Conference Transcript - RNAC 2026-05-19

Mitchell Kapoor, Analyst — H.C. Wainwright

Hello, everyone. My name is Mitchell Kapoor. I'm a senior biotech analyst at H.C. Wainwright. It is my pleasure to welcome you all to the Cartesian Fireside Chat, and I have the great privilege of introducing Carson Bruin, the CEO of Cartesian. Carson, thank you so much for joining us.

Carsten Brunn, CEO

Thanks, Mitch, for having me.

Mitchell Kapoor, Analyst — H.C. Wainwright

So maybe for those in the room who are not up to speed on the Cartesian story, you could provide a brief overview of the current pipeline and the current efforts for Cartesian.

Carsten Brunn, CEO

yeah so thanks for the opportunity so we were an mrna carty company focused exclusively on autoimmune disease late-stage clinical phase three in my senior gravis we had strong data in the face to be which was the first placebo-controlled study of a cell therapy in mg which was published in nature medicine we saw deep and durable responses and we in the phase three taking some learnings from the face to be moved the endpoint to four months from three months, tightened the patient population, and that's currently enrolling in our main effort. We also have a phase two in adult myositis, dermatomyositis, and endosynthesase syndrome, which is currently enrolling. And then we have the third study is a juvenile dermatomyositis study, and we do have pediatric rare disease designation, which, if successful, could lead to a PRV, which just got renewed as a program by Congress. So I think that's interesting. Fundamentally, I think, from an approach, we give mRNA CAR-T, so we don't have to do lymphodepletion up front. We give multiple therapeutic doses, six weekly infusions. We don't use an integrating vector, so this can be done in an outpatient setting. You don't have the risk of secondary malignancies. We don't have to follow patients for 15 years. And then also from a safety profile, we haven't seen any CRS or ICANs. And the last fact is that we're targeting BCMA, actually. A lot of the DNA CARTs actually target CD19. And there's a good, obviously, reason for that as well. But we think BCMA is a more precision-targeted approach. BCMA is expressed on the cells that actually produce the pathogenic antibodies, bodies, the long-lived plasma cells. So you get the root cause of the disease. And then there's a second mechanism. It's also expressed on plasma dendritic cells, which are non-B cell lineage. They're myelot lineage. And PDCs play a key role in interferon-1 responses, so early inflammatory responses. So it's a dual mechanism of action. And you don't really touch the B cells by targeting BCMA.

Mitchell Kapoor, Analyst — H.C. Wainwright

Great. And so could you just maybe set the stage with explaining a little bit about the Aurora trial and the design and what you can say about enrollment cadence now that we're coming up on this mid-2027 runway window that funds through this catalyst. Are you still comfortable with that timeline and just help us on how enrollment's been going?

Carsten Brunn, CEO

Yeah, so the Aurora study, as I said, is a phase three placebo-controlled, 100-patient study, one-to-one randomized. the primary endpoint is MGA reduction of three points at months four versus placebo. So we've taken some learnings from the phase 2B where the endpoint was at months three, and we've tightened the patient population to ACHR-positive patients, and it's driven that seronegative patients, you see a strong placebo response, you have more noise in the response. So most MGA players actually have focused on ACHR-positive patients. It's the majority of patients. It's about 85% of patients. It's a global study, US, Canada, and Europe. And we have done this under an SPA, a special protocol assessment, which is always a certain risk when you engage with FDA around this. This can backfire, can be a long negotiation. They don't like your protocol, but I'd rather have the discussion early on. So we did this as a de-risking. Since we're running a single study only, And this is a very short, luckily, conversation with FDA. So we're running under an SPA, which means they've reviewed the SAP, the protocol, and basically agreed the study is positive. We can file a BLA with a single study. So from that perspective, it is de-risked. Enrollment is progressing nicely. We have guided that the study will read out before we run out of cash and with some cash to spare. We have cash to the mid-27, so you can do the math. And we'll likely guide in the near future, give more details around timing. But the study is enrolling well. All the sites are up and running. There's good patient demand. And what really helps are two things. This is given an outpatient setting, so no lymphodepletion up front. I think that's a key difference. And also the placebo patients, actually, they get aphorised and they get product-made. they're infused sham infusion but then after the endpoint they have an opportunity to be rolled over to active actually so every patient has a chance to be on active which is not the case in all phase three studies actually so we you know we had good interest from both the physician side and also obviously

