Good morning, everyone. Thank you for joining us at the first day of the Needham Company Conference, Healthcare Conference. My name is Gil Blum, and I'm a Senior Biotech Analyst. It is my pleasure to have with me today Fred Aslan, the CEO of Artiva Biotherapeutics. Fred, kind of hard to ignore what's going on in the markets today. I'm going to actually start with tariffs, tariff exposure, anything you want to add there, and follow up with, you know, kind of the changes in the FDA and if they mean anything for you guys.
Look, I am probably not the smartest person you could be speaking with with regards to these things. I think I am following with curiosity and fright as much as you are what's happening. With regards to FDA, it does seem like they did choose like an insider, right, to take over Peter Marks's job, which gives us some comfort.
Like a lot of those layoffs that were happening were not going to be impacting the reviewers. We'll see. I don't know, you know, I run a company. I know that whenever there's chaos on one side of the company, it impacts the other side of the company. Time will tell on what that is going to look like. For now, we are focused on execution. You know, I do, I feel pretty lucky and blessed that we were able to raise the funds that we did during our IPO last year. We ended the year with approximately $185 million. That gives us enough runway to get to the end of 2026. I think the best thing we can do right now is just put our heads down and execute. We think we're working on a very compelling therapy.
I hope that by the time we're able to demonstrate what we have, that markets are more permissive, looking for good ideas of things that can make a difference to patients.
Okay. Let's forget about, you know, the underlying environment. Let's talk about Artiva technology and the focus indications here.
Yeah. We were one of the first entrants into this area of B cell depletion in autoimmune disease following the work done by Georg Schett, where he demonstrated that autologous CAR- T, by actually doing a very deep B cell depletion, was able to drive, you know, most of his patients into remission, without requiring any additional drugs. We entered this field coming from oncology because, again, we were very compelled with what we saw in our NHL data. I'm sure we'll talk about our NHL data as kind of the program continues. We believe that we can deplete B cells deeply. Most importantly, NK cells have a very different safety profile than the modalities that actually leverage T cells for their work. We'll talk a little bit more about that. Our lead product is called AlloNK. It's an allogeneic NK cell.
It's off the shelf, cryopreserved. It's vialed in an infusion-ready media. You can thaw it at the bedside. It's a 5 minu-10 minute IV push. This is as close as cell therapy has come to biologics. The combination of the ease of use, the accessibility, and the safety profile, I think, positions us well as having a very deep B cell depleting agent that can actually be used in the autoimmunity setting and, more importantly, in a community autoimmunity setting, which is where most patients are treated, right? Today we are running two trials. One is a company-sponsored trial. The second is an investigator-initiated trial. We're exploring a number of different autoimmune indications, lupus, RA, others. Very importantly, our investigator-initiated trial is actually being run in a community setting.
This is actually a pretty special therapy, a pretty special setting to demonstrate the power of our therapy because we're talking about a community rheumatologist who treats his patients in his infusion chair, sends them home, and then if they have a fever or an infection, he can actually manage them as outpatients and only bring them in if it's something serious. We think that this is a really important setting to be testing this drug because ultimately that's where we think that our therapy can have the most impact and be most accessible.
Excellent. You actually answered quite a few of these questions, but one point I do want to spend a little more time on is to put in perspective the differences in manufacturing. Let's say AlloNK versus a CAR- T versus something that's iPSC-derived and allogeneic. Just give people an idea of, you know, the difference in scale here.
Yeah, absolutely. auto CAR-T, you know, is actually a pretty involved procedure, right? The patient needs to be screened, you know, over a 30-day period to determine whether they qualify for it. If they do, they have to undergo apheresis, right? As most of your listeners know, apheresis is a process where it looks like a dialysis machine. You sit there for a few hours to actually collect your cells. Those cells, via a non-scalable process, right? It's an individual batch process for a single patient. Those cells have to be expanded. They have to be genetically engineered. That can take several weeks. The patient is asked to come back to the center.
