All right, well, good afternoon, everybody, and thanks again for joining us at the 44th Annual TD Cowen Healthcare Conference. I'm Yaron Werber from the biotech team, and it's a great pleasure to moderate the next panel with my colleague Jayna Hun. We have today 2seventy bio. To my left is Chip Baird, incoming CEO. To his left is Anna Truppel-Hartmann, Senior Vice President of Oncology Clinical Development, and then to her left is Vicki Eatwell, Chief Financial Officer. Team, thank you so much for coming. We appreciate it. Thanks for having us. So lots to talk about in the space, and we're actually doing our myeloma panel, I believe, right after this one with two KOLs. Let's talk a little bit about the upcoming ODAC panel, March 15th. You're going to be in the afternoon session. There's obviously another CAR-T that's going to go in the morning that day. Both of you have now gone through the SAG-O, essentially the sister process in Europe. Both of you have gotten through the panels. Obviously, we don't have all the details, but it looks like with broad labels, we're waiting for the official approval. So there's a little bit more understood now about the panel. It looks like it is probably going to be about survival and the survival trends for both companies. Any sense yet as to just kind of simplify things? The data look pretty good for both companies. Historically, at least, EMA was a little bit back in the Revlimid days with secondary malignancies. They had a higher bar. You both got through the CHMP. Why do an ODAC panel? Yeah, that's a good question. That can be for a variety of reasons. Sometimes the FDA wants actual advice from the panel. Sometimes it can be a way to set a new message or a new bar for the industry. So lots of different things that can be behind the panel. We know the FDA has been increasingly focused on overall survival, which is a hard endpoint, whereas progression-free survival has been used and was the primary endpoint in KarMMa-3, our study that is behind this panel on this application for expansion in the third line. So PFS was our primary endpoint. We hit it early, had extremely statistically significant results, and we also measured overall survival as a key secondary. I think the FDA, in principle, wants to make sure that those are moving together and pointing in the same direction in favor of Abecma. We presented data at ASH this past December, which detailed that data from a strict ITT analysis, which showed in that ITT analysis that has a ratio of 1- 1.01, so comparable. And then importantly, when we adjusted for the crossover design of the study, that analysis favored Abecma. So we feel good heading in based on the precedence that you cited there, both in Europe as well as Japan, where we had a similar outcome on the similar dataset. That being said, we're not taking anything for granted, and it's been leading the charge along with our colleagues at BMS in terms of getting ready for that. Is there when if FDA wants to maybe air out and get some advice about trial design, what can be done? Because it definitely looks like early on for both you and obviously Janssen, Janssen Legend, there was an adverse initial sort of eight-week differential while patients are getting bridging therapy, and it looks like they might not be getting quite as intensive a bridging therapy, and maybe that can explain for the difference. And then there's obviously a catch-up post-CAR-T. So is it a question of now just doing a more substantial longer-term follow-up? I mean, the follow-up's already going to be very long. Is it going to be looking at secondary malignancies and sequencing and maybe better sequencing at baseline? Is it going to be to make sure the same bridging therapy gets used early on, or what can they really do? You hit on a bunch there, and that's an honor to comment, but I think generally understanding the true ITT analysis, which is the strictest way the FDA can look at it, which is from the moment of randomization, how do the two groups perform? And inherent in a CAR-T is you need to collect cells, you need to go manufacture those cells, which takes time, and then deliver those cells back to the patient. So there is a gap in there. In the case of KarMMa-3, there was per protocol a single bridging treatment that would be given. And so for many of these patients who, again, were triple-class exposed, so rapidly progressing disease, there were early deaths, and in many cases, those were patients who died before ever having a chance to receive the Abecma. And so implications could be, and as we've moved several years down the line since the initiation of those studies, the importance of bridging, aggressive bridging, tumor debulking, those things all correlate with those patients who have those deep and durable responses. So those are all things that I think will play out in the discussion. But what else should we add there in terms of how to think about those different factors? Yeah, thank you, Chip, and thank you, Yaron. You hit all on the points. I'd like to reiterate that KarMMa-3 is a study that included patients with heavily pretreated early line. It's two to four prior lines. Patients still had to be triple-class exposed as well as refractory to last therapy. So options in this setting are limited, and patients in KarMMa-3 received the same optionality for bridging therapy as in the centers of care aren't given. Nevertheless, we had this restriction of one cycle only, a long washout period prior to infusion that led to some patients not being infused. And I think that's a very critical point. And when we designed this study, I think the body of evidence around the importance of bridging therapy was not available at that point, and we know that nowadays. With early line treatment, we also believe that bridging therapy is going to be much more efficacious than