45th Annual TD Cowen Healthcare Conference. I'm your own Yaron Werber from the biotech team, along with my colleague Jane Hun. It's a great pleasure to introduce and moderate the next panel with 2seventy bio. To my right, really needs no introduction, Chip Baird, CEO, and to his right, really needs no introduction, Vicki Eatwell, CFO. Thank you. Ladies and gentlemen, thanks for joining us. We appreciate it. Yaron, thanks for having us, and thanks to the broader TD Cowen team for having us here today. Lots to talk about in the myeloma market. There's multiple dynamics going on with Abecma, obviously Carvykti, and bispecifics coming in. Maybe let's talk about sort of the latest with Abecma. What are you seeing in the market now? How is the drug being used? Yeah, sure. I guess before I go, I will make forward-looking statements today, so I would encourage people to read our SEC filings and do your own homework on the company. Out of the way, yeah, no, we're, so it's March of 2025, so we're four years into launch now, and we're about one year into the third-line launch. We have expanded the label into a much broader third-line setting, and that's been great to see. We have seen real utilization in the third-line. We could. Oh, yeah. We've seen, as I was saying, we've seen real uptake in the third-line. We think that is the sweet spot for CAR-T, and that's based on over thousands of patients treated, but both an efficacy profile supported by the studies, by publications, but also real-world evidence. I think the class grew dramatically in the third quarter, both for us and for our competition. I think the fourth quarter was a little bit flatter. I think as we look forward into 2025 and beyond, I expect continued growth, but probably a more measured pace. I think we've made progress on the manufacturing side. As a class, we think patient demand remains strong for these therapies. The one-and-done nature of these therapies is very powerful and very compelling for patients. I think what we're starting to see is more at a site-specific level, that that probably ends up being the governor of how much growth and how we see moving forward. The last thing I'd say is, obviously, there's a lot of talk about and focus on the top line, and we focus there, but also we remain focused on the bottom line. How do we drive not only as many positive patient outcomes as we can, but how do we drive the business? How do we make this a profitable business as a product and then, in turn, a profitable business for 2seventy bio? There we're dangerously close to break even, which we can talk about more later in our chat. Okay. Let's maybe talk a little bit. What are some of the drivers in Q3 for the growth, for you and the class? Yeah. What were the dynamics in Q4? What do you see in the class? Yeah. I think third quarter was the first full quarter in the third-line plus setting. We were approved, and our competitor was approved on the same day in the second quarter last year. It takes about 60 days from the time you identify a patient to the time you treat them, and it turns into revenue. We did not see a lot of effect in the second quarter. Third quarter was the first full quarter in this broader third-line opportunity. There we grew 42%. The class grew pretty substantially. That was a big step up. I think some people may have gotten ahead of themselves to say, "All right, well, 42%, let's just keep quarter on quarter growing like that, and we'll take over the world." I think in the fourth quarter for us, we for the first time saw some patients deferring treatment through the holidays. When you think about a patient, and again, third-line patient, different than an acute patient in a fifth-line plus salvage setting, a little more time and effective bridging options can be used so that patient's not getting lympho depleted on Christmas Eve and in the hospital through the holidays. Our eighth model kind of predicted one thing. We saw something slightly different that could give us a bit of a tailwind in the first quarter, but again, we'll see as those results come in. It sounds like Q4 in general, as these drugs really move up, we should expect kind of seasonality, quote unquote, Thanksgiving, some. Yeah, I think you might. Again, this is first time through for us, so I think we're not over-indexing on that, but it is an effect that we think was there, was observable. As you think about with the third-line label, how did the commercial emphasis sort of shift? I mean, the commercial emphasis continues to be on describing the broader data set in terms of the safety and the efficacy of the product and the efficacy we demonstrated in the KarMMa-3 study. That was the first phase III controlled study against standard of care. A stat-sig safety efficacy benefit there. Really arming the field for us to describe those data to be able to effectively interact with the HCPs that they call upon. We've also focused on expanding the number of sites, the site footprint. Today we're at more than 140 sites in the U.S. I think we're getting to that point of kind of diminishing returns. Of course, we're at the major centers, the centers you would have heard of, but I think at a secondary and tertiary level, that does help with patient access and incrementally helps in terms of the top line. Yeah. Last year was a launch year. This year, I think we're going to be targeted and focused, and I think we've done a lot of work to segment the sites. Broadly, there are sites that have been kind of tried and true prescribers. There's folks I would categorize more as fence-sitters, and then there are sites that have been loyalists for the other product. I think each of those, we show up in a different way with different