They're hospitalized for usually 10 to 14 days, and they have to hang around the hospital for at least another two weeks after that, because you have to monitor for these serious side effects that can happen with auto CAR-T, right? What we are proposing is completely different. We're talking about, we source material from umbilical cord units. We call up a blood bank. We ask for a cord that has the characteristics that we want. That's usually present in 15% of the cords out there. From one umbilical cord unit, we can make over 4,000 vials of 1 billion cells each, right? So one umbilical cord unit, 4,000 vials, that could allow us to treat hundreds to thousands of patients depending on the dose that we are using. These vials are vialed with an infusion-ready media.
Basically, we can code through cold chain logistics, we can ship these vials anywhere in the country, really, most parts in the world. These vials are thawed at the bedside, five, ten minute IV push, the patients are observed, and then they get to go home. This is as close as cell therapy really has come to biologics. When you ask about the other off-the-shelf approaches, you know, let's explore them. You could do peripheral blood-derived NK cells or other products. Let's talk about the challenges with each one of those so that I'm being intellectually honest. The challenge with umbilical cord-derived NK cells is that in umbilical cords, the NK cells are very immature. You need, as part of your manufacturing process, to actually activate them and make them mature by the time you're giving them to patients.
We know that we can do that as part of our process. I should tell you, we are a spinoff of a Korean company called GC Cell. They have been developing this process that we're using today for over 15 years, right? The reason why our process is as mature and scalable and robust as I described is because there's been a lot of trial and error to get us here. This challenge of activating immature NK cells into mature NK cells is something that we have tackled. When you're dealing with peripheral blood and GC Cell had experience with that, the challenge there is that you have NK cells of variable maturity and variable activity. When you're starting with initial material that is variable, there's a higher chance that you could cause a lot of variability with the end product, right?
That's one of the challenges. The second challenge is genetic engineering, right? We have a lot of experience with genetic engineering ourselves. Genetic engineering introduces potential advantages, but it can also add a number of variability issues. It's also a yield hit. Whenever you take a cell and you have to manipulate it, you have to introduce lentivirus, it's not all the cells that get transduced the way you need. Even there, there's a lot of variability that you get. We're not close enough to the manufacturing process of our peers, but those are some of the challenges that they have to get through. If you're dealing with iPSC, the advantage there is that you're dealing with an immortal stem cell that you can manipulate however way you want. Once you have that cell, it's not an NK cell.
You have to differentiate it into an NK cell. Once you do that, then it's no longer immortal. That differentiation process is not as straightforward as just expanding an existing NK cell. Once you have what you believe is an NK cell, you do have to expand it so that you can give billions of cells. That offers its own challenges there. Like I said, I'm not as close to other companies' manufacturing process, but what I can tell you is that we are really proud of how advanced and robust our process is today. The result of all this is that we project that we could make vials of a billion cells for $1,000 or less, right? We could be an order of magnitude, if not, you know, two lower than what it costs to do auto CAR-T today.
Remember, that's the cost to do auto CAR-T if you're doing it yourself. If you don't have a manufacturing facility and you're outsourcing it to someone, then you're spending hundreds of thousands of dollars per patient, whereas, you know, our cost is significantly lower. That's one of the reasons why our burn compared to our cell therapy peers is significantly lower than pretty much every one of our peers out there.
Very helpful description there. I do want to spend also a second on the safety profile and as it specifically relates to autoimmune diseases. Do you think this gives you an angle here, especially the complexity that's associated with the treatment administration in that setting? What do you think are the potential commercial ramifications?
Yeah, I believe that it's a significant advantage. I would argue that there's only one reason that people should care about NK cells. And the one reason is that when NK cells kill B cells, whether that's in the context of cancer or whether it's in the context of autoimmune disease, we do so without the runaway cytokine release syndrome that you see whenever you're using T cells. Whether you have an auto CAR-T, an allo-CAR- T, or even T cell engagers, you are requiring T cells to expand, to activate, and then to kill B cells. When that happens with T cells, that causes cytokine release syndrome. What we have learned from the oncology experience is that if you don't intervene fairly quickly with an IL-6 monoclonal, that can actually escalate and that can actually drive you into the ICU setting, right?
