Well, good morning, everybody, and thank you once again for joining us for our Fifth Annual Oncology Innovation Summit. I'm Yaron Werber from the biotech team, and it's a great pleasure to moderate the next session with 2seventy bio with my colleague, Jayna Hann. With us today are Chip Baird, CEO, Anna Truppel-Hartmann, Chief Medical Officer, and Jenn Snyder, SVP of Corporate Affairs. Ladies and gentlemen, thanks for joining us. We appreciate it. So, Chip, maybe we'll start out with... There's been, we're getting a lot of questions these days about the market sort of dynamics in general, in CAR T. You know, Q1 was a bit soft for the CAR T agents. Bispecifics are, you know, continuing to kind of get some uptake. What are you seeing in the market right now from a dynamic, just even CAR T usage broadly? Yeah, Yaron, thanks for the question, and thanks for hosting us this morning. Pleased to be here. Yeah, look, I think the multiple myeloma market and CAR T market continues to be incredibly dynamic. We're about seven weeks now since our third line approval from FDA, so in the early days of launch here. And really, since we've been on the market, it's been dynamic. It's been affected by things like manufacturing capacity and different competitive entrants, and understanding the importance of sequencing, real-world evidence. So many factors that can affect perception among treating physicians and utilization. In the end, what we know is CAR T is a transformative therapy for patients with myeloma, dating back to the original KarMMa study, patients who had exhausted all available treatment options, who were on their way to hospice care, putting those patients into durable remissions is simply a remarkable result. And we've built on that with the KarMMa-3 data, which we can get into here. But you know, again, as we've said, the first quarter was what we expected, which was flat. We had been clear on that. Second quarter here, too, just given the lag between the approval in early April and then, you know, from enrollment to apheresis to treatment, you know, we'll only begin to really start to feel the revenue impact late here in the second quarter of the additional third line patients. That being said, we have a lot of reasons to believe, and we can get into them, in terms of the return to growth for Abecma. As you know, the company's squarely focused on that now, with clear road ahead. We, we've knocked down the regulatory risk. We have a burn rate that is manageable and potentially break even operations here in 2025. So we've bought ourselves the time, and now we have the data set, and we've got a committed partner. So all those reasons give us confidence from these levels and return to growth. And in general, is the fifth line sort of, you know, and the fourth line opportunity sort of fully tapped out? I mean, we're seeing even softness from Carvykti in Q1, and- Yeah ... and, you know, as we talk to a lot of centers, they are talking that they do have capacity for both agents. So we're getting a lot of questions these days about the level of demand. Yeah. Well, I think that gets to sequencing and the understanding of the sequencing. So look, I think in a capacity-constrained world the availability of a off-the-shelf option made a lot of sense. And today we are at a point where we have unlimited capacity for the fifth-line and third-line demand that we're starting to see. We know Carvykti has made progress on capacity as well. We believe that message takes time for treating physicians, community centers, folks to understand. And again, you know, there's a fifth-line dynamic, but there's also an earlier line dynamic. Being here in the third line, being here in the third line alone, with one other approved CAR T, is a much bigger market opportunity, and it's one where we're really the only player. So again, these dynamics are all gonna be playing out over the course of 2024 and into 2025. But no, we think CAR T still has an important role to play in patients who are already at that later fifth line setting. But, you know, at the same time, we're moving aggressively into the treatment of third-line patients. And so what are some of the barriers to getting sort of an earlier stage patient moving on to CAR T? Or, or- Yeah, I don't... I mean, we- Uh, processes ... you know, again, it's early days, so I think, you know, ask me that question again in a quarter or two here. But certainly, some of the traditional barriers in terms of reimbursement challenges or step edits or things of that sort, we've not seen, and that's consistent with the launch that we had in the fifth-line setting. So, that's terrific. You know, I think geography can be another barrier, particularly for people who are remote, for people who have to travel across state lines, so things like that. And again, most of our business to date has been focused in larger academic centers, but we've been clear about the importance of expanding the geographic footprint in the United States to cover all patients, particularly in the more rural settings. You know, and then I think the last thing for third-line