messaging and different allocation of resource. Yeah. You're talking about a measured pace and site-specific connotations or factors. You just mentioned some of them, just kind of they're adopters, they're fence-sitters, they're loyalists to another product. Is that sort of what you meant by the site-specific dynamics, or is it also their own capacity internally and how they process things, or both? Both. I Both. I mean, so yeah, I mean, I think from a demand perspective and a utilization perspective, that's definitely true. You can look across the business and across these sites, and they kind of segment. Again, that can change over time, particularly when a site who's never had a neurotox issue has one and experiences that, that can move them from one category to another. They may not have written an Abecma script for a long time, and all of a sudden, if they have one of those events, which can be that's not a good outcome, that can drive them back towards utilization of Abecma. We have seen that effect. The other thing you hit on is an important topic, which is just the capacity. I think what's interesting about that dynamic is it's not just us versus our competitor. For a given site, and pick a major center, their CAR-T capacity, yes, is in the myeloma and the BCMA-directed field, but it's also thinking about CD19s. It's also thinking about solid tumors now have commercially approved products. It's also thinking about clinical trials. All of those become important institutional priorities. They're going to do all of that. Our BCMA CAR-T fits into that larger field. Those sites are growing. They're growing the number of CARs that they're deploying, but it's not exponential. That's more linear. I say that's where I continue to think that the growth that we will see over time will be linear versus exponential. When we were on this panel two or three years ago, the whole conversation was the number of slots per week and how do you do the ramp and when will that be. I think looking forward, it'll be more driven by we've gotten there both as a company and as a class, and now it's going to be how do you help those centers drive their capacity over time. The capacity gateways or inpatient beds, is it. That's sort of it can be you've hit on two big ones, but apheresis and collection. We even had people talking about, could you do apheresis somewhere else? Do you have to be in that center to do it? It turns out even the apheresis process, which is a phlebotomist, it seems like pretty straightforward. The protocol with which you do that in this highly regulated process and this manufacturing process and the fidelity that you need to have to that kind of leads you back towards a center of excellence that kind of has that infrastructure around it. We're thinking creatively about how to do that. Anytime, and this is kind of operations management, anytime you get rid of one bottleneck, then you move down the line towards the next one. Yes, apheresis, beds, staff, these are all some of the things that are the constraints on capacity today. When you're looking at the 140 sites, I imagine 25%, 20% of them are the real users probably, right? I would say 50, again, not a hard number here, but tilde 50 is like where the majority of the business happens or more than half of our business happens, those major centers that are. That's pretty out of the 140, so. Yeah. Yeah. There, we're present there. The competition's present there. The CD19s are present there. They're kind of fully. How much is the community adopting CAR-T now? We've started to see that. I think that can be a release valve over time. I think that's going to depend on physicians' own comfort there. It's going to depend on there's aspects to reimbursement. There's aspects of when does a patient experience, if they experience CRS, when do they experience it, and how that patient flow goes. That's not without risk because if that comes on, those patients need to be managed. Good news is relative to seven or eight years ago, I think we're much better at doing that, but they need to be nearby and they need to be more in a hospital setting if they're having a more severe CRS event. Yeah. I mean, it sounds like soon there's going to be some networks that are going to open up in the community setting. Is that something that you, Bristol, and you're targeting at this moment, kind of helping centers open? How does that process work? Yeah. I think we've to date have been focused on more traditional clinics, but yes, I think the community setting is one that is another frontier here. As I just said, I think could open more capacity out in the system. I don't know if I said it at the top, but if you look at the end of the year for the fourth quarter, if you take our fourth quarter sales and you take competition's fourth quarter sales and you annualize those sales, we're at roughly 20% penetration into the third-line setting. I think our view is there's a lot of room to go in terms of getting more patients. There's certainly from a patient awareness, patient demand, we feel a strong pull. These patients, a surprising number of these patients are familiar with the brand names and are educated coming in. The one-and-done nature of the therapy, I think, also is a draw. We have patients asking for CAR-T. We believe from a demand perspective, there's a lot of room to run. I think the question we get all the time, you're embedded in what we're talking about, you're asking is like, how quickly can we get there? How quickly can we satiate that? Again, it's much less about our manufacturing capacity, much more about how do we deliver in these treatment centers. Yeah. Jane? Yeah. Just to follow up a little bit, you mentioned that obviously