I actually think that, you know, a lot of investors have entered this field of autoimmunity and they haven't actually paid attention to what happened in oncology. There's a lot of very wealthy data, very valuable data that you can actually look in the oncology setting that is very relevant to what's happening in autoimmune disease. For instance, in the early days of auto CAR-T, a very high proportion of patients were getting grade 3 and 4 CRS because they hadn't yet discovered that tocilizumab can actually prevent that. The labels of the auto CAR-T products that had been approved and the TCEs that had been approved all, you know, suggest that there's a high rate of grade 3 and 4 CRS. In the real world today, that doesn't happen as much.
You get grade one and grade two CRS because physicians are very quick to intervene with tocilizumab. How concerning is runaway CRS if you're in the hospital setting? Not concerning at all. A patient has a fever, you give them tocilizumab, it's unlikely that that's going to escalate, right? This is one of the reasons why in the autoimmunity trials today, we don't see very high rates of grade 3 and 4 CRS. Some people say, "Oh, it's because in autoimmunity, it's different." I'm not convinced about that because we never ran a trial where we are not giving tocilizumab to patients to actually understand whether in these auto CAR-T trials in autoimmune disease, they would escalate to grade three and four. Right now, most of the data that we are seeing in autoimmune disease, the moment somebody has a grade 1 CRS, they're being given tocilizumab.
That is part of the reason I believe why we're not seeing that escalation. Now let's talk about the commercial implications. If you have the risk of runaway CRS, the problem that you have is if you're trying to treat a patient in the community setting and let's say you've given the therapy and then you send them home and then they call you saying, "I have a fever." Now, as a physician, you're thinking, "Is this runaway CRS?" Because if it's runaway CRS, I have to bring them in and give them tocilizumab. Am I going to take that chance? How many of the patients that I treat that are now calling me because I have a fever do I have to bring back because I'm worried about runaway CRS?
That is the advantage of NK cells because with NK cells, you do not have that runaway CRS. If they are calling you with a fever, you do have the time to say, "Well, take a Tylenol. Let's see what happens in 12 hours. You know, call me again. Could this be the start of an infection? Let's watch it," right? You do not have that luxury with a lot of these T cell engaging modalities or the T cells themselves. We believe that commercially, NK cells are emerging as the modality with the profile that can be the most consistent with community administration. Now, time will tell. We need a lot more data across all the different modalities, including ours, for us to say that.
I would say that one of the things that excites me the most about what we're doing is, one, the safety profile that we have seen in oncology, as well as the potency of our B cell depletion, which again, we've seen in oncology.
Okay. Can you also discuss the target optionality that's associated with your approach? These are non-engineered NK cells. Why do you guys decide to move on with CD20 first?
Yeah. So, we are, thanks for reminding me to mention this. We're using a non-genetically modified NK cell. There's a number of advantages. Because we are not genetically engineering the cell and we're not introducing a CAR, as you point out, we need to use a monoclonal to do the targeting, right? So the mechanism is monoclonal binds to the B cell, then the FC portion of the monoclonal binds to the NK cell that activates the NK cell and the NK cell kills the B cell, right? The advantages of that is that you could use different monoclonals, right? So we are starting with CD20 monoclonals. Why are we doing that? We're doing that because there's been approvals for CD20 monoclonals in the autoimmune setting, right?
Because we are doing a combination of NK cell and monoclonal, the agency will ask us, "What is the relative contribution of the monoclonal versus the NK cell?" By working with monoclonals that have already been approved or are in the guidelines for the indications that we're interested in, the FDA has plenty of data on what the monoclonal does on its own. What we are looking for is for an effect that is materially stronger than what you'd get with the monoclonal alone, right? One of the advantages of being able to swap out monoclonals is that you can target different cell populations. You could use a CD19 monoclonal and there's at least one of them approved. You could use CD38 monoclonals or at least a couple of them approved.
