All right, so flipping straight into the next session. Thank you for joining this session with Caribou. My name is Alec Stranahan. I'm a senior biotech analyst at Bank of America covering Caribou, and I'm pleased to be joined by Rachel Haurwitz, President and CEO of Caribou. Thanks for being here.
Thanks for having us. We really appreciate it.
Great. We have got time for a mini fireside here. Maybe just jumping in straight into it, Rachel, maybe at a high level, walk us through sort of the current pipeline strategy and sort of the refined approach, balancing the cash and pushing assets forward.
Yeah, absolutely. Just a few weeks ago, we disclosed a number of critical decisions we've made, prioritizing the continued development of CB-010 in lymphoma and CB-011 in myeloma. In concert with this, we discontinued two Phase 1 programs in AML and in lupus. We've also discontinued preclinical research. That allows us to really meaningfully advance these two programs, 10 and 11, to critical inflection points and to significantly increase our runway. We were able to revise guidance from funding our operating plan into the second half of 2026, all the way now into the second half of 2027. Alec, I should share, of course, these are all open-label Phase 1 studies. We are able to learn real time what's happening in these programs and ultimately make data-driven decisions. Doubling down on 10 in lymphoma, 11 in myeloma, this is really driven by the data.
Our enthusiasm for what we're seeing and what we've shared through these discussions is that we're seeing encouraging efficacy in both of these programs. In particular, with CB-010, seeing continued evidence that it has the potential to be on par with auto CAR-Ts. Encouraged about the future of these programs.
That's great. Obviously, that's the goal, right, is alleviate the logistical burden of auto while delivering comparable or better on the efficacy side. Maybe starting on CB-010, eagerly awaiting the updates in the second half of this year. I guess, what sort of classifies success here or would maybe dictate a go, no go to a registrational study?
Yeah, absolutely. What are we looking for? We are looking for an allo CAR-T that drives results just like the auto CAR-Ts. That's really the full picture. It's overall response rate. It's complete response rate. It's duration of response. The data we've committed to for the readout in the back half of this year are really kind of laser-focused on this 20-patient cohort that we're enrolling, where we're intentionally applying our partial HLA matching strategy. For each of these 20 patients, we're ensuring that they receive a dose of CB-010 where they and the donor share at least four of the 12 HLA alleles. This will allow us, hopefully, to confirm what we have thus far seen retrospectively, that modest HLA matching can drive outcomes that look to be on par with auto CARs.
What we have done by pushing out some of these timelines is ensuring that we have sufficient follow-up to really answer that durability question. In particular, we have committed that for those 20 patients, a majority will at least be at the six-month mark. Some will be meaningfully beyond the six-month mark. We are really looking for an overall profile that looks and smells and sounds like an auto CAR-T.
OK, that's great. I guess, what can you share sort of about the patient characteristics and the ANTLER trial and how these have maybe evolved over time?
Our dose escalation work, going back to the very beginning of this program, was in third line and later patients. We enrolled 16 patients in dose escalation. Based on the very encouraging data, we went to the FDA then to seek permission to really leapfrog directly into the second line setting. They granted that. Everything since then has been exclusively in second line patients. That has allowed us to work in our target population. That is the population that we would be making that go, no go decision for the pivotal trial. As we first started that work, we're inherently working at sites that have ready access to auto CAR-T cell therapies. Necessarily, our trial has been kind of selecting for patients who have disease characteristics, meaning they are too sick to wait.
They are part of that vast majority of patients for whom auto CAR-Ts can never be the answer. Actually, commercially, it's only 20% of patients who are getting auto CARs. There's a big chunk of that 80% who simply will never be able to wait. We know that biased initially for sicker patients in a number of ways that we can measure. As we've continued to work and accumulate data that not only we are excited about, but physicians are excited about, and been able to leverage XUS geographies where access to auto CAR-T looks different, it's allowed us to, I'd say, modestly shift the profile of patients. We're seeing some who look a lot more like the commercial auto CAR patients and some for whom I think allo will always be the answer.
OK. Is there maybe a particular threshold on ORR CR rate that you'd maybe put out there to help frame expectations or that you'd want to see versus other options in the second line setting?
Yeah, that's a great question. I would say a good way to kind of measure and visualize what we're looking for is to look at, say, PFS curves from the auto CARs and some of the data that we've put out historically. I imagine that is a way we will continue to visualize some of this because it captures so much of what you just asked about in one graph, right? It's really looking at the total number of patients who respond and critically how durable those responses are. Even what we've done historically is do our best to plot our data on top of some of the auto CARs to really paint that picture of similarity and outcomes. I expect we'll use proxies like that going forward as well.
OK. Do you think PFS is still kind of the gold standard as an approval endpoint in this setting?
It's a really great question, which probably leads me to we are actively discussing the potential trial with the FDA. Stay tuned. We expect that when we put out these data, we would be in a position to describe the pivotal study at that point in time. I will say the two approvals in the second line setting for the auto CARs, the primary endpoint was EFS.
OK, OK, so slightly different. Got it, got it. OK, the other update we'll see second half is CB-011. Maybe talk about this asset and sort of how the competitive landscape here for BCMA-directed therapies has evolved in multiple myeloma.
