Hello, everyone. Good morning. This is Mani Foroohar from Leerink Partners with my partner. Welcome everyone back to day two of the Leerink Global Healthcare Conference. We're in my adoptive hometown of Miami. Welcome everyone back, and hopefully the audio is coming through clear. I'm hosting the Caribou Biosciences team this morning. I've got Tina and Sri. How are you guys doing, and how's Miami treating you?
Good. It's nice to be in the sunshine. Thank you.
Yeah. Thanks for having us.
Well, a pleasure. Before we go diving into Q&A, let's have a quick update on where we are on data throughout this year for the pipeline. Separately, we'll start chatting events, funding strategy, et cetera. Let's reset the table in terms of catalysts for the year.
Sure. As you know, we put out clinical data in November for both vispa-cel and for CB-011. This year, it's another busy year for Caribou. We're going to have additional follow-up from the vispa-cel dataset in 2026. Like we had a medical meeting, we initiated dose expansion for CB-011 late last year. We'll have both follow-up from the dose escalation data we put out in November, as well as additional data from dose expansion that we just initiated. Look for those updates in 2026.
Okay. Let's talk a little bit about how we think about financing strategy and how that aligns with execution timelines, pivotal design, et cetera, which I guess is a question for you, Tina.
Let me start, yeah, with the plans for the pivotal trial. Right now, we are in discussions with the FDA to finalize the design on a phase III randomized controlled trial with vispa-cel against standard of care in second line, large B-cell lymphoma in patients that aren't eligible for transplant and/or auto CAR T cells. This allows us to do a randomized controlled trial of about 250 patients with a PFS endpoint, and we are in final discussions around the statistical design, the patient and the control arm. That will be coming in the first half of this year, and then I'm gonna hand it over to Sri about how that will lead to our financing efforts that will be required to run that trial.
Yeah. Tina noted, those discussions are ongoing and really to initiate the pivotal trial, there are two things that have to happen. One is conclusion of the discussions with the FDA on the pivotal trial design, and then securing sufficient capital to fully fund the study through data readout. Now, we don't have to have all that capital on our balance sheet the day we start the study, but we need to have line of sight to that capital to say we're fully funded through data readout. We expect that after we have concluded our discussions with the FDA, that would enable us to have those discussions with potential investors and funders of the trial. Now, we're thinking about funding across multiple different options.
Equity capital markets are certainly one source of that, but also looking at potential business development and other, I'd say, more structured types of financings, non-dilutive sources of capital as well. We wanna be very thoughtful about how we fully fund this program.
Let's talk a little bit about some of those partnership BD non-dilutive sort of approaches. How do you think about where we are in terms of market demand for partnerships and assets like this? All right. As the company is now on the other side of Pfizer's negotiation right of negotiation, how do we think about where demand is for these assets, and who would be the right partner? L ike what profile of company? I'm not asking you to like name a name and restrict everybody .
I think a couple of things. One, the timeline for business development is something that not fully within our control, certainly. As we think about how we fund the clinical trial, certainly that is an option, but it's not, I'd say, the base case to fund our pivotal trial, just because of the timing component of it. It takes significant amount of time from not just Caribou, but also potential partner on the other side. On types of partners, I'd say there are a couple of different classes. One are groups that are in cell therapy today that believe in the technology and made investment there and understand what we're doing with allogeneic cell therapy and the potential access benefits.
There are other pharma companies that aren't in the space, but we offer significant advantages with vispa-cel that look very different from traditional cell therapy. We've talked to you before about cost of goods being one of those, right? Vispa-cel cost of goods are anticipated to be 96% lower than auto CAR Ts. That looks more like a drug or something you can build a business around. There are companies out there that have not gotten into cell therapy out of concerns about the economics there, where a drug like vispa-cel could make much more sense given those dynamics.
Let's talk about the economics of this business. I think one of the challenges that cell therapy has faced, both fundamentally in the physical world, but also in sentiment in the minds of investors, are concerns around cash generation, margin profile, distribution, timing, combination of issues that all add up to how quickly can this business become an attractive business. Talk to how that has evolved in your conversations, and also a little bit where you are in terms of moving out of the most challenging segments of that business model out towards community, out towards outpatient, et cetera.
You wanna talk about that part first?