That gives you the opportunity with a single cell therapy that you don't have to manipulate or engineer a new product, you can use it to go after a variety of different targets and possibly even use them in combination, right? Now, the final advantage since we're talking about not being genetically engineered of working with a cell that is not genetically engineered is, number one, the scalability that I mentioned to you in terms of how scalable our process is. Part of that scalability is because we're not genetically engineering the cell, right? There is a yield hit that happens whenever you are genetically engineering cells and that can cause the variability. The second advantage is if you are a genetically engineered cell, if you run a trial, you have to monitor these patients for life because you don't know about the impacts of insertional mutagenesis, right?
One of the advantages of going into clinical trials without genetically engineered products is that you don't have to do that kind of follow-up because it's never been shown that products that are not genetically engineered can actually cause these secondary malignancies. I understand that it's a hypothetical risk and no one really knows how much of a risk that really is, but operationally and from a burn perspective and a cost perspective, way simpler to be working with a non-genetically engineered cell.
I know this is early days, but where would you envision AlloNK fitting in the treatment algorithm as it relates to autoimmune diseases?
Yeah. Look, what we are going for are two things. One is we're going for efficacy that is clearly and obviously better than the standard of care. Now, the standard of care is different across different autoimmune indications, right? I would argue that the way I would want investors to look at our product is on an indication-by-indication basis. They would hear from us, "Here's the indication we're interested in. Here's the standard of care in that indication. This is the efficacy that we have shown in that patient population. And then here's the safety profile, which proves that this could be used in a community setting," right? We are trying to run the trials right now to be able to demonstrate that.
Now, because it is convenient enough that you could use it in the community setting, we would argue that initially you would use it after you failed the standard of care. Over time, I think this is a really important point. Most patients with autoimmune disease, they're not living in remission, even with the standard of care. They still have active disease and that active disease is causing damage. It makes sense that in order for your product to get to a point where you're trying to address those patients that are less severe, you have to first demonstrate that you can have a big impact in the patients that have no other options and have very severe disease. Our desire is to first demonstrate that we can actually address the unmet needs of patients that are not addressed by the standard of care.
We would love to see this move up in line. Not only are we taking care of the patients that have failed the standard of care, but we can give patients a chance to have an intervention earlier in their disease progression where you can stop that inflammation on its track and avoid these years of accumulated fibrosis and scarring that can happen across the different autoimmune diseases.
As you mentioned previously, I do want to discuss some of the experience you guys have accumulated in oncology. Most of the data has been generated in Hodgkin's lymphoma. Maybe just walk us briefly through the results and how do you think they translate into autoimmune disease, as you mentioned, depth of B cell aplasia, for example?
Yeah. So we have, there are, at this point, when you think about it, we have treated close to 70 patients in the oncology setting, right? Twenty-four of these patients were treated as part of the Affimed trial where they combined our NK cell with their NK cell engager. Again, we saw there, these are results that they presented at ASH that our NK cells can really drive up the efficacy of their biologic. We have data now in 45 patients in NHL. Again, what we saw there is when we combine our NK cell with rituximab, we saw a level of efficacy that looks very compelling in line with autologous CAR T. Let's talk about that specifically. We have a cohort of 14 patients.
These are all the patients with NHL that we treated that were naive to auto CAR-T and received our NK cell together with rituximab, right? Fourteen patients. Why am I focusing on this cohort? Because I want to try to make a comparison between our data and auto CAR-T data. When you look at where most auto CAR-T data has been generated in NHL, it was generated specifically in patients that were at around like three lines, so the third line, in patients that had aggressive NHL. Of those fourteen, thirteen of those fourteen had aggressive NHL and only one of them had indolent NHL. I point this out because it's not that hard to drive a complete response in an indolent patient. It's very hard to drive a complete response and a durable complete response in an aggressive NHL patient.
Out of this cohort, the majority of the patients had a complete response, approximately 62%, which is in line with the complete responses that we have seen with the auto CAR-T across all the ones that have been approved in their labels, which have been in the 50% range. Most importantly, we track these complete responses over time. What we have seen with most of our peers is that whereas many of them were able to drive an initial complete response, those complete responses progressed by the time you got to the six-month mark, right? What was really special about our data, and the latest cut of that data was presented during our IPO and we plan to make future disclosures on that, is that we saw that most of the patients that had a CR actually had them beyond the six-month mark.