in the late line. So we learned a lot for this space and for CAR-T cell therapy in general that patients need to be bridged effectively. And also we have been publishing data at last IMS where we showed what actually effective bridging therapy does to the outcome. And in the KarMMa-3 subpopulation of patients who had decreased disease burden at time of infusion, we had a median PFS of over 20 months. That tells exactly or speaks to the fact that early line patients can be bridged more effectively, and in real world, we will have more options or physicians have more options to bridge effectively in addition to having not the suboptimal time of exposure being treated until infusion, etc. When you're talking about more optimal bridging, and you talked about a single, is it a question of just when you say single, it's a single cycle, 28-day, single month of cycle as opposed to doing eight weeks of bridging? Yes. So we had one cycle, which means normally that's one treatment course. And depending on the regimen, that is almost several days, but it is kind of once given. And then there was no opportunity to give another cycle. In addition to that, we had the requirement of washout time. And then in addition to that, not every patient received bridging because it was optional. So we had even a segment of patients who didn't receive any bridging there. Okay. Yeah. So definitely putting pressure on those patients while they're waiting on the patient who are doing so. The other thing to mention too in the commercial setting, and since that time, our turnaround time and in-spec metrics have gotten even better. So for a commercial patient, we can turn it around in less than 30 days, greater than 90% in-spec. And so those things will matter as well in terms of real-world outcomes, we think, in the third line setting. Yeah. Okay. So bridging is definitely going to be important, one of the things they can discuss. In terms of monitoring and sequencing for any baseline variants for SPMs over time, I think the companies, well, you already are on the hook to do 10 or 15 years of follow-up anyway. And in terms of sequencing, you're already sequencing the tumors at baseline, right? Is there any more surveillance you can do relating to any potential transformation? Are you referring to T-cell malignancies or general secondary? Well, I don't know what they would look for. It could be potentially both, although you only had one, not the other. So I like to say that, first of all, per USPI, any patient has to be followed up for secondary malignancies, and all of those cases will be reported immediately to BMS. And so we have a very good overview on the real-world setting, even on the secondary malignancies. With regards to the T-cell malignancies, I think there was a potential risk identified by FDA. Therefore, every single CAR-T in the commercial space received this Black Box Warning to make sure that physicians or treaters are aware of this potential risk. I also have to say that there were still small numbers of these T-cell malignancies, and so far, no causal relationship between the CAR-T cell therapies and the T-cell malignancies has been identified. With regards to other secondary hematological malignancies, in case of an Abecma in our clinical trials, as well as all the wealth of data that we have generated in the real-world evidence, an Abecma has the same rates of secondary hematological malignancies as you would expect from any myeloma patient. This frequency of secondary malignancies is higher because those patients have been exposed to previous therapies, lenalidomide, etc. So they have a bit of a higher rate. Myeloma patients, in general, have a higher rate of secondary hematological malignancies, but with an Abecma, we haven't seen any increase of it compared to the background rate. There's no warnings in the label? No. Exactly. Anna, do you want to talk about KarMMa-9? Yeah. So the phase 3 KarMMa-9 trial evaluating Abecma in newly diagnosed patients with suboptimal response to transplant started, I think, late last year. I was kind of curious why you chose this as the population for your newly diagnosed instead of, say, kind of 1L transplant eligible. A very good question. There are multiple reasons why we chose the KarMMa-9 study design. So first of all, transplant has been a standard of care over the last decades in myeloma, and patients who can receive transplant in a newly diagnosed setting will receive transplant, and it has been very efficacious. So far, now, all the therapy has been proven to be better than transplant, so we believe it's going to stay standard of care. And then in addition to that, there is still a very high unmet need for patients who do not respond well to this transplant. There are still patients who have less than a complete response or less than a very good partial response post-transplant, and those are the patients that do not well. So we are now, with our KarMMa-9 study, treating exactly those patients to deepen their response post-transplant and make them more possible to have a longer duration of response. The main reason why we've selected that's kind of the strategic concept, and I believe in this setting to be addressed due to the high unmet need. Moreover, we have very, very compelling data in this setting with the KarMMa-2 cohort 2C data. We just presented an update at ASH where after 40 months of follow-up, you have a complete response rate of near to 80% of patients that had initially less than a very good partial response. We have very nice durability data in addition to that. And patients who received lenalidomide maintenance post Abecma was optional, but those patients who received the maintenance post Abecma did not relapse so far. None of those patients have relapsed. These data gives us a very high confidence of a positive outcome of KarMMa-9 and