Welcome to Third Annual Healthcare Innovation Conference. My name is Yatin Suneja, one of the Senior Biotech Analysts here at Guggenheim. It is my pleasure to welcome our next presenting company, Cabaletta. We have a few executives from the company here with us. We have Steve Gavel, who is the Chief Commercialization Officer, Anup Marda, who is the Chief Financial Officer. We have Arun Das, who is the Chief Business Officer. Gentlemen, thank you so much for your time. I think you just came here from ACR, so I would love to sort of get a little bit of an update there. Perhaps maybe make some opening comments and tell us some of the learnings and the data that were presented at ACR, and then I have prepared a little Q&A, and then we will go into that.
That sounds great, Yatin. First of all, thanks for having us. It is a pleasure to be here. Just as a brief, very quick reminder for folks, we are Cabaletta, developing CAR T therapies for patients with autoimmune disease. That is what we have been since the founding of the company in 2018. Like you said, just coming off a really important medical meeting at ACR where we were able to showcase both safety and efficacy data across the portfolio of indications that rese-cel, our lead CD19 CAR T program, is being evaluated in. I think the summary of that data, and excited to go into more detail, is we are seeing, based on this data, the vision for rese-cel that we had four or five years ago come into reality and sharper focus.
Across the portfolio, the choices that we made years ago around a well-characterized routine manufacturing process, weight-based dosing, a 4-1BB co-stimulatory domain, a fully human CAR, these are the choices we made back in 2022, 2023, and the data that we have showcased, I think, are now highlighting what type of profile those choices yielded. From a safety perspective, we presented 70 patients' worth of data across a number of autoimmune diseases, all patients treated with the same single weight-based dose of rese-cel, and we see a low frequency of CRS, a low frequency of ICANS. 94% of patients have no CRS or grade 1 CRS, a fever. 96% of patients have no ICANS. There is no IEC-HS observed across any patient that has been treated, reported to date.
We think those choices are really crucial ones to help yield the profile we have that we think allows us to make CAR T a reality in the autoimmune space. On the efficacy side of things, we were able to present data across a number of different rheumatology conditions. Dermatomyositis, where at one year, patients who discontinued their immunomodulators prior to infusion of rese-cel at one year saw major or moderate TIS responses. Again, off all immunomodulators for the duration of follow-up. Most of those patients were also off steroids. In lupus nephritis, we were able to see 100% of patients who obtained a repeat kidney biopsy achieve DORIS remission at their latest follow-up visit, and these follow-ups were anywhere from six months to two years. Again, discontinuing immunomodulators before and staying off those immunomodulators, and again, either off steroids or on low-dose steroids.
In systemic sclerosis, we were able to see patients also followed out to one year, 70% of them hitting the very stringent ACR-CRISS 50 standard composite endpoint across a number of different domains. It is consistent and fairly reliable, the ability to discontinue patients off their immunomodulators, give them a single dose of rese-cel that is a weight-based infusion, and then see them allowed to stay off those medicines and oftentimes discontinue their steroids as well. It is a really exciting time. Thank you for asking.
Very good. Let's, I think there were like three key presentations, at least according to me. Maybe we can dive a little bit deeper into all these presentations. For the myositis study, obviously, there was the durability that was presented, but I think to me, what I saw was that not only your product is providing durability, but there is a depth because you were able to capture one additional patient. Just talk about the durability and depth of responses you are seeing with the product in myositis particularly, and how does that read through into the pivotal program that you're running?
Yeah. I think the most important connection between the phase I/II and the registrational program in myositis is, it is a very similar program. It is similar sites, the same dose of drug, similar patient characteristics from an inclusion/exclusion criteria that allow us to take that phase I/II data and have increasing confidence in the way that we've designed the registrational study. What we reported from the phase I/II data was the one-year outcomes of patients. Like you said, we saw actually one patient who at the week 16 time point had a temporary sort of blip in their total improvement score, but because that patient never received a dose of immunomodulators for the duration of follow-up, they continued to be followed and counted as a potential, and they could count as a potential responder in the analysis.