there are some dynamics with centers preferring one product over the other, but kind of at the doctor-patient level, are there any patient subsets that kind of preferentially get Abecma just for the safety signal or the manufacturability? Yeah. We get that question a lot too. I don't, certainly commercially, we don't niche it. We don't say, "Well, it's only for this kind of patient," or, "It's only for older patient," or something like that. I think our view, and for the centers that we've had good business, repeat business, consistent business, I think the view is that with effective bridging, we can make Abecma look very close to the competitive alternative in terms of median PFS, other measures of efficacy. The alternative is harder to do, which is, can you make the competitor product as safe from a delayed neurotox and Parkinsonism liability perspective? While there's certainly a lot of study on that, we don't know why they're different mechanistically. The data have been pretty clear that there are important differences there, but we don't know why mechanistically. We don't know yet how to predict which patients might be more highly susceptible to those, and we don't know how to reverse it. I mean, those are serious liabilities. I think they become more, our belief is those become even more important as you talk about even earlier aligned studies and thinking about the front line because today our view is between transplant, quad therapy, the options available to patients that are newly diagnosed are pretty powerful, pretty compelling, and that benefit risk and taking a risk on a neurotox event or treating your myeloma for something, that's harder to do in a front line setting. Right. That is our view. Yeah. So basically you're saying that you think that maybe second and third-line is realistically where CAR-Ts are going to land? That's what we yeah, that's the sweet spot from our view. That was a lot of the calculus behind our decision. That and cost and being kind of fiscally minded, fiscally disciplined was the rationale behind the decision to stop KarMMa-9. Right. Right. Right. Right. We had a high degree of confidence that that study would work based on what we'd seen in KarMMa-2C. I mean, that was a really tough call because he'd love to get there, but it was going to be, I think we've disclosed it, $80 million-$100 million of savings just on our side. That speaks to the capital requirements to study these in large, it was a 600-patient study. Again, the trade-offs and the options available when we designed a study like that in 2020, 2021, it's very different than what's available today. We think patients are well served in the front line setting. We think CAR-T has a really important role to play in the third-line setting, and that's a market, as I've said, we're still in the early innings of getting to it all at roughly 20% served. Right. Right. Do you have any sense of kind of, I know the third-line launch is still ongoing, but what percent of patients are kind of in third-line versus fourth-line versus fifth-line for Abecma usage? Yeah. We do not collect, I mean, I think it skews towards the earlier, but we do not for. HIPAA. Patient privacy and HIPAA-related concerns, we don't explicitly collect that information at the time of treatment. We do some studies, kind of market research more retrospectively and kind of following up with centers, but when we apheresis a patient and manufacture for a patient, we actually are blinded to are they third, fourth, fifth, what line they are. Right. Okay. You mentioned that obviously bridging therapy is going to be very important. If you're effectively bridged, you can reach kind of similar efficacy to competitive products. How is that factoring into your education efforts to physicians? Yeah. I mean, I think that's a key point. Again, we need to stay within what's published and what's out there. I do think that the real-world evidence studies that have been conducted by consortiums and other treating physicians have really helped underscore that. Those are presented at medical meetings. I think the IMS 2023 showed that with effective bridging in sort of a KarMMa-3 like a triple-class exposed patient population, you saw a median PFS of 20.7, which is very close to what was seen in CARTITUDE-4. Again, always caveat, super hard to compare directly against trials, but certainly with triple-class exposed and effective bridging, you could see much greater PFS and just a deep, more durable response. All right. You mentioned that you are kind of basically already there in terms of capacity. What does that actually mean in terms of kind of slots? We have not sort of said out loud how many patients a month or patients per year, but I would say if you want a slot today, we are able to very quickly make a slot for that patient and manufacture. No constraints, no queue, which is something that even as recently as 2023, we were living with of, "You want a slot? We can treat that patient in two, three months' time." No queue today, and that is a great place to be. Right. I think we have the ability to step it up too as the market continues to expand and we have continued growth in our business, we're well positioned to continue to meet demand. Great. Even as you kind of increase penetration in third-line, it's kind of a very large patient subset at 16,000 in the U.S., you're still kind of at capacity to meet that with no wait time. That's right. Wow. Okay. Yeah. With the ability, as Chip said, to increase capacity further within the existing walls of the current manufacturing facility. Right. Everything is basically on the hospital side now with the apheresis and the bed space, as you said. Yeah. I think that's right. I