Mitchell Kapoor, Analyst — H.C. Wainwright

patients that's wonderful so the biggest question in the room is when do we get data no so I mean I guess on to what you can see around it if you're if you'll answer it that's great but you know I guess to keep it within the mid 2027 runway how confident are you you know are you confident with the enrollment pace or do you need to increase screening throughput randomization pace manufacturing anything that you know helps us get to timing yeah I mean I all

Carsten Brunn, CEO

can say is that we are confident that we'll deliver the study on time. The one thing I can say is we actually have increased manufacturing output, which I think is a positive, that the study is enrolling well and patients are pulling through. So we feel very confident. And obviously it's a process. We started a study last year in May, and there was a time when the government and basically cut NIH funding. So a lot of sites were looking for additional funding. So it was a bit longer negotiations around funding. And then we had a lot of new sites in Europe and they take longer from a regulatory perspective. The trade-off is, interestingly enough, in Europe, MG is treated more in tertiary centers. So it's much more concentrated. So you actually have more patients coming through. So it's a trade-off. So there's definitely good learnings throughout. But I think there was no real surprises. I mean, there's always surprise when you run a phase three, but then not really, actually. I think the NIH funding was probably the biggest kind of hurdle where I said, hey, we've got to keep this in budget. Excellent.

Mitchell Kapoor, Analyst — H.C. Wainwright

Okay, great. And can you remind us if you'll wait until one-year durability to file for approval or you'll file on the four-month efficacy? I guess just the nature of the importance of the durability kind of weighs in on different aspects of the bar for what's meaningful. So maybe you can help us.

Carsten Brunn, CEO

Yeah, no, it's a good question. but there's a very clear answer. So we'll file with the four months data. That's the primary endpoint. But you're right, the 12 months data is important, especially for the payer component, for the payer negotiations. So the plan is to file four months and then do a supplemental BLA once we have the 12 months data. We'll likely have the 12 months data, which is controlled data from the phase 2B in the clinical trial section of the initial approval. So we'll have some data already on the label, but we definitely need it for pair negotiations for sure.

Mitchell Kapoor, Analyst — H.C. Wainwright

Okay, and when investors think about the bar for approval versus the bar for that 12-month update, can you help us frame both of those readouts to understand what we should look for?

Carsten Brunn, CEO

Yeah, I think the one piece that should give investors peace of mind is the consistency of our data actually throughout. And usually the way this goes is you have good phase 2A data, then phase 2B doesn't look as good, and then phase 3 looks a bit worse. We actually saw that our phase 2B data was slightly better than our phase 2A data in a controlled setting. So I think that's very encouraging. So it's been very consistent, what we have seen. And then we've seen, because we got that question when we released the four months data of the phase 2B, we said, oh, it looks great, but we don't know whether that's durable or not. And we have seen this is actually very durable. So, and, you know, I think there's no reason why this shouldn't be the case. And we do have, I think what gives us confidence is that we do have placebo-controlled data from a controlled study from the phase 2B, which is published, so which we can use.

Mitchell Kapoor, Analyst — H.C. Wainwright

Okay. And is there a particular result or bar that you would be looking for that would be clearly approvable? And then, I guess, related, but, you know, durability becomes a component, you know, strong enough to drive adoption.

Carsten Brunn, CEO

Yeah. Yeah. It's a good question. So, I mean, people always look for efficacy, of course, but we've done a lot of market research. Most physicians don't know the MGA reductions of the F-ser antagonist or the complement inhibitors, which is interesting. Then they confuse if it's placebo-adjusted or not. So you get all kind of numbers. Actually, the most important driver of adoption is probably the durability of response. The fact that, because, I mean, the F-19 have been very successful. I mean, the stuff works. You get good reduction, but it's very transient. I mean, it's a symptom reduction. And what physicians haven't seen before is that you give a single course of therapy, six weekly infusions, and you get maintained that response over 12 months. I think that's really the differentiation that we bring to the table to have that durability of response. And I think that's what gets physicians excited. And specifically, if you look at what's called MSE, minimum syndrome expression, we saw in the overall patient population, it was 33% at MSE between months 6 and 12. And then the apple-to-apple comparison to the FCR antagonist in the patients with our prior biologic, actually 57% of patients had immunocytic expression between months 6 and 12. And that's transformational if you ask a physician. And, of course, I mean, I think the MGA detection we see are strong. But to our surprise, actually, it's not what really going to drive adoption. It's that durability of response. Because if you're a patient, you're constantly seeing a neurologist because you need new scripts, you're fighting with the pairs to get another course of therapy approved. With DECARD-8, if the phase three is successful, you have a single course of therapy and you're good for at least a year and probably longer. Yeah, that's great.

