Okay, I think we are live now. Good morning, everyone. My name is Yatin Suneja. I am one of the biotech analysts here at Guggenheim. Welcome to our SMID Cap Therapeutics or Biotech Conference. Our next presenting company is Cabaletta. From the company, we have a couple of executives here. But with me, I have Steven Nichtberger, who is the President, CEO, and Co-founder. Steven, why don't you maybe take five minutes, just tell us about Cabaletta, what milestone that we and investors should be focusing on, and then we'll go into sort of a fireside session.
Yeah, so Cabaletta is entirely focused on the treatment of autoimmune patients with cellular therapy. In particular, our lead program is a construct called Rese-cel, which previously was known as CABA-201. Rese-cel is now in clinical studies across the US, with most recently, we've set about 46 clinical sites, which is far more than any other company in terms of clinical site enrollment presence in the United States when it comes to cellular therapy of any sort for autoimmune patients. The next closest company has 30 clinical sites. That's a large pharma company. Behind them, a small biotech has maybe 12 or 15. Behind them, the whole allogeneic industry has 15 or 16 clinical sites. If you don't have clinical sites, you don't get patients. The Rese-cel program is enrolling at a pace of about one patient per week. We have been doing this since October.
This is not a blip. This is a trend. It is our reality. We are manufacturing at that pace. We are treating and dosing at that pace. We do not expect it to slow down. The reason is our clinical data. We most recently reported in association with the J.P. Morgan conference that in the first 10 patients we had treated with follow-up more than a month, 90% of them either had no CRS or had a fever. We also reported that 90% of them had no ICANS whatsoever. A really safe profile was emerging. We also reported that patients were resulting, the resulting efficacy outcomes were that they were going off of all their medicines the day that we infused them with our product. They were staying off of all their medicines for the duration of follow-up. The immunosuppressants were gone.
The steroids were being tapered. What we are seeing continues to be not a diminishing of the treatment response with time, but a deepening of the treatment response with time. That's something that, as the weeks are now passing and these data are maturing, we will be presenting more data to answer your question of near-term interesting data that we'll be presenting or items that are of interest. We'll be presenting in two different medical/scientific forums in the next few weeks or months. We will update on the patients. As of the J.P. Morgan conference a couple of weeks ago, we'd said that we had dosed 10 patients. We won't report data before the 29-day primary endpoint. You can expect, if we present in February, maybe 10, maybe 11 patients' worth of data, with continued follow-up on both efficacy and safety for all of the patients.
Maybe at a much higher level of focus for our company is the intention to meet with FDA in order to reach agreement, to gain agreement on a path to registration for the lead program, for the initial indication that we will take forward. We believe that the data we have in hand is compelling, both in terms of safety and efficacy. We think it's transformative to the field of treatment of these patients. We believe that it supports the sort of clinical trial design that we are proposing to the agency. Having clarity of the path to phase three, if we can achieve what it is that we believe we can achieve, where you have these complete responses that are not seen otherwise.
If it's myositis, which has always been our lead indication, has always been our focus as a company, there are about 75,000 patients in the United States who have myositis. About 80% or 90% of them would meet entry criteria if they had an exacerbation. You're talking about a very, very large cohort of patients who would be eligible for treatment, both in our trials if we gain agreement with FDA on the design, which is not too different from what we currently are running, quite honestly. You have to have the disease. It has to be active. You have to have antibodies. You have to have failed a couple of other therapies. For context, just to get a sense, all of the CD19- CAR T treatments ever administered total about 50-some-odd thousand right now for cancer.
There are more than that in terms of myositis-eligible patients. That is only one of 11 different indications that we're actively pursuing in individual cohorts in six or seven different clinical trials. We are excited.
Got it. Very good. You touched a little bit on the recent update from January, especially on the safety side. Can you just review for us, please, the data that you presented at ACR, specifically as it relates to safety on the subset of those patients? They were lupus patients. They were myositis patients. What was remarkable about those data? At least in that cohort of patients, what should be our expectation in February when you present the data?
You raise a really very important point. Safety is what's going to differentiate. We just recently did a review of all of the CAR T that's ever been administered in the world for CD19- CAR T for autoimmune patients. We're now well over 100 patients. There was a time in 2023 and 2024 where we all had to be like shit. As we go forward, we now know what these drugs do. Unlike what we're seeing with the early trials in other modalities, autologous CAR T, there's hardly a report of any patient, at any dose even, that doesn't have a treatment response that is almost always complete. Our expectation for the field is that you're going to see 80% to 90% complete, durable responses off of all medicines. That is astonishing. That is game-changing.
