CAR-T Topic Panel EULAR 2026 Save

You're listening to a RheumNow podcast coming to you from London, and you are '20 26. Enjoy. Hello, everyone. Welcome to RheumNow's panel on CAR T cell and cellular depletion therapies. This is a special session post ULR twenty twenty six in London, where we were at last week, looking at all the latest and greatest in rheumatology research and drug development.

It was a busy week. This panel of experts were out there looking at this category to see what was new and this is a hot new area. So let's get into it. We'll do two rounds of our favorite presentations. I'm Jack Cush from Dallas, Texas.

Janet?

Janet Pope, London, Ontario, Canada.

Youse.

Hello, Doctor. Youse Yousef from Leeds, United Kingdom.

And Al.

Al Kim, St. Louis, Missouri.

Okay. Let's get into it. Let's begin with, Youssef. What's what was your favorite from the meeting?

Yeah. So one of my favorite, is post post '79. So this is about allogeneic CAR T therapy. So the product is from Fit Therapeutics, FT819. The background of this is that we can improve the scalability of the CAR T therapy.

Also, you can reduce the manufacturing time from the autologous and also reduce costs. In the development of this FT819, they do have two regimens. One is regimen A and also regimen B. The difference between the two regimens, the regimen B doesn't have any conditioning. In the regimen A, which is the one that presented in the poster, there are also two conditioning that they compare.

One is using the low dose cyclophosphamide and another one is using bendamustine. So in terms of the development, were looking into various connective tissue disease, including lupus, myositis, scleroderma and vasculitis. But in the poster that they presented, only sixteen patients with SLE. These patients are severe refractory and had lupus nephritis, and some of them didn't. The longest follow-up that they did have is up to twenty four weeks.

In this study, in terms of the condition, so what they could see was if you use the bendamustine, they tend to have a more rapid B cell depletion and tend to have more rapid clinical efficacy compared to the cyclophosphamide. In terms of the efficacy, almost all patients responded, and the safety profile looks good as well. So there were only four patients out of 16 who had CRS two or less. So no above that, no icons. And importantly, with the allogeneic, there is no evidence of graft versus host disease in this up to two years follow-up.

And as well, there is no hypogammal globinemia. So I think this is really interesting to see that by using low conditioning with bendamustine, we do see favorable efficacy and safety. And it'll be interesting in the next conference, if they could present larger number using the no conditioning in a regimen.

Yeah, there are so many aspects to the initiation and the conduct of these trials that, we forget that these early phase trials are more about safety than they are about efficacy. And so you mentioned the acronyms ICANS and CRS. Al, do you wanna address those as major safety issues in these trials?

Yeah, sure. So I think that the experience from oncology has clearly shown us that cytokine release syndrome or immune cell associated neurotoxicity syndrome, CRS and ICANS respectively, are the main reasons why people have to be hospitalized for these therapies, which dramatically increase costs. These are very easily treatable conditions if they're recognized early, right? But they pose major toxicity if not recognized early. In fact, they can lead to mortality, particularly ICANN.

So I think that these are really important proof of principles generally that they are occurring with less frequency and less severity in autoimmune patients compared to oncology patients, which is encouraging.

Yeah, and I like that the allogeneic approach seems to be very popular here. It's got advantages. And then, you know, use of conditioning is sort of like the do we or don't we, and it's sort of like me standing in front of the mirror before I go out on Friday night about what I'm going to wear. But there needs to be some clear choices about that. And I think that this particular data was good.

Anybody else have a take on the study? Al, you, I think you were also interested in this.

Yeah. So I give Fate a lot of credit for doing several different things with this trial that are unusual. This modified reduced lymphodepletion, no one else is doing that, including the no lymphodepletion. Of note, they did present that data a week ago at ASGCT in Boston, and they showed three out of three got SRI4 and only two out of three got LDAS. I think what you were seeing with this pattern, both the regimen A and regimen B is not as good as full lymphodepletion for lupus.

And I think this is an interesting precedent that they're starting to set up. But the other companies can't show that because they haven't taken the chance to do something like a reduced lymphodepletion therapy.

And Janet, what are you looking for as far as outcomes in these studies? Are you looking just to meet an endpoint or are you looking for something superlative?