Sure. Let me talk about the clinical part first. You know, what we've been able to do with an off-the-shelf allo CAR T cell is get immediately cell therapy to patients. This is required at academic centers as well as community centers. We're doing our ANTLER trial at academic centers. We're enrolling patients that can't wait for auto CAR T cells or they don't have enough their own T cells to make an autologous product. The demand is there. There are patients that cannot wait or cannot access auto CAR T, and we think it's about 75%-80% of patients. A lot of those patients are being referred into these academic centers, but then can't wait the two to three months it requires.
Even if those academic centers have something immediately available, what we know from our ANTLER trial and what we hear from other sites that we're talking to is then they'd have something immediately available. That patient wouldn't have to wait those four, eight, 12 weeks to get their autologous CAR T-cells. Once something like this is out in the market, we think there's a lot of demand, both at the academic centers for the patients that are getting referred, but of course, we're also talking with these sophisticated community centers that haven't yet invested in the infrastructure needed for CAR T-cells because of the complexity of the manufacturing of autologous.
When they hear we have something that we can just ship on demand and they can start lymphodepletion and infuse immediately, that's something as Sriram Krishnaswami mentioned, they're used to doing. They have infusion centers. They have the hospitals that can care for these patients if they have toxicities. A lot of these centers, as many of them who are taking up bispecifics already are, ready to start thinking about taking on an allogeneic CAR T-cell. Those are really the two sectors clinically that will allow us to get to more patients at the academic centers who already are comfortable with CAR T-cells and these sophisticated community centers that are now getting more and more comfortable with bispecifics, cytokine release syndrome, and are ready to have a one and done allogeneic CAR T-cell in their armamentarium.
I wanna touch base on the complementary side of that, which is the product side and where what you guys have disclosed and how we should think about building out a donor base, what an appropriate donor base would look like, here globally, et cetera, to supply the broad universe, so all possible patients, and operationally what that looks like in terms of accumulating an adequate supply for any hypothetical future launch.
That's a great question. Right now as we prepare for pivotal trial, we think we need about 10 lots. 10 different donors, 10 lots to get enough doses to match all of our patients, 250 patients in the trial at two or more HLA match, with an average match of seven. We think that this would supply the U.S. population. We can get 200-300 doses per lot. This is thousands of doses that will be ready for the pivotal trial. There's only 9,000 probably patients in second-line large B-cell lymphoma. You can imagine we don't need many more lots for launching into that indication in the U.S.
We're already starting to look, you know, at HLA diversity and what we would need in the freezer to supply anyone on demand in other regions. We think it would just take other lots, you know, supplementing our diversity in the freezer, to go outside of the United States. We're just starting those efforts, especially as we're starting to think about the global clinical trial, but also, as you mentioned, out into the land of possible. Well, we know with one manufacturing suite in the United States, we can generate 9,000 doses a year. As I mentioned, that would supply the U.S. for a whole year if we had 100% of patients being treated. You can imagine we can scale as we would need to, both for the U.S., in different indications as well as ex-U.S., with very small footprint.
Just to note that one suite Tina talked about is only 500 sq ft. It's at a U.S. CDMO, and the process we have today is commercially ready. We're going to have batches ready to go when we start the pivotal trial for a process that we believe is already commercially ready.
Let's talk a little bit about moving back to the pivotal trial. Obviously, one of the questions is what's the right site selection? We've seen site selection and investigator experience be really important in terms of execution of trials. This has been, I think, the most extreme example of that was Allogene. I'm dating myself now, four years ago with an off-trial administration of a drug, which obviously created challenges there. I think we were all around for that. Not me to name check anybody.
Obviously, how do you think about site selection, U.S. and globally, and what the right patient population is, to reflect the most commercially viable label and the extent to which that patient population in the pivotal translates into label discussions, which in this case is a little more delicate because you've got a standard of care that exists. This isn't a blue ocean with no approved therapies.
In second-line large B-cell lymphoma, patients who are not eligible for autologous CAR T-cells and are not transplant eligible, there's actually not a standard of care, which is why we are negotiating with the agency a control arm of immunochemotherapy possibilities, things like Pola-BR, and other immunochemotherapy. Because these patients can't access the standard of care, as you mentioned and as I already mentioned when we were talking about access eventually to this drug, even for the clinical trial, our big academic centers have these patients that aren't transplant eligible and can't wait, either socially or medically, the months it takes to auto CAR T.
