Okay, I think we're set. Welcome, everybody. I'm Doug Tsao, Senior Analyst at H.C. Wainwright. We are thrilled to have Cabaletta Bio represented by the company CEO, Steven Nichtberger. It's been a sort of eventful journey for the company over the last few years. You've got a lot of data coming out in the next few weeks, and just maybe sort of step back and sort of talk about that data, as well as broadly how that advances you in terms of your overall sort of mission as a company.
Yeah, so first, thanks for having us. We are really excited about the next month or two. It has been since 2022 when we first licensed CABA-201, which is now Rese-cel, our lead CD19 CAR T product autologous for autoimmune patients. The data that we'll be presenting in the next few weeks in October at multiple medical meetings that I'll talk about in a moment is the culmination of a lot of work.
This is a hotly competitive space. I think we've been fortunate because we've made some strategic choices with Rese-cel that now, in hindsight, look in some cases prescient and in other cases just maybe lucky. We chose to have myositis be the lead indication back in 2022.
We publicly disclosed that at some point in 2023, and we have not only not wavered from that, but we have reiterated that that turns out to be an excellent first indication. The reason being, in lupus, which is just about everybody's first indication, there are 35 cell therapy competitors competing for patients, and even after they launch, if anybody ever does, they're competing with the research enterprise that's a highly profitable research enterprise.
In our case, in myositis, there's a couple of competitors that are substantially further behind us with good programs and good products, but we expect fully to be first to market in the treatment of patients with myositis based on our agreement with FDA, which basically is that we will run a trial in our existing RESET-Myositis program.
We will add an arm, and that arm will have approximately 15 patients followed for approximately, well, less than 24 weeks. And the primary endpoint is going to be the TIS score, the same score that was used for IVIG approval in myositis. And in that case, it was at 16 weeks. That's the agreement with FDA: 14 patients to access 70,000 U.S. patients with the disease, of whom approximately 16,000-20,000 are indicated by interviews with physicians.
And I'm talking about hundreds and hundreds of physician interviews. About 16,000-20,000 of those patients, in the case of myositis, are likely to be eligible for Rese-cel on the day we launch. So a very big market accessed by only 14 patients in each of two cohorts. One cohort is 90% of the myositis population. The other is 10%.
We'll present data to answer your question with that sort of preamble. We'll present data on our phase one to myositis patients, not some of them, all of them, and we'll read that data directly against our actual primary endpoint with the approach that FDA and Cabaletta have agreed is our registrational approach.
You'll know by the end of October whether or not Rese-cel in the same trial, just a different arm, has already done what it is that we need to do in order to get a BLA filing in 2027. So it's the same sites, it's the same drug, it's the same dose, it's the same investigators, it's the same trial.
So we feel great about that and look forward to presenting that information at ACR, along with interim updates on scleroderma and lupus, both of which we expect to have agreement with FDA on a pivotal approach by the end of the year. So we're talking about multiple pivotal programs in literally hundreds of thousands of patients, the first of which is myositis. That'll be at ACR.
In addition, in October, at the very end of the month, we're going to be presenting data on myasthenia gravis, something we really haven't even talked about, but has been very, very rapidly enrolling in our program. And so there's a real unmet need in myasthenia gravis that it has caused us to take notice. And we're looking forward to presenting that initial clinical data in myasthenia gravis at the end of October at AANEM, which is a neurology meeting.
And then on October 9th, we're presenting data on Rese-cel with no preconditioning. Now, we're doing this trial not because patients aren't actively showing up at a very fast pace in our RESET Rese-cel program with preconditioning.
We're doing it because in certain selected indications, taking away the preconditioning, if it were possible, would be a really good thing. And so at a late-breaking clinical trials session of the ESGCT meeting on October 9th, we'll present the lowest dose cohort in the RESET-PV trial, which is without any preconditioning at all.