Well, I mean, we're always looking, as you said earlier, for safety, but I think we're really looking for not just short term benefit, but I think we're looking for long term immune, true immune reset. I don't think people are going to be in remission forever, but drug free remission or getting to doris remission I think should be an outcome, at least in lupus trials. So I'm looking for something beyond what maybe the T cell engagers might promise us.

Use last word on this, where do the authors think they're going to go with this?

Yeah, so I think they're going to expand the numbers for that regimen B with no conditioning. And after that, I think they are going to go for phase two and B with comparator groups.

Interesting. Al, what's your favorite?

Yeah, so it's very closely related to users poster. It's POS0694. It is describing an autologous CAR T, that's a CD19 BCMA dual targeting in lupus and lupus nephritis called ICG-three eighteen. The targeting aspect is not that interesting actually, and the autologous is obviously not that interesting, but they also chose a limited lymphodepletion therapy, using cyclophosphamide, no fludarabine. As you just talked about, the efficacy is not as good as if you do a full lymphodepletion.

But what's unique about this particular CAR T product is that it's also armored, I. E. It carries additional payload and it encodes actually an IL-fifteen with an IL-fifteen receptor alpha chain that allows it to make its own IL-fifteen and use it on the same cell. IL-fifteen is important because it's one of the two cytokines that allows for CAR T cells to expand and survive once they are delivered into a body. And that's the reason why we have to do lymphodepletion in the first place because if there are too many T cells, there's too much competition for IL-fifteen.

So this mitigates this in some ways by being able to supply its own IL-fifteen. So here they took 10 patients with lupus nephritis. And I think what's fascinating about this is the fact that they had nine out of ten that had doris remission, which is quite remarkable. There was CRS, nine out of ten of them had CRS, but all of them were grade one, no ICANS. And due to the fact that they're targeting BCMA, they did get a lot of infections.

They had four out of ten, three Covids, one due UTI, and everyone was hypogammaglobulinemia, which is again going to be a feature of BCMA. So again, I think what the other problem we're seeing with these abstracts is that multiple variables are being moved at the same time. So there's lymphodepletion reduction here with the IL-fifteen that's armored, but they're also targeting BCMA. And you have to wonder which one's controlling what in terms of the efficacy. But I think if we can extrapolate from our full lymphodepletion in lupus targeting CD19, it seems that CD19 is sufficient for lupus.

I'm not 100% sure what we add with BCMA. But nevertheless, again, there treatment strategies

that

are out there being used in oncology, now being copied and pasted in a room to be able to try to reduce lymphodepletion. Because the number one reason why we can't enroll a patient for CAR T, it's the lymphodepletion, they don't want that.

Yeah, well, it's a really scary aspect. I think it scares the doctors maybe more than it does even the patients. And that's a gigantic problem. The problem sometimes is, you mentioned that they get CRS, cytokine release syndrome, does that mean they also needed to be treated with tocilizumab?

Yeah, so the authors didn't report that, at least in the public facing data. And so we were unable to obtain whether or not they needed therapy. But I think that this is an interesting question moving forward is whether or not we can find ways to be able to either risk stratify or even identify in real time through biomarkers, those that may be requiring therapy and as a result need to be hospitalized versus those that can stay purely as an outpatient. Again, we're moving many steps ahead of where we're at right now, but I think that is kind of what the goal we're thinking about.

When you cause hypogamma in these people, a number of them are gonna need IVIg.

Oh yeah, gotta carry it in your pocket. Literally, these people And it's a problem with BCMA, right? We know this is going to be an issue. And so it's really interesting. I don't know how that conversation occurs that you need to be revaccinated against everything including your childhood vaccines.

Right, right. All right. Again, these are big steps, these trials. I think that's important. And I think it's important in getting a workforce of people that are comfortable using these therapies on these patients that really is going to advance the science.

And we need to have this workforce because when when this all started, you know, with Chet's cohort and whatnot, you know, I think one of the craziest things was the scramble for new investigators for new drugs. And a lot of us had, know, a lot of experience with biologics and inpatient infusions, whatnot, but this was a whole new game. But we have now a lot of competent people doing this research. I think it's encouraging. Janet, what do you have?

So I have something that actually goes along what we've just discussed. So this was poster six seventy eight, and I picked it because I want to know which car and lupus to drive, so to speak. So this was a smart little comparison of two CD19 CAR T therapies in lupus, and what they were trying to do, they had five patients in one group and seven from the other, so they got all the raw data to really compare allogeneic versus autologous. So there was five in one group, seven in the other. So this isn't randomized, these are people coming out of the trials.

