On initiating this trial. I'd like to spend just a few minutes focusing on the CB-010 ANTLER trial since this will be the dataset that we're able to share at ASCO in just a few weeks. CB-010, as I mentioned, is our off-the-shelf CAR T cell therapy targeting CD19 for non-Hodgkin lymphoma. It benefits from a knockout of PD-1, and as far as I know, this is the first allogeneic CAR T in the clinic with a PD-1 knockout. Really, the purpose of the PD-1 knockout is to take the brakes off the CAR T cells to prevent premature CAR T cell exhaustion. We know these are foreign to the patient's immune system, and they'll be rejected fairly rapidly, and we want to ensure that while they are present, they pack as much an anti-tumor punch as possible. Last year, we concluded dose escalation.
We evaluated three different dose levels: 40 million, 80 million, and 120 million CAR T cells in each case as a single-dose regimen across 16 total patients. Last year, we disclosed these initial data, and the headline is that CB-010 can drive the kinds of durable responses achieved with auto CAR Ts. We took these very encouraging data to the FDA and had been working, of course, in largely third-line and later patients, and asked for permission to move into the second-line setting for our continued clinical development, and they greenlit that. And so we've now conducted all of our dose expansion work in second-line large B cell lymphoma patients. We set the goal of enrolling 30 patients in dose expansion, and we have now concluded that. And so these 30 patients will be the centerpiece of the ASCO presentation a few weeks from now.
We'll be able to share safety data, efficacy data, translational data, including both PK and PD, and we'll also be able to disclose the recommended phase II dose that we have selected. Additionally, we get to look back at dose escalation and provide an update on the patients who remained unstudied as of our last update a year ago. Quite intriguingly, as we look at the 46 patients who've been dosed in ANTLER between dose escalation and dose expansion, we've made a really interesting observation, and that is, by chance, about a third of these patients happen to receive a dose of CB-010 manufactured from a donor who had partial HLA matching relative to the patient. And those patients who happen to receive these partially matched products are having better outcomes on this trial. Now, biologically, this probably makes a lot of sense.
The transplant field has obviously demonstrated the importance of HLA matching. However, this is, to our knowledge, the first time this has been seen with an allogeneic CAR T. So part of what we'll be able to do at ASCO is really dig in on the details of these data. We'll be able to, for example, look at both efficacy and PK sliced and diced by different levels of partial HLA matching to share with you the data that got us really excited about the potential power of using partial HLA matching to improve outcomes for more patients.
Now, we'd like to prospectively confirm what we've thus far seen on study, and so we're now creating a new 20-patient cohort that we will enroll to intentionally provide partially HLA matched product to those patients to see if we can confirm the signal that we have thus far seen in our dataset to date. Assuming that we do, this strategy will then underpin the phase III pivotal trial that we anticipate initiating for CB-010 in oncology next year. So quickly to wrap up, and then Susan, looking forward to chatting with you a bit, a number of key milestones are upcoming for our company. As I've highlighted, we're looking forward to seeing many of you at ASCO in just a few weeks to dig into the initial dose expansion data for CB-010 in oncology.
Additionally, we have committed to the first look at dose escalation data for CB-011 by the end of this year. We're continuing to make progress on CB-012 in AML, and we anticipate initiating the GALLOP trial for CB-010 in lupus by the end of this year. And as I mentioned, we are well resourced to continue doing this work. We ended Q1 with $346 million cash on hand, giving us a runway into the first quarter of 2026. With that, thank you. And Susan, I look forward to chatting with you.
Yeah. So, Rachel, I think we should get right into the hot topic, which is data at ASCO. Just as a quick reminder for everyone in the room, can you talk a little bit about what we saw with the dose escalation data and whether or not that's a good benchmark to think about the upcoming dose expansion data?
Yeah, great, great question. So the dose escalation dataset was 16 patients spread across three different dose levels. And at this point, we were broadly enrolling across many different subtypes of relapsed or refractory B cell non-Hodgkin lymphoma. And they were largely third-line or later patients. So top level, 94% overall response rate, 69% complete response rate, and I think most excitingly, 44% of the patients achieved a CR at six months or later. I know there's nothing magic about six months, but it's a really important tool in the field for measuring the potential long-term outcomes for these patients. And if you look at the auto CAR Ts in the third-line setting, usually about a third of patients are in CR six months post-dosing. So to see 44% of these patients in CR six months later was very exciting. Now we've moved into the second-line setting.