And we'll have translational data, some clinical data, really looking to see, is there biologic activity? Is there a treatment effect that looks the same or different from the dozens of patients we now have with preconditioning? And maybe that'll give us some clues on clinical, and we'll see what's presented on October 9th. So that's sort of what's happening in the next couple of weeks, the data, and the context is what I was trying to provide.
That's very comprehensive sort of a lot of places, directions to go. Maybe just starting with the preconditioning issue and what is the significance of that data. I'm curious if you've gotten feedback from the FDA on what it might take to get an approval for a preconditioning-free regimen.
So let me go right to the last question. No. We haven't gotten feedback from FDA on what it would take because we have yet to say publicly even that it works or doesn't work. We're lowest dose cohort, and the reason for doing the preconditioning trial biologically is that there's a paper published by one of our scientific founders years ago in myeloma, which is the closest to autoimmune disease as you can get when it comes to the number of B cells you're trying to kill. Unlike leukemia or lymphoma, myeloma, the plasma cells are in magnitude.
The B cells are about normal. So it's a good harbinger of things to come for autoimmune disease. So we said, look, no preconditioning is not going to work. It never has. Maybe it never will. But if it were to work, what would you do with it? Why would it matter? Why it would matter is in myositis, our lead indication, in scleroderma, perhaps our second most important indication, patients are not asking to stop lymphodepleting them before therapy.
They just want a drug that actually delivers efficacy of the sort they're seeing in the trials that CD19 CAR T autologous products have delivered. They can't wait to get their hands on the drug evidence. The enrollment is really beyond our expectations, and we're thrilled with that.
No preconditioning regimens are of interest, however, in disease states where there are many options. If you think about it, lupus, there's a bunch of approved drugs. Myasthenia gravis, there's a bunch of approved drugs. The opportunity to go into the hospital, or I should say not the hospital, but to the doctor's office to say, "Oh, you have lupus.
We've tried everything, and you're going to get a CD19 autologous CAR T." The patient says, "What does that mean?" Well, you're going to go downstairs, and you're essentially going to donate some blood. You're going to have apheresis. That takes half a day, and it's complicated compared to a blood test, but you'll do that. You'll go home, and six weeks later, eight weeks later, whatever it is, you're going to come back, and we're going to infuse your cells as an outpatient.
You're not going to do preconditioning for three days before. It's just, "Give us your blood. We will give you your cells." You go home that day. You wait for two weeks, stay nearby the hospital, and you're done. You're not taking medicines anymore. Your disease melts away. And I'm not fantasizing. About 80%-85% of the time, that's what we're seeing. That's what we're seeing.
It's ridiculous. The patient benefit is so profound in all of these disease states that the patients are showing up in enrollment, and the doctors are telling us they want to use the drug as soon as it launches. But if I could get rid of preconditioning for Lupus and Myasthenia Gravis, that would do two things. It would expand the market, make it simple to use in a context of a lot of opportunities for different therapies, and particularly in Lupus, this is really interesting.
This was pointed out to our leadership team by our controller, and so picture, I always say our team is a very high-performing team of people who have been with the company for seven years since we founded it, and everybody is the first person in the job, and people don't run away from the company no matter what happens.
Our controller, who's been with us forever, said, "You guys are trying to figure out where to use no preconditioning." FYI, I just wrote my fifth reimbursement check from Cabaletta to a patient with lupus for fertility preservation. We only have six young women who are of childbearing age who could have asked for it, and five did. Our enrollment in lupus is a quarter as fast as every other indication.
There's 35 competitors. No wonder. But more than that, if you don't want to take the risk of being infertile, you don't want the preconditioning. And so this is based on both conversations with physicians and actions of patients. It's really clear. The vast majority of the 35 cell therapies are using preconditioning in lupus.
If the data on October 9th suggests that we might have benefit without preconditioning, we have years of advantage over everybody because nobody else would do the trial. We're asking the hard question. Do the cells alone actually have a treatment effect? This is only the low-dose cohort on October 9th, and we're doing other things along the way. It may be a higher dose cohort is required. It may be that there's other things that we have to do, but there is an awful lot of learning that's going to come in October.