So it's a total of 12 patients, you know, almost half in one group, half in the other. So they wanted to compare the molecular responses from the two groups and looking at the improved cytokine signatures, obviously trying to find how many, like are you on single cell seq, etc, having mostly only naive B cells of the ones that would be considered pathogenic. So they also want to look at interferon and neutrophils. So the answer is I don't really know, but they're similar, but they're not identical. So as a for instance, they have all these graphs, myeloid cell compartment, B cell compartment, the NK cells and what's happening there.

And comparing autologous with allogeneic, there are definitely different little clusters. They are not fully overlapping, but in my mind, not knowing totally how to read this, it looks like they would be in the same sort of logarithmic change. So in my mind, it looked kind of the same even though they weren't identical. They also looked at how you would change other other, you know, TC cell talk and cells. So they looked at ones less likely to be involved, but they looked at monocytes of various time points as well, and they were looking at some other things that might be kind of more interesting to us.

So they looked at then the bottom line is the effect size of the lupus, I'll say immune reset, which is really going to be a composite endpoint of a lot, pre versus post CAR T. And frankly, as far as I could tell was of the twelve patients with lupus, It looks like in general, whether you got allogeneic or autologous, that the immune reset looked pretty darn robust in all those groups. It wasn't a 100% overlap again and some confidence intervals around it. They went on to look at interferon and plasma cells and neutrophils, and again there were some changes between the groups that got the one kind of CAR T and the others, but they were mostly quite in line. So I think the bottom line is here, it might not matter at least from this study whether you get allogeneic or autologous, you're probably going to be appropriately immune reset.

But there's another thing of what we just talked about is if all these had lymphodepletion protocols that were the same, that would make them more the same. And I'm pretty sure on these two studies they lymphodepleted. So we just talked about less lymphodepletion or none, you're going to get less sort of your naive CD cells being present at the end. So I think it's it's a good question, but in they tried to answer it. But for me as not really knowing all the all the pharmacokinetics and also all the cell biology at the cellular level, I think it doesn't really tell us the answer.

So my question is, how are we going to know that we've accomplished this concept of immune reset? Is it a phenotypic characterization or can it be genotypic or based on transcriptomes? Mean, Janet, do you have a feel for this?

Right. So because these are both lupus trials, I mean, the other thing that in all the lupus trials they're looking at, which is neither phenotypic but it's downstream, they're looking at full neutralization of double stranded DNA, normalization of complements, looking at some of the ENA autoantibodies and saying they should disappear in a certain time frame. And it's not always by one hundred days, but they should go down rapidly and then they kind of lower down more slowly after that. So I'm not exactly sure. I think you'd probably also want to say how many of what used to be the pathogenic branch of the variety of our B cells are now basically naive.

Al, would you say something different sort of speaking from the bench side of things?

Yeah, you know, I think we still are struggling to actually define this. I think we've loosely used all these changes in the immune system that are detectable to define immune reset. You know, in fact, Paul Brunetto, who's Chief Medical Officer at Hinge Bio, and myself, we're co heading an effort through the Lupus Research Alliance to actually try and figure out how to define immune reset. I mean, we have to start from the beginning, but I agree with you, Janet. I think from a molecular perspective, in terms of subsets, yeah, I'm more naive than memory.

In terms of other molecular aspects, we're looking at B cell repertoire reset. In other words, their B cell repertoire becomes much more heterogenic, less oligoclonic, which makes sense because the autoimmune response is very selective. And then once you get rid of it and now you homogenize things, it looks reset. But does that actually mean it's going to drive efficacy? I don't think we have that answer yet either.

Probably yes, probably.

But since that's the holy grail in all of this, we better start defining it. Let me move on to my chosen presentation. This was an oral presentation, OP008, the COMPARE trial, CAR T cell therapy in rheumatoid arthritis patients. They introduced the data on six patients who had refractory RA that was ACPA positive. The patients entering the trial had failed generally around four or five biologics targeted synthetics ranging from three to eight.

They had very active disease generally in the high disease activity category and as high as 28 or 6.2. All of them, were pretreated with fludarabine and cyclophosphamide, and then received their one infusion of something called, I don't remember, what was it called? We

call it Mivo auto.

