Welcome to our H.C. Wainwright BioConnect Conference. I'm Robert Burns, senior biotech analyst and managing director at H.C. Wainwright, and I'm joined by Tina Albertson, the CMO of Caribou, and Sri Ryali, the CFO of Caribou. Thank you for joining us today.
Thanks for having us.
Why don't we start from a broad high-level you know, overview of the company. For those who may be unfamiliar with Caribou, talk to us a little bit about your tech as well as your pipeline.
Great. Thank you. Caribou is advancing two allogeneic CAR T-cell programs. Our first one is vispa-cel. This is an allogeneic CAR T-cell. It's targeting CD19 in large B-cell lymphoma. Our second one is CB-011. This is our allo CAR T targeting BCMA in multiple myeloma. Caribou has a next generation CRISPR-Cas base technology that really has built on the original technology such that it's much more specific and has a lot less off-target editing. What this allows us to do is multigenic editing while maintaining the integrity of the cells. This allows us to armor cells.
for vispa-cel, that means we have knocked out PD-1, which is the checkpoint pathway that's very important in lymphoma biology. With CB-011, we've taken another tactic where we have armored the cells, where we've knocked out HLA-1 and really immune cloaked the cells in myeloma in order to have longer persistence of the cells. What this means for our lead program, vispa-cel, is that these cells have more anti-tumor activity for the time that they're around. We see these cells persistent for about 30 days. During those 30 days, we get deep durable responses due to the increased anti-tumor activity of that product. As I mentioned already for CB-011 in myeloma, we've taken the tactic of trying to improve the persistence of those cells.
We see about twice the amount of persistence in that program, so we think that the immune cloaking is working in-
CB-011.
You know, before we actually dive into the pipeline, I sort of wanted to talk about, you know, the CAR T landscape in general, cause there obviously have been a lot of recent developments, and new tech that's sort of moving its way into the field. In particular, there's been a lot of enthusiasm around in vivo CAR T. You know, how are you thinking about this development within the cell therapy landscape, from a competition standpoint? Where exactly does allogeneic CAR T sort of fit into the treatment paradigm if in vivo CAR T actually has legs to it?
If we think about where we're at today, auto CAR T are clearly the gold standard for second-line large B-cell lymphoma right now. 75% of patients can't access it, or they can't wait for it. They're either medically ineligible, or they can't access due to geography or other financial constraints. There's 75% of the patients that need something faster or that could come closer to them out in the community. For allogeneic, off-the-shelf CAR T cells like vispa-cel, this is a sector that we feel like we can really be a market leader and give these long durable, you know, potentially curative agents to more patients.
The other benefit of allogeneic CAR T cells is they are from donor healthy T cells, and we've learned through treating over 140 patients at Caribou that young donor T cells matter a lot.
Yeah
for durability. Both auto CAR T and in vivo rely on the patient's T cells. We think there will always be a place for allogeneic CAR T cells, especially in these patients that have T cells that are neither not enough in number or not as functional. You know, in vivo is very early on. We already see that there's some safety signals that are coming out. There's a lot of engineering and things that they're gonna have to figure out over the next five to 10 years. I think for allo, we're ready to go. We're headed into pivotal trial.
Yeah
Hopefully this year with vispa-cel. We think that allo is well poised, really to increase the number of patients that can get these potentially curative agents.
Yeah. Why don't we focus on vispa-cel for the time being, also known as CB-010? You know, I know you presented data late last year with regard to vispa-cel. Talk to me a little bit about those results that you saw and, you know, how does this data set stack up against some of the comparators here?
Yeah. Late last year, we presented and disclosed clinical data on both our programs for vispa-cel. In particular, it was really the first time, with a meaningful data set, 35 patients that had gotten vispa-cel made from young donor that was partially matched at HLA, a modestly two out of 12 alleles. We showed efficacy and safety on par with auto CAR T, which a lot of folks never thought we'd see with allogeneic CAR T cells. We saw a plateau in our PFS curve with a 12-month PFS of 53%. Very high ORRs and complete remission rates that rival the auto CAR T. In fact, they look identical.
With a safety profile that's, you know, the best of the auto CAR T, much like liso-cel or Breyanzi, where we know that that product can be given in community centers because of the low rates of grade 3 CRS and neurotoxicity. We're really excited about having an off-the-shelf agent that looks just like auto CAR T, but you can take it out of the freezer when you need it and not have to manufacture. Patients won't have to wait 8 - 12 weeks.