So why couldn't competitors simply try to replicate what you do if the data reads out in terms of success without preconditioning?
Yeah. So Doug, the answer to the question is I hope they do because it'll be awesome for patients. They will be years behind us. For us to get to this data with a known dose, we already knew our dose with preconditioning, to go into every different patient category, every different patient disease type is going to respond differently at some level in terms of side effects, the number of B cells.
The whole biologic pathway is different, and we have enough data, enough patients now to know this. And where do I come from with these statements? Our translational research organization to this day receives the samples from Erlangen, from Professor Schett's clinical studies. The clinical samples go to our lab, in addition to, of course, other places, for us to tell him what's going on with his patients.
We have truly unique and terrifically well-informed, experienced, and skilled people looking at all of the translational aspects of cell therapy in autoimmune patients. That insight is going to be really important and on display on October 9th when we present the no preconditioning data, and we look at the different cytokines, the different markers, the B cell population, the T cell populations.
The companies who would follow us in the no preconditioning path if it were positive ultimately, and we're just doing the low dose and biologic and translational data initially, but if it's positive, there's a lot of risk and benefit calculation and understanding that the world is just not aware of yet unless there's things going on that we don't know about.
So I think this is not as straightforward as people will think it is today. It's not as straightforward as we thought it might be upfront. And look, let's play it out. And if five companies do it behind us, that's awesome.
And maybe going back to myositis, because as you indicated, that sort of has become your sort of focus and priority indication. What about it led you to myositis, and do you see similar clinical utility across the three predominant subtypes, DM, ASyS, and IMNM?
Yeah. So great question. We did a very comprehensive review of all indications where CD19 CAR T could be effective therapy and safe therapy could be highly desirable. Myositis rose to the top for many reasons. The first, the data. The Schett data in ASyS and DM patients is profound. You treat, and at 29 days or so, you see a dramatic elimination, melting away of clinical symptoms.
You see a very safe profile, and you've got a transformed life for every patient that's treated. So for me, it starts with the data. That was compelling. However, to your question, we didn't know if DM would be the same as ASyS, would be the same as necrotizing myositis, IMNM. So we have two cohorts agreed with FDA. One is DM and ASyS together because they do tend to respond the same, and they are similar. They're not necrotizing muscle.
And then the necrotizing group, the necrotizing group is only 10% of all the patients. We have agreement with FDA to do it. Whether we choose to go forward or not will depend on the data that we see and how that data flows. But ASyS and DM is 90% of the market opportunity. Go, go, go, unless on October 24th, we show data that says it wouldn't have worked.
So we're going to show you the data at the end of October that it either works or it doesn't work. ASyS, DM, IMNM, and we'll make the choices of where and how to go forward. The clinical data is what drove us first. Then behind that, the unmet need. There is one drug approved for the treatment of myositis in this country, dermatomyositis. You can use IVIG.
That means as a patient, you're going to go to the hospital for two days this month. You'll spend a half a day each of those two days, and you'll get IVIG infusions. Your insurance company won't be terribly happy. It'll cost them about anywhere from $300,000-$400,000 a year for you to get this modestly effective therapy that is associated with side effects. But it's the only thing you got.
So the backdrop of therapy, limited options, and the only thing that's out there is extremely expensive chronic annual therapy. And then really on top of that, not expected by us, but a gift, frankly, Vyvgart, a terrific drug developed by an incredible team, is going to launch in myositis. If you look at the dose they use in their phase three myositis program, we believe the cost of that dose is about $440,000 per year.
It's not curative therapy. It's added to existing therapies. So as a payer, Vyvgart will be presented as a drug you could use chronically in the same 20,000 patients who today get IVIG out of the 60,000, 80,000 patients out there with myositis. What if Cabaletta walked in shortly after, which is sort of the timeline is lined up that way for BLA? What if we walked in shortly after and said to the same payer, "Maybe it's a value-based agreement.