also the fact that we are treating an unmet need population. I see. So if you were able to recap the KarMMa-2 results in KarMMa-9, that would just be considered what you would consider a bar for success? Yes. Yeah. Great. And so there's no plans at the moment to do any other first-line kind of treatment populations just in inadequate response to transplant? This is currently the publicly available plan, yes. I see. Maybe just to add to that, that would put us with a label of more than 20,000 patients in the U.S. addressable between all of these different studies. So again, I think it speaks to there's more than one strategy that could be valid. There is a shoot-for-the-moon strategy, which is displacing or capturing a meaningful share of transplant. There's another strategy that says not everyone does well with transplants. Both could be successful and both lead to a market opportunity commercially that we think is substantial and could drive value and could drive a lot of great outcomes for patients. So again, it gets to, I think, kind of the bear thesis versus our belief, which is winner take all versus there's lots of different places and pockets to play in the myeloma landscape. Our view is that's been the history of the space since the beginning of drug development. In KarMMa-9, what would be the control in that setting? We already opened up the study, and it's running. The control arm is the standard of care, which is induction, transplant, followed by Len maintenance. Right. So it's head-to-head against Len maintenance, basically. Yeah. Except in both cases, you have to have a suboptimal response? Yes. The patient population is the same. Yeah. VGPR. Exactly. Usually, Len maintenance at that point can be two to three years, right? It's until progression, or it's fixed two years? No, it's until progression. However, some data say that patients' median duration is two years, depending on the toxicity profile, but we have it until progression in the study. Yeah. And it's 25 mg or 10 mg or 25 mg of Revlimid? That's a bit more complicated because it's depending on the timing, when they receive it. We have a kind of a step-up dosing, and then we also allow for physician's decision as well. Yeah. There's no Len maintenance in your arm? It's a one-and-done? No, there is Len maintenance also in the area. And that's the data that I just referred to for the KarMMa-2 cohort 2C where we had this promising outcome. Not to say that those who didn't receive maintenance in KarMMa-2, they had also a very good outcome, but specifically the ones with that. Yeah. So it's earlier. Got it. And then just to go back, has the FDA indicated a new PDUFA? You obviously haven't announced it, so we assume you don't have a new PDUFA. So yeah. Yeah. Our original PDUFA date was December 16th. We learned in November that FDA wanted to convene a panel. That panel's now a double-header for both commercially approved BCMA CAR-Ts, one in the morning and then ours in the afternoon. But there is no new PDUFA date assigned. Often, PDUFA dates come a handful of weeks after the ODAC, but in this case, we don't have a specific date. Our hope, and certainly our plan commercially, is to be ready from a launch perspective on the heels of that ODAC meeting. And as soon as we have more to share, you'll be the first to know. Have you had a chance to talk to FDA about that a little bit to get some sense kind of how they're thinking? They sort of committed to getting back to you as soon as possible? I think that'll be an ongoing conversation. But again, our launch planning is to be ready to go shortly thereafter. We know our competitor product has an April 5th date for a PDUFA. They had filed later. And so in the end, in most cases, they need to move on and do other reviews and other cycles. So I think coming to a conclusion on this one is in everyone's interest, but we certainly wouldn't, I suppose, to speak for FDA. They'll have to tell us. And again, we'll share as soon as we know more. Usually, 30 days pre-PDUFA, now the PDUFA, if we're to go back now to November, there's a beginning of a draft label discussion back and forth. Can you comment whether you've crossed that bridge yet with FDA? No, I can't comment there. I think we would expect on the other side of ODAC to be into those label discussions and negotiations. Okay. Maybe just give us, let's go back about a month or so. You announced a transaction with Regeneron. Can you just give us an update, kind of the latest on timing to actually get that deal closed? Sure. Yeah. We reiterated on earnings yesterday that the expectation is closing that in the first half of this year. Just as a reminder, we announced that at the end of January, the sale of basically all the non-Abecma R&D assets to our partner, Regeneron. Along with that, they're taking about 160 of our R&D staff. They're taking a substantial portion of our real estate footprint. And that's terrific. They're a science-first organization, tremendous track record, 35 years with the same leadership team just building all such great products and value. They have a very different time horizon. They have a very different cost of capital that enables the right kind of investment in those R&D assets. So I'm super excited to see what they're able to do with that side of the business. What it does for us is really streamline and focus the business on Abecma. That's both for the 65 people who will remain, including the people here on this stage, and gives us a very different cost structure. So we're taking $150 million out of the cost structure this year, $200 million out of the cost structure next year, runway beyond 2027. So from a financial overhang or potential any future dilution, I think we feel really good about where we sit. And as a result, it doesn't take a lot for us to break even and become a cash-flow positive, profitable