Based on the cut that we shared during the IPO, there was at least one patient that was at the 18-month mark. We had a bunch between nine and 12 months and really demonstrating that with our product, when we drive that B cell depletion deep enough and we drive that CR, it is fairly durable. Why is that helpful in the context of autoimmune disease?
If the name of the game here is deep B cell depletion in the periphery and in tissue, I believe that if you can eliminate B cells from the periphery, which is what we've shown, and you can eliminate NHL lesions from the tissue, which is what we've shown, and it's durable, which gives you conviction that this is actually happening at a deeper level, you don't have a lot of these clones around that are able to sort of expand and make the cancer progress, that we ought to be able to do it in autoimmune disease. Now, time will tell, but we are pretty confident based on that data on the efficacy side that we should have a good position to actually drive good efficacy in autoimmune disease.
On the safety side, as you know, in all of these autologous CAR T trials and T cell engagers that have been approved and allogeneic CAR T trials, patients have to be hospitalized. That was not the case when we took AlloNK and rituximab into the oncology setting. Even though these were patients in their late 60s with three prior lines, we were able to treat these patients as outpatients. This is really important. They got their lymphodepletion, they went home. They got their NK cell and rituximab, they went home. Most of them never had to be hospitalized. The ones that did were hospitalized because of a fever or an infection. Even there, they were treated empirically with broad spectrum antibiotics, antivirals, antifungals.
They received Tylenol, other, you know, fever suppressants, but you didn't see this need for an acute observation of runaway CRS because NK cells across the board don't actually do that. That combination of efficacy and safety is the reason why we have many reasons to believe that we have a good product here targeting autoimmune disease.
Great. I do want to spend some time on the clinical program as well. The company is currently sponsoring a phase I in an ongoing ISD. Just give us a quick rundown of those two studies and kind of the differences there and the rationale.
Yeah. We started the company-sponsored trials in the CAR T centers, the academic centers that you typically go to, right? As you know, it is complicated to get these trials up and running. It's the reason why so many investors are focused on sites and enrollment is because it has been taking the field a while to get up to speed, right? Part of the reason there is because, you know, when you approach these academic centers, you are requiring the rheumatologist to agree with the oncologist as to what they're going to do. The rheumatologists are allowing the oncologist to be the ones giving the lymphodepletion, but then the patient is under the care of the rheumatologist. Normally, you don't have to do that when you're running a clinical trial. You pick a department and that's the department you work with, right?
One of the advantages of our therapy is that we do not have to run them in CAR- T centers. We can actually run them in non-CAR- T centers. That is actually where I believe we are going to end up finding most of the sites that are going to be working with us. You see, I have to applaud the work by the autologous CAR- T companies who were the first to actually get to these CAR- T centers and they had been working with them for a long period of time, right? For us, by the time we all arrived in the CAR- T sites, they already had a number of CAR- T trials that were already up and running. Now, when we approach the non-CAR- T sites, it is a very different story. These are sites that have run trials for pharmaceutical companies before, but they are not CAR- T sites.
They had been following the benefits of cell therapy in autoimmune disease, but they had been unable to participate because they're not a CAR- T site. When we show up with a therapy that is actually safe enough, right, to be used in a non-CAR- T site and has the potential to be very efficacious, that is pretty well met. You know, with time, we will be able to share the details of that execution with investors. For now, we continue to do the work there. As we mentioned in a press release recently, we have completely revamped our development team to bring in autoimmune expertise. When you look at our team today versus our team from, you know, 12 months ago, it's a very different team. Twelve months ago, it was a team that could run oncology trials.