At one year, with that patient being off immunomodulators for the duration of follow-up, they actually achieved the endpoint that we would consider as being most important in this space, which is at least a moderate TIS response, again, while being off immunomodulators and either off steroids or on low-dose steroids. It really highlights the fact that the emerging data seem to show the potential for rese-cel to actually have deepening responses over time in patients who receive this one-time infusion.
Got it. I will come back to the LN and SSc, but let's conclude the myositis discussion because that's where the pivotal program is running, right? How is the enrollment there? What is the I think you updated the guidance in terms of when the data is going to be expected. Talk about that. What are your expectation? What will be actually disclosed? If you have to look at this phase I data, it seems like you really cleared the bar by wide margin, but just put all of that in perspective for us.
Yeah. For enrollment, let me turn it over to Anup, then back to me for the data. Anup, do you want to talk about enrollment?
Yeah, sure. In the last few weeks, Yatin, we've seen multiple patients enroll in our myositis pivotal study. We've seen the screening pipeline increase significantly as well. I think what you're alluding to, in the summertime, we did see a slowdown in the study, which we believe was caused by the adverse safety events, which other cell therapy players had. As soon as those kind of adverse events came to light, our Chief Medical Officer, David Chang, and his team reached out to all of our investigators, providing them with the information, clinical and safety, which Arun had mentioned earlier, on rese-cel, reminding them of kind of the weight-based dosing, the well-characterized manufacturing process, et cetera. We received significant feedback from them as well. We had good discussions with them, following our reach out to them.
Based on the uptick in enrollment that we see in the screening pipeline and the discussions we've had with the investigators, we moved our guidance to the first quarter of 2028 for BLA submission, and we feel good about that. The good news is we have the cash to get us to the first quarter of 2028 as well, and we extended our cash runway as well. That's kind of where we stand from an enrollment perspective. I will pass it back to Arun to answer the rest of your question.
Yeah. So on the data front, I think, and just reflecting on what we heard at ACR, I think it was fascinating because this year's ACR was really the first major meeting where I felt like there was a transition between CAR T is a novel modality that is showcasing some interesting data, to this class could be a real class of drugs for the rheumatology community to address patients with meaningful autoimmune disease. So the difference being the conversations around what patient should we be treating, how do you select the right patient to receive CAR T therapy, because the experience is growing. Even in our phase I/II study, we had investigators from multiple different sites enroll patients, treat patients, and we're seeing that enthusiasm, that experience really feed forward into what the registrational program looks like.
The similarities of the design from the phase I/II to the registrational, I think, are key in enabling our view that these outcomes that we're seeing in the phase I/II have a lot of There's a lot of relation potentially to the phase III study. Even, and I think this is worth mentioning, we recently had an FDA interaction where from that interaction, we're now planning to submit the phase I/II data, the one-year data of which we presented a couple days ago, but that phase I/II data in our BLA submission for myositis, so that it is able to potentially count for durability of response following a single dose of rese-cel. Those are patients whose data we may have two or three years worth of which by the time we submit the BLA.
Yeah.
Very important in our discussions with a number of different stakeholders.
Got it. How important is the juvenile myositis? What does that give you?
Yeah. I think first off, it is an important segment where the urgency to treat amongst physicians and caregivers is significant, and we are seeing that in the enrollment of the program across that phase I/II program. That is number one. Number two is the opportunity to include the juvenile myositis data in the myositis BLA application enables the potential for a priority review voucher, data pending. If juvenile myositis is included in our label, that opens up the opportunity for a priority review voucher, and we know based on recent activity in that space, that is a meaningful opportunity to continue to fund the company and fund operations based on what recent activity has been.
Got it. The priority review voucher, if needed, can be monetized, Anup, right?
That is right.