We will have U.S. academic centers enrolling our pivotal trial, but we also have the opportunity to expand out into these sophisticated centers that are, as I mentioned, doing bispecifics. We, as Caribou, will be evaluating each of these sophisticated community sites to make sure they have all of the things required for infusions, toxicity management, getting all the algorithms in place, really, as a way of showing we can do this on launch as well. Our pivotal trial will be, you know, the chance we get to expand out into the community centers, find the physician groups that are willing, you know, to have the CAR T-cell teams that will be required with the support of the hospitals behind them, to run the trial.
Of course, you know, clinical trial requires a lot of other infrastructure that's not required for CAR T-cells, so it'll be a subset then of what's eventually going to be able at these community centers that could do it in a commercial setting. That's the United States. When we think globally, the autologous CAR T ineligible and transplant ineligible population, we need to go to countries that also have an aspect of access challenges. These have to be countries that have autologous CAR T-cells, so that they'll be relevant to the United States and the FDA when those data are reviewed. We're looking at countries that have access to auto CAR T, therefore, these sites also have experience with cell therapies. They have the systems in place, but they can't get them to all their patients and also are looking for an off-the-shelf, readily available CAR T.
In the U.S., a lot of the community sites Tina talked about that we're targeting are administering bispecifics today, so they're equipped to deal with a lot of the toxicity events that arise from this class of therapies.
You've talked about standard of care and access, and in the real world, the existence of a standard of care and being able to access therapy collapse to the same thing from the patient perspective. If you can't get the care, it's clearly not standard. That hasn't always been the view of the agency. Obviously, decisions around control arms have become contentious, if I may make a political statement. What is the state of your conversations with the FDA around the extent to which a control arm should be standard of care as defined by best possible data in sort of a platonic sense, capital P, or standard of care being determined by what's accessible to patients in the real world financially and based upon distribution systems? How has the agency defined what they call standard of care in the context of what will eventually be a registrational review?
It's a great question, though we're continuing to have those conversations. Things like Pola-BR are on the list of things that they're willing to accept as a control arm. I can't necessarily speak to where we're gonna end up finally, but we're confident that immunochemotherapy will be the standard general type of therapy in the control arm. Clearly, these patients are auto CAR T ineligible, so that standard of care will not be required for the control arm.
Let's talk a little bit about the state of your discussion with the agency. Obviously, there have been and this is a conversation I've had with, I think, now 15 different companies over the course of less than a day. Let's talk about how your conversations have changed or not changed at the agency. How much stability have you had in terms of counterparties in your particular review process? Have you seen any changes in terms of capacity, resources, et cetera? Obviously, the agency's gone through a volatile period of a couple of years.
vispa-cel has RMAT, we have had regular access and frequent access to the FDA over the last couple years as we've discussed paths forward. Our team has been quite stable, our review team. It does take a very official process to talk about every, you know, issue, which is why I think it takes, you know, all these cycles of interaction. That perhaps takes longer now than it used to. But we have had very productive interactions with the agency and are continuing to have very productive interactions. We're confident that we will soon get to those final discussions for the pivotal trial.
Can you remind me on the timeline for the discussions and the venue in which we should expect to hear feedback from you guys?
Yeah. We haven't put out specific guidance on timing other than to say our goal is to initiate the pivotal trial later this year, and in order for that to happen, we need to come to conclusion with the FDA here, before that.
I'm gonna hop off this topic. Obviously, the company has generated some internal data in myeloma. You've looked at autoimmune applications, et cetera. Talk to me about opportunity set to monetize that data that's in-house and to find a new home for that data, either internally dependent upon financing resources, but also externally, to allow that data to find itself, to find a place to be monetized and move forward to benefit patients. Like how do you think about the value of those resources and where that data set that's in-house can go?
I think CB-011 is a great example. We put out data in November on a robust data set of 48 patients worth of data that had been treated at different dose levels, including 12 at our recommended dose for expansion. Very strong initial data. The next phase there was an expansion cohort, which we have the resources to run and have initiated and expect that data later this year. In parallel to that, we're looking to have our first discussions with the FDA on the regulatory path for CB-011. The combination of longer follow-up from the data we put out last year, plus additional patients where we're looking at both these prior BCMA-exposed and BCMA-naive patients, and the regulatory piece could all come together and potentially lend itself well to partnering discussions. Do you want to comment on autoimmune?
