Perfect. Okay, welcome everyone to the afternoon sessions. My name is Kelsey Goodwin. I'm one of the biotech analysts here at Guggenheim. I'm delighted to welcome the 2seventy team. Here with me, I have the incoming CEO, Chip Baird, and the Senior Vice President of Clinical Development, Anna Truppel-Hartmann. Welcome everyone. Awesome. Thanks for having us. Yeah, thank you. Yeah, so let's, let's get started. You recently announced an exciting and new strategic path forward for the company to focus on Abecma. Why don't you walk us through the details and the rationale here? Yeah, sure. Thanks, Kelsey. And thanks for inviting us to be part of the conference today. And I would also say we may make forward-looking statements, so make sure to do your homework on the company. Last week we announced an exciting strategic pivot for the company. We reached an agreement with Regeneron to do an asset purchase of all of our R&D assets, so everything but Abecma, which is our commercial program. So this involves about 160 of our R&D employees becoming part of Regeneron. All of the programs, about two-thirds of our real estate footprint, related IP and technologies, all moving over to Regeneron. This is Regeneron is a company that we've been partnered with since 2018. They have the same while it's a big company, they are science-driven and I think share a similar amount of excitement about cell therapy as a modality and as a platform. And as you know, Regeneron's famous for being a very successful platform-based company. So, that made them a very natural company to be talking to about this move. And the maybe the why behind what we did is, between the time we founded 2seventy in the fourth quarter of 2021 and now, the markets have just become a tougher for funding early-stage research in the cell therapy setting. And as a small-cap public company, it was becoming increasingly difficult to keep up with the programs and the needs of those programs. And so Regeneron has a long-term horizon. They have a very different cost of capital. And so, we've landed those programs and those people, in what we like to say fertile soil. Mm-hmm. So, an incredibly good outcome. And we have downstream participation over time if those programs are successful, which we expect they will be. So then that leaves 2seventy. And 2seventy now, on closing of this deal, which will be in the first half, hopefully sooner than later, but first half of the year, will be an Abecma-focused company, commercially focused, single asset. And there our goal and we can get more into it, but our goal is to get Abecma back on track, back towards revenue growth and showing to others what it could be. We now have the runway to do that. So we have runway beyond 2027, which is another way of saying we're no need for dilution or any forms of financing in this setup. We've taken about $150 million out of the cost structure this year, closer to $200 million next year. Our focus is on driving the Abecma performance and doing everything we can to support that, getting to a stance of cash flow break-even as quickly as we can. And I think if we can do that and really demonstrate the value of Abecma to the outside world, over the next couple of quarters, we think there's a lot of value creation ahead of us. Mm-hmm. So that's, at a high level, what we talked about last week. We're now, you know, focused on executing against it. Great, great. And so for 2022 and 2023, we saw some strength for Abecma and then followed up by a couple of slower quarters. Maybe just walk us through kind of the key dynamics since launch that impacted and drove sales and kind of the trajectory that we've seen to date. Sure. Yeah. So Abecma was approved in the first half of 2021. And in the first two years of launch, a lot of the commercial dynamic was driven by supply. There was so much demand in this fifth-line-plus setting and simply not enough capacity from us in BMS making Abecma, as well as a competitor product from J&J. And together, you know, while both sponsors were making progress, it was not enough to satisfy demand in that setting. That started to change in 2023, as the first commercially approved T-cell engager came on the market and as both CAR-T sponsors, CAR-T manufacturers made more progress with capacity. And so we quickly found ourselves in a spot in mid-2023 where there started to be enough capacity. And in that in-between time, T-cell engagers had taken a share. You know, for a doctor to say, "Hey, you can get a CAR-T slot six months from now. You can take a T-cell engager today," very valid decision to take that T-cell engager. Mm-hmm. That dynamic has shifted and switched. So there's a lot of almost reprogramming or re-educating on that. The data there is supportive. The data there suggests that the sequencing of a CAR-T, prior to a T-cell engager, promotes the best outcome for patients. Mm-hmm. So on that front, that's the clear message. It's backed by data. We think that's, I think that's gonna come with time. Then on the CAR-T side, there are now two products approved. They're, they're both in the fifth-line-plus setting. They're, they're both about to, we believe, pending FDA final decisions, expand into broader label, earlier lines. And that dynamic, and we can, we can talk about it more specifically, but we expect it will play out over time. Mm-hmm. and, you know, again, we're gonna be for Abecma moving into, potentially a third-line-plus setting, roughly 16,000 patients, we believe, based on epidemiology available, so much bigger than, market than today. and that's, you know, the history of myeloma. It's never been, winner-take-all. And so we're, we're looking forward to competing in the earlier lines and prepping for that, coming here very soon. Great. And, looking forward, as you mentioned, you know, one of the main goals being returning Abecma to growth. How should we think about the potential levers there? And what can be done