Maybe it's not, but the data suggests you're not using any IVIG or Vyvgart in any patient that we're treating for the next year, two years, I don't know." Are we going to price at the same CAR T pricing that has led to margin squeeze and, frankly, tough business models?
Or are we and others like us going to look at the value delivered to the healthcare system and price accordingly and responsibly? So if they're coming out at that kind of price, or if IVIG is at that kind of price annually for modest effect, and what we're doing is 80%, 85% of the time, you're off all your medicines. You're not going to the hospital again because you don't have symptoms.
What's that worth? And now you look at the autologous business model. It is not the one that we all have come to know. And frankly, hey, it is exactly the opposite. It is a highly productive, highly valuable franchise that all of the autologous companies are going to be able to engage in because, number one, cost of goods are coming down with automation and with expertise.
And frankly, the supply of autologous manufacturing in the world has blossomed with all of the major pharma companies now bringing everything in-house. So all of the CDMOs, the guys that we care about, are looking for good business. And so it's a great moment to be securing commercial supply.
And that side of our margin equation is also going to be, I think, better than we expected. The pricing opportunity, without speaking exactly what pricing will be for Cabaletta or Rese-cel, the value opportunity is really near and present. And so you don't have to be an Excel whiz to understand. We might have a tiger by the tail.
We might have a compelling clinical profile, first to market, followed by scleroderma, perhaps first to market there with a safe drug that looks to be highly valued and valuable when the options are expensive therapy annually that's not as effective and may or may not be as safe.
Maybe just on a follow-up with myositis, as you noted, the DM and ASyS arm is just one arm. Are you sort of enriching to ensure that you at least have a minimum?
That's a really good question.
Of one of those subtypes? Because you could just, I mean, you're talking about only 15 patients, so it could just be random that.
It was left to our discretion. We do have a plan and thoughts. But look, DM is 70% of the market. It's 70% of the patients. So the vast majority of any trial should be DM. You need to have some ASyS in there as well if it's a combined group. And the final thing I'll say is it's powered with 50% failure rate.
So if the first seven patients out of 14 or the first eight out of 16 or whatever the final numbers are turn out to be responders, the trial has to be positive. And if it's positive, we have agreement with FDA that we can terminate the trial early and submit the BLA. So we need to have 35 patients with myositis treated with safety data.
We need to have 100 patients treated in the program across all indications treated with safety data. That is already more than 60% enrolled, and in myositis, we've already treated or are treating, have enrolled, whatever the right way to say it, have enrolled, I guess, at least 18-20, maybe more patients, so we're really in excellent shape to hit our milestones as we have for years now and to maybe exceed if we get a little bit lucky.
And I know we're sort of in what I call stoppage time here. I don't know if you're a soccer fan, but.
I am.
Football. Football.
Who gets to determine how much time we have?
I do. But in terms of where you are, in terms of the overall patients, you talked about sort of needing to get to 100 patients dosed. I think after Labor Day or around Labor Day, you talked about having 38 patients dosed. It sounds like you're right now at around a patient a week, maybe a little below that. How do we think about the rate of not just enrollment, where the numbers look really strong, but actually getting product, getting infused?
Yeah, so as we are preparing, most of our phase one, two cohorts are filled. We're simply enrolling patients in expansion phase, we call it, of our phase one, two trials across the program in order to generate more safety data.
What we really want to do is have patients who are about to enroll move right into our pivotal programs, and so we're working with sites to be able to do that and doing it pretty effectively, so whereas there was a time when we were like, "More is better, more is better, more is better," at the end of the day, we need the right patients enrolling in the right trials, and that's what our team has been managing to.
We are not increasing, let's say, the backlog of undosed patients. That number is stable to diminishing slowly. Then maybe it'll pick up again as we get into phase three or pivotal expansion across the board.
Have you dosed any patients in the pivotal studies for myositis?
