinds of outcomes that we're seeing with KYV-101 now being studied in MS. This gives us a lot of hope that we can bridge from this initial neuroimmunology presence with SPS and MG into larger indications like MS.
We are going to be sharing some updated data on that in Q4 of this year. We're also going to be sharing some new data of KYV-101 in rheumatoid arthritis, which is another large indication with significant unmet needs, even though there are a lot of obviously available therapies there. There are a lot of patients that are refractory to those. We believe this really opens up the door for us in terms of new indications and will allow us as an organization, as we continue to build, to expand into these larger indications moving forward.
Wonderful. I wanted to touch upon KYV-102. Could you help us understand, you know, what is the next-gen impact to the franchise and how do you see 102 fitting in the pipeline?
Sure. For those of you who are not familiar, KYV-102 is our next-generation construct that builds off the backbone of KYV-101. It uses the same CAR construct, but on a new manufacturing platform. This is a rapid manufacturing platform, which is going to allow us to reduce the turnaround time and significantly reduce cost of goods, which is going to be really important for us. Second, it actually uses whole blood from patients, which is fairly unique, which is going to actually streamline the market access and the patient journey for these patients by eliminating this step, a needed step to go for an apheresis prior to getting the CAR-T therapy. We believe by making it more convenient for patients, as well as reducing the turnaround time and cost of goods, we can use this to expand, bring this therapy into the community closer to patients.
As you touched on a few minutes ago, as we expand into larger indications like MS and RA, we think this is going to provide us opportunities in order to address those patients.
Excellent. Finally, if you could just recap, there's a lot coming up in the next 12 to 18 months. Could you just set the stage for investors, the different catalysts to expect as we go forward?
Right. I think we've got a lot of near-term catalysts that we're really, really excited about. First and foremost, like I said, we're heads down now, fully enrolled on the SPS trial, but reading out those results in the first half of next year and also aiming to file the BLA in the first half of next year as well. In terms of Myasthenia Gravis, we have an interim Phase 2 readout that's happening in the fourth quarter of this year. As I said earlier, we're well underway in terms of enrolling our pivotal registrational Phase 3 study, which is going to be really exciting as our second indication as a company. We touched on it. We have new data or updated data in multiple sclerosis, as well as new data in RA coming in the fourth quarter.
We are also planning to file the IND in the second half of this year for KYV-102. So many, many things that we're advancing. I believe we're moving forward in a very focused manner, specifically around this neuroimmunology franchise, which is allowing us to create a lot of synergies and allow us to get this first-mover advantage into the marketplace. Really excited about all the progress we're making. Obviously, more excited about what's coming up ahead.
Excellent. Thank you so much, Warner, and thank you so much to the Kyverna team. Really appreciate you all being here. Thanks to the investors that joined us today.
Thank you, Mitchell.
Thanks.