think that's where we see it. Again, it's different from one clinic to the next in terms of exactly what they're solving for, but we want to—we're there with them. Again, I think they will continue to grow over time. Right. I know that you're not really working on obviously moving Abecma earlier line because obviously third-line is a very nice setting to where you think that CAR-Ts will land, but are you generating any other kind of supplementary data sets to show Carvykti efficacy or safety, or is everything now more reliant on kind of real-world data? It's primarily on real-world data. These studies all have long follow-up periods and tails, and there may be incremental publications that come out of that, but I think more of the evidence generation is focused on real-world and IITs and other non, I would say, registrational directed studies. I think that longer-term experience with the product is important. We think the real-world evidence is a key element. Again, I think the consortiums that have been thoughtful and have done a really nice job of compiling data across products and helping make more like-for-like comparisons. Every CMO and MD I've worked with, it's verboten to make cross-trial comparisons, but I think some of these consortiums and real-world evidence efforts get closer to kind of understanding what the truth may be in terms of how these different products line up. Good question. Oh, yeah. Take questions. Any questions from the audience? Maybe I'll throw in a quick question. You noticed that you're dangerously close. You're on the verge of profitability. Would you give guidance this year on Abecma sales? Not yet. I think we'd like to see another quarter or two because the third quarter was strong. The fourth quarter, we moved back, we think, to some seasonality, but we'd like to get our feet under us over the next couple of quarters to kind of project that line. I think in this environment, unfortunately, even if we came out and said guidance, I don't think we get a lot of upside credit for it. It's mostly exposure, and it's still show me the results. We are going to focus on what we can control and focus on execution. As you think about what are the drivers of cash flow positivity this year? I think you were talking about. Yeah. From a finance perspective. Yeah. I guess I would just say we've, I would reiterate our prior guidance on this. We've guided that $300 million in total U.S. sales results in 2seventy break-even as a whole company. So it doesn't take that much for us to reach break-even. And as we've previously guided, we expect to be able to achieve that before the end of 2025. With Bristol, it sounds like you're even as a JV are operating toward a profitability goal. Yeah. I think the product already has had profitable quarters and operating profit, commercial profit. Obviously, ultimately, to get to a 2seventy break-even, we have our own cost structure that, as Vicki said, has been really streamlined and went down greatly from even where we were a year ago. I think with Bristol, I think we have a shared priority of, yes, how do we maintain and grow the class and grow our share, but how do we do that also from a margin perspective? How do we continue to optimize the margin? That is cost of goods. That is the focused commercial investment. That is looking at overhead. That is looking at all the levers. You listen to their earnings call. They are focused on the bottom line as well. They are focused on cost containment at a macro level. That is important there too. How many employees are currently at 2seventy? We have about 64 employees today. Okay. Very precise. Most of whom are deployed on the quality testing and Abecma support. Yeah. As you think both of you kind of strategically, you'll be break-even and the goal will be to continue to grow Abecma. What's the future for 2seventy? Twelve months, twenty-four months from now? I'm glad you asked. I think a year ago, our focus was to go all in on Abecma. We sold our R&D business to Regeneron. We sold our gene editing product and program technology to Novo and massively streamlined the cost structure. A year ago, we said we could potentially break even in 2025. The next question was, "What are you going to do when you get there?" Our answer at the time at 2seventy bio was, "You ask us when we get there." Now we're there. I think we've shown it. The team's done an amazing job of getting through that work. I think it creates—our goal is it creates strategic optionality for us. I think this is an attractive business. I think with another couple of quarters, a predictable business, you make a profitable business. That becomes attractive to larger companies. I also would say that within the field of cell therapy, investors and a lot of pharmas have focused in other areas. You can look at the valuations of our peer set. That is our own valuation. That can be disconcerting, but also in there lies opportunity. With a strong cash balance, over $180 million of cash at the end of the year, very modest break-even. Fourth quarter, we burned $9 million. That quarterly burn continues to get smaller and smaller. We are on a glide slope towards cash flow break-even. I think we do have real strategic optionality, and we are hoping for a transformational year here. Yeah. Any final questions, Jane? Not that you've got them. Okay. You're reporting Q1. Before the 2017, 2019? We're reporting 2024 results before March 17. Yeah. Okay. You've moved on. We already reported. We put out the key results on February 6th in conjunction with BMS's quarterly earnings. We'll add incremental color and file our 10K between now and St. Patrick's Day. Right. Terrific. Chip and Vicki, thanks for joining us. We appreciate it.