And so I would say we're reframing the benchmark. Same theme, different datasets. So previously, we were really benchmarking against the three trials that led to the initial third-line approvals of KYMRIAH, YESCARTA, and BREYANZI. Now we're laser-focused on the second-line large B cell lymphoma patient population, and in particular, I think you'll see us really leaning on ZUMA-7, given that YESCARTA is really the lion's share of the commercial market in the second-line setting. We really think that's the bar to focus on. And our fundamental goal for CB-010 is to develop an off-the-shelf CAR T cell therapy that can meaningfully rival the auto CAR Ts.
Great. Thank you for that. Can you talk a little bit about safety and just some of the HLA type data that we'll see as well?
Yeah, absolutely. As we look back to dose escalation, safety was certainly quite encouraging, a generally well-tolerated safety profile. Obviously, people tend to focus on, on three key things: CRS, ICANS, and infections. Especially as you look at the rates of grade three or higher of those, CB-010 was either in the same ballpark as or, or favorable compared to the auto CAR Ts. In fact, there were no cases of grade three or higher CRS, which we were very encouraged by. So certainly look forward to the opportunity to look at similar metrics now in dose expansion in this 30-patient cohort. We'll be, of course, particularly focused on CRS, ICANS, and infections as well, but certainly we'll, we'll widen the aperture a bit to discuss some of the other potential AEs. I'm sorry, what was the second part of your question?
Just to talk a little bit more about the HLA type matching data.
Yes, absolutely. So this is really a biological hypothesis that some of my colleagues had right from the get-go. And therefore, the trial was actually designed intentionally to collect HLA typing on both the patients and the donors. And so over time, we've been accumulating a larger and larger dataset. As I mentioned, we've now dosed more than 46 patients on study. So it's given us the opportunity to really dig in and look at patients who, by chance, received partially matched or not matched product, and really evaluate over time what the potential impact might be in terms of, say, overall response rate or duration of response. And really, quite intriguingly, patients who received partially matched product above a certain threshold were really having better outcomes on the study.
I would say we'll be using PFS as the metric to really focus on a measurement of duration here, recognizing that's really the goal at the end of the day is not just to drive initial responses, but to ultimately drive durable responses for these patients. It's a still-in-progress trial, right? And so I want to set expectations there too. Whereas last year, we were at a point where every patient had at least six months of follow-up and really focused on the six-month CR rate as a key metric. This year, that's not the case. This is a more recently enrolled part of the study. The median follow-up for these 30 patients is four and a half months, something like that.
And so I think PFS ends up being a really good tool since we have a range of follow-ups for these patients to understand how our data compare against, for example, ZUMA-7.
Great. Thank you for that. Just a little bit on the future clinical development plans. Do you think that, depending on what you see with the HLA matching data, that that might be used in a pivotal trial? And how feasible is that?
It's certainly my expectation. So we're, we're planning this 20-patient cohort so that we can prospectively confirm what we've already seen retrospectively in the dataset. My own personal guess is, is that we will see this recapitulated. And so I do expect it will underpin the supply strategy for our phase III trial. So to your point, what does that look like? At ASCO, we'll be able to share a quantitative description of, of what I'm about to say, but it's actually a fairly modest number of distinct batches that we would need from distinct donors on hand to be confident that we could supply the vast majority of patients with this partially matched style of product. And we believe that we'll be able to have that supply on hand in time for starting the, the pivotal trial next year.
So we do expect that this will be an all-comer style trial, using this partial HLA matching strategy.
Great. Very exciting stuff with CB-010. Let's move along and discuss some of the other pipeline assets, sticking with CB-010, but maybe going into I&I, which has been quite the topic in cell therapy. Can you talk a little bit about the data that you guys observed, which made you confident that CB-010 might be active in lupus?
Yeah, absolutely. Look, it, it starts first and foremost with safety and with efficacy. Certainly, as, as you look back, even at the dose escalation data that we shared last year, incredibly encouraging to see a generally well-tolerated safety profile and the kinds of durable responses that have been demonstrated by the auto CAR Ts. So that tells us a lot about what CB-010 can do, right? It tells us about, its ability to target cells, whether they're in the lymphatics or in extranodal tumors. It tells us about its ability to deeply debulk tumors that ultimately result in these long-term durable outcomes for some of these patients. I think on top of that, you could start building an additional case looking at some of the key translational data points. And I'll highlight B cell aplasia in particular.
If you look at some of the recent data from Dr. Georg Schett and his colleagues, they've treated admittedly a small number of lupus patients, but the outcomes have been quite profound with these single doses of autologous CAR Ts, and they have shared the B cell aplasia data from those patients. What we have observed is on par with that. So looking forward to our opportunity at ASCO to be able to share some of those data as well.
