All right. Good morning, everyone. Welcome to Healthcare Innovation Conference. This is our inaugural conference. It's my pleasure to welcome our first presenting company, Cabaletta Bio. From the company, we have Steven Nichtberger, who is the President, CEO, and co-founder. We also have other executives from the company here in the room. So with that, we'll get started. Steven, could you maybe give us an overview of the company? Maybe spend five minutes talking about who you are, what are some of the up-and-coming milestones, and then we'll go into the fireside session.
Yeah, sure. Excuse me. So, thanks for having us. Appreciate everybody being here. So, Cabaletta was formed in 2017, actually, to develop and launch the first targeted curative cell therapies for patients with autoimmune diseases. And that has since become very fashionable. For us, the sort of exciting prospect is that when we took CABA-201 in as an in-licensed binder and created the product that is now CABA-201, we were really well prepared to execute. We knew how to stand up clinical sites, how to design the clinical programs to win in a very hotly competitive field. So, as we stand here today, Cabaletta is developing a CD19 CAR T product with a 4-1BB co-stim domain, which we believe is the safest profile to bring to autoimmune patients. We currently have a remarkable industry-leading 40 U.S. clinical sites enrolling patients.
So while I guess there is a lot that is not known about our data and the emergence and the progress, the doctors are speaking, the sites are speaking with their engagement. So we have 40 clinical sites up and enrolling for 11 different indications: lupus, lupus nephritis, multiple forms of myositis, which, by the way, will become very important over time, I believe, to evaluate each of these in a separate cohort. In addition to myositis, we have scleroderma, myasthenia gravis, pemphigus vulgaris, and multiple forms within these. So we are most excited, I suppose, by two things. One is the prospect for moving very rapidly from here on towards, we hope, the registrational trials that will come after these initial Phase I and Phase II studies are completed.
And second, to doing it with a product that we think will compare favorably with any other product out there for patients who have unmet need that is really profound. If you have scleroderma, there's a 50% chance from the time you're diagnosed that you're dead in 12 years. If you have myositis, really severe outcomes, lupus nephritis, 10 years survival, 40%, you either have renal failure or death. So these are really sick patients who are young women, typically, who we know, and when we present next week, a bolus of data from both the lupus and lupus nephritis, as well as multiple forms of myositis, as well as scleroderma data next week, you'll begin to see what we are seeing, which is, number one, strong enthusiasm for patients, for the sites. But number two, the prospect of providing patients what patients want.
What we're asking as we move into the ACR presentation next week is not, did every dot match what Professor Schett showed that got us all excited? That's not the right question to us. The right question is, when a patient seeks therapy from a physician, what are they looking for? They're looking for a drug-free clinical response that allows them to wake up every morning and not think of their disease. So they don't want symptoms and they don't want drugs. And any company that can do that reliably, reproducibly, repeatedly, and safely is going to have, we think, a great prospect for use in autoimmune patients.
So, as we go into ACR with a bolus of data coming, we're excited about the prospect of meeting the needs of patients and physicians for patients, drug-free clinical responses that make them forget about their disease because they're not taking drugs and because they don't have clinical symptoms. And for doctors, it's diminishing the prospects of organ failure. And if we can do those things, patients win, physicians win, and ultimately Cabaletta wins.
Got it. That was good. I think you already gave a sneak peek into ACR. But let's step back. CD19 has become a very interesting target. It's sort of like a renaissance that we are seeing in terms of development, different modalities. So how do you see this as a target one, different modalities that are being explored, and where does CAR T cell fits in?
God bless Professor Schett for having the courage to treat the first 20-some-odd-year-old lupus woman whose kidneys were failing and all therapies were failing, and today she remains cured. That opened, I think you're correctly pointing out, a renaissance. Let's remember, that's a pilot study at a single site where perhaps subjectivity is subjective, these assessments that might be said. But the objective ones are clear, and they look like they are sustained across the industry in terms of most of the data in well-run studies. There are going to be, as there are in any fabulous target like CD19, there are going to be many modalities. Let's remember that the largest drug in the world, with a black box warning, by the way, for a decade strong, was an autoimmune product.