We expect to initiate the myositis pivotal arm of that program this year.
Okay. And to that point, though, not to parse things too much, but that's what we do. You said that you're sort of enrolling patients. All the initial cohorts have been enrolled, and you're now over-enrolling. You're not holding patients back. So does that suggest that you have sufficient demand for myositis that there's no need to sort of hold back to get to the, you know, ensure that the pivotal arm goes back?
We've had years of doing this. We're really comfortable, and the more data we present, the more we're seeing patients and physicians want to enroll a second, a third, a fourth patient. Because patient number one comes back, that was your worst patient, and you put them in, and they came back, and they're disease-free and they're drug-free, and it's now three months, six months, nine months.
What are you going to do? You're going to look at the next patient in line who you would have enrolled, and you're going to want to give them that gift of life back. That's how patients feel. We all, I as CEO, our team, investors, I think, nobody appreciates that autoimmune disease has taken a backseat to cancer for way too long. It's the other side of the equation.
These patients, if you know them, if you live with them, they suffer terribly. Not all, but those 20% who are the worst case of all of the diseases we are treating. Myositis, half of all the patients have moderate to severe disability on a standard disability scale. They have a threefold increased risk of death from cardiovascular disease and cancer. A third of them use a walking assist device.
Most of us don't even know anybody of those 80,000 patients. We hear myositis like, "Oh, so your muscles are weak. Big deal. Big deal. Life-changing big deal." That's what we eliminate. We hear it from the patients and the doctors. No, we don't have to hold patients back to enroll.
Okay. Just so you can keep it really short, because you did make a comment.
This is the hardest thing he's asked me to do all day.
You did make a comment about patients come in, they enroll, you take the blood, and then hang out for two weeks, and then they get reinfused.
Yeah.
How do you think about the competitive threat from, I think, Novartis has talked about like a two-day process?
Yeah.
And that's certainly something that other companies in the space have talked about, these sort of rapid manufacturing. How important do you think that is? Because in theory, I think about it, if I have comparable efficacy or I'm not differentiated in efficacy, I'd rather spend two days at a hotel waiting to get reinfused than two weeks.
Yeah, we agree. So let's be very clear about our terminology. Two-day manufacturing means instead of the usual seven to nine days of the month-long autologous turnaround time that is average, currently it's seven to nine days. They're taking the seven to nine down to two. They still have to do all of the quality assurance, quality control, evaluation of the cells before they go out the door.
They still have a three-week turnaround time instead of a one-month turnaround time, if I can use relative numbers. So it's not a two-day turnaround time. It's a two-day manufacturing process, which is but one element of a very long and complicated autologous processing effort. That's the first. The second, and I'm keeping it short, the second is we've interviewed or done research with over 600 physicians across all six of our indications.
They have told us the following things matter to them with autologous CAR T, and particularly with a Rese-cel profile that in our studies was described as being far less effective, far less safe than Rese-cel actually is. On the back of that, what they told us is the top priority is efficacy, measured by how deep is the response, how often do I see that response when I give it to 100 patients, is it 100 or is it not, and how durable is that response.
Efficacy is number one. Number two is safety. How much CRS, how frequently, how severe. How much ICANS, how frequently, how severe. Over 90% of the patients we treat have either no CRS or they have a little bit of fever. Over 90% of the patients we treat have no ICANS at all.
The third thing they care about is whether or not there's lymphodepletion. The fourth, fifth, sixth things are separated meaningfully from those top three. Do I need apheresis or not? And the turnaround time is the last in the list. How fast I can get my treatment is far less important than is it effective, is it safe, do I need lymphodepletion.
These are the things that matter. That's why we prioritized a no lymphodepletion approach over getting the blood test instead of apheresis to the clinic. And we're still working on that, but it's not as important to the doctors. So that's why we chose to do what we do. I hope that was fast enough.
That was fast, but I'm going to have to blow the whistle now. Thank you.