Great. And just for everyone in the room and those who are watching at home, can you talk about the importance of allogeneic versus auto, especially in I&I indications?
Yeah, absolutely and enthusiastically. And it's very different from the oncology setting. So I'll start there and then transition into SLE. In oncology, many of these patients are facing incredibly rapidly progressing disease, and time to treatment is the North Star. And I think really drives the value of an allo over an auto in that particular setting. I'm not sure that the timelines work out the same in lupus. And in fact, it's very different drivers for why we're hearing tremendous enthusiasm from rheumatologists for an allo approach in particular. Interestingly, if you think about your average lupus patient, they're usually on a handful of different meds trying to maintain stability of their disease.
Yet, to actually undergo apheresis, to have an auto CAR T product manufactured, they would have to go off most, if not all of those meds for 3+ weeks in order to be eligible for apheresis. That's a pretty tough ask of most of these severe patients. Our understanding is that perhaps, quite reasonably, many of them don't want to do that. And so I, I think an allo CAR T is, is really quite attractive in that setting.
Yeah, absolutely. Maybe just looking a little bit further ahead even, how are you guys thinking about the commercial opportunity for this and, perhaps partnering or, you know, taking the assets, yourselves out?
Yeah, great, great questions. Look, long term, we see really significant opportunity for what's actually a quite large patient population. Obviously, we and others are starting in a fairly well-defined small, you know, severe relapsed refractory patient population. And I think that gives us a beachhead to ultimately think about longer-term clinical development in a broader patient population. And this probably ties to your prior question as well. As you start to think about really the potential of the scale, the sheer number of patients who could be served by a cell therapy, they certainly see a lot of advantages for an allo over an auto as you think about the numbers game as well.
In terms of the best path forward, you know, for all of our assets right now, we actually fully own them, which I think is a real strategic advantage for us right now. And I think any small company is always thinking about that balancing act of do you partner, if so when, sooner may bring in certain strategic expertise or capabilities, but typically the longer you wait, the better value you get and retain as a small company. There's no perfect answer to that for sure, but it absolutely is factored into our long-term strategic planning.
Great. So, I definitely want to chat about the other two assets. Let's start with CB-011 and maybe just a little bit of context about the multiple myeloma space and some of the developments there. How are you guys thinking about positioning CB-011?
Yeah, fantastic question. You know, I think we have to go to KOLs pretty humbly and ask them, you know, does CB-011 need to look like CARVYKTI to be relevant for you? That's obviously a pretty high bar. And really quite interestingly, they uniformly say no, you know, CARVYKTI is great, but really the benchmark in their minds is the one other thing that is broadly available and readily available to this patient population, which is the bispecifics. And so to them, that's the target. They would love to see an allogeneic CAR T that's in the same ballpark in terms of response rates. And they also share an expectation that an allo CAR T would have a better safety profile with respect to infections than the bispecifics would. And so that's how we're thinking about the potential positioning of CB-011.
So, seems a little off topic, but it's related, I promise. Can you talk a little bit about manufacturing and how much capacity you guys could get up to? Because, just for context, you know, J&J has some trouble meeting the capacity, meeting the demand for CARVYKTI right now.
Yeah, it's a very on-topic question. I agree. This is one of the obvious benefits of allogeneic, right? In the auto setting, quite simply, it's one manufacturing, one for one dose for one patient. Whereas in the allogeneic setting where we sit today, we get tens of doses per manufacturing run, and that's what I'll call our phase I scale. We see line of sight to meaningfully scaling from there. And so certainly comparing against the autos, the scale is dramatically more attractive for allos.
Great. So let's chat a little bit about CB-012. I think this is definitely big innovation. We don't have anything in AML with cell therapies. Can you talk a little bit about why it's been so challenging to develop cell therapy for AML?
I mean, look, it's an incredibly tough disease, right? So I think right off the bat, it's an incredible challenge. And I think unlike lymphoma or myeloma, where clearly for some patients an autologous CAR T strategy can be incredibly impactful, I just think it's a disease where auto CAR T is not going to be the right answer or maybe ever the answer for these particular patients. So I think we've seen slow movement initially where folks have had trouble enrolling in trials because it's hard to find patients who have good enough T cells to make an auto CAR T. I also think target selection is super challenging. CD19 is a very special target. BCMA is also a pretty special target. For many other diseases, they're not this sort of long laundry list of obvious special targets.