Yeah. You know, I know you're using a partial HLA matching strategy. Talk to me a little bit about the percentage of patients that you can actually treat with that HLA matching and with regard to your cell banks.
Actually, it takes a very modest number of lots, to match 99%+ of patients at 2+.
Okay.
At the time of launch of trial, we model that it'll take maybe 10 lots.
to match 99% or more of the patients at 2+. We'll use a best match strategy, this will all happen in the background. The patients won't be waiting for or ever not be given a dose of vispa-cel. This will be done where we'll have these 10+ lots in the freezer. When they're, you know, signing up for the trial or ultimately in the commercial setting.
it will be a simple blood test. As they get started with their lymphodepletion, we will have algorithms that'll figure out what the best matched lot is.
send them a dose of that, in time to infuse.
Okay. There won't be a sort of lag time here.
No, there's no lag. In fact, in our clinical trials currently, you know, we've had patients that have reached eligibility and started lymph depletion on the same day because we can then ship the drug while they're getting their lymph depletion 'cause there's no risk for manufacturing failure.
Yeah.
Right? The site doesn't have to wait to have the dose on site to know that that patient's going to get CAR T.
Yeah. You know, I know at the upcoming EHA meeting, we're gonna be seeing some updated data from ANTLER. A lot of excitement around this data set. Help frame investor expectations with regard to what they can expect to see and sort of what should be the takeaways once that data is revealed.
You know, I think for ANTLER, it's likely gonna be more of the same. This is more months of follow-up on the same patient population. It really is just cementing the data that we have already as we move into pivotal trial. We'll probably talk about this later, but when we think about comparing this to non-curative agents such as the standard of care for these kind of patients, what it will do is set us up for the conversation on the chance of technical success as we move forward into pivotal.
Yeah. You know, obviously within the pivotal trial, you're going to be going after the second-line setting. I know a competitor just dropped some interim futility data not too long ago. That was in the front-line setting. I'm curious to get your thoughts as to how you see that second-line opportunity sort of evolving as we look at that trial as well as ZUMA-23.
Yeah. It's a great question and we've done a bit of market research and talking to folks to try to understand what impact that might have on a second line population that can't access auto CAR T or ineligible for auto transplant, and it's actually a very modest impact even on their highest success. Part of the reason is most of the patients that get into second line have never had a response to first line. So they're not in remission with an MRD positive result. They actually still have active disease. Those are not patients that are going on to cilta-cel after, you know, onto that trial.
Yeah.
Those are patients that would go immediately to second line therapy, and those are the patients that we would enroll on our trial. Similarly with ZUMA-23, you know, these are very high-risk patient population randomizing against R-CHOP. You know, we're waiting for data on those. Getting something like axi-cel into the front line.
Yeah
setting into the community is gonna be very challenging, for all the reasons of access, but also, you know, the safety profile of that product. I think, safe to say, we think there will be a meaningful unmet need in second line.
Okay
for a long time.
You know, I do know that there is a CD19 targeted ADC that's being combined with a CD20 bispecific in the second line setting. I wanna get your thoughts as to how you see that regimen sort of stacking up against vispa-cel, because it potentially also could be deployed in the community setting. I wanna get your thoughts there, and I'm pretty sure you know which regimen I'm talking about.
It's a great question. Both ADCs and bispecifics are agents that you give ad infinitum until they progress. These are weekly, monthly infusions that aren't curative. You know, right now, bispecifics are being used off-label in second-line large B-cell lymphoma. Some have had some failures in regulatory trials in second line. We know that's an uphill battle for some of these agents that aren't curative in second line. Vispa-cel just has this wonderful space where we are one and done, off-the-shelf, potentially curative agent that will look very favorable against a regimen, you know, that's weekly to monthly infusions for a year or more.
Yeah. you know, I know that you recently reached alignment with the FDA with regard to the pivotal trial of vispa-cel. Talk to me a little bit about that trial design and when you expect that trial to actually start.
Recently, we have our RMAT for vispa-cel. We have been discussing with the agency over the last several years different options for what vispa-cel pivotal trial might look like. We came to alignment with them earlier this year on exactly what we disclosed in the fall, which is a phase III study in patients who can't access or wait for auto CAR T and also are not eligible for auto transplant, which is the only other curative agent available for these patients. That means that we can run a randomized controlled trial against agents that are not curative. The median PFS in the literature for these regimens in high-risk patients is about 4.5 months.
That means for 250 patients randomized 1:1 with a single dose of vispa-cel, we have a very high chance of technical success, with the plateau that we see on our PFS curve. We have alignment on our control arm regimens.