In fact, our head of translational research was just asked to edit the first version, the first edition of a new textbook on the cellular therapy of autoimmune diseases. This is changing medicine. This field will change medicine. The differentiator, as we always believed it would be, is going to come in safety. You asked about the safety data we presented at ACR. Before I go there, let me tell you that what we saw was emerging a profile that looks like it's safer than what others are seeing, which, well, wait a minute. If everybody is equally effective and you want to be the safest, why do you believe yours is safe? Most of our patients have no side effects. Period. We reported 90% had either no side effect, no CRS, or fever. We reported that 90% had no ICANS of any grade.
Why is that the case? I think the answer lies in weight-based dosing. There are those who manufacture fast or slow or faster or very I don't know what people are doing. I know what we're doing. We're doing weight-based dosing. We're doing that because that's what Professor Schett did originally. Dosing matters. We're the only company doing it. By giving the proper dose, I think we're coming to really the Goldilocks scenario where you have enough efficacy and activity, and you're seeing a very light touch on side effects. The ACR presentation gave us early reason to believe that the safety might be actually pretty compelling. We're now dosing it one a week. We're starting to see a lot more safety data. I wouldn't be sitting here saying this if I didn't believe that we're going to be able to play this out.
That's where I was. I want to also focus on the adverse event that was a shock to the company and to the investment community and, frankly, to the field. In myositis, I think we had at ACR, I forget exactly what we reported or not at that point, but we had one fever, and everybody else had absolutely no side effects. The fever was not treated with tocilizumab and came and went. In lupus, we had one fever and nothing else. Everybody else had no side effects. In scleroderma, we had one and our only grade 2 CRS that was not treated with tocilizumab but instead just needed a bag of IV fluid. These were very minor. Think about the side effects of rituximab or steroids or any of the drugs that are used for any of the diseases we treat today.
They're all worse than what I just told you about. The one side effect that was problematic for everybody and was shocking was a lupus nephritis patient. And to give you the background on this patient, this is a 24-approximately-year-old woman with severe lupus despite eight, nine, 10 different medicines used over time, five of which she was on when she entered our trial. Two weeks before she came into the study, approximately, she was hospitalized with pericarditis fluid around the heart, which was related to her lupus. She was treated for that with a pulse of steroids. It wasn't infectious, they thought. It was due to inflammation. The steroids reduced that shortness of breath and that fluid. She was sent home. She seemed and did fine. She wanted to get her cells. It was deferred by us, by the doctor. We all agreed at some point, she's very stable.
Let's go ahead and administer the cells. She did fine. On day nine, she developed CRS grade one, followed by hospitalization because that's what you do, CRS grade one at day nine. While in the hospital, she started to have change in mental status, diminishing consciousness. Overnight, she went from a little bit not clear thinking to pretty much not responsive the next morning. By that night, she had been fully treated with a routine regimen of ICANS treating drugs. She was fine the next morning. She was back to normal. We subsequently gave a full discussion about this at ACR, which included not only the fact that what caused her change in consciousness was non-convulsive seizure activity. The electrical activity in the brain went crazy because in translational assessment, we now know her cytokines were through the roof.
Why were her cytokines through the roof? We did sequencing of the T cell receptors. We did T cell receptor sequencing. What we learned was that there is a single clone of T cells that was present in the patient at that time. That clone, half the cells approximately had our construct in it, and the other half did not. What that tells you is that the expansion of that clone was not due to our construct. It was due to probably an infection or some occult thing that was not recognized clinically. It expanded both the cells that happened to have been transfected and the ones that were not from that clone. That became the dominant T cell in that patient.
Because we were this side story that was expanded dramatically in this patient, you saw, and we showed in a poster at ACR, really dramatically different profile of PK and PD effects on cytokines in this patient. The long story follow-up on this patient is that she's now cured. And her quote shown at ACR is, "If I had to do it all over again, including the scary side effects, I would want to have CABA-201." That's her quote. In this very unusual case with this occult infection and this expansion of a single clone, the ability of our incredible scientists to really dig in and understand what happened, for us to confidently say out loud, this was an outlier. This is not the profile of our drug. We have seen no other ICANS in any other patient dosed.
The CRS profile looks pretty modest relative to any measure. We feel great about the side effect profile. We think we understand that patient. That patient, as I said, had the most terrific outcome. She was hospitalized repeatedly with this pericarditis, with other side effects. She was on five medicines. She was 24 years old. Her kidneys were failing. All of it melted away, as it does with most patients.
Yeah. So far, at the ACR or the recent efficacy data that we have seen, it's only three types of patients. We have the lupus, myositis, and scleroderma. In this February update, should we expect any new indication? If not, these 10-11 patients, just if you can articulate how many within each group we should anticipate.