kind of near-term, longer term? How do we get there? Yeah. You know, commercially, we've been doing a lot of work with BMS to expand manufacturing. And that's been successful. And again, I think that that's been a long-lived strength of the product over time, which is the step-ups in capacity, manufacturing, in spec, which is not easy to do in CAR-T production. We're greater than 90% in spec and then the turnaround time. So turnaround time has been consistently 30 days or less. And that's really important, particularly in later-line patients who have rapidly progressing disease. So we've focused on manufacturing. We're focused on the commercial footprint. So the number of treatment centers that are validated and online to deliver therapy has continued to grow. And we continue to make investments there. And then I think commercially, and this will come more with the expansion into the third-line label, is detailing the benefits of Abecma, both from a safety perspective and the important differentiating factors in our consistent safety profile, as well as the efficacy profile and how that measures up. And, you know, as we understand the data from KarMMa-3 better and better, as we see more real-world evidence, we think it's a very competitive profile. We think it's a profile that's not understood neither by the investment community nor by treating physicians. And so we know what we need to do. And BMS, I think, is aligned on educating there. Having the label to be able to go out and promote in a compliant way with treating physicians, that'll be important. That comes very soon here as we come up to an AdCom and a PDUFA action. Mm-hmm. Got it. Maybe building upon that, the real-world data that you mentioned, I guess, how does that build upon the initial KarMMa-3 dataset? And how does it make it Abecma more competitive with Carvykti than maybe people realize? Yeah. That's, I'll ask Anna to comment on that. I'd just say, we've been pleased to see the results we've seen in the clinical trial setting, reproduced in even a patient population that in many cases wouldn't have even qualified for the KarMMa-3 study. They were more progressed, the sicker patient pool, and to see the kind of consistency of results there has been really encouraging. But there's been more real-world evidence is evolving. And so Anna is probably closest to that to comment. Yes. Thank you very much, Chip. So for real-world evidence, we were very pleased to see that at ASH there were multiple, new groups, bigger groups and smaller groups presenting their real-world evidence data in the myeloma field, which is adding on to the whole body of evidence of Abecma, but also other targeting BCMA targeting agents in the field. And I do think it's incredibly encouraging to see that these data are always consistent with our clinical trial data. And that also is true to the fact that Abecma was enrolling KarMMa-3 or we were enrolling KarMMa-3 one study, at a time where there was such an unmet need and patients were very sick and were seeking really the treatment. And we had to enroll very sick patients who went to the hospice. So again, that showed us that KarMMa-3 was a study that was conducted in a very, very heavily treated patient population. And now the real-world evidence, obviously, not everyone would have been eligible for the study and may even not have had the option before. But now we are seeing exactly in that same population and the same consistent benefit in efficacy as well as safety. And I think that's very encouraging. Also from a safety perspective, consistent, lower-grade CRS and neurotoxicity rates and very few severe CRS and neurotoxicity; non-ICANS toxicity seems to be also very low and not so much associated with Abecma. So I think we are very pleased to see that myeloma patients in the real world can benefit as well as they did in the clinical study. And that's not often seen. Mm-hmm. Got it. Great. And then, for the KarMMa-3 trial, the randomized phase 3, so Abecma had a PDUFA date originally set for late 2023. Mm-hmm. Maybe just remind us the key findings of KarMMa-3, what Abecma showed and, you know, versus the control arm. Yeah. Anna, do you wanna take that one? Happy to do that. So KarMMa-3, just as a recap, is, was the first, randomized, CAR-T study in multiple myeloma. And, looking at patients, heavily treated patients again, but in an early-late setting. So the patients have been triple-class exposed, meaning having, having already been exposed to, PI, proteasome inhibitor, lenalidomide, as well as, anti-CD38 antibody. So they have seen the most effective classes of therapy already and, were refractory to the last line. However, they were earlier in the line, and which is also representative of the real world, actually, because more and more patients getting treated with daratumumab early on. So, it is very much, a patient population relevant, today. And, what we have seen is the primary endpoint was progression-free survival. And we have had a very significant, outcome there with a hazard ratio of 0.49 versus the standard of care arm. Also the safety profile was very much consistent with what we have seen before, no, like, very low numbers of severe CRS and neurotoxicity, very predictable, as well as the non-ICANS toxicity, no neurological toxicity that wouldn't be expected from a CAR, as well as also very consistent rates regarding secondary malignancies, which means very much very low rates in the 1%-2% range, which is consistent with the background rates in myeloma patients, and no T-cell malignancy. So really safety profile very much as expected. When it comes to overall survival was, of course, a key secondary endpoint. And we had the pleasure to present the data at ASH and also explain the data there. There, the hazard ratio was 1, meaning there was no difference between Abecma and the standard of care arm, which is in the light of the fact that we made a very patient-centric