business. And so that's a really privileged place to be. And again, we and the board, it's a calculated bet, but it's the one we feel very good about in terms of our opportunity to return Abecma to growth. Yeah. And so as you think, Chip, as you're coming in as the new CEO imminently, as you think about sort of the two-year, three-year horizon for 270, what's the plan? With success for Abecma, what does 270 look like in two or three years from now? No, that's a great question. I think success could be even earlier than that, which is by the end of this year, we start to actually prove that there is a return to growth, that there's a commercial trajectory that we can value. Because right now, we're valued close to cash, right? And we have a commercial asset that did $358 million of revenue last year. And it's really because of this bear thesis - it's going to go to zero - kind of mentality. I think if we can disprove that in this third-line setting, if we can show growth, point to that growth quarter on quarter, I think we can demonstrate value and before long be in a stance where we can definitively say, "Hey, we're break even. We have no needs for future dilution." What's next, I think, is your question. Part of our answer is, "Ask us when we get there. We're focused on getting from here to there, starting with ODAC next week." But if we're there, I think what we've done is created optionality. That could be more financial optionality, whether it's returning cash to shareholders or buying back shares or adding things to our business at that time. We're not there yet. To be super clear, our goal is to get to that moment of break even and profitability as quickly as we can and not be distracted by other things. Until we're there, you should not expect us to add new ideas or new research projects or new things to our business. We're singularly focused on getting there. We've got a great team of operators and people to execute on that plan. Yeah. And the clinical side, Anna? I mean, can you talk about what is Bristol going to do on KarMMa-9 versus what is 2seventy going to do? Yes. So the operation or the clinical operation is at BMS. We are strategic partners in that sense. We are involved in any of the discussions, but we are not executing in the sense. But we are always part of execution and also going to. The JV and also committee. Yes. I'm also going to investigator meetings or something like that. Yeah. Your role is mostly co-commercialization? Well, and quality and manufacturing as well. So of the 65 people that we have, the majority of them are focused on quality operations, QC testing. That's all a central part of the manufacturing process for the Abecma supply chain. Okay. Jenna, do you want to take the first questions? We've changed the order. It's a three-year approval. So I have a better order in my head. So I'll continue with my order. Can we talk a little bit about supply? So the S12, as a plant, was cleaned up in June. You've done that historically. Are you going to stay in the same sort of cadence, that that's sort of when you're going to do the cleanup, or can you maybe take certain suites down and keep other suites sort of up and running? And then secondly, maybe give us a little bit of a sense on supply and demand dynamics in the last two quarters or so. I think for a while, there was a lot of demand and not enough supply. It looks like supply kind of evened out a little bit. So, just give us a sense where you are now? Yeah. Thanks for the question. I'll take that. I'll start with your second part of your question first, which is just to say that what we experienced in the first half of 2023 was a bolus. That bolus in this supply-constrained environment has now, sorry, that demand has been met. So as we headed into the second half of 2023, we were both experiencing other competition from TCEs and other competitors. As we sit here today, we have enough supply with our partners at Bristol Myers Squibb to meet potential third-line plus demand. So that's important. We also have the ability with BMS to increase that supply within the scope of their existing facilities. So obviously, Bristol Myers Squibb has other cell therapy products that are commercialized, and they have the ability to continue to step up in drug product capacity at their plant if the demand is there for it. So we feel good about where we are. With respect to your first question, as part of sort of a normal aseptic manufacturing process, there will be potential shutdowns. But as you insinuated, there are ways to be a little more planful about that in the future. And so we're working with our partners at BMS to think about how that happens in the future. You have enough supply, even given the expected uptick in demand post third-line label? We have enough supply today to meet the third-line plus demand for the near future. Yeah. Lentivirus production, that's no longer a gaining factor? It's no longer. As some of you may know, we have an ongoing sBLA for a suspension lentiviral vector, which allows us to be more efficient both on the cost side and the usage side. We're excited to see that pull through to our cost structure. Okay. And then from the same plant, you can also supply KarMMa-9 as well. Correct. That same plant, is it supplying Europe, or Bristol has a separate plant in Europe now? They're in process of setting up their own supply for Europe. And so currently, the plant in New Jersey, it supports the global supply chain. Okay. But I think they're opening a second plant next year, is it? Yeah. In Holland? In Netherlands. The Netherlands. Yeah. Yeah. So that'll take the pressure off. And to Vicki's point, that gives us more optionality as we have these scheduled, I would say, maintenance, not cleanup, but scheduled things you need to do when you're in an aseptic manufacturing situation. Going