Yeah. With vispa-cel, I mean, I think we're even more excited than we were before on the activity of vispa-cel and its opportunity in autoimmune. Obviously right now we do not have an active program in autoimmune, but we still do have an active IND. You know, as we get that program moving forward, I think we would be very interested, either internally or with an external party, to go back into autoimmune since we know CD19 CAR T cells can really benefit patients in that situation.
It sounds like that's something that you would see primarily as a partnerable asset rather than something you'd move in internally. Or am I, or is that the wrong way to think about it?
For autoimmune?
Yeah.
You know, as I mentioned, we have an open IND. I think as we look at life cycle management of vispa-cel, we're gonna start weighing those opportunities. I think it's a big opportunity, obviously. As we think about our resources and where we allocate them, I think we will, you know, very seriously be thinking about what the next steps would be when we have the capital to do so.
Perfect. I don't wanna gloss over CB-011 that you brought up. I just slid right past. I owe you an apology there. Let's talk a little bit about that data. To clarify, to what extent Caribou has control over that asset completely or, are there any residual information rights that are retained by Pfizer, within the constraints of what you guys have disclosed, obviously?
Yeah, we have control over that asset. Pfizer is sort of a friend at the table. They have information rights where we share updates on the program and a right of first negotiation, which expires later this year. That is a program that's wholly owned by Caribou.
Great. We've talked a little about the CB-011, like corporate structure. We've talked about the sort of ANTLER study, pivotal, et cetera. Let's zoom forward to the other side of pivotal data and sort of how to commercialize an asset like this globally. Obviously, we've talked about the U.S. opportunity. I presume that, you know, when you look out globally, that you will need local manufacturing facilities elsewhere 'cause you may need a little bit of a donor mix depending on the population by country. I know we talked about this earlier.
Yeah.
Is it reasonable to assume that that's something that would land with a in-country partner in places like Japan, Europe, et cetera?
I think we would need depots there for supply, for ready access, you know, so when the patient's ready in some of these regions, we would probably want a supply depot. I think the actual manufacturing, we haven't talked a lot about this, so, but when we get to that situation, as Sri mentioned, it's a very small footprint in our CDMO that can generate thousands and thousands of doses. I imagine we would scale locally, in the U.S. and then just ship our supply elsewhere. As I mentioned, it doesn't take very many donors to diversify the HLA. It might be, you know, that we need a handful of patients of different HLA diversity to fill in gaps that would help us, you know, go globally into certain regions. I imagine we would supply those. You know, we would generate those ourselves.
Mm-hmm
have supply depots. That's future speed.
On the commercialization piece, we see ourselves as being able to commercialize vispa-cel in the US. But you're right, ex-US, I think the path there will go through partners. On myeloma is a much bigger commercial opportunity, as you know, which is why we think that's ripe for partnership as well. Look, I think if we're on the other side of pivotal data and we've got options for ex-US partners, we're looking at myeloma, that opens the door for some of your prior questions on other indications or the life cycle management.
That makes sense to me, and I think I wanna touch base on something that I continue to get questions from investors. I guess an addendum to the last question. Which is not just the local manufacturing and how to think about the depot dynamic. How much HLA variability is there globally in terms of what you would need for a product to treat patient populations in places like China, Japan, et cetera, that have a different ethnicity mix? Does that translate to the HLA matching dynamic needing to be a different product or simply a subtly tweaked manufacturing process? Like, will CB-010 be the same product in different geographies or can it be, I guess is the underlying question.
It's a great question. I think we're starting to evaluate that HLA diversity. As we talk to the regulators in those countries, I think we may get that answer, and would probably, you know, need to do further evaluation. You know, as we mentioned, the COGS here are quite low, so the ability to have another 10 batches for different regions, you know, is something that's quite achievable. I do believe this would likely be the same product despite different regions, but again, we would have to, you know, talk with the regulators about that in the future.
Great. That makes sense to me. I think we've hit on the key points. Obviously, we're running out of time here. Thank you so much. I'm looking forward to seeing more of this data and moving forward to pivotal.
Are we.
Yeah. Thank you, Mani.
Thank you for having us.
Thanks, guys.