That's how we ran the NHL trial. Now it's a team with a lot of experience in autoimmunity. The advantages of the IIT, which is being done in a community setting, is to almost provide the proof of concept that everything that I just told you is real, right? This is a community rheumatology practice. There is no oncology involved, right? This is the, you know, the lead physician in that practice. And he treats, as I mentioned before, patients in his infusion chair, sends them home, and manages them as an outpatient, right? We don't have too many other companies in the cell therapy space that have actually done this and shared data with this. We think that this provides the validation in order to be able to make the claims that we're making.
You see, the other thing that's important to note is when we went to FDA to run even our company-sponsored trials, the FDA had a different set of requirements than they did for the other cell therapy companies. They just said that we have to take the very first patient in any cohort, just the first patient, and hospitalize them for a 24-hour observation. Just the first. All the other patients don't have to be hospitalized at all. That's very different than the protocol from autologous CAR- T, as well as some of the other allogeneic cell therapies where you do have to hospitalize these patients, right? More and more we're gaining conviction that that's how we differentiate ourselves from the other companies in the space is by demonstrating the ability of our therapy to be used in the community setting.
Okay. That is very helpful and actually answered a couple of my extra questions here, especially as it relates to the relationship between oncologists and rheumatologists and centers, which has been an issue and is how most T cell-based studies have moved forward. A compulsory study status question. What kind of data should we expect at your upcoming disclosure, number of patients, like some follow-up? I mean, we ask this literally every time.
Yeah. Look, we haven't guided a specific number of patients, but we will provide some guidance prior to that data actually coming out. You know, the goal of this disclosure is to really try to show to investors that we believe that we are headed in the right path, right? That's the value of actually making interim disclosures is to show people that you're on the right path. You know, let me actually give you an example. You know, we recently saw what happened to IGM, right? They started a trial and we didn't really get updates for a while. All of a sudden we get a press release saying, "Hey, the data just doesn't support continued development." The value of interim data is to actually show investors where you are headed, right?
Because the alternative is to say, "I'm going to go silent for a long time until I have the data that I want." I think the issue there is that there's a lack of transparency. Investors don't really have a way of knowing whether you're headed in the right direction or not. What we're hoping to show is that we believe we are headed in the right direction. We're trying to be transparent to show what we have done and where we are. Of course, I think that this is just the beginning of a number of different disclosures, which will come over time.
I think that one of the problems that we have as a field today, and I'd be curious in your thoughts around this, but I think one of the problems is we are all companies that deplete B cells that could target a large number of different indications. We haven't said which ones we're actually going to do. We all started in lupus because that's where the initial work was done. Now you're an investor. You have 20 different companies that all deplete B cells that all started trials in lupus and you don't know what they're going after. How do you figure out which ones do you like the most? I think this becomes a lot easier once companies start to say, "Here's the indication that I'm going to lead with. Here's the standard of care in that indication. Here's my data compared to that.
Here are the other people that I'm actually competing with. It won't be 20, right? It's 20 in lupus, but I bet you it won't be 20 in scleroderma, 20 in myositis, 20 in vasculitis, 20 in RA. It won't be. I believe that the future of this space is going to be specific companies that probably have two or three or four competitors within a given indication. Based on their target product profile, as an investor, you can say, "I actually think this is likely to get to the market and to have a bigger share for this reason or that reason." We're not quite at that inning. We're still at the inning where we're trying to show that the therapy actually works from a mechanistic standpoint.
We're going to try to be really thoughtful about how we do these disclosures so that we can both be transparent as well as guide investors to where we ultimately want to get to.
We do have some data at this point. Where do you think the bar is for you? You know, what would make you decide, "Okay, this is good, this is not good"?
We do. We do have quite a bit of data. You know, let's talk about that. I feel like in many ways, what Schett did was remarkable because it gave us a vision, you know, for a place to go where you could have incredible results. There is one part that was a little bit of a disservice. It's the fact that in Schett's hands, right, the results are truly remarkable. I would argue they have not been replicated by anybody, right? The level, you know, so let's pick on a few items. Take lupus patients and their proteinuria. We have not seen any other data set by anyone that basically shows, "Yeah, I give them auto CAR- T, I eliminate proteinuria in every patient," right? We haven't seen that from anybody. Take lupus with SLEDAIs of zero.