Mitchell Kapoor, Analyst — H.C. Wainwright

That's great. And so when we think about the placebo response in MG, can you help contextualize how Aurora mitigates that, but also what our expectation should be to level set? Is part of the risk mitigation on the baseline severity you're enrolling, background therapy, randomization, anything that can help us understand how to evaluate placebo response.

Carsten Brunn, CEO

Yeah, I mean, the placebo response has been a real challenge for MG trials, and it's interesting, actually, over the years, there's more and more of a placebo response, actually, and I'm not sure everybody has a really good explanation for that. One reason, obviously, it is a physician-administered PRO, it's a patient-reported outcome, so, and the difference of the FCR antagonist, you chronically also give placebo in the study, whereas in our phase three, you basically get six weekly infusions, sham infusions, and then you're off therapy. And so one of the things specifically we have done is we have taken the seronegative patients out because they have been the sole driver of the placebo response. And that's consistent with pretty much all MG trials that they have focused on ACEs are positive patients, you get less of a placebo response. The other key difference is that we pushed out the endpoint from month three to month four. So if you're a patient on placebo, you get the last infusion on week six, and then we measure basically the parameters at month four, and you're not getting any medication. And in the phase two, we have seen that at month three, you're almost back at baseline. And we think by pushing out to months four, you're definitely going to be back at baseline. So you have a huge separation versus active arm. So I think between pushing out to months four and focusing on ACHR-positive patients, we pretty much mitigate the placebo risk.

Mitchell Kapoor, Analyst — H.C. Wainwright

And then at month four, placebo crosses over, right?

Carsten Brunn, CEO

Correct.

Mitchell Kapoor, Analyst — H.C. Wainwright

So then at the 12-month update, you'll have the residual time for the placebo group. So you might be able to see stronger Delta between the placebo

Carsten Brunn, CEO

Yeah, the crossover actually is not a good group to look at And the regulars don't really care about that that much Because it's an artificial you'd never encounter in real life actually Right, so it's it's it's not I think the more the more important piece is going to be The durability of the active arm I think to look at I mean that's that's I think Obviously the prime endpoint is the most important for approvability but then I think for commercial uptake it's the 12 months data.

Mitchell Kapoor, Analyst — H.C. Wainwright

Okay, great. Yeah, and then so based on your discussion with payers, what's kind of the thing that they're looking at most? I think you'd mentioned the durability will be more important, so the month four will be interesting, but they care more about maybe the 12-month follow-up. And then reduction in chronic, you know, FCRN or complement use, the outpatient redosing flexibility, what do they care about? Can you like rank some of those things?

Carsten Brunn, CEO

They care about how much does it cost them for a year, right? I mean, payers always think in one-year increments. And so we had initial payer discussions, and they see their profile as very favorable because you have six weekly infusions, and then you have no further cost, actually, for the payer. You don't have the consistent going back to the neurologist, getting new scripts. and obviously they would like to see reduction in in other medications as well but just showing them the profile of deep and doable responses I think that's that's differentiated pairs don't look beyond months 12 if you go further I think redosability is like next year's problem or in two years problem so that I think hasn't been as strong as a driver I think that the durability is

Mitchell Kapoor, Analyst — H.C. Wainwright

what they're looking for. So I would imagine like the case would be, you know, the payer could could look at a therapy that's durable for one year or longer and they say this is a chance to not be on FCRNs for a year or more. So how, you know, whenever they typically don't look past 12 months, I guess it seems like in this scenario they might want to keep, you know, that in mind for pricing potential. I don't know, you know, can you help relate those? Well, yeah, I mean,

Carsten Brunn, CEO

I mean, one thing is that, you know, the EFSA have been successful, but payers don't actively manage their class necessarily. I mean, it's still pretty small in the biggest scheme of things, right? So I don't think that's a key driver initially. I think they look, of course, you know, you get fewer hospitalizations and other cost savings potentially. But I don't think, first of all, I don't think we're going to have a prior auth situation, for example.