back to demand, how many sites have you opened so far? Is each site sort of capped in terms of they get two, three, four slots, and that's the way it is? Is it that you can now match demand to wherever it's coming from as needed? So we haven't been super vocal about the exact number. I think from a BMS perspective, that's something of a competitive intelligence. But we've opened a large number of sites now in the U.S. We continue to add to that total. We think that is meaningful as we move into secondary and tertiary markets to help patients who maybe otherwise aren't able to travel a long ways to receive CAR-T therapy. So we think that matters, and we think that helps. In the end, the original academic centers, centers of excellence in larger metropolitan areas and bigger catchments, those are going to continue to be the main drivers for the business. And there we're quite active with those sites and continue to be in there all the time talking about Abecma and look forward to talking about the data as we get through this process in the third line. And so it sounds like you're going to really build your presence in the community setting. Any sense right now of the volume, how much of it is community-based sort of versus real tertiary centers? We haven't shared that level of detail. I would say, though, that the main centers are still a primary driver of the business, but the secondary, more tertiary centers are contributing. And I think are, as we've said, sort of necessary but not sufficient in terms of getting back to growth. Getting back to growth is also going to be driven by well, it's really going to be driven by three things. One, we've talked about before, which is manufacturing prowess, on-time, inspect, continuing to deliver. Second is the consistent safety profile for Abecma. And again, we've highlighted those data. We think the known safety profile, the known neurotox profile is important, particularly as we move to earlier line settings where patients have more choices, physicians have more choices, and those liabilities may matter more than where they do in a late-line setting, right? Then the third is the efficacy profile. And there, I think to some of the data I was describing earlier, we think we have an opportunity to describe and start to close that gap from an efficacy perspective. The outside world, in many cases, has assumed sort of it's game set match to the other CAR-T out there. And we believe that's not the case. And we look forward to describing those data. We need to do that in a compliant way on the heels of this regulatory process plan. Yeah. Any questions from the audience, by the way? Go for it. Can you set up a question on the structure of that deal? Do they have the option to buy the rest of the company to change that, or they're more interested in that? No. Good question. The question was, does Regeneron have an option to buy the balance of the company as part of this deal? The answer is no. There's no preemptive rights or anything like that that come along with it. They're really focused on the research side of what we're doing. Again, they believe in the modality. This is the Regeneron cell medicines business is what it will become. And they've made other very successful platform plays. And so again, really excited to see what they do with this. Yeah. What do they want? It gives you the long run. Yeah. I think what we've bought ourselves is time for Abecma to get back to growth. So what we wanted to avoid is if there's a situation where we're approved in the second quarter, but it hasn't shown yet, by the time we get to June 30, it's not like all is lost. So long as we see the growth, whatever shape that is, whatever that takes, we've got the time now to do that in a way that doesn't create pressure needing to raise or other considerations. We've bought time for the asset to do it the right way. Again, it's the only thing that matters to us. So I think there's something to be said too for having one thing to focus on and doing everything you can to get it right. Yeah. And maybe. Sorry. Go for it. 20,000 patients plus third line and later? No, that's more like first line. And that's with the KarMMa-9. And again, we need to get the data, but it's something like that. I would say the third line plus, though, north of 16,000 patients would be, based on how we're thinking about the label, would be a good starting point, which is roughly four times as large as the current label and the current set of patients that are on label today. So much bigger opportunity. And again, not winner-take-all, but we think we can have a meaningful role in that market, and we look forward to competing. Yeah. We were asked about the plant. Is it twice a year? The aseptic therapy? No. So we did a scheduled shutdown last year, which was the first since we'd launched. It's been two-plus years. And that was a pretty big one. Again, I think we'll probably stagger that more, do it more incrementally. And again, having multiple manufacturing sites approved gives us more flexibility in that. Because again, when a patient's product comes in, we're not going to not manufacture that product. We need to keep those patients moving through at pace. But I think we'll have more optionality on that in the future. I know we're out of time, but maybe final question. Any sense, what percentage of usage right now is purely outpatient? I don't know that we've commented on that. Yeah. Yeah. Is there a move toward that slowly? Slowly. I mean, I think the view is having the patient where are they going to be observed? And if there's kind of the early. Is that the same? CRS or ICANS that manage and then discharge. Earlier discharge. Yeah. Exactly. Okay. Well, terrific, team. Thanks so much for joining. We appreciate it. It's good to see you. Thank you. Awesome. You too. Good to see you. Good to see you.