patients, and again, it's a different calculus in the fifth line, is the benefit risk and the safety profile, and I think that's one where we have a demonstrated consistent safety profile. We are differentiated in terms of the black box warnings that are associated with our product, and you know, we think those those larger neurotoxic risks for a patient in a third line where there are other treatment options available, we we think that is important as physicians and patients settle upon the best course of therapy. And what kind of patients do you think are best candidates or likely to be the early sort of adopters for CAR T? Is there any sort of profile, and what's your marketing message? Yeah, look, I think, it's, hey, you know, what we've seen, again, is patients who are under the care of treatments under the care of physicians at more academic centers. So one thing, you know, we're not niching the product. We're not saying, "Oh, you know, this is for older patients," or this or that. This is for all patients under the label. Again, triple class exposed, refractory. These are patients that we studied in KarMMa-3 that are progressing rapidly, and where we've shown that treatment with CAR T, with Abecma specifically, can make a difference for them. But again, our go-to-market strategy, line of attack for the third line setting is all comers. What do you... You know, one of the things we're hearing from physicians is that it's for a CAR T, they might wanna move to an earlier population in a younger population with higher risk. Is that sort of what you're hearing? Or, you know, with Abecma, given the safety profile, you can also go elderly with patients with more comorbid sort of conditions. So maybe how are you kind of thinking about it? I think it's both. I think, patients who, you know, for, for older patients, for older patients, you know, certainly the, the safety profile makes a lot of sense. And again, we've studied a, a sicker, more rapidly progressing set of patients in KarMMa-3, and so there, I think the data are clear, relative standard of care of what, what Abecma can provide. But Anna, anything you would add from a medical perspective in terms of how to think about those- Yes, thank you, Chip, and thank you, Yaron. It's a pleasure to be here. When it comes to Abecma, the beauty of it is we have studied KarMMa-3 in a triple class exposed patient population, and all subgroups benefited from the treatment with Abecma, as is shown in the forest plot. Everyone significantly had improved PFS. Also, patient with high risk, but also all comers, standard risk patients, and independent of age. Therefore, I wouldn't say that there is a need to restrict the patient population for Abecma in this third line plus setting, since we have shown benefit across all subgroups. Yeah, so that's kind of what I'd like to add. Okay. Yeah, that makes perfect sense. Can you just remind us how many centers currently are open for using Abecma? And can you give us any sense, what's the distribution of use by, like, the first quartile versus, let's say, the last quartile? Yeah, Yaron, I'll take that. It's just over 100, about, I believe about 115 centers here in the United States today. And, you know, I would say the original academic centers are the make up the bulk of the volume. Again, some of these more remote centers, I think, are serving an important need for patients who live in more geographically remote regions. But I think the bread and butter of this business, you know, remains the major academic treatment centers that we're that we're all familiar with. As you think about sort of progression, are you thinking about opening more sites? What would drive more uptake, you know, in some of those sort of smaller, smaller sites? Yeah, we have a plan to continue to increase the center footprint and continue to expand out. And, you know, I think that's just gonna be a longer term narrative in CAR T rollout and CAR T adoption. And again, we get these questions a lot to say, "Well, it was vector that was capacity constraining, and then it was drug product, and maybe now you have drug products." So is there a capacity constraint in apheresis or is there a capacity constraint in the number of beds or the number of centers? And the answer is yes to all. We think about all, you know, some of those we have more direct control over in terms of the supply chain. Others, like the center footprint or how many beds or things like that, we have less. But in the end, you know, physicians, particularly those more associated with academic centers, are well aware, well-versed in CAR T therapy. You know, they have it, they wanna be part of it. And I think for the more remote regions, more of the community setting, I think that's still an education process. But you know, we believe that will continue to evolve over time. The other thing we've seen is patient demand. Patients are aware of CAR T therapy and the benefits, and, you know, really, we hear it consistently, the one-and-done nature of the therapy, the ability to, after all these different lines, to forget about myeloma, and you