In Schett's hands, all of Schett's patients got to a SLEDAI of zero, maybe the exception of one or two patients out of 30, but it's a very small percentage that did it. In most other people's hands, whether you're looking at Novartis, whether you're looking at, you know, the data from BMS or Cabaletta or Kyverna, you're not seeing everybody drive patients to a SLEDAI of zero. I think that investors are going to have to determine, based on the available data outside of Schett, what is kind of that bar. I think that that bar shouldn't be based on how does it compare to Schett. It should be based, how does it compare to the standard of care? That is going to vary on an indication-by-indication basis. Let's go back to lupus nephritis. We recently have seen interesting data from Gazyva, right?
It was a 46% complete response rate. Now, I remind your listeners that that was on top of MMF and that was on top of steroids. When you compare what the complete response rate was versus placebo, which was not really placebo, it was MMF and steroids, I think that that had a 33% versus a 46%, which Gazyva was able to achieve. Still, it is 46% complete renal response. That is actually a good number. I will also note that they did not share data at 12 months. They shared data at 18 months, which suggests that perhaps you have to actually follow these patients for some time for there to be some healing of the scarring in the kidney or the fibrosis in order to see the result.
I would argue if that is the bar, right, assuming Gazyva gets approved and it has a 46% complete renal response on top of steroids and MMF, if you want to develop a product in lupus nephritis with a cell therapy or a TCE and you expect it to do well commercially, then you need a better target product profile. You need to be more efficacious than that, and you need to be at least as safe, if not safer, than what that is showing in order for it to move the needle. I think that this analysis that I just did for you is one that needs to happen across every indication. By the time we are coming out to you and saying, "Here's an indication we like," we would do that by saying, "Here's the target population we're going after in that indication.
Here is the data that exists today based on the standard of care in that population, and this is what our target product profile looks like," so that then you can say, "Yeah, I do think that you guys can address an unmet need in that patient population." You see right now, it's 20-30 companies that all seem to be doing the same thing. I completely understand why investors at this point have more of a wait-and-see approach until we define ourselves a little bit better.
A related question, this has to do with clinical study design at a later stage. Do you imagine or do you envision seeing something like a PFS-like endpoint, you know, treatment-free interval type endpoint for actually it could be any of these indications, especially given what you mentioned where, you know, late-stage lupus nephritis patients, you're not going to reverse their fibrosis?
It's a very good question. I would say that that's going to be TBD. Let's share where we are. Where we are is that as a field, right? Where we are is that Kyverna has had that first conversation with FDA, and it was agreed that they could pursue a registration direct to trial in stiff person syndrome without a comparator arm with X number of patients, right? That is a relatively small indication. Maybe what they were allowed to do there is going to be specific to the fact that it's a smaller indication. We know from Cabaletta that they're going to be approaching the FDA to talk about myositis. That'll be really interesting to see whether they're going to have to use a comparator arm or whether they're not and how many patients they're going to have to show.
The question you bring up about something like PFS is an interesting one. Will the FDA look at different endpoints than they're used to seeing for the approval of these products? I'm not sure. As you point out, I think medication freedom could be one of those angles. There seems to be some level of consistency across that for the auto CAR-T. Could that be an endpoint? Maybe, I don't know. Could the notion of having a no flare be an indication, though? I'm not sure that's a good one because it could take a long time for the flares to develop, right? Recently, I was looking at the Gazyva data, and you know, I think patients on Gazyva took two years to flare, whereas patients that were not on Gazyva took 18 months to flare.
I'm not sure that progression-free in the sense of a flare is going to be the optimal one. What I can tell you is we're all collecting all sorts of endpoints for every patient that we're enrolling across these trials, and we're going to be trying to sort out where do we see the biggest benefit for the patient that then you could have the conversation with FDA. TBD if the FDA will agree to utilizing different endpoints because, as you know, sometimes some of these endpoints are hard to validate, particularly if you don't use something as objective as, let's say, flare freedom, which, as we discussed, may not be the best one to use from a time to demonstrating impact.