Mitchell Kapoor, Analyst — H.C. Wainwright

Okay, okay, very helpful. And then, you know, your RNA-based CAR-T design has a lot of advantages. DNA-based CAR-T is also on the horizon. Can you walk us through some of the differentiations for folks about mRNA CAR-Ts, the redosability, et cetera?

Carsten Brunn, CEO

Yeah, yeah, so I think, I mean, we almost see ourselves competing with the biologics, actually, not the DNA CAR-Ts. The DNA CARTs are basically, you know, cancer drugs being repurposed, and they come with a certain risk-benefit profile. And I think, you know, you go, if you kind of put yourself in the patient perspective, or even the physician, a neurologist can do cell therapy, traditional cell therapy. This, you know, DNA CARTs have to be given in an inpatient setting by a cell therapy center. So you give chemotherapy up front to wipe out the immune system, which comes with risk, cytopenia and other things. And then you give a course of therapy. The cells proliferate, don't know when to stop. So you have the risk of CRS and ICANs. And obviously they're trying to control the dose, but it's a reality that is pretty complex to manage. So by giving that safety profile, it's more of a last line of therapy. And specifically, I think in MG, there's very few patients that actually are ending up inpatient. There are some who have a myosthenic crisis, but with so many oral therapies now also making their way into this field, I think there's less patients really in crisis. I think there are other indications like lupus nephritis. There are frequent flyers in the hospital. I think there you can have a discussion, does it make sense to consider DNA CAR-T, whereas we want to be seen much earlier in the treatment decision for a neurologist, because a neurologist can use DECARD-8 in their practice as long as they have an infusion chair, so they can give DECARD-8. So we would be more competing with the F-serum antagonist with the complement inhibitors rather than the DNA CAR-Ts. Obviously, we get grouped CAR-T, mRNA or DNA. So, I mean, we wish all the DNA-Karty companies well and the LNG&E companies. I think it's good for cell therapy because I think many investors group cell therapy as one bucket. But I think from a competitive play, especially in MG, we see more the FCR antagonist kind of as our competition, if you like, or we're competing for patients with those groups.

Mitchell Kapoor, Analyst — H.C. Wainwright

Okay. And one of the things you mentioned stood out to me that, you know, as long as a neurologist has an infusion chair, they can administer Descartes. How uncommon is it for a neurologist to not have an infusion chair? Is that something that's quite standard?

Carsten Brunn, CEO

Yeah, I mean, not every neurologist has that. But we would target specifically neurologists that actually administer, you know, biologics. So you target – the nice thing about MG is it's a well-defined physician group. It's about 2,000 neurologists. And out of those, probably you have 10%, 20% drive early adoption. It's a very focused launch, actually. They're going to be familiar with the business model of, you know, they basically want to fill their chairs. They have infusion centers. And the infusion time is very similar to a biologic. It's about a two-hour procedure altogether. You come in, you get premedicated, Benatryl and Tylenol. You get the infusion. It's about half an hour. you stay for an hour observation like a biologic and you go home so it's it's it's going to be very similar from a the only difference is you you have to plan in one apheresis step in before where they have to come in um for about a three hour apheresis but other than that it's it's it's

Mitchell Kapoor, Analyst — H.C. Wainwright

a model they're very familiar with actually okay wonderful um i wanted to touch on redosing uh that that has been an advantage for mrna carty story um you know maybe familiarize the audience with that ability, but also kind of where you guys stand today with how many patients you've redosed. At one point, you had shared a few patients. Anything else you can provide on how those patients continue with follow-up or any additional patients you've redosed, the ability to see redosing data in the future, et cetera?