know, weekly or biweekly infusions and other visits is a profound thing, a meaningful thing for these patients. So, we've seen pull from the patient side as well. When you're looking at current usage in the academic settings, what's been the rate-limiting sort of gaining factor? Has it been literally just availability of patient and patient demand, sort of, in fourth- and fifth-line setting? Do you see any... You know, and also, what are you seeing in terms of capacity? As you said, number of beds, ability to apheresis- Yeah ... things like that. Yeah. You know, I think for, as you know, in the first two years of launch, it was, it was capacity on our side. The availability of vector, the availability of drug product, you know, the ramps, the step-ups that we talked a lot about. You know, today, we're in the fifth line plus setting, so, and kind of going back to the early part of this year, much more dynamic next, multiple CARs, TCEs, you know, basically the community setting versus referral to the academic setting. You know, our view is with this third line approval for us and, and for Carvykti as well, it, it is a very different market now. And, again, we're in the early days of that. And what we've heard, and we've seen, interesting analysis reports on, you know, the number of beds as a, an important capacity constraint. We haven't, we haven't really felt that yet. Last thing I would say is just, you know, as, as you think about these trends, you know, one of the things that we have seen is that it is very site specific. And so it's- you can talk to a handful of sites and, you know, come up with what you think the picture is. But, you know, with, with the number of sites that we cover, man, each of these stories is unique and the dynamics driving. So again, I think, ask me this question again in a quarter or two, and I think we'll be able to speak a little more about some of these third line dynamics. Got it. And by the way, for the audience, if you have any questions, by all means, let us know. You can either email me directly or use the Wall Street Webcasting website, and I can just ask the question on your behalf. You know, one of the things that we've been doing a lot of kind of checks, and again, at big academic centers, some of them are going all in, and are building capacity, they're building wards, they're building new services, both inpatient and outpatient. Some of them are, you know, a little kind of slower, even though they're heavy users. A lot of them so far have said that they sort of ran out of patients. Now, admittedly, they're doing a lot of clinical studies, so they ran out of patients kind of in fourth and fifth line, and they do intend on moving it up. Yeah. So I think the question becomes, you know, we're hearing your capacity is increasing, right? And you have a lot of capacity. Your competitor's capacity next year is going to double, sort of, all in, including clinical studies, and that includes commercial. So not doubling- Yeah ... the commercial capacity. When we ask centers, can you sort of double usage? You know, in the big academic centers, it's not clear that they're planning on sort of doubling usage in the next year. So a lot of it's gonna, you know... Again, overall capacity depends again on moving to the periphery. What sort of gets a community center to start using from not being a user before? Yeah. I mean, I think this gets to the build, and this is where we have been making these investments in these more remote centers. You know, it's. I would say operationally an even bigger lift than opening a clinical study in terms of getting... You know, this is a center that has not been deploying CAR T in the commercial setting. There's. It's a significant build in terms of capabilities, in terms of the processes, in terms of documentation, everything that goes along with that. You know, so you know, it can take six plus months to open one of these centers and but we view that as an investment for exactly the reasons that you highlighted is if you want to continue to grow the business, it's both gonna be increasing utilization at the major academic centers, as well as building out the bottom of the base across the country. So it's gonna be both. And you know, again, just as a reminder, you know, we did, just to talk about the numbers for a second, you know, we've been in the $50 million range here the last two quarters. In the first quarter of last year, we did $118 million, second quarter was $115 million. So, you know, at that level, at those levels, just getting back to those levels back when we were in just the fifth line plus setting—that puts us on a path with these cost reductions that are made to be breakeven or better, right? And so, you know, to say, like, can you get back to those levels with this much larger market opportunity with a, and again, we should get into some of the data, but a bigger data set in earlier line patients that tells an even better story for the product. Like, yeah, like, we absolutely believe that. What is the peak of the curve look like in, you know, three, four years out, and how do these