We haven't sliced and diced it that fine yet, but we are going to be starting to do that more and more. At the pace of enrollment that we're now seeing, we're going to have meaningful cohorts of information in each indication. That's when we're going to start parsing data by indication this way. I would expect in February that we talk about the one-month follow-up. These are patients who were enrolled back in November, probably, who were dosed in early January or in early December. We'll have one or two-month follow-up on the most recently treated. In the early days, we only had lupus and myositis and then subsequently scleroderma. We'll have data on those three cohorts. The next data I would anticipate would come from the pemphigus program, which has its own profile.
Yeah. You just mentioned deepening of response with time. What do you mean?
Yeah. As in the academic literature, patients clear different clinical and translational hurdles with different timelines. It turns out not only are the side effect profiles different by indication and by sub-indication, but the efficacy profile and the time to treatment response differ by indication and by subtype, as well as the time to resolution of any individual marker in a given patient. We've presented, and it's now well known, that in myositis, certain subtypes just respond more slowly. IMNM has a slower response time, and it's more modest. The muscle damage seems to be maybe permanent. You know what? They're still improving a year on, two years on. In the academic and in our own hands, we're seeing these curves that are maybe it's like 45 degrees of improvement in the TIS or in the MMT, however you want to measure these things.
Each of the markers, like dsDNA is a good example. There was a lot of questions about our lupus data at ACR. Hey, you have dsDNA, which is a marker of lupus. And it's still persisting in all three of your patients. To be clear, two of them were followed for four weeks by that time, dsDNA doesn't clear in four weeks. One of them was followed, I think, for three months or six months. I don't know exactly. People said, in the academic data, it wasn't like that. The truth is, in the academic data, it was like that. You need to dig into the details to understand because this is all published, but you have to really be honestly an expert and spend full time figuring it out.
In the new j ournal paper that was published by Schett and colleagues, they said they had no dsDNA at three months, at six months in their lupus patients. As is widely known, we have a translational partnership that is exclusive with Schett. We have his patient samples. Unlike most companies, we do not send him our samples and ask him to do some work for us. He sends us his samples because we are world-class experts in translational research of autoimmune cell therapy. With his samples in our hands, we ran the dsDNA studies on his samples. There is indeed double-stranded DNA for longer periods of persistence, let's say, than he has reported. We subsequently have published that with him. The reason his data are different from the data we generated is we have a more sensitive assay.
We're using a Luminex assay for those who know the field. He didn't, right? He was using what he had available to him as an academic. That explains why we had dsDNA persist and he did not. People are looking at all these nuances. I got to tell you, dosing one patient a week and having data across all of these different indications, it's not going to be very long before we don't worry about whether dsDNA exists. We're going to worry about whether patients are disease-free, drug-free, and happy. If they are what they want to achieve, and what we want to give them so badly is their life back.
If they can live and not feel that they're a patient every morning because they're taking a handful of pills or they have to go to the doctor tomorrow or they can't make it to their kids, whatever, or they can't go to work today or next week, they have an exacerbation, if they cannot be a patient anymore and they're free, that's what we want to give them. I think we are going to.
Got it. When you say this deepening of response with time, it's not just one or two patients. It's across all patients, across different.
Across all indications.
Yeah. That's what you're saying. All right. Very good. I wanted to also touch briefly on the PV study. Where are we? I know you have enrolled a patient. I think there is no lymphodepletion, so that could be transformation for the space. Just articulate when we should expect data, dosing, and the doses that you might be using there.
Yeah. We haven't specifically spoken about the doses, but it is a dose exploration study. FDA, because of the data that we had on our binder from our partners where we licensed the binder from, we know and we have permission from FDA to go threefold higher in dose. So somewhere in that range, we have a trial which has multiple sequenced arms. We're looking to see at what level we have efficacy. We believe we will have efficacy without preconditioning. The reason we believe that is the subject of a separate discussion. If you're interested, I can go into it. The generation of that data, it depends which dose is effective first. The first patient is enrolled. I don't know how many sites. It changes quickly, but it's probably a half a dozen sites that are opened or opening very soon.
We will start to see patients enroll in the pemphigus study. We are really excited about the opportunity to explore this because it is a complete game changer. Just for clarity, we will not launch our first product first day out the door without preconditioning. We do not yet know how durable it is. Even if we all get excited that you can do this, will it be as durable? Can we do B cell receptor sequencing sequentially and see that we have eliminated all the old B cells and there will not be a recurrence? We just do not know. Stay tuned. We are excited as you are, but we have to wait and just let it bake.
Got it. With regard to the FDA interaction, what is the sequence there? I think you have said in the first half you're going to meet. So I'm just curious, will you wait for the minute? When will you communicate to the street? And what should be the communication with regard to the first indication? Is it mostly myositis focused or is it broader?