Yeah, the unmet need for cell therapy in myeloma is even more severe than lymphoma, right? I just said a moment ago, only 20% of lymphoma patients are getting auto CARs. Only about 10% of myeloma patients are getting auto CARs. When we talk to myeloma physicians and ask them, what does an allo CAR need to look like to be relevant and appropriate for your patients, they always point us to the bispecifics. That is the only other asset class that is readily available and broadly available off the shelf to this much larger patient population. What they are hoping to see from CB-011 or any allo CAR would be efficacy on par with a bispecific. Let's call that at least 60%-70% overall response rate.
We think a baked-in expectation that the one-and-done nature of an allo CAR is superior to a bispecific, where you are stuck on this repeat dosing for months as long as you can tolerate it with the really quite profound prolonged infection risk that comes with it.
I see, I see. That kind of leads me to my next question, which is, how would an off-the-shelf option maybe ease adoption of cell therapies? You mentioned that they're quite effective, right, on ORR, but 10% penetration is pretty low and probably lower than a lot of people would have expected based on the data. Do you think an off-the-shelf option is really the solution here if you can get in the ballpark?
I think it's a critical piece of the puzzle, right, because it solves for both rapid access and scale altogether, right? Even in our myeloma work, where we are doing clinical trials at the sites that have ready access to CAR-T and ABECMA, we're still rapidly enrolling this study. I think it's truly demonstrative of just how significant that unmet need and therefore opportunity is.
OK. I think you maybe already kind of touched on this, but do you think on par efficacy versus auto is required here, or maybe something in between, say, a bispecific or the cell therapies could be actionable given the increased convenience?
Yeah, look, what physicians tell us is they'd love to see an allo CAR that's at least on par with the bispecifics and that that for them would be a really meaningful tool in the toolbox for their patient population. Shoot for the moon, right? Better would be better. We think that that profile alone would be incredibly attractive for this patient population.
OK. When you think about sort of the efficacy metrics that's maybe most important, we talked about PFS maybe taking over in the LBCL setting. Is that kind of the metric here too, or is response still sort of the?
Yeah, it's a great question. I think there are a few pieces of the puzzle to highlight here. Of course, overall response rate. I think it's important to look at the fraction of patients who have a VGPR or better, certainly the fraction of patients who have a CR, restringent CR. On top of all of that is the ability to measure MRD negativity. We know that's really critical in the myeloma setting. It demonstrates critical depth of response and can be prognostic of long-term outcomes. Our update will include all of those metrics. We know MRD negativity rates are critical.
OK, OK, that makes sense. One question we've received from investors is just on the manufacturing and supply side of an allo program. Presumably, it should be much easier to scale for a launch. It is also not an antibody. There is a little bit more complexity. How do you see manufacturing sort of evolving at Caribou? How do you sort of scale up? How quickly could that happen if you do get good data?
Yeah, I think scale is absolutely one of our advantages. For example, with CB-010, our process today results in enough cells from just one run for 200-300 doses. It really just immediately changes the equation from the end of one auto CAR-T strategy, where instead a turn of the crank is 200-300 doses. They have a long shelf life, right? Typically, cell therapies can sit in the freezer for years and maintain their activity. It really gives us the opportunity to completely change the game as we think about supply.
OK. And that's kind of the scale today in-house at Caribou, right?
Actually, we develop the processes in-house. We do not do our own manufacturing. We have outsourced that. Again, we're able to leverage great expertise in CMOs who we partner with. We don't have to invest in our own brick and mortar to do this work.
OK, OK, that makes sense. That gives you flexibility on the capacity side as well. I guess you talked about sort of the refined pipeline strategy. Maybe talk about the updated cash runway. I think it's into second half of 2027 now. What's sort of contemplated within this guidance? What sort of steps of de-risking does this kind of encapsulate?
Yeah, great question. Yes, our guidance is into the back half of 2027. It allows us to deliver on all the things that we've been talking about in terms of these critical data updates. It does not contemplate, say, running the pivotal for CB-010 or doing dose expansion for CB-011. However, there's sufficient flexibility that we could do some of the setup work for a pivotal study at risk ahead of raising the capital necessary to execute on the pivotal study.
OK, OK, that makes sense. I guess in the last few seconds we have here, is there maybe one key focus point that you get from your investor conversations here at the conference or elsewhere that would be helpful for people to hear? Just maybe something that's misunderstood about the story or a differentiation point that you think is underappreciated?
Yeah, I think a big question that people often bring to the field, especially when they're new to the field, is will allo CAR-Ts ever result in durable outcomes for patients? We've been doing this long enough now that for some of these patients, we know the answer is yes. For example, our very first patient dosed with CB-010 was almost exactly four years ago. He remains in complete response. There are an increasing number of additional patients who are past a year, past multiple years, still in complete response. I think it's really encouraging not only for our work, but for the field to demonstrate that allo CARs can drive durable responses.
Yeah, and that's the sense I hear as well. There's folks that were maybe in the initial wave of interest and are now revisiting things. It's crazy to think that the first patient dose with CB-010 is four years out. Great to see the progress. Looking forward to the second half updates. I think we'll have to leave it there for time. Please join me in thanking Rachel for the great discussion.
Thanks, Alec. Really appreciate it.