Yeah, Mivo auto. Thank you so much. They need to shorten that up for me especially. They did, you know, expected, show full B cell depletion, significant neutropenia along the way, and from the podium spoke as if this was the second coming of the tortillas. But they showed a steady decline in disease activity.

There was some CRS, there wasn't much in the way of ICANS. It was seemed to be fairly well tolerated, but when they talked about the, you know, from first thing he said was everybody achieved remission. I thought, woah, that's not quite what I read, but okay. But then you see this steady decline in dash 28 scores, and I just went straight to the graphic that showed the ACR twenty, fifty, 70 scores at week twelve, twenty four, and 52. At week 12, only fifty percent of people received an ACR twenty.

And the best responses were out at one year where now these are significant numbers. And again, this is an uncontrolled observational. Now they do have other patients that are enrolled, like another dozen patients that are enrolled, did not present any data on. They did show that rheumatoid factors and ACPA levels dropped, but they didn't go to zero in everyone. But on the other hand, some of my colleagues were upset that ACPA didn't drop very much at all, but you know, they did.

Those people that dropped to three hundred, four hundred started out in ACPA of two thousand. So they had significant drops in autoantibodies, and this was associated with efficacy. But this is the, for me, why I went here is because, CAR T and cellular depletion therapy seems like it's the great hope for autoimmune therapy and it's being applied across the board. And we've seen great results with lupus and really encouraging with scleroderma. I'm not so sure about myositis and I'm not at all sure about RA.

And this says it might could work in RA, but I don't think it's quite the magical bullet it's looked like in lupus. So I'd be really interested in the three of you and your comments on this report because you certainly are following this data more than I. Al, what do you think?

Yeah, so I'm so happy you presented this abstract because I think it highlights a whole bunch of different things that you nicely covered. And the other one too that we just transitioned off of is that immune reset appears to be happening in these people, but we're getting very variable responses. Some are best getting MDA, some of them do hit remission, but they're all hitting immune reset. So I think the disease state itself appears to play a critical role, I. E, are you even B cell responsive?

Multiple sclerosis being another example, anti asynthesis syndrome being another example, where we're seeing that there are certain diseases that you can reset their immune status, but it doesn't seem to matter.

Yus, what did you think?

Yeah. So I think like what Alan and yourself mentioned as well, I think there's quite like a heterogeneity in terms of the immunopathogenesis. So it may be RA is more varied. So that's why it's harder to target how much depletion you can achieve with all this CAR T or BCMA and all sorts. But I think there might be other immune thing that need to be targeted.

So maybe a little bit lagging behind compared to, for example, like lupus and scleroderma. So

Janet, you're a clinical trials researcher. Someone comes to you with an allo CD19 prep or BCMA, and you can enroll anybody you want, autoimmune disease, and they'll give you four categories. Are you enrolling your RA patients on this?

Well, so far with the data we have, I was underwhelmed. By the way, the guy presented it really well, but it was a little bit discouraging. By the way, these patients were not all the most difficult to treat. They had in fact failed things, so they were difficult to treat, but they hadn't been recalcitrant to everything. So here's what I think if I were going to enroll an RA patient, I'd say let's turn the clock back.

Let's look at an earlier RA with not much damage but has not responded to a lot of stuff. Because the chance of responding well to your fourth advanced therapy, if you haven't on the on everything CSD MARS in the last three, is pretty sparse. So it's a law of diminishing returns, but it brings up a concept of maybe immune dimming, not reset, which I will talk about after.

Okay. Let's move on to our last selection. Yus, you want to go give give us yours?

Yeah. That's yep. So my quick one is presented at a late breaking abstract. So l b zero zero four. So two is a company and three is a crowd.

So this is a progression from BiTE, which is the bispecific T cell engager to now development of TRITE, so t r I t e, so trispecific antibodies. So usually the antigen, you know, would be c d nineteen and c d three, which then, you know, of course, that's the molecule of the of the bite to bring it together and and and cause apoptosis from the T cell activation. But this time they added CD28 as well. So the reason for adding the CD28 is to provide a co stimulation, and this will then induce more T cell activation also to reduce the T cell exhaustion. So it's really priming for that.

And this early results data were presented in a patient with lupus nephritis. So there were 12 of them, severe refractory, so had multiple failures to other biological therapies before. Because it's still early, so they did have data for eight patients out of 12 at six months and also have six patients up to week thirty six. So at six months, all of them had SRI4 response, whereas week 36, there's a five out of six responded. I think there's a two overlays, overlying data.