Two of those are polatuzumab-containing regimens in case they don't get that in the front line, either combined with BR or R-GemOx, and then tafasitamab and R-GemOx for those patients that have gotten polatuzumab in the front line. We see a lot of excitement in both the academic and the community sites for this study. We are already engaging with those sites. We plan to have sites in both of the community where they can't access-
Also in the academic centers that have auto CAR T. That's where we enrolled our ANTLER 1 study for patients who can't wait.
You know, when we think about those two control arms, obviously those two regimens have different efficacy profiles, right? I'm curious to get your thoughts as to what is the market share that pola is, you know, attaining in the front-line setting, just so we can sort of figure out what the sort of breakdown between those two control arm regimens is gonna be. You know, just so you can sort of gauge or try to predict what the control arm is gonna generate holistically.
We're estimating about 20%, 25% or pretty equal usage of all of our control re-
Okay
regimens, in our control arm, and partly because this will be a global study. In the U.S., polatuzumab is probably used in about 30% of frontline patients.
That differs on type of site.
Yeah
different patients. We expect both in the U.S. and globally that this will differ between sites and patients.
Okay.
Overall there should be equal. As we've done our feasibility, that's why we're having four regimens.
Yeah.
There's a desire to have kind of options for these patients, 'cause each patient in front of them might need something different.
Okay. Why don't we shift gears now to CB-010. You know, can you remind us about the data that we saw for that agent late last year? How it stacks up against sort of the BCMA-targeted bispecifics in CAR Ts? 'Cause obviously that's a very burgeoning field. That's very crowded.
CB-011, as I mentioned before, is our BCMA allo CAR that's immune cloaked. We disclosed data on 48 patients from our phase I study last November, where we disclosed that we picked a recommended dose for expansion. That's 450 million cells. In the 12 patients treated at that regimen who had not seen BCMA targeted therapies before, we saw very high rates of response and complete remission, with 91% of those patients achieving an MRD negative state, which for myeloma is one of the most important.
Yeah
endpoints. We are currently expanding that.
that cohort in expansion. We've also disclosed that we're starting to treat patients who've previously had BCMA agents before, since that's one of the largest growing sectors of unmet need. We know that some of the failure mechanisms for auto CAR T and even bispecifics that target BCMA are due to the patient's own T cells.
Yeah.
We think the allogeneic BCMA-targeted cells may have a benefit for those patients.
Okay. You know, considering that extensive landscape of BCMA-targeted agents in multiple myeloma, while also acknowledging that, you know, for dose expansion, you're gonna be looking at both BCMA naive and BCMA exposed. I'm curious to get your thoughts. As you think about those two subpopulations, what do you view as the go/no go signal to move forward with CB-010 in each of those populations?
I think right now, you know, we're getting our numbers higher in both of those populations. We do still think the bispecifics are our benchmark for both of those populations. In BCMA, naive patients, we have exceeded that bar.
which is why we're continuing to expand. We just got RMAT for CB-011.
Yeah.
We look forward to talking to the agency about opportunities both in BCMA naive and BCMA-exposed patients. The exposed patients, there's not a lot available for them.
The bar will be lower. What exactly is that bar, I think, is yet to be determined. We'll wait. We're anxiously awaiting those data in the future.
Okay. you know, what sort of expectations should investors hold? Cause I know initial dose expansion data is coming later this year. You know, how should investors be thinking about that data release?
I think at EHA, what we have disclosed is we will have follow-up on our dose escalation patients.
The same patients that we talked about in the fall.
Yeah.
The expansion patients will probably be later in the year.
We're having a robust enrollment. This is an agent, again, also, at sites that have auto CAR T and bispecifics, and there's still an unmet need for an off-the-shelf one-and-done agent. I think we're really excited to continue to enroll expansion and share those data later this year.
Okay. Well, last question from me, and this is directed at you, Sri. Can you remind us what your cash on hand was as of end 1 Q, and what sort of operational runway that provides?
We ended Q1 with about $120 million, just under $120 million in total cash, and we've guided that that funds the company into the second half of 2027. What that gets us is the expansion cohort for CB-011 that Tina's been talking about. That's fully funded off our balance sheet. We're also able to initiate some of the critical startup activities for the vispa-cel pivotal trial, ANTLER 3, but we'll need to fully fund the ANTLER 3 study through data readout.
Okay. Well, that's really all the questions I had. Are there any questions from the room? No? All right, well, thank you for joining us today. I really look forward to all the data that's gonna be coming out from Caribou this year.
Thanks for having us.