Got it. Okay. With regard to I might have more question, I will come back. With regard to the other two presentation, both on the LN and the SSc, just highlight, I think, especially the improvement in lung function, the magnitude that you were seeing. I do not think we have seen anything like that with any modality. Just touch on that a little bit. Where is that program? How is that going to move into the pivotal phase after myositis?
Yeah. The SSc registrational program has initiated, and it is with a focus on patients with interstitial lung disease and a primary endpoint that is measuring the change in percent predicted of forced vital capacity, FVC, which is an objective measurement of lung function. These are patients who, as assessed by really a community of rheumatologists, represent probably the most severe autoimmune rheumatic disease that exists today. These patients progress rapidly, and they can progress severely. CAR T can have an impact is something that we are seeing in the phase I/II study. In the patients that we reported out to one year, the average improvement in FVC improvement was 9% from infusion to one year out.
This is in a setting where the approved standard of care either lessens the decline of lung function over time or at best stabilizes that lung function in patients with severe ILD. The fact that we're seeing meaningful improvements in lung function and the fact that those are being seen in patients who have discontinued their immunomodulators, who have discontinued their antifibrotic drugs, who are oftentimes on no steroids or at a minimum on those low-dose steroids, is really something that, to your point, is not seen in the community. That's where we see, again, the enthusiasm and urgency to treat in that population is something we're very focused on and excited to have that trial initiated and up and running now.
Got it. With regard to the lupus, obviously, it was interesting, almost 100% maintenance of, let's say, responses. Where is the lupus program from next step perspective? Are you going to wait for, let's say, no preconditioning data before you decide?
Yeah. I just want to focus for maybe 30 seconds on the importance of that poster, because it is really a testament to David Chang, our Chief Medical Officer that Anup Marda mentioned earlier, and his team in leading a potential redefinition of how clinical responses are measured in this space. That poster, which showed 100% of patients achieving DORIS remission based on this repeat kidney biopsy, is potentially changing clinical practice. What we are seeing is that CAR T therapy can help resolve disease activity in the kidney. Even if you have some residual chronic damage that causes proteinuria, the biopsies are showing either no disease activity or very limited disease activity, indicating that these patients may be getting really a sort of full healing from what rese-cel is able to do. Now, I say that because I think it's an important testament to sort of what's going on.
In terms of next steps, you are exactly right. We are currently evaluating the PC-free approach in lupus, and in the first half of next year, we plan to give a go-forward kind of direction on the PC-free program, and inclusive in that, as it relates to indications, a plan for what we would do in lupus. That is something that we are waiting for data. We are collecting data, waiting for it to emerge, and then having a go-forward plan in the first half of next year.
Got it. Very helpful. I think we captured a lot on the efficacy side. Undoubtedly, I think it is remarkable efficacy. Let us focus a little bit on the safety side. I think Anup Marda was commenting a little bit on that, but love to understand, because when I read your press release over the last, let us say, few months, I think there is a subtle distinction you are trying to make where the safety stands out, differentiated. Just talk a little bit about that. What is the perception in the community? Obviously, the setback from Bristol and Novartis didn't help the space. What are you doing to make sure your product in itself is completely differentiated or is viewed differently than the rest of the class?
It is an astute observation, I would say, number one. I would focus ourselves squarely on rese-cel, the data, and the choices that we have made. I think what we are seeing is that, and those choices I referenced at the beginning of the presentation around well-characterized routine manufacturing process, weight-based dosing, fully human CAR, choice of co-stimulatory domain. We designed, we implemented those choices because we thought it would optimize the benefit-risk in this population. From a safety perspective, what we are seeing is that the vast majority of our patients do not see CRS. 90%, 94% of them see no CRS or grade 1. A similar percentage see no ICANS. There is no IEC-HS across the entire set of treated patients.