So they finished at week twelve months and they seem like they sustained SRI4 response there. So it's early preliminary results. There's not much significant safety signals compared to other advice you might expect, but something that maybe we are looking to in the future. And also I would expect if we are following the oncology in the next year or so, we might also get a trike, which is like they replace CD28 compared to using NK cells, so they call it a triche. So that will be way forward.

So these are parenterally administered, I assume?

Yes, yeah.

Okay. And other advantages to this form of therapy over CAR T?

So I think the advantage is easier to administer just trying to minimize the risk of the T cell exhaustion. So I think that's the reason why we're adding the CD28 to become three. But we still don't know. We need longer follow-up data, whether the patient would relapse or whether repeat dosing would be effective as well.

Al, do you see there are companies that are struggling with whether they should be developing CAR T or these B T cell engagers instead?

Yeah, I mean, you mentioned this too, but there's no LDC with engagers and that's the very attractive way to be able to move into why people are moving into engagers on top of the fact that it's much cheaper to make. But their efficacy hasn't been as robust as the CAR Ts at the first generation level. I would consider this to be a second generation because they are trying to mitigate some of the issues of the first generation inducing T cell energy that can happen with the first generation. So this is, I think, an important proof of principle, but it's certainly not the answer.

Right. Okay. Let's move on. Al, what's your last one?

Yeah, so the last one I'm doing is abstract LB003. And this is an interesting abstract because they actually had multiple abstracts on a product called AB 101. And what this is, is trying to address the question of how can we deliver cell therapy as an outpatient completely, right? Avoid everything inpatient. And so what this approach is, is that it's an NK cell therapy.

It's not CAR NK cell. There's nothing modified in the NK cell itself. Although the NK cell is not normal, it comes from donors that have a high affinity naturally occurring variant in CD16, which is the Fc receptor. So this will enhance ADCC through NK cells. Now you may have heard this story before because obinutuzumab and other type two monoclonal antibodies do it the exact same way but from the opposite ends of the lens.

They're modifying the Fc tail enhance their affinity to normal CD16. Here you have enhanced CD16 that's present in about ten percent of the human population. So they studied it in RA, which is obviously a more difficult disease to study. And unfortunately, you still need LDC or lymphodepleting chemotherapy. Here they use flu sigh.

But remarkably, they had zero cases of CRS and zero cases of ICANS in all the patients they treated. I think they treated at least six. And they did see people improve varying amounts. Some people went to mission, others went into moderate disease activity. But of those that were treated, three out of the four that were on DMARDs were able to stop.

Three out of three that were on prednisone at screening were able to stop. And they also saw similar results in N of-1s in Sjogren's and in scleroderma. So it's kind of an interesting approach. Again, I don't know if this is the final answer, but I thought I would never see an abstract but pure cell therapy for at least three to five years. But we got it this year.

Are they taking the tact that this is going to be easier to administer?

Yeah, think so. And again, this would be the right approach to do using these particular NK cells because this binding affinity business for NK cells is really, really important. Of note, every patient had to get rituximab in order for the NK cell to act. I forgot to mention that. They have tested this with obinutuzumab too in lupus, but then not see increased toxicity.

So there seems to be a ceiling effect here, but the bottom line is that you add your favorite monoclonal antibody to your favorite cell and you can chase them with these NK cells and deplete them.

Interesting. All right, very novel. That's why it was a late breaker at UR twenty twenty six. Janet gets to back cleanup.

Right, so I'm talking about Doctor. Hector Chanoi gave the win, which is what is new for inflammatory myositis. It was a June 5 packed room in the plenary room. It wasn't a plenary, but in that great big room. So I'm going to tell you maybe three points.

So the first is I'm quoting him. He said immune reset may be asking the earth and we need to consider immune dimming, especially in our patients with SARDs and multi drug failure. So I heard a lot about immune dimming. It seemed every time that a T cell engager didn't do as well. They said, we're immune dimming, and then maybe you can put them back on the drugs and they'll be better because we haven't fully reset them.

So that's one thing. He also said we really probably have to rethink not only what SARD patients go in, but even because he was talking then about inflammatory myositis, is which inflammatory myositis patients would you put in? The recalcitrant ones are probably going to be bad news in that they might not be responsive. They might even have a higher burden of, I'll call it epitope spreading for lack of a better word, that it just might be the totally wrong group. He was asked about what about the MDA five who already have early ILD?