I think the field has been reaching around a little bit looking for what the right target or set of targets could be. And as we looked at it, it was very important to us to find a target that was broadly expressed in AML so that we could really think about developing a product for the broader patient population rather than a subset of the patient population. And yet at the same time was a target that is not expressed on healthy hematopoietic stem cells. Because if you're successful and you're going after a target that is shared across both compartments, that means your cell therapy is necessarily a bridge to transplant because you not only blew up the tumor cells, you probably blew up the hematopoietic compartment as well.
So the really big long-term vision for CB-012 is that it could have disease-modifying activity on its own. That's why we think CLL-1 is a great target to choose for this disease. I'll also mention, given the complexity of the disease biology, this is also really where we're bringing sort of the full force of the chRDNA technology to bear. So from an editing perspective, we're using both the PD-1 knockout strategy and the immune cloaking strategy together in one cell therapy. So ultimately that means five genome edits go into the manufacturer of CB-012, three knockouts, two separate site-specific insertions. There are not a lot of platforms that can get you a cell therapy like that. And so we're really excited the chRDNA technology can make a cell therapy that looks like CB-012 with high enough efficiency while maintaining genomic integrity.
Thank you for that explanation. Very helpful. And just, a little bit more about what to look for since there are no approved cell therapies in AML. How are you guys benchmarking CB-012, and what does success look like to you guys?
Yeah, it is, really humbling how severe the unmet medical need is, and also just how different the KOL feedback is, right? Compared to the conversations we have in, say, lymphoma or myeloma, physicians have very sophisticated and specific quantitative metrics for how they define success. We hear AML physicians say things like, some responses for some of my patients would be nice, please. And, and when you really start to push on them, you know, quantitative metrics like maybe 25% of patients achieving a CR would, would be a real win in this patient population. Recognizing that many of them are, are at least in the near term hoping to push their patients to a CR to then be eligible for transplant as that still really remains the gold standard in this space. So it's very different from lymphoma and myeloma.
Certainly the enthusiasm that we have seen from investigators for our AMpLify trial is just, it's through the roof. I think it's directly reflective of how little there is for these patients today.
Great. So we have just a few minutes left. You know, Caribou has made a lot of progress, really exciting assets. How do you think about pipeline prioritization, and you know, are there other indications or assets that you might want to invest in, but can't right now because of capital constraints?
Yeah, I think no matter how much capital we raise, there are only so many things we can do and, and do well. I, I think it's super important for small biotech companies to think a lot about prioritization. You learn something new, either preclinically or clinically, that informs a better understanding and, and you make new decisions. Maybe I'll give two specific recent examples of prioritization decisions that we've made. One is that we hit pause on an asset that we used to call CB-020. So this was the first program we'd articulated from our CAR-NK platform. It was focused on ROR1 with an eye to treating solid tumors. And we ultimately just felt we didn't have the right pieces of the puzzle to meet our objectives and that it made the most sense to go pencils down on that program and use our resources elsewhere.
A place that we have recently chosen to emphasize using resources is autoimmune. And that's really driven by the encouraging safety and efficacy that we've seen with CB-010 in oncology and obviously the external data demonstrating the real potential for CAR T cell therapies in lupus and potentially other diseases and led us to choose to prioritize developing CB-010 in lupus as well. Certainly as we think about autoimmune broadly, there are probably quite a number of other potential future opportunities, even within the scope of CB-010. No doubt there are other diseases that, or indications that'd be quite interesting to say nothing of the potential of some of our other pipeline programs in autoimmune or the capacity to go back to our cell therapy platforms to build a new one from scratch.
Great. Thank you. We have just a minute left. I want to give the audience an opportunity to ask any questions. If not, I have one more for Rachel. Okay. That's totally okay. Happens often. So, just, you know, can you talk more about the manufacturing and how that will change over time as the programs mature?
Yeah, absolutely. So to date, we have internal process development, internal analytical development. So our internal team owns the very first handoff from research, really developing the process, scaling it up, optimizing it, and then they tech transfer it to CMO partners who actually make the materials for us. We see line of sight to our current network of CMOs supporting not only our continued clinical work, but also potential commercialization as well. And I, I think this really speaks to where the scale of an allogeneic CAR T is just completely different from the scale of an autologous CAR T. Now, never say never. We may choose in the future for strategic reasons to build our own manufacturing facility, but that's not in the cards today.
Great. Thank you so much for being here with us today. That's, that's the end of today's presentation with Caribou.
Thank you, Susan. Appreciate it.