More importantly, and that is important, but we also have established a foundation of translational data led by Gwen Binder, our President of Science and Technology, Samik Basu, our Chief Scientific Officer, where we are beginning to understand why rese-cel is behaving the way that it is behaving. So, a combination of cytokine data that we measure pre and post-infusion, understanding the PK/PD of rese-cel in detail, and understanding potential differences across individual autoimmune diseases that may help guide our development choices in each disease with rese-cel. These are all really important learnings and insights that we have gathered to help inform, first, to help understand why we are seeing the safety profile we are seeing, and potentially what choices we make going forward.
Great. Steve, I would love to hear from you a little bit, because these guys are going to develop it and then hand it over to you to sort of market it.
Exactly.
How has your perception sort of evolved since you joined, both on the efficacy side, the safety side, and the overall profile of rese-cel? What do you make about the safety updates that we have seen in the field so far?
Yeah, thanks, and thanks for being with me this morning. A couple things, I guess. When I started a year or so ago, our tox profile always seemed to be a key differentiator amongst the class. We were continuing to monitor that, and then over time, as you mentioned, there were some AEs recently with our competition, and it seems like we've been obviously continued to differentiate on the toxicity side. What I was most interested, quite frankly, in is whether or not durability would continue forward.
Yeah.
Right? Because you could have a safe drug, but if it doesn't work, you have a different issue on your hands. What's so nice to start to see read out now is the durability data, because until you have it's really just conceptually something you hope to get there. I think the thing for me is when we were doing a lot of our initial research or primary research with the insurers and asking them to respond back on conceptual TPPs, one of the things, as you can imagine, they wanted obviously a safe product, but also they wanted to see a product that would at least cross over to one year plus in terms of durability. Now you're seeing that. Now this fictitious potential product now is actually coming to reality now. From that perspective, that's very exciting.
The cherry on top as relates to myositis, though, is the juvenile population, because if you can imagine these young children that have now this awful diagnosis, from a payer perspective, you could only imagine not only is it a great thing for the patient and families. But when you monetize the impact that these products have of the lifetime of a child, it's substantial. So that has changed a lot because in the early going when I was here, juvenile was kind of conceptually something that we were hoping for. That's now coming more into view, and from the payer perspective, that's even a bigger value proposition for us.
Got it. Got it. Thank you for that. In terms of the commercial opportunity and the prep work that you're doing for myositis, could you just maybe put that in perspective?
Sure.
What sort of payer engagement, how you think about the community setting adoption?
Yeah.
And all that stuff?
Yeah. Given that we, in my mind, how I'm viewing this route right now is you potentially have three cohorts of patients coming online. You've got adult DM, you have a juvenile population in myositis, conceptually very different populations, and obviously scleroderma, which one we're very excited about given the unmet need there. We're looking at from a commercial perspective across that view of three dimensions as opposed to just your initial launch in terms of how we go out and address the market. Going out of the gate in dermatomyositis, because it's a very different population than per se a scleroderma, we're being very strategic in terms of our site selection.
We've done a fairly thorough analysis about juvenile and adult in terms of maximizing where the patients are located, and we're being very mindful of where we site certify to ensure that they're within a commutable radius to our patient populations, because these patients are relatively healthy. One of the things, the big difference, one of the big differences here is that this patient population is highly mobile. Also back to the value prop for this patient population, it's quite extended. Again, we're being very deliberate. We're not going to oversize initially, but again, we're thinking in terms of the end game or at least mid-game being how do we properly size now to accommodate ultimately a scleroderma launch in not the too distant future. We didn't even get into that concept, but it's not that far off from when we actually launch in DM.
Got it. Then just, like, how does the safety profile translate into outpatient-
Yeah.
Setting dosing?
Great question. Thank you.
What percentage?
Yeah, yeah. Arun did a really great job of going through the numbers with you. The CRS onset and severity and frequency is unprecedented in terms of CAR T therapies, especially as related to some of the CAR Ts I worked on prior to coming to Cabaletta Bio. So that opens up the door significantly. Now, we have to be mindful, however, we're dealing with obviously some large impact events that just occurred in this class with competitor products here. So the marketplace, rightfully so, has come back in terms of let's wait and see now, rightfully so.