The need, the unmet need in patients with autoimmune disease is for those patients as meaningful as it is for the cancer community and as investors and as biotech executives, I would argue. We don't understand how severe the unmet need is. I hope that ultimately the field evolves so that bispecifics will have a role. I don't think they are a magic bullet any more than I think we are a magic bullet. I do think that every patient's going to need a different form of therapy, going to prefer a different form of therapy. The more the industry can bring forward, the better off we all are. We believe that our therapy will be among the most reliable, most durable, most complete opportunities for efficacy for a drug-free clinical response that avoids any symptoms in patients and does that reliably and durably.
If we can deliver on that promise, no matter who else is successful, we win. Why? Two things. If I assume, as many are assuming today, because pharmaceutical companies have chosen to invest in what they know best, the bispecific opportunities that are out there, those will make their way forward. Are they going to be perfect? Will every patient have a complete response to every single dose of bispecific? And if not, what's the next therapy that those tens, hundreds of thousands, maybe millions of patients are going to go for? Are they going to go backwards to rituximab or cyclophosphamide or methotrexate or azathioprine? Or are they going to go to CAR T therapy for a more durable, more reliable, deeper clinical response? We believe the latter, not the former.
Therefore, we're really thrilled with the opportunity to proceed through our clinical program with a pace that I want to point out to you is accelerating. The site openings speak for themselves. We have 40 clinical sites in the U.S. currently open. We will update in the near term just how many patients have enrolled as well as have been treated. In the next week, we have ACR presentation, and we hope to update on all of that. That matters a lot because as we move through our clinical program, where six patients in any cohort gives us the opportunity to speak to FDA about Phase III registrational trials.
If our pace of enrollment is accelerating and we have 40 clinical sites, you can do the math pretty quickly to figure out that we may be in Phase III before many of these companies even start talking about the two clinical sites that developed the three patients' worth of data that now have six months of follow-up, and shouldn't you be excited? We really love our prospects, and the hard work now is in front of us to execute the enrollment, the treatment of patients, and to reveal the true profile of CABA-201.
Got it. Got it. Now going to your product, could you just put in perspective what is 201, CABA-201, the data that you presented at EULAR? If you can just highlight some of the key takeaways and then also set the stage for ACR. I think you just gave a teaser, but the breadth of the data, what exactly we should be looking at? Are you really answering the question what patient wants there, drug-free remission?
So CABA-201 is a very straightforward 4-1BB containing fully human binder that is designed to replicate the Schett murine binder. We believe we've chosen the right dose because at EULAR, we presented two patients' worth of data, one in myositis, the other in lupus. Both of them had, and we were incredibly deep in our disclosure because it was only two patients' worth of data and because we were drawing a lot of conclusions. I would tell you that we believe we've chosen the right dose, and we believed that we were choosing the right dose because we designed CABA-201 to be very similar to the Schett product and because the preclinical data suggested that our dosing could be the same as his dosing and we would have similar effect.
So the dose of CABA-201, in our minds now having been established, the key is going to be to execute on the clinical program. Our clinical program, in addition to CABA-201 and its design, whose safety should be excellent and whose efficacy should be sort of foreshadowed by what we've seen elsewhere, our clinical trial design is the other overlooked opportunity that we're looking at in 2025. So we have, as I said, 11 different subsets of patients. Every one of them is incredibly homogeneous. As you will see in data presented not only by us, but by others, not every patient who has an autoimmune disease has the same risk of side effects. Not every patient type within myositis responds with the same pace of response. We've shown that before. The IMNM patients respond at a slower pace than the ASyS patients who were presented by Schett previously.
Beginning to think about 2025, number one, CABA-201 and its, we think, predictable prospects. Number two, the clinical trial design, which allows us, we believe, in some of these indications to not start a brand new Phase III program and open clinical sites for that program, but rather to modify the current protocol, to add a new arm to that protocol if needed, to extend the enrollment in a protocol, whatever the proper design is, as we will agree with FDA, to then execute without any delay between Phase II and Phase III. While it's possible to do that from a basket trial, not every site is a lupus site or a myositis site. When I tell you we have 40 sites, every one of those sites is expert at what they are open to do.