study design where we allowed patients to receive Abecma upon progression in the control arm. 56% of patients received Abecma after progression in the control arm. This is very actually encouraging to see that we have a hazard ratio of 1. It is confounded by the crossover design, and that was very patient-centric and needed at that time because the high unmet need of patients in myeloma is there. So that's going to be part also of the ODAC discussion that is coming up. We are preparing very well to be ready for this. Got it. Maybe just building on that, yeah, maybe just kind of to the extent you're able to give some color on, you know, what you anticipate the AdCom will cover, how you will kind of defend the, the value prop of KarMMa-3 and, and what, potential, you know, date of approval might look like to the extent you have these. Yeah. I mean, I'll take the last one. I think Anna can comment to that. I think it was at a prep meeting yesterday, with our partners at BMS. But yeah, the panel's on March 15th. And while we can't guide specifically, you know, the hope would be that we have a final action shortly thereafter. Hard to, again, we can't guide specifically on that. But maybe do you wanna comment on the focus of the panel? Yes. So, as I think everyone is aware, the data of overall survival are in focus. That has not only to do with the fact that we had a crossover design, which complicates, of course, the analysis, but it's also the focus of FDA in the last year that they look at overall survival as a very key and point to show that there is no detriment of the investigational agent. And of course, that's gonna be the focus of the conversation. We feel really prepared and in our dataset and confident. And of course, we are very happy to collaborate with BMS on that, who are incredibly experienced in conducting ODACs. Therefore, we are feeling confident for the next weeks. Great. Maybe just one thing to add on that. I think that same dataset has been the basis of similar processes in Japan and Europe. And we've had successful outcomes there. So, you know, I think the prep from those regulatory interactions, the learnings from those interactions, I think informs how we plan to show up with FDA next month. And again, we're looking forward to the engagement and being able to highlight the data. And, you know, I think we feel good about the prospects for expanding this for more patients here in the United States. But, of course, we have to get through the meeting. Yeah. No, that's a good reminder. And then less so on for the AdCom, but obviously, it happened around the same time. So there was, you know, kind of some investor questions. For the broader CAR-T class, of course, the FDA was investigating T-cell malignancies. And, maybe just kind of provide some color there on how it was concluded and, you know. On the T-cell malignancies? Yep. Yep. Yeah. I mean, at a high level, the commercial CAR-T class, let's say, has, as a class, a black box warning that's being implemented, related to T-cell malignancies following treatment with CAR-T, and the risk that those T-cell malignancies are vector-driven or CAR-positive, in effect. We've not seen patients treated with Abecma that have vector-driven or CAR-positive T-cell malignancies. But of course, we follow patients in clinical trials and commercial settings. You know, we have a lot of safety monitoring behind that. So, you know, it's a bit of a, at least with regard to Abecma, hypothetical, but, you know, it's, I think they cover all bases that way. We've not received any black box warning related to hematologic malignancies, secondary malignancies such as AML or MDS. As Anna said before, our background rate of those is in line with natural history. Those can also be worrisome malignancies. But again, we do not have a label that way. Great. Then assuming, you know, KarMMa-3 does get approved and the label expands into the third line, and beyond setting, I guess maybe talk about how the commercial opportunity will grow from the existing label in how it will change, you know, moving into the third line. Yeah. So today, again, estimates vary. It's tough to know with precision. But start by saying myeloma is a very large disease. And even in the fifth-line-plus setting, you know, our epidemiology would suggest about 4,000 patients on label in the United States today. Again, different people have different numbers there, but that's the number we use. We believe that the third-line-plus label that we're in front of FDA for now and if successful would be closer to 16,000 patients in the United States. So roughly a fourfold increase. And again, we've grown capacity. We have available capacity. But certainly, there's not capacity between ourselves and J&J to satisfy all of that. So, you know, we're looking forward to and planning towards a third-line launch here. And, you know, we plan to go after all eligible patients. We're not thinking kind of niched, but we think it's a very broad, broad opportunity. And we're excited to, to get after it. Great. Maybe just a bit more color there on capacity. I guess have you or Bristol kind of given any guidelines or quantified the extent to which, you know, you plan to grow capacity as you kind of enter this market that could be quadruple the size? You know, how should you think about number of slots? Yeah. No, we haven't shared those numbers. I think what we can say is that we've made successful step-ups in the past. We have the footprint to increase further. And we balance that with you know trying to achieve you know relatively high rates of capacity utilization 'cause that's you know from a business perspective thing to do. But I think the team has been really efficient and very successful and very planful in terms of those step-ups. And you know at the right times we'll look to you know make the increases we need to have the appropriate capacity. Got it. Great. And so, in