But it's our intention, and it's actually evidenced in a registration study in terms of the number of patients that have enrolled and also being treated in the outpatient setting in a registrational trial. The beauty of that is that clearly, those events have not deterred providers from using rese-cel in the outpatient setting as part of a registration study.
Got it. Then maybe just, like, short comment if you can make. Can you maybe help our audience understand the nuance between the reimbursement in the I&I setting versus the oncology setting? Are there certain nuances which is maybe more beneficial or more advantageous?
A couple quick ones. The obvious is the patient T-cell viability. When you're dealing with cancer patients in late-stage myeloma, their T-cells don't obviously manufacture very quickly or well. Out-of-spec rates exploding all over the place, it's evidenced all over the place. You don't see that here in autoimmunity. These patients are healthy, so we have a much better manufacturing success rate than you see historically. Then the other thing, you mentioned outpatient. CARVYKTI, when I was leaving, we were running about 40% of all new patient infusions were given in outpatient clinics and hospitals.
We are seeing that now in our clinical trials with rese-cel running at a quicker trajectory than what we were seeing with CARVYKTI. So I see a rapid adoption in terms of outpatient, but by the same token, we're going to do this safely. We're not going to push it too hard. We're going to do it obviously with the guidance of our investigational sites and sites that we've certified. But over time, for sure, there's definitely a strong movement to get that in the clinic.
Got it. On the PC-free preconditioning free regimen, could you maybe give us an update there? I think you're going to provide more like a wholesome update next year. What would that entail? How are you prioritizing it across different indications?
Yeah. We are currently in the next higher dose cohort of PC-free dosing and evaluation in pemphigus and in lupus. We have recently opened up a PC-free prioritization in the myasthenia gravis study. We have three indications right now that are each evaluating various doses of the PC-free rese-cel. For us, it's important to gather a substantive data set, both in terms of number of patients and length of follow-up, to be able to gather and provide a go-forward direction for the program.
What I think we don't want to do is provide an incremental data set on a few patients that doesn't necessarily provide the guidance for what decision we're making or why we're making that decision. In the first half of next year, we expect to have a substantive set of data and amount of follow-up to be able to provide that go-forward direction across the entire program.
Got it. Very good. Very helpful. Anup, question for you. How is the financial health of the company? What does the cash runway look like? How are you capitalized?
Yeah. We just reported earnings a couple of weeks ago, $300 million of cash. That takes us into the first quarter of 2028 at this point in time, which is in line with the BLA submission timeline we provided.
Got it.
Look, the stock price is where it is right now, right? Let's acknowledge that. I think we just came out of ACR and feel very excited. We've gone through these kind of cycles before, and at this point in time, we have data, we have safety, we have efficacy. We've got a very supportive investor base. I think when situations like this happen, like what happened in the summertime, I think how companies handle themselves is really important. David Chang, our Chief Medical Officer, he's been doing this for more than 30 years. I think the interactions that he had and the approach he took to help investigators understand rese-cel and our clinical and safety profile, I think has and will continue to be helpful for investigators, patients, et cetera, in the community.
Got it. Got it. Yeah. I mean, I think the next 12 months is going to be pretty busy for you guys, right? Obviously, pivotal data is what everybody's going to be keying on, but PC-free update and all these pivotal studies ongoing, commercial perhaps, so it's going to be pretty significant. I agree with you. I think on the efficacy side, no doubt, right? These are truly remarkable efficacy profile that we're seeing. The durability is pretty good. Its safety is what I think the field needs to get comfortable on. I'm glad that you were able to do what you were able to do and accelerate the enrollment. Well, thank you, gentlemen.
Thank you.
Really appreciate it.
We appreciate it.