dynamics play out? I, you know, your crystal ball is probably as good as ours, but I think, you know, kind of stepping back, like, from these levels, oh, my God, like, we, we absolutely should be able to grow. And I think that's wholly unappreciated right now. It's, it's a lot easier to think about, you know, phase one data and the, and the possibility of what's to come than kind of where we are, and, and we understand that, and, and it's shown me. But, again, we believe, our board believes, like, from these levels, we, we absolutely can, can see some meaningful growth. Yeah, absolutely. When you're looking at patients, let's say in KarMMa, and then, you know, KarMMa-3, are all the sites now open commercially? And do you have a sense, you know, are they all using kind of a Abecma actively currently, or a lot of them are doing clinical studies now? I think most of those sites that, you know, continue to be involved in clinical studies, you know, those academic kind of scientific scientist/physician investigators that we work with, they, you know, they're always going to be involved in clinical studies. And again, I would say that the I don't have it in front of me to tell you, like, every single site that we've done a clinical trial with is now using the product commercially. But, you know, feel pretty comfortable to say the vast majority are. And, you know, what's been interesting is we've seen centers, and we've seen it in Europe, and, you know, we are seeing it in the U.S. as well, where maybe they switch to the competitive product, or they switch to more TCEs, and maybe they go several months without writing a Abecma prescription. And we've seen that reverse. And we've seen people come back online, and I think that's gonna be a key part of the return to growth, is getting physicians to take a fresh look at the data, to take a fresh look at their own data. And I think when they do, you start to see that the efficacy profile here is a lot closer than what conventional wisdom is. You know, all you have to do is look at the real-world data to to start to see that. Again, I think that's an important part of our commercial strategy, our communication plan here in 2024 and beyond. Yeah, got it. Okay, maybe, next question, is KarMMa-9. So that study in, you know, just after first-line usage in patients who are not adequate responders, Mm-hmm ... it is currently enrolling. It started enrolling sort of late last year. Can you talk a little bit about the timing for that data? You know, how would that, you know, ultimately fit in against sort of quadruple therapy or triple or quadruple therapy in first line? Yeah, I'll ask Anna to comment in terms of the design there and why we picked it, and kind of some of the earlier concept studies that helped inform that. But in terms of timing, I think it's too soon to say. It'll be driven by enrollment and kind of event analysis. So I think we'll be able to get more specific as we get a little further into the study. But maybe, Anna, I know that our strategy in the front line is different than J&J. And again, it just speaks to the breadth of the opportunity and kind of where do you want to play. So can you talk about that, Anna? Yes. Thank you, Chip. Yeah, so we selected KarMMa-9 out of several reasons, and the first one is that transplant is still center of care in the newly diagnosed setting, in patients who can receive transplant, and no other therapy has shown yet, as being an improved outcome over transplant. In addition to that, you specifically mentioned that the quadruple therapies may change the newly diagnosed landscape, but also there will be an abstract at ASCO talking about those data. And also, again, we can see that less than 50% really achieve a CR post-transplant, and that's exactly the patient population we're studying in KarMMa-9. The patients that do not optimally respond to transplant and do have still a significant upside potential with regards to the efficacy of a product, and that's where we are studying KarMMa-9. And finally, I'd like to say that the data supporting this patient population is coming from the KarMMa-2 Cohort 2C study, which is a phase 2 study, and we presented it several times. The last time at ASH was the most recent update, that we showed a CR rate of 77% in patient that had less than a VGPR. Not less than a CR, less than a VGPR. And we really believe that these and then in the PFS data look very promising as well after three years. And therefore, we do believe we have a very compelling data set supporting Abecma in the suboptimal responders post-transplant. So therefore, we are very excited to continue to enroll the study. And as Chip said, we can't disclose any kind of further details on the timelines, but we are, we are very much putting all the efforts behind that KarMMa-9 study. Well, terrific. Chip, Anna, and Jen, I think we're at time. Thank you so much for joining us. We really appreciate it, and we'll continue to follow closely. Yeah. Thank you so much for hosting. Yeah, thanks, guys. Have a great day. Absolutely. We'll see you soon. Thank you. See you soon. Okay. Bye-bye.