So it is not common that a myositis site also has tons of lupus patients. There are some sites like that, but most of the sites are highly specific in their expertise. And we've combed through and developed site openings that are directed towards maximizing the ability of that site to recruit patients of that type. So the clinical design, we think, is going to come into play in 2025 as an accelerant for us to get to a launch status for CABA-201. I didn't mention, and I want to come back now to mention, on August 10, six weeks after we presented a perfectly clean safety profile on the first two patients at EULAR , to our surprise and to the surprise of the industry, frankly, we reported that one of our patients had a grade four ICANS event.
They had nonclinical seizures, so there was seizure activity, but nothing evident on the outside other than loss of consciousness for the patient. That patient is now four months out, and we very much look forward to presenting, as we've said for some time now, our belief and data to support our belief that this patient was distinctively different in their cytokine profile and in their status before infusion as well as after, that the infusion of any activated T cell would have been met by cytokines that were distinctly different from every other patient that we've ever seen. And we think we understand why. We've done profiling of B cell receptors. We have a very deep scientific discussion that will be presented at ACR on that patient.
We think that patient and the side effects associated with that patient are an outlier, but we embrace the opportunity first to educate ourselves and the industry on what this whole category is going to face, and number two, to present to you at ACR the outcomes, efficacy, and safety of that patient along with their impression of their experience. Because at the end of the day, it doesn't matter what I think, and it doesn't matter what investors think, and it doesn't matter, frankly, what patients think. It doesn't matter what doctors think. What matters is patients who got CABA-201. What do they think? How do they feel about, in this case, the worst side effect profile we can imagine experiencing in the early days of this development program? How does that patient feel about CABA-201?
So we hope to present all of that information so that investors can be the judge for themselves of the prospects for Cabaletta and for CABA-201.
So at the ACR, how many patients worth of data do we anticipate?
We haven't specifically said, and it's more just information management, not updating in little piecemeal. In August, we were manufacturing for five patients simultaneously. If you use that as a guide, what we've said previously to make it succinct, you would expect seven or eight patients to be presented at EULAR with follow-up as long as six months in that cohort.
Got it. For the first two patients and then the third patient, right, obviously we're going to have a longer follow-up. Just if you can articulate for us, how are these patients doing? Are they sort of meeting some of the internal bar that you had established for them?
So I can't give you a preview of next week's data because then you and I would be spending a lot of time in jail together. But what I can do is I can say.
I think you can disclose and file an 8-K after this call.
It's true. I could. I could. But then my team would shoot me. So here's how we're measuring success, and it is exactly what I said. And this is what I think all of us should be looking for in all therapies. Can you provide a drug-free clinical response that leaves the patient with no symptoms, waking up in the morning, forgetting they have their disease? Can you halt the progression of organ failure? And can you do it reliably? That is to say, not in a half of patients or 75% of it. Can you do it in all patients? Now, it doesn't have to be all patients to be a product, but those who are talking about, well, half the time we're going to have a success. Okay. I don't know what that means. The other half needs something.
When you fail at something, what are you going to get? A more reliable, durable therapy. Autologous CAR T is the only thing that has proven, and in fact, many of the other therapies have proven they cannot yet demonstrate durable, reliable, complete responses to get patients off of therapy, all therapy, reliably. All immunosuppressants should be gone in just about all patients, maybe all patients. That's the bar, right? I think the team that does that, the drug that does that first, has the prospect of winning for the time being. After that, you have to innovate, right? So everybody in the allogeneic space today either has substantial preconditioning required to prevent immune rejection, or the future therapies will be gene-edited very substantially in some cases, right? Five, six, eight edits. All of that requires both time and toxicity.
So for CABA-201, our response to this is pretty simple. Stay focused on what's best for patients. Get rid of the apheresis step. So we've demonstrated and we've presented and we will be presenting more data on our intention to bring a whole blood, a blood test essentially. So draw blood as you would a blood test and use that blood as the basis to manufacture CABA-201 instead of an apheresis. We believe this is going to happen, and we intend to bring it into one of our launch indications or more, depending on exactly what our ongoing studies show us about the reliability of the approach. That's going to eliminate the hurdle of finding enough apheresis spots and competing with cancer, right? So it opens up the opportunity. And it diminishes the differences between CABA-201 and future therapies.