And he said, yeah, maybe that would be a good candidate. But he didn't sound fully optimistic on any of the immune CAR T sort of, I guess, thinking in the early days of inflammatory myositis. And then the final thing is these are very heterogeneous patients. So I don't think there's going to be a one size fit all, even if you're going to lymphodeplete and then give what you think, even if it's an autologous CAR, not an allogeneic in these patients. So to me it was an excellent review.

We also had beautiful slides, he spoke really well, but it was a little bit sobering for me. I think it put me back into reality a bit.

Nomenclature clarification, SARS? Oh,

sorry, SARS, the Systemic Autoimmune Rheumatic Disease patients. Not SARS as in COVID, SARS CoV-two. Or

as in slow acting rheumatic, you know, it's-

Yeah, they weren't called the slow acting rheumatic drugs, but the systemic autoimmune rheumatic disease patients.

So why is it that there has been, think it's odd to me as an outsider to myositis that the CAR Ts have not done as well in inflammatory myositis. It could be for the heterogeneity that you point out, Janet. But on the other hand, and this is true, true unrelated, whatever, is that dermatomyositis patients with ILD respond really well to JAKs. And any of our diseases with ILD, nothing really works. The best we can do is level them off and keep a stable FVC, but you can turn things around in those people.

So it's clearly a different kind of disease, this is what I'm saying. But does anybody have insight as to why they're harder to treat?

I'm gonna give you a guess, and I don't know that it's true. This is like off the wall and not proven or anything, but if you're doing lupus nephritis, I mean it is a systemic autoimmune disease and you do have antibodies and stuff, but look at the surface area and within in the target organ of two kidneys. I realize we want the rest of their lupus good too. If you think of inflammatory myositis, your muscles have huge blood flow but you've got all these because unless if we're talking distal muscle like inclusion body which we're not, we're talking proximal muscle. But I think the surface area and the blood flow and the clearance out of these muscles every every time you move, you're probably changing clearance, changing, you know, what penetrates in and out.

It's a lot of volume. Maybe you need far higher doses, but I'm making it up. I don't have a clue.

You know, right now it's king of the hill. Someone's got to knock it down. Anybody have another idea? Jooz?

Yeah, think it's due to the heterogeneity that you were talking about just now. We're talking about inflammatory myopathies. Say, you have the dermatomyositis subtype and then you have the MDA5 antibody, for example, well dermatomyositis, G1 and everything. So it's quite hugely varied and I'm sure there's various pathogenesis that may be just targeting B cell only is not going to be enough.

So Al, before we came on, you had mentioned that you thought that this cellular depletion research area was really hot at ACR, but boy, it got a whole lot hotter here at ULAR. What are you expecting going forward in the next six months?

More diversification. And I think this is gonna make it extraordinarily complicated to summarize. There's so much innovation going on both in car construct space, CAR engineering, and also T cell engager engineering, right? And you just mentioned one of those, the tri specifics. There's no real bounds in the innovation when you look at the oncology and their experience.

And so these are rapidly coming over into autoimmunity. I just, it's gonna be somewhat overwhelming because the best idea won't be fully tested and won't win. Right? There are other complicated reasons, I. E.

Venture capitalists, investors, and angel investors, right? There are muddying the waters. So I think that's the reason why these type of platforms are important. We can really apply rigor to make sure that the wrong narrative isn't put forward.

And how far are we away from a randomized controlled trial? Placebo controlled, active control?

Yeah, I'm surprised that some of the phase two trials that are out there remained single arm open label, right? Interesting. And I think right now it seems like that the FDA is making a position that we'll have to figure that out ourselves later,

right? And hard to recruit an RCT because people who want CAR T are going to drop out if they're randomized even if it's a pretty decent control arm. They're going to drop out and say well I'm going to this other center because they're going to fly me there and do it. I think patients are going to have a difficulty unless if they have, oh, a year you can cross over and they might even drop out then. So I'm not saying that it's wrong.

I think we need controlled studies, but it's very difficult to recruit them.

Yeah, I don't think we get smart until we have controlled trials. We're still in discovery, which is a really important phase, and we've come a long way in two years. So I want to thank our panel for a really great discussion on a really complex subject. I want to encourage the audience to tune into more of these post ULAR panel discussions. Take care.