addition, you're also running the KarMMa-9 study. Remind us the design there and kind of what patient population that's in and how we should think about how that would further, you know, grow the commercial opportunity. Yeah. Anna. I'm happy to speak a bit there about the design. So our KarMMa-9 study is a newly diagnosed multiple myeloma in patients who have a suboptimal response post-transplant, so less than a complete response, which is a very high unmet need population, because these patients are known to relapse faster and also are kind of getting into the relapse setting quicker. And so what we are, our design is to provide CAR-T to those patients with suboptimal response to transplant. And we are randomizing that towards lenalidomide maintenance, which is the standard of care. And we have started enrollment half a year ago, and it's going well. And so to the commercial opportunity, I don't know if you if you want to say something about that. Yeah. I mean, commercially, that, if successful, would get us north of estimated 20,000 patients in the US on label. You know, again, that's gonna play out over the next several years. And I think, stepping back, you know, we believe the whole space and the opportunity, you know, it's again not winner-take-all. And it's not gonna be determined in the next 90 days. We're, you know, I think we're incredibly fortunate with BMS to have a partner that's got a, you know, 5-10-year horizon on these things and on the cell therapy business and on the investments required to compete. And I think with the changes we talked about at the beginning here, I think we're able to invest along and ride along on that journey. Yeah. Great. And then I guess looking forward, as you're saying, you know, kind of over the next couple of years with the evolving competitive dynamic from the CAR-T assets and then also the bispecifics, you know, with KarMMa-3, with KarMMa-9, where do you think Abecma kind of has the strongest value proposition? And, you know, where is it best suited in the broader, like, full multiple myeloma market? Yeah. You know, I, I think what Anna took us through on the front line is an interesting one 'cause I think it's not all-comers. We're not trying to replace transplant. But I think both with KarMMa-9 and we touched on it. It's probably a longer conversation on KarMMa-3. But the, the patient population that we picked there is a rapidly progressing one, is an underserved one. And, and so I think I think, an underappreciated part of the story is, is, how we've thought about the design of these studies and the patients that we're going after 'cause I think they're they are ones that we could bring a real benefit to in the commercial setting. In terms of where we fit and how we compete, I, you know, I think it's there's three pieces. There's the manufacturing side, which I think we've talked about and is a source of strength. There's the safety profile, which has been consistent and I think is, as data emerge and become clearer, you know, may offer different advantages, may be different than, than other treatment alternatives. And I think the safety profile becomes even more important as you move into the earlier line setting. And, patients have more choices. And, the trade-offs between, high-risk side effects, become perhaps more stark. And then the last is on the efficacy side. And I think there, there is a, a story to tell and a story that will continue to evolve both between the real-world evidence and, understanding some of the factors that contribute to efficacy. You know, it's become increasingly clear, for instance, that the quality and depth of bridging therapy and tumor debulking is correlated with the depth and duration of response. And so that's, you know, something that we're emphasizing in our own data and when we interact with physicians. The high-risk factors like extramedullary disease and high-risk cytogenetics, you know, all of those play a role. Very tough to compare across study, though we know people love to do it. But I think that's where the real-world evidence and physicians' own experiences with the drug will inform treatment patterns over time. So again, that's why we take a very long-term view on this. And again, we like the setup. And we're really excited about 2024. Yeah. Great. Maybe just to wrap up then, I think you spoke to cash runway. But maybe just remind us, you know, maybe cash runway or, you know, when we flip maybe to cash flow positive with the franchise and then what we should look forward to in 2024. Yeah. Sure. So, as we announced last week, we have runway through 2027. And so again, obviously, the need for any capital formation or dilution of any kind, for as far as our planning horizon is, we expect to spend $80 million-$100 million this year in terms of net cash spend. And that's using, you know, fairly modest Abecma assumptions. Depending on the trajectory of Abecma, you know, we could be cash flow positive as soon as next year as a business. Again, that's not yet guidance. We need to see a couple quarters here from Abecma. But our focus is getting there as sufficiently as we can, doing what we can on the cost, structure side, which, again, we've taken big steps on, doing everything we can to support and communicate the value proposition for Abecma, and not get distracted from the mission. It's one mission. It's a clear one. You know, I think in terms of the setup for 2024, the regulatory interactions next month, hopefully, a PDUFA action shortly thereafter and an expansion in the third-line label. Then, you know, plotting, quarter by quarter. You know, again, we're set up for success. We're highly motivated. And we think we've got a really, interesting and, you know, perhaps underappreciated story to tell. Yeah. Great. With that, I think we're up on time. Thank you, Chip. Thank you, Anna, for joining us. And, thanks everyone for joining us. Thank you very much. Thank you. Thank you.