Yeah. I think it's safe to say that we have never wavered from myositis being the path to victory for Rese-cel. Our belief in it has been reiterated by, number one, the clinical data we have seen. Number two, the fact that just about every clinical site is now enrolling their second, their third sequential patient. As a reminder, that does not happen, right? In lupus trials, historically, you enroll 0.1 patients per month, i.e., one patient per year. In the Saphnelo development program, in the Benlysta development program, these are common pharmaceutical products, the leading categories in the field, the leading products in the field. They enrolled one patient per site per year on average. In our myositis program, and that's why we knew we needed a lot of sites, right?
That has nothing to do with cell therapy, autologous, preconditioning, all of these things that people arm wave about. There are a lot of them that arm wave about it, but the problem is they're not treating patients. We are. The doctors want to use the drug. The patients want to get the drug. None of these are barriers that are preventing nearly 50 US clinical sites from actively enrolling. After they see the results in the first most difficult to treat patient that they gave us, and the patient comes back off all medicines, tapering or off of their steroids, symptom-free, happy, no longer a patient, how long do you think it takes to get the next patient enrolled? It doesn't take a year, right? We're starting to see two and three patients at each site in the myositis program.
That will be the first one out the door. The only other comment I'd make here is in myositis, there are a couple of few competitors. It's a very focused field. There aren't 100 sites across the US that do myositis in a focused way. In lupus, there are north of 30 or 35 cleared INDs for cellular therapy in the lupus population. There are US companies and academics trying to treat lupus patients, over 30, different products. In myositis, I think there might be three.
Okay. I want to touch on a few more things. For the myasthenia gravis and MS, where do you stand on those two sort of indications? When should we expect an update there?
Yeah. Myasthenia gravis, we now have, I don't know, a half a dozen sites plus or minus that are opened and starting to enroll and getting excited about ramping that program up. I don't anticipate we're going to present data publicly soon on the myasthenia gravis program. It's just a matter of we have to ramp up the machine. On MS, we took a very well-discussed, well-informed decision, which is let other companies go after MS first. This is a CNS disease. Do you get adequate penetration? T cells do penetrate. Do you get adequate penetration? At what dose? What is the response? Is it reliable? And which population? Persistent, relapsing, remitting, active, not active? There's a lot of variability. In a world of biotech that is so challenging for any company developing any drug, why would you start there?
For us, that's gravy on top of a really large market opportunity in myositis, in lupus, in scleroderma. I would say scleroderma is just like myositis. The patients cannot stop showing up once they realize the doctors realize the treatment effect that they're seeing.
Yeah. Okay. A few more questions. There has been a lot of talk about TCEs and CAR-Ts. You are obviously a CAR T focused player. Just talk about the commercial dynamic, how they both will exist if they are in the market together.
We have always believed, we've talked about this back in 2020. We've always believed bispecifics will have a role in autoimmunity. Somebody will figure out how to get one to work because so far they haven't. The expectation we have is that bispecifics will replace rituximab. They'll replace methotrexate. They'll replace cyclophosphamide and azathioprine. They'll be really good therapy for a lot of patients. They will not be durable, curable, reliable treatments. There will be failures. There will be those who recur on those drugs when they finally get a dose that works and if it's safe enough. If that occurs, you need something to treat those patients. I think it's obvious. You're not going back to all the other drugs that I mentioned. You're going forwards into an autologous CAR T space.
With the number of patients we need to treat and just to put a marker on it, at today's price for CAR T for cancer at $500,000 per patient, it takes 2,000 patients to make a billion dollars in revenue. The margins on cell therapy are not what they were in 2017 when Yescarta launched. You're talking about $525,000. The accepted price commercially is about one and a quarter now. You're already at acceptable margins. The question is how much better can we do? That'll be the subject of our next discussion.
All right, Stu. I'm going to summarize this then, at least in context of what we will expect in February. You're seeing good enrollment, 46 clinical sites. The most amount of sites. You are enrolling one patient per week.
Dosing one patient.
Dosing one patient per week. In the next few weeks, we're going to get data on 10-11 patients. Most likely going to be the same subset of patients, right?
Same subset with a couple of additional, a few additional patients.
You feel comfortable making a point that you are seeing deepening of response. At least the patient that you presented at ACR, we should see sort of further improvements.
I think that's true. The most important point I would close with is we have very high expectations. We will be able to meet with and report on the meeting after we see the minutes from FDA directing us on the path to approval, the path to filing a BLA on a lead indication for Rese-cel.
Very good. Steven, thank you so much.
Thank you. Appreciate it.