I do want to spend kind of the last minutes here on competition. We did touch on some of these topics, but to kind of reiterate them. Which data set from, you know, all these studies that are currently going on, would you consider the most relevant to you guys when it comes out?
Look, at this stage of the game, I would say that all of these data sets are furthering our understanding of the field, right? I look back when you and I started our conversations when we only had the Schett data and we had a certain view of the world. Then some of the initial auto CAR T data came out, and we started to say, "Oh, there may be something about the inflammation versus fibrosis that one needs to tease apart," right? Same questions about safety.
In the beginning, people were like, "Oh, all of these therapies are going to be really safe." Now we've seen ICANS, we've seen CRS, we've seen that even the T cell engagers, which were deemed to be very safe, we saw that in the German academic experience, eight out of the 10 patients that were treated on teclistamab had CRS and had to be treated with Toci. I would argue that both on the efficacy as well as the safety side, all of that data becomes really relevant for us to have an idea of how we are doing, you know, from a mechanistic and safety perspective compared to everyone else. I really want us to get to a point where we are now focused on the indications of interest.
We're talking about our therapy in the context of that indication and not just talking broadly about targets and, you know, hypothetical cellular biological things that may not be as relevant as specific endpoints that we would use in order to get these drugs approved.
Given all the products out there, who would you say is the closest to your profile? Allogeneic includes lymphodepletion, that kind of thing.
I mean, I have to point to the NK cell companies as being the ones closest to us because I do think that NK cells do stand out in terms of not having this risk of runaway CRS. On the lymphodepletion side, what I would argue is in our hands, we have seen lymphodepletion to be quite tolerable, right? Lymphodepletion is something that you can do. You can be sent home. You can be given prophylactic antibiotics during the one to two to three-week periods when you are lymphodepleted. Even our cancer patients tolerated it pretty well. I believe that right now, what we should be focused on is efficacy first, right? We have the luxury of focusing on efficacy first because we do not have a narrow therapeutic index like some of these other modalities do.
I am a fan of lymphodepletion at this stage of the game because I think it's tolerable, and I think it could really help differentiate us in terms of having better efficacy than some of the other off-the-shelf modalities that are choosing not to do it. I mean, I'll be the first one to say, if you can deliver an equivalent amount of efficacy, compelling efficacy, and you can do it without lymphodepletion, I mean, of course that that's better. I am not sure that's necessarily a choice that we have. Time will tell, right? If everything works, regardless whether you use lymphodepletion or not, the modalities that do not use lymphodepletion have an advantage. I do want to point out, we have not seen to date in the field any cell therapy with compelling efficacy in the absence of lymphodepletion. We have not seen that, right?
There isn't a single data set out there in the absence of lymphodepletion where you would say that is like very good data, right, compared to what you see with auto CAR-T. Time will tell.
I do want to stop there and open the floor up for questions to see if anything comes up. Maybe one here. There's a, you know, Chinese company, Rui Therapeutics. Any thoughts on the data? I'm sure you had a look at it. Not a ton disclosed there.
Yeah, so I would argue, you know, it was very encouraging for a few reasons. One, it seemed to be in line with what we have seen from other cell therapy approaches. You know, we only had limited follow-up on those patients, but that was a nice number of patients. And there were a number of them that were on durable remission, right? So I would say that's a pretty good encouraging start. Yeah, anything else I could tell you on them?
I mean, it was a very open-ended question.
Yeah, look, being an NK cell, you know, developing an NK cell product, I like having that data out there because in case investors are wondering, can NK cells actually do the trick of actually deplete the B cells and drive clinical results? Rui was able to show that you can do that. Now, I'd love to see more follow-up, particularly because some of the Rui data, the initial patients with the most follow-up were dosed at the lower dose. It'll be interesting to see whether that efficacy strengthens, you know, with higher doses. I thought it was a very encouraging initial data set because you don't have too many 20-plus patient data sets today. That was nice to see and encouraging for the field.
All right, we're at time, Fred. Thank you so much for your time today.
Thanks for having me.
We look forward to seeing the data.
Sounds good.