Carsten Brunn, CEO

Yeah, I mean, one of the advantages of mRNA is you can redose it. So you don't use an integrating vector. It's transient by design, so you can redose. We've done this in a number of patients now. We have three patients that we've published on. They're from the Phase 2 A study. Two patients had to be redosed after months 12 and one after 18. And what's interesting what we see actually, very different to cancer, the second time around we see even deeper and more doable responses. So in two out of the patients, they were basically in minimum symptom expression again for longer than before. I think the longest is out now over 12 months. and then the third patients had an MGA reduction at months 12 of 9-point reduction. And I think it makes sense if you look at the biology. Unlike cancer, we have melignant cells. They come back with a fury. You have a finite number of cells that you go after by targeting an autoimmune disease. We go after the long-lived plasma cell from the bone marrow, and whatever you didn't hit the first time around, you get with the second course of therapy. It'll be interesting to see. And when we started out, we thought maybe this is an annual therapy. It looks like this is not. You know, we have patients in the phase 2A that are in year 3 now with a single course of therapy. And so we'll see what, you know, the real treatment paradigm will be, but we don't think it's going to be a chronic therapy every year. And for some, it's, you know, they're done with one or two treatment cycles.

Mitchell Kapoor, Analyst — H.C. Wainwright

What do you need to do from a regulatory perspective to get a second treatment cycle, you know, I guess, as standard protocol?

Carsten Brunn, CEO

Yeah, I mean, I think initially we probably don't need it. I don't think the FCR antagonists have a redosing label, actually. So I think, you know, if you basically fall into the initial treatment criteria of MGL over 6, you'll be eligible. It'd be, I think, down the line, more of a payer discussion probably. Understood.

Mitchell Kapoor, Analyst — H.C. Wainwright

But so on that, I guess, dynamic with payer pricing, et cetera, COGS has been a lever for you all that you had mentioned. So can you help educate the audience about, you know, how you can potentially have a couple of doses within 1A pheresis? us what it looks like from a COG standpoint, and how that might translate into a pricing advantage too.

Carsten Brunn, CEO

Yeah, so it's, you know, when you hear DNA Cartier, you think high price, and that price is driven, the cost is driven by the use of lentil vial vector. That's expensive, so what DNA Cartier manufacturing does, the A4Es, they transfect the cells right away with lentil vial vector, and then it's, you basically give a cell a viral infection, so they don't go that well. We A4Es, we grow the cells into the billions, and then we use electroporation to introduce the mRNA at the end. So that's significantly lower cost. And then we also have our own manufacturing site, actually. So we control. We're not competing with anyone. I think that's the other advantages. We haven't given hard guidance on cost of goods, but I think we're guiding investors more to think these are more biologic-like gross margins than a DNA Carti from an overall cost perspective.

Mitchell Kapoor, Analyst — H.C. Wainwright

A lot is looking like more biologics versus Cartis.

Carsten Brunn, CEO

At least in MG, it does.

Mitchell Kapoor, Analyst — H.C. Wainwright

Yeah, interesting. Great, so maybe finally if you could just give us a preview of the 2026 and 2027 for Cartesian, kind of the upcoming catalyst, the look ahead for the company, and anything we didn't touch upon today that you think might be relevant for folks in the room.

Carsten Brunn, CEO

Yeah, I think the biggest catalyst for us is to face three readout in MG. I think that's the biggest commercial opportunity. We have real data. It's a real indication. I think people underestimate the unmet need in the marketplace for a therapy with such We'll have data from our phase two Triton study in dermatomyositis. I think that's going to be interesting as well. It's a large opportunity, and we'll have data on JDM within cash runway. But I think the biggest catalyst is MG. And I think the other maybe bit of a sleeper still is, and we've kind of started guiding around this around J.P. Morgan, is that we have a number of MTAs with companies that have in vivo delivery systems because we use mRNA payloads, and they're autologous right now, but they can be used in vivo as well. I think most of the autoimmune approaches in vivo use mRNA, and we have two proven payloads. And there are a lot of LNP companies out there, actually. So we have some – it's early work, but obviously it's a hot field. I think it's still years out. I mean, it's not a direct competition, but it's probably the next wave. Like, how do you carry those benefits from autologous into an easier manufacturer, from a manufacturability, and how do you reach more patients? Because, you know, autologous manufacturing, you can't scale up. You have to scale out. So it's patient by patient. So there's an advantage for in vivo just to reach larger patient populations.

Mitchell Kapoor, Analyst — H.C. Wainwright

Thank you so much, Carson. Really appreciate your time today. Thank you to the Cartesian team. And thanks to all of the investors in the room for joining this fireside chat.