The second thing that we're doing is we're actively recruiting at seven clinical sites across the U.S. right now for CABA-201 with no preconditioning. And I would argue this is the most important trial in the industry right now. Because if CABA-201 works with no preconditioning, either at doses that are currently being used or at higher doses, and I'll describe why in a moment, it changes everything. Because the one thing that doctors and patients tell us is if you can get rid of the Flu/Cy, that's a really big deal. Not only for the simplicity of the regimen, but now instead of going to the doctor and saying, "Oh, I have scleroderma and I need to get CAR T therapy." Well, if you're going to get CABA-201, first thing you're going to do is stop in the apheresis and make an appointment. You're going to have apheresis.
We're going to send that back and manufacture. You'll come in and you'll have preconditioning three, four days, and then you're going to come in and get an infusion. That's today's process. Imagine that the apheresis goes away and all you're going to do is go down to the lab, not schedule an appointment, just go down to the lab and they'll draw 10 tubes of blood, purple top tubes of blood, and that gets sent into our manufacturing facility and that's the basis of CABA-201 manufacture. The next thing you do is come back and we're going to infuse your cells. No preconditioning.
Now if you're a patient, if we can get to a similar point where we believe we can have drug-free, durable clinical responses that are complete for the patient, and you can do it by simply drawing some blood and then administering cells, say a month later, three weeks, whatever the number is, who's going to do better than that?
Going back to the ACR or the next presentation, in order for you to answer these questions about drug-free remission, is there a particular or a minimum follow-up that you need? And would you have that in this presentation at ACR? And how should we think about, let's say, the next six months?
Yeah, this is a really complicated question. We hope to do our part in letting investors understand how we view durability and the translational science required to demonstrate durability. We think that durability is best presented by waiting nine months to have the baby, but can we do something to predict that you likely will maintain your durability? And we think the answers lie in sequential B cell receptor sequencing, which is to say, before you had any therapy, what is the profile of the B cell receptors that you have in your body? And having profiled you after therapy is administered and we see the reemergence of naive B cell populations, what are the B cell receptor sequences you now have? How many of those overlap? If the overlap is 20%, you've missed 20% of the B cells.
It's very nice that you have a tissue biopsy that says you got all B cells or you have blood. It doesn't matter. Lymph node biopsy, the follicular centers, it doesn't matter. You have the B cells that were there. There's a 20% chance that you missed the pathogenic B cells because 20% of B cells were missed, right? If on the other hand, you have 1% of the old B cell sequences still present, you have a 1% chance. But wait a minute, only 1% of the B cells, actually far fewer, are causing the disease. And depending on how the B cell receptor sequencing evolves both in one patient over time and across many patients, you can calculate the risk of recurrence due to a failure to eliminate the prior B cells. It's really complicated.
I walk you through it because we're going to be saying this a lot because everybody's arm waving, "We're going to reset the immune system. We reset, look, we reset the immune system." And the reset involved the continuation or addition of new immunosuppressive agents because the bispecific or the NK, whatever, didn't actually work for even 12 weeks. But somehow everybody's resetting the immune system. So the more rigorous we can be in defining that and understanding what it is to truly eliminate all B cells, we think the better off patients and physicians will be when they choose the therapies that are going to be most durable.
Got it. In terms of the protocol amendment that you had to make after August 10, does that impact or is there any impact on clinical trials enrollment and where you are on the enrollment front, the type of patient that you have been able to enroll so far?
Since that announcement, everything has moved more quickly. More sites, patients, everything. I want to be really clear. There is nothing unique about CABA-201 when it comes to our safety profile in our opinion, and the ACR presentation will present data and everybody will make their own judgment. The third patient we presented with the very severe side effect profile has the baseline cytokines and all of the measurement of CABA-201, its response after administration, everything about that patient was unique and distinct, and we believe that that was a unique situation. As we treat more patients and we show more safety data, there don't need to be any opinions, right? The facts will speak for themselves.
But the fact that investigators continue to sign on with multiple sites in some cases opening on a given day, multiple patients being enrolled on a given day, this is a different world that we're in, right? 2023 was painfully arduous. Early 2024, the same pain that the industry is going through right now to find sites and open sites, we had that. We're beyond that now and we're into moving towards registrational trials if our data support the opportunity to do that. And we're thrilled with that prospect.
Very good. I think that's all I have, Steven.